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Sample records for administration oral

  1. Oral administration of taxanes

    NARCIS (Netherlands)

    Malingré, M.M.

    2002-01-01

    Oral treatment with cytotoxic agents is to be preferred as this administration route is convenient to patients, reduces administration costs and facilitates the use of more chronic treatment regimens. For the taxanes paclitaxel and docetaxel, however, low oral bioavailability has limited development

  2. 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....

  3. 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.

  4. Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration.

    Science.gov (United States)

    Rawlins, M D; Henderson, D B; Hijab, A R

    1977-04-20

    Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose. PMID:862649

  5. Oral High-Dose Ankaferd Administration Effects on Gastrointestinal System

    OpenAIRE

    Akbal, Erdem; Köklü, Seyfettin; Astarcı, Hesna Müzeyyen; Koçak, Erdem; Karaca, Gökhan; Beyazıt, Yavuz; Topcu, Güler; Acar, Bilgehan; Ergün, Dilek; Haznedaroğlu, İbrahim Celalettin

    2013-01-01

    Background and aims: Ankaferd Blood Stopper (ABS) is a herbal extract obtained from five different plants. It has a therapeutic potential for the management of external hemorrhage and controlling gastrointestinal bleeding. However, ABS's effects are not unknown on gastrointestinal systems. The aim of this study was to assess the effect of short- and long-term systemic exposure and gastrointestinal safety following the oral administration of high-dose ABS in rats. Methods: Eighteen healthy adu...

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

    Science.gov (United States)

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

    2016-09-01

    The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. PMID:27288650

  7. 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. PMID:26000370

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

    Science.gov (United States)

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

    1981-05-01

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

  9. Metabolites of isocorynoxeine in rats after its oral administration.

    Science.gov (United States)

    Chen, Ya-Ping; Lu, Min-Nan; Hao, Jing-Chao; Li, Mei-Hong; Hattori, Masao; Wang, Wei

    2015-01-01

    This work presents the metabolites of isocorynoxeine (ICOR), which is one of four bioactive tetracyclic oxindole alkaloids isolated from Uncaria hooks used commonly in the traditional Chinese medicines and Kampo medicines. After oral administration of 40 mg kg(-1) ICOR to rats, bile was drained and analyzed by LC-MS. Two phase I metabolites, namely 11-hydroxyisocorynoxeine (M1) and 10-hydroxyisocorynoxeine (M2), and two phase II metabolites, namely 11-hydroxyisocorynoxeine 11-O-β-D-glucuronide (M3) and 10-hydroxyisocorynoxeine 10-O-β-D-glucuronide (M4), were isolated from rat excreta and bile, respectively, whose structures were elucidated on the basis of CD, NMR, and MS. PMID:25633191

  10. Thermal antinociception after dexmedetomidine administration in cats: a comparison between intramuscular and oral transmucosal administration.

    Science.gov (United States)

    Slingsby, Louisa S; Taylor, Polly M; Monroe, Taylor

    2009-10-01

    Dexmedetomidine 40microg/kg was administered either intramuscularly (IM) or oral transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal nociceptive thresholds and visual analogue scale (VAS) sedation scores were obtained before and at regular intervals up to 24h after test drug administration. The summary measures of overall mean threshold, overall mean VAS sedation plus onset, offset and duration of analgesia were investigated using a univariate general linear model. There were no significant differences between treatment groups. Data are presented as mean+/-standard deviation: delta T mean increase over time (IM 6 degrees C+/-3 degrees C, OTM 6 degrees C+/-2 degrees C); overall mean VAS (IM 43+/-9 OTM 39+/-1); onset (IM 35+/-32 and OTM 30+/-40min); offset (IM 96+/-56 and OTM 138+/-135min); duration (IM 61+/-47 OTM 99+/-124min). Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM administration of dexmedetomidine 40microg/kg produced similar overall sedative and antinociceptive effects. PMID:19577498

  11. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Science.gov (United States)

    2012-07-06

    ... adverse effects include respiratory depression, decreased blood pressure, coma, respiratory arrest, and... oxycodone for oral administration (including tablets, capsules, and oral solutions) that are labeled for... oral solutions. FDA has approved a number of immediate-release oxycodone tablets, ranging in...

  12. Effect of oral L-arginine administration on exhaled nitric oxide (no) concentration in healthy volunteers

    OpenAIRE

    Ogata, Hiroshi; Yatabe, Midori; Misaka, Shingen; Shikama, Yayoi; Sato, Suguru; Munakata, Mitsuru; Kimura, Junko

    2013-01-01

    We previously reported a case of pulmonary hypertension, where the symptoms were improved by oral L-arginine (arginine) administration. Arginine may increase nitric oxide (NO) production in the pulmonary artery. Exhaled NO may reflect pulmonary artery NO production. It has been demonstrated that exhaled NO concentration is higher in patients with allergic diseases, but whether oral arginine administration alters exhaled NO is unknown. Therefore, in this study, we investigated whether oral arg...

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

    OpenAIRE

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

    1985-01-01

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

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

    OpenAIRE

    Li-Jen Lin; Chung-Jen Chiang; Yun-Peng Chao; Shulhn-Der Wang; Yu-Ting Chiou; Han-Yu Wang; Shung-Te Kao

    2016-01-01

    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 p...

  15. Governing New Guinea. An oral history of Papuan administrators

    NARCIS (Netherlands)

    Visser, L.E.

    2012-01-01

    This is the first time that indigenous Papuan administrators share with an international public their experiences governing their country. These administrators were the brokers of development. After graduating from the School for Indigenous Administrators (OSIBA) they served in the Dutch administrat

  16. A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin)

    NARCIS (Netherlands)

    C.J.H. Gerrits; I. Hudson; J. Verweij (Jaap); D.D. Von Hoff; J.H.M. Schellens (Jan); H. Burris; J.R. Eckardt; A.S.Th. Planting (André); M.E.L. van der Burg (Maria); G.I. Rodriguez; W.J. Loos (Walter); V. van Beurden

    1999-01-01

    textabstractProlonged exposure to topotecan in in vitro and in vivo experiments has yielded the highest antitumor efficacy. An oral formulation of topotecan with a bioavailability of 32-44% in humans enables convenient prolonged administration. Pharmacokinetic/pharmacod

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

    Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

    2016-01-01

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

  20. Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs

    OpenAIRE

    Cohen, Anne E.; Bennett, Sara L.

    2015-01-01

    Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 μg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation...

  1. Transfer of orally administrated iodine-131 into chicken eggs

    Energy Technology Data Exchange (ETDEWEB)

    Uenak, Turan E-mail: unak@sci.ege.edu.tr; Yildirim, Yeliz; Avcibasi, U.; Cetinkaya, Berkan; Uenak, G

    2003-03-01

    Radioactive iodine-131 as both as free iodide (Na{sup 131}I) and covalently bound to aniline (aniline-{sup 131}I) was added to the drinking water of two Leghorn laying hens as a single dose and also as a cumulative dose over 1 week. The radioactivity of the principal parts of the eggs, i.e. shell, white, and yolk, was measured, and the radioactivity levels per gram material, and percent of the total radioactivity were calculated. The radioactivity measurements were continued for 1 month following the administration of {sup 131}I. In the case of the single dose administration, the results obtained showed that about 15% of the total radioactivity administered as Na{sup 131}I was transported into the egg structure; compared to only about 1% for aniline-{sup 131}I. After cumulative administration, about 15% of the total administered radioactivity was transported into the egg structure with both forms of {sup 131}I. This was probably because of metabolic cleavage of iodine bonds in the labeled aniline molecules during the longer period of exposure. These results also showed considerable accumulation of {sup 131}I in the egg yolks. In the case of the single dose administration, {sup 131}I can be detected in eggs up to about 20 days after administration, and up to about 30 days, in the case of the cumulative administration over 1 week.

  2. 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 < 0.01). An unfavorable outcome was associated with low concentrations of 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. PMID:26538245

  3. 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.

  4. Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs.

    Science.gov (United States)

    Cohen, Anne E; Bennett, Sara L

    2015-11-01

    Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 μg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation was achieved in all cases. PMID:26538668

  5. 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.

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

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge;

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    OpenAIRE

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

    2013-01-01

    BACKGROUND: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.METHODS: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 sam...

  9. Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

    OpenAIRE

    Freedman, Stephen B.; Steiner, Michael J.; Chan, Kevin J.

    2010-01-01

    Editors' Summary Background Although many episodes of gastroenteritis in children are mild and can be managed with oral fluids, including oral rehydration therapy (ORT), some cases are severe enough to require hospital admission for intravenous fluids. Administration of an antiemetic (a drug that reduces nausea and sickness) can be clinically effective, especially ondansetron, (a drug that belongs to a class of drugs known as selective serotonin receptor antagonists), which is safer than othe...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  11. 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. PMID:27580104

  12. Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration.

    Science.gov (United States)

    Ostrovskaya, R U; Mirsoev, T K; Romanova, G A; Gudasheva, T A; Kravchenko, E V; Trofimov, C C; Voronina, T A; Seredenin, S B

    2001-10-01

    Experiments on rats trained passive avoidance task showed that N-phenyl-acetyl-L-prolyl-glycyl ethyl ester, peptide analog of piracetam (GVS-111, Noopept) after oral administration retained antiamnesic activity previously observed after its parenteral administration. Effective doses were 0.5-10 mg/kg. Experiments on a specially-developed model of active avoidance (massive one-session learning schedule) showed that GVS-111 stimulated one-session learning after single administration, while after repeated administration it increased the number of successful learners among those animals who failed after initial training. In this respect, GVS-111 principally differs from its main metabolite cycloprolylglycine and standard nootropic piracetam. PMID:11782792

  13. 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

    2015-12-01

    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.

  14. 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.

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

    Science.gov (United States)

    Lin, Li-Jen; Chiang, Chung-Jen; Chao, Yun-Peng; Wang, Shulhn-Der; Chiou, Yu-Ting; Wang, Han-Yu; Kao, Shung-Te

    2016-01-01

    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. PMID:27403425

  16. 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.

  17. 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 a...... conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival.......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...

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

    Science.gov (United States)

    Lin, Li-Jen; Chiang, Chung-Jen; Chao, Yun-Peng; Wang, Shulhn-Der; Chiou, Yu-Ting; Wang, Han-Yu; Kao, Shung-Te

    2016-01-01

    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.

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    intraperitoneal immunization without adjuvant was measured, and oral tolerance induction against beta-LG after administration of either an aqueous solution or water-in-oil (w/o) emulsion of beta-LG was evaluated. RESULTS: LPS contamination of beta-LG provoked a beta-LG-specific IgG2a response, as well......'s milk. It is not well established, however, how this presence of LPS affects oral tolerance induction. METHODS: We studied the effect of LPS contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen-specific immune responses. IgG1/IgG2a production upon......-LG was contaminated with LPS. CONCLUSIONS: LPS contamination of an aqueous protein solution does not affect oral tolerance induction, whereas LPS present in emulsion prevents oral tolerance induction towards the food protein....

  1. 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.

  2. 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;

    2016-01-01

    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 a...

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

    Science.gov (United States)

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

    2005-09-01

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

  4. 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 18

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

    International Nuclear Information System (INIS)

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

  6. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    胡永秀; 赵文明; 钱娴娟; 张力平

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gabriela A. Albarellos

    2013-02-01

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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Nagelschmitz J

    2014-03-01

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

  12. Role of neutrophils in hepatotoxicity induced by oral acetaminophen administration in rats.

    Science.gov (United States)

    Smith, G S; Nadig, D E; Kokoska, E R; Solomon, H; Tiniakos, D G; Miller, T A

    1998-12-01

    Acetaminophen (APAP) is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbidity and mortality, secondary to hepatic toxicity. To date, the mechanism(s) whereby APAP induces liver injury remains to be delineated. This study investigated the potential role of neutrophils as contributors to liver injury in rats administered sublethal doses of APAP. Oral APAP administration (650 mg/kg) was associated with increases in serum alanine transaminase (ALT) levels indicating biochemical evidence of significant liver damage. Furthermore, histological analyses verified significant hepatocellular necrosis as well as enhanced myeloperoxidase staining in these liver specimens. However, if animals were pretreated with antineutrophil sera prior to APAP administration, neutrophil counts remained depressed, ALT levels were significantly decreased, and the degree of liver injury was attenuated on a histological level. Taken together these data suggest that neutrophils mediate, at least in part, the hepatotoxic effects of oral acetaminophen administration in rats. PMID:9878321

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

    Science.gov (United States)

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

    1997-06-01

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

  14. Transcytosis, Antitumor Activity and Toxicity of Staphylococcal Enterotoxin C2 as an Oral Administration Protein Drug

    Science.gov (United States)

    Zhao, Wenbin; Li, Yangyang; Liu, Wenhui; Ding, Ding; Xu, Yingchun; Pan, Liqiang; Chen, Shuqing

    2016-01-01

    Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

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

    Institute of Scientific and Technical Information of China (English)

    黄燕萍; 罗永梅; 王攀峰

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  17. 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

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

    Science.gov (United States)

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

    2009-04-01

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

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

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    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.

  20. Pharmacokinetics of homoplantaginin in rats following intravenous, peritoneal injection and oral administration.

    Science.gov (United States)

    Cong, Youquan; Wu, Song; Han, Jingjing; Chen, Jun; Liu, Hang; Sun, Qiwen; Wu, Yu; Fang, Yun

    2016-09-10

    The purpose of the present paper was to study the pharmacokinetic characteristics of homoplantaginin, a major active ingredient of Salvia plebeia R.Br. In this study, the effective partition coefficient, in situ absorption in rat intestinal segments and in vitro biotransformation of homoplantaginin by rat intestinal bacteria were determined. In addition, homoplantaginin was administered to rats by intravenous, peritoneal injection and oral administration. The concentrations of homoplantaginin and hispidulin, a metabolite of homoplantaginin, were determined by a validated highperformance liquid chromatographic (HPLC) assay. After intravenous, peritoneal injection, the concentration of hispidulin could not be determined. In contrast, after oral administration, hispidulin and homoplantaginin were simultaneous quantified, homoplantaginin was rapidly absorbed (Tmax=16.00±8.94min), reaching a mean Cmax between 0.77 and 1.27nmol/mL. The absolute oral bioavailability was calculated to be only 0.75%, and the area under curve (AUC) of hispidulin was about 5.4 times than that of homoplantaginin. The poor oral bioavailability may be attributed to the biotransformation of homoplantaginin by rat intestinal bacteria. PMID:27474945

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  2. Pharmacokinetics of firocoxib in preweaned calves after oral and intravenous administration.

    Science.gov (United States)

    Stock, M L; Gehring, R; Barth, L A; Wulf, L W; Coetzee, J F

    2014-10-01

    The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14-day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography-tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two-compartment model for i.v. administration and a one-compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T1/2K10 and T1/2β were 6.7 (4.6-9.7) and 37.2 (23.5-160.4) h, respectively, Vss was 3.10 (2.10-7.22) L/kg, and CL was 121.7 (100.1-156.7) mL/h/kg. Following oral administration, geometric mean (range) Cmax was 127.9 (102.5-151.3) ng/mL, Tmax was 4.0 (2.6-5.6) h, and T1/2K10 was 18.8 (14.2-25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1-117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half-life in preweaned calves. PMID:24708198

  3. 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.

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

    Science.gov (United States)

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

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P < 0.0330) after topical application (992 ng g−1 [95% CI 482, 1503], 944 [95% CI 481, 1407], 492 [95% CI 248, 735], and 455 [95% CI 153, 756], respectively) than after oral administration (150 ng g−1 [95% CI 84, 217], 186 [95% CI 118, 254], 82 [95% CI 49, 116],and 221 [95% CI, 135, 307], respectively). Conclusion Topical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  6. Plasma and milk kinetics of eprinomectin following topical or oral administration to lactating Chinese Holstein cows.

    Science.gov (United States)

    Wen, Huiqiang; Pan, Baoliang; Wang, Yuwan; Wang, Fangfei; Yang, Zhenzhong; Wang, Ming

    2010-11-24

    Chinese Holstein, bred by mating the Holstein-Friesian to Chinese Yellow Cattle, is a major dairy cattle breed in China. Eprinomectin is widely used in the treatment of nematode and ectoparasite infections in lactating cattle. The pharmacokinetics of eprinomectin in the plasma and milk were determined in Chinese Holstein cows following topical (at 0.5 mg kg(-1)) or oral (at 0.2 mg kg(-1)) administration. For topical administration, the concentrations of eprinomectin in plasma reached peak values (C(max)) of 16.16 ± 6.02 ng ml(-1) at 3.20 ± 1.30 days (T(max)). In milk, the C(max) values of 2.28 ± 0.85 ng ml(-1) were obtained at 3.48 ± 0.65 days. The MRT values were 5.00 ± 0.96 days for plasma and 4.65 ± 0.60 days for milk. The AUC values were 91.00 ± 25.32 ng d ml(-1) for plasma and 10.53 ± 1.55 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.124 ± 0.041. Significant differences were found in C(max) and AUC of eprinomectin in plasma between Chinese Holstein and Prim Holstein following topical administration. It was probably due to the lower storage of body fat in Chinese Holstein than in Prim Holstein. For oral administration, the concentrations of eprinomectin reach peak values of 30.02 ± 5.73 ng ml(-1) at 1.60 ± 0.55 days in plasma and 3.14 ± 0.88 ng ml(-1) at 1.40 ± 0.27 days in milk. The MRT values for plasma and milk were 3.00 ± 0.46 and 3.18 ± 0.55 days, respectively. The AUC values were 98.46 ± 24.75 ng d ml(-1) for plasma and 10.42 ± 4.22 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.104 ± 0.022. Compared with the topical administration, a significantly shorter MRT of eprinomectin in plasma was obtained following oral administration, which would shorten residue time of this compound in faeces and reduce its ecotoxicological effect. The low exposure of eprinomectin in milk would favor the use of eprinomectin in lactating Chinese Holstein for topical or oral administration. PMID:20851527

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

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    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.

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

    Science.gov (United States)

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

    2014-04-23

    Postsurgical oral self-administration of analgesics in rodents is an interesting technique of providing analgesia, avoiding the negative effects of manipulation. Several strategies, using gelatin or nutella, have already been described. However, rodents require some habituation period to reach a good intake because of their neophobic behavior. The current study aimed to explore whether buprenorphine when mixed with an extruded diet offers a potential treatment option in the pain management of mice using a triple approach: by measuring the spontaneous intake in healthy animals; by using the hot-plate test; and finally by assessing the drug's ability to provide postoperative analgesia in a surgical intervention of moderate severity (intra-utero electroporation). Mice consumed during 20 hours, similar amounts of extruded diet alone, mixed with glucosaline, and mixed with buprenorphine (0.03 mg per pellet) or meloxicam (0.25 mg per pellet) both of which were diluted in glucosaline, showing that no neophobia was associated with these administrations. Relative increase from baseline latency (% maximal possible effect) in the hot-plate test at 20 h of administration was significantly higher for oral buprenorphine in diet 0.03 mg/pellet, and diet 0.15 mg/pellet, compared with placebo and no differences were found between those oral administrations and subcutaneous buprenorphine 0.1 mg/kg measured 3 h later. The treatment was also effective in attenuating the reductions in food consumption and body weight that occur after surgery. These data suggest that providing buprenorphine with the diet is a feasible and effective way of self-administration of analgesia in mice and does not cause neophobia and may easily contribute to the refinement of surgical procedures. PMID:24759572

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

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    Ravi S.Talluri

    2009-10-01

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

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

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1981-07-01

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

  11. Oral Administration of Surfactant Protein-A Reduces Pathology in an Experimental Model of Necrotizing Enterocolitis

    Science.gov (United States)

    Quintanilla, Hector D.; Liu, Yuying; Fatheree, Nicole Y.; Atkins, Constance L.; Hashmi, Syed S.; Floros, Joanna; McCormack, Francis X.; Rhoads, Jon Marc; Alcorn, Joseph L.

    2016-01-01

    OBJECTIVES Necrotizing enterocolitis (NEC) frequently results in significant morbidity and mortality in premature infants. Others reported that mice deficient in pulmonary surfactant protein-A (SP-A) born and raised in a nonhygienic environment succumb to significant gastrointestinal tract pathology, and enteral administration of purified SP-A significantly reduced mortality. We hypothesized that oral administration of purified SP-A can ameliorate pathology in an experimental model of neonatal NEC. METHODS Experimental NEC was induced in newborn Sprague-Dawley rat pups by daily formula gavage and intermittent exposure to hypoxia. Purified human SP-A (5 μg/day) was administered by oral gavage. After 4 days, surviving pups were sacrificed, and intestinal pathology was assessed by histological examination of distal terminal ileal sections. Intestinal levels of inflammatory cytokines (IL-1β, IFN-γ and TNF-α) were assessed by ELISA and levels of toll-like receptor 4 (TLR4) by western analysis. RESULTS 61% of the gavaged rat pups that survived to day 4 met the criteria for experimental NEC after hypoxia while treatment with SP-A significantly reduced mortality and assessment of NEC. Intestinal levels of pro-inflammatory cytokines were significantly increased in pups exposed to hypoxia. Administration of SP-A to pups exposed to hypoxia significantly reduced IL-1β and TNF-α levels, but had little effect on elevated levels of IFN-γ. SP-A treatment of hypoxia-exposed pups significantly reduced expression of intestinal TLR4, key in NEC pathogenesis. CONCLUSIONS In a rat model of experimental neonatal NEC, oral administration of SP-A reduces intestinal levels of pro-inflammatory cytokines and TLR4 protein, and ameliorates adverse outcomes associated with gastrointestinal pathologies. PMID:25539191

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

    Science.gov (United States)

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

    2006-06-01

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

  13. Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity.

    Science.gov (United States)

    Lee, S Y; Huang, C K; Zhang, T F; Schofield, B H; Burks, A W; Bannon, G A; Sampson, H A; Li, X M

    2001-11-01

    There is no satisfactory therapeutic intervention for peanut allergy, which accounts for most life-threatening food allergic reactions. Since IL-12 has been found to inhibit allergic airway responses in a mouse model of asthma and to cure Th2 cytokine-mediated murine schistosomiasis, we hypothesized that IL-12 treatment might also inhibit peanut allergic reactions. Consequently, we investigated the effects of oral IL-12 treatment in a murine model of peanut allergy and found that oral administration of liposome encapsulated rIL-12 could both prevent and reverse peanut hypersensitivity and could reduce histamine release, peanut-specific serum IgE and IgG1, and fecal IgA levels. Oral IL-12 treatment also increased IFN-gamma but did not decrease IL-4 or IL-5 levels. We conclude that oral rIL-12 treatment has therapeutic as well as preventive effects on peanut allergy, which are associated with increased IFN-gamma production. PMID:11683581

  14. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

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    Iwao Sasaki

    2010-09-01

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

  15. 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...

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Harigae T

    2016-06-01

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

  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. PMID:26102179

  20. 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.

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

    International Nuclear Information System (INIS)

    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 [14C]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 14C-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 14C-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

  2. Pharmacokinetics of gallium nitrate after oral administration in adult horses--pilot study.

    Science.gov (United States)

    Pollina, G F; Zagotto, G; Maritan, P; Iacopetti, I; Busetto, R

    2012-10-01

    Gallium (Ga), a metal in group IIIA of the periodic table, has shown a remarkable activity against bone resorption and could therefore possibly prove useful in the treatment of certain diseases in sport horses, for example navicular disease. The aim of this study was to gain more information concerning the kinetics of Ga after oral administration of gallium nitrate (GaN) in adult horses. Six horses received a single dose of 10 mg/kg of GaN mixed with the food ration. Absorption was slow (T(max) = 10 ± 3 h, T(½abs) = 2 ± 0.8 h), and a C(max) of 26 ± 11 μg/L was achieved. Excretion followed a one-phase elimination model, with a long half-life (T(½el) = 52 ± 14 h). By means of a mathematical model, we estimated that the plasmatic levels should reach 93 μg/L (1.33 μm) at steady state, following the repeated daily administration of 10 mg/kg of GaN. A three times lower concentration has been demonstrated as effective in inhibiting the osteolytic activity of osteoclasts in vitro. The results of this study suggest that the administration of oral GaN at a rate of 10 mg/kg per day may be considered for future clinical studies. PMID:21913939

  3. 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. PMID:25433717

  4. Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

    Science.gov (United States)

    Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

    2016-06-01

    Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. PMID:26964683

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

    OpenAIRE

    Balani, Tarun; Agrawal, Seema; Thaker, A. M.

    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), ...

  6. Medroxyprogesterone acetate plasma levels after a single oral administration of two drug formulations.

    Science.gov (United States)

    Pannuti, F; Strocchi, E; Longhi, A; Comparsi, R; Camaggi, C M

    1986-08-01

    A comparison has been made between the absorption of oral medroxyprogesterone acetate (MPA) in an aqueous suspension preparation and in syrup form. Plasma drug profiles were measured after a single administration of the two formulations in 17 advanced cancer patients. On average the standard form (aqueous suspension) gave peak levels which were lower than the syrup mixture. However, the wide intersubject spread in MPA plasma levels observed in both groups did not allow any statistical significance to be assigned to this difference. PMID:2945648

  7. Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients

    OpenAIRE

    Malingré, M M; Beijnen, J H; Rosing, H; Koopman, F J; Jewell, R C; Paul, E M; Huinink, W W ten Bokkel; Schellens, J H M

    2001-01-01

    Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocker cyclosporin A (CsA). Now we tested the potent alternative orally applicable non-immunosuppressive P-gp blocker GF120918. Six patients received one course of oral paclitaxel of 120 mg/m2 in combin...

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

    Directory of Open Access Journals (Sweden)

    Makoto Akao

    2015-01-01

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

  9. 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...

  10. 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

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

    Science.gov (United States)

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

    2012-11-01

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

  12. 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.

  13. Localization of chyle leakage site in postoperative chylothorax by oral administration of I-123 BMIPP.

    Science.gov (United States)

    Sugiura, Kimihiko; Tanabe, Yoshio; Ogawa, Toshihide; Tokushima, Takeshi

    2005-10-01

    The authors present a 71-year-old woman who had a right chylothorax after right upper lobectomy for lung cancer. As the chylothorax was considered to be due to thoracic duct injury at the time of operation, lymphoscintigraphy was performed by oral administration of I-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP). After visualization of the stomach and intestine, abnormal accumulation of the radiotracer was found initially around the right pulmonary hilum and then spread laterally in the upper pleural cavity, indicating chyle leakage in the region of the right pulmonary hilum. Scintigraphic finding was well correlated with the subsequent thoracoscopic observation, showing chyle leakage from a lymphatic tributary near its confluence to the thoracic duct at the level of the azygos continuation. The disruption site was ligated by video-assisted-thoracoscopic-surgery procedure with successful termination of the chyle leakage. Lymphoscintigraphy by oral administration of I-123 BMIPP is thought to be a useful method for localization of chyle leakage in patients with chylothorax induced by thoracic surgery. PMID:16363625

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

    Directory of Open Access Journals (Sweden)

    Tae Hwan Kim

    2014-01-01

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

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

    Science.gov (United States)

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

    1998-10-01

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

  16. Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration.

    Science.gov (United States)

    Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S

    2008-10-01

    The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning. PMID:19000263

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

    Directory of Open Access Journals (Sweden)

    Zhang ZH

    2012-07-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  19. The effect of the oral administration of polymeric nanoparticles on the efficacy and toxicity of tamoxifen.

    Science.gov (United States)

    Jain, Amit K; Swarnakar, Nitin K; Godugu, Chandraiah; Singh, Raman P; Jain, Sanyog

    2011-01-01

    The present investigation reports on the conditions for preparation of tamoxifen loaded PLGA nanoparticles (Tmx-NPs) for oral administration. Tmx-NPs with >85% entrapment efficiency and 165.58 ± 3.81 nm particle size were prepared and freeze dried. Freeze dried Tmx-NPs were found to be stable in various simulated GIT media (pH 1.2, pH 3.5, pH 6.8, SGF & SIF). No significant changes in characteristics of Tmx-NPs were observed after 3 months accelerated stability studies. The cell viability in C127I cells was found to be relatively lower in Tmx-NP treated cells as compared to free Tmx treated cells. CLSM imaging reveled that nanoparticles were efficiently localized into the nuclear region of C127I cells. Oral bioavailability of Tmx was increased by 3.84 and 11.19 times as compared to the free Tmx citrate and Tmx base respectively, when formulated in NPs. In vivo oral antitumor efficacy of Tmx-NPs was carried out in DMBA induced breast tumor model and tumor size was reduced up to 41.56% as compared to untreated groups which showed an increase in tumor size up to 158.66%. Finally, Tmx-NPs showed the marked reduction in hepatotoxicty when compared with free Tmx citrate as evidenced by histopathological examination of liver tissue as well as AST, ALT and MDA levels. Therefore Tmx-NPs could have the significant value for the oral chronic breast cancer therapy with reduced hepatotoxicity. PMID:20934747

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

    Science.gov (United States)

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

    2015-08-01

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

  1. 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

  2. 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. PMID:25115596

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration.

    Science.gov (United States)

    Ellefsen, Kayla N; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2016-03-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  8. 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.

  9. 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.

  10. 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. PMID:27463556

  11. 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

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

    Science.gov (United States)

    Kim, H S; Kim, M S

    1990-12-01

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

  13. 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.

  14. 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......-94%). The morphological distribution of resistant bacteria was not affected by the doxycycline therapy. Thus, local doxycycline therapy resulted only in a transient increase in resistance in the oral microflora....

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

    Directory of Open Access Journals (Sweden)

    Lee CM

    2014-12-01

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

  16. Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature

    Science.gov (United States)

    Eek, Daniel; Krohe, Meaghan; Mazar, Iyar; Horsfield, Alison; Pompilus, Farrah; Friebe, Rachel; Shields, Alan L

    2016-01-01

    Objective The emergence of various modes of administration for cancer treatment, including oral administration, brings into focus the importance of patient preference for administration. The purpose of this research was to evaluate the administration preferences of cancer patients, specifically between oral and intravenous (IV) treatment, as well as the factors contributing to preference. Methods A literature search was conducted in OvidSP to identify research in which the preferences of cancer patients for oral or IV treatment have been evaluated. Data were analyzed in two stages: 1) those articles that directly compared preference between modes of administration were tallied to determine explicit preference for oral or IV treatment; and 2) all attributes associated with patient preference were documented. Results Of the 48 abstracts identified as part of the initial OvidSP search, eight articles were selected for full-text review. One article was removed following full-text review, and seven additional articles were identified through a gray literature search, yielding a total of 14 articles for evaluation. In Stage 1, 13 of the 14 articles compared preference, of which eleven articles (84.6%) reported that patients preferred oral treatment over IV, while two (15.4%) stated that cancer patients preferred IV treatment over oral. In Stage 2, the most frequently reported attributes contributing to preference included convenience, ability to receive treatment at home, treatment schedule, and side effects. Discussion Evidence suggests that oncology patients prefer oral treatment to IV. Rationale for preference was due to a number of factors, including convenience, perception of efficacy, and past experience. Further evaluation should be conducted, given the limited data on patient preference in oncology. PMID:27601886

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

    Science.gov (United States)

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

    2010-12-01

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

  18. 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.

  19. 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.

  20. Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis

    International Nuclear Information System (INIS)

    Fullerenes characterized as an antioxidant are believed to reduce various reactive chemical species, such as free radicals, and their characteristic features have been disclosed to furnish many useful medical technologies. Despite the numerous applications for the biological efficacy of fullerenes, less is known about the toxicity of fullerenes in mammals. Hence, the protocol was designed to determine the acute oral median lethal dose and evaluate the acute toxicity of fullerenes when administrated as a single dose to Sprague-Dawley rats. In an acute toxicity test, fullerenes were administered once orally to a single group of male and female at a dose level of 2000 mg/kg. No deaths were observed and the body weights in both sexes of 2000 mg/kg group increased in a similar pattern to the control group. Genotoxicity of fullerenes was also assessed in a bacterial reverse mutation assay (Ames test) and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. Although structural chromosomal aberrations were induced at up to 5000 μg/mL, there was no significant increase in the frequency of chromosomal aberrations at any dose level regardless of presence of S9. Fullerenes did not cause genetic damage in Salmonella typhimurium TA100, TA1535, TA98 and TA1537 and Escherichia coli WP2uvrA/pKM101. These results indicate that fullerenes are not of high toxicological significance

  1. Dose-dependent ultrastructural changes in rat cornea after oral methylphenidate administration

    International Nuclear Information System (INIS)

    Objective was to investigate dose-dependent ultrastructural changes in rat cornea after oral methylphenidate (Ritalin) administration. This study was conducted in the Dept. of Anatomy, Gazi University, Faculty of Medicine, Ankara between March and May 2005, with a total of 27 female prepubertal Wistar albino rats, divided into 3 different dose groups (5mg/kg, 10 mg/kg, 20 mg/kg) and their control groups. They were treated orally with methylphenidate and eye tissue was removed to process for electron microscopic studies. We observed that all cells and prominently basal cells of the corneal epithelium show dose-dependent degenerative changes such as apoptotic bodies, chromatin condensation and ondulation in their nuclei and crystolysis of the mitochondrion. In the stroma, the most evident finding was the increase of the collagen fiber. In addition to dose-dependent changes related to apoptotic process, which is chromatin condensation in their nuclei, electron dense material accumulation and percicellular edema in the cytoplasm were also seen. In the endothelial cell lines, disruption of the junctional complexes, vacuolization in the cell cytoplasms and crystolysis of the mitochondrion's with rough endoplasmic reticulum cisternae activity were observed. Ritalin is inducing an evident degeneration, especially in epithelium cells with increasing doses. Ultrastructural cell organelle composition degeneration with stromal fibrosis has negative effect on cornea dehydration. In light of these findings, we believe that the Ritalin treatment dose needed to be kept to a minimum to maintain healthy cornea ultrastructure and related physiology. (author)

  2. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.

    Science.gov (United States)

    Golasik, Magdalena; Herman, Małgorzata; Olbert, Magdalena; Librowski, Tadeusz; Szklarzewicz, Janusz; Piekoszewski, Wojciech

    2016-04-15

    Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients. PMID:26892718

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

    Science.gov (United States)

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

    2016-04-01

    Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection. PMID:26164467

  4. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.

    Science.gov (United States)

    Golasik, Magdalena; Herman, Małgorzata; Olbert, Magdalena; Librowski, Tadeusz; Szklarzewicz, Janusz; Piekoszewski, Wojciech

    2016-04-15

    Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients.

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

    Science.gov (United States)

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

    2015-04-01

    Propolis, a natural product derived from plants by honeybees, is a mixture of several hundred chemicals, including flavonoids, coumaric acids, and caffeic acids, some of which show estrogen-like activity. In this study, the estrogenic activity of crude ethanolic extract of Brazilian propolis was determined using several in vitro and in vivo assays. Propolis was found to bind to human estrogen receptors (ERs). Furthermore, propolis induced the expression of estrogen-responsive genes in ER-positive MCF-7 and Ishikawa cells. These in vitro assays suggest that propolis exerts estrogenic activity; therefore, in vivo experiments were conducted using ovariectomized rats. Oral administration of propolis (55 or 550 mg/kg/day for 3 days) significantly increased uterine wet weight and luminal epithelium thickness in comparison with the corresponding values in the corn oil-treated control group. Moreover, propolis induced ductal cell proliferation in the mammary glands. These effects were completely inhibited by full ER antagonist ICI 182,780, confirming that the effects of propolis are mediated by the ER. Our data show that oral intake of propolis induces estrogenic activity in ER-expressing organs in vivo and suggest that Brazilian propolis is a useful dietary source of phytoestrogens and a promising treatment for postmenopausal symptoms. PMID:25786527

  6. Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals.

    Science.gov (United States)

    Hovanessian, N; Davis, J L; McKenzie, H C; Hodgson, J L; Hodgson, D R; Crisman, M V

    2014-06-01

    The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half-life was approximately 11 h. Firocoxib was below the limit of detection (firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg. PMID:24749691

  7. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    Science.gov (United States)

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

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

    Science.gov (United States)

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

    2003-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-01-01

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

  11. Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs.

    Science.gov (United States)

    Collins, Sean P; Labelle, Amber L; Dirikolu, Levent; Li, Zhong; Mitchell, Mark A; Hamor, Ralph E

    2016-09-01

    OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug. PMID:27556265

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

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    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.

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

    Science.gov (United States)

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    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. PMID:24489866

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

    Science.gov (United States)

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

    2006-08-01

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

  15. 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,...

  16. Oral administration of levan polysaccharide reduces the alloxan-induced oxidative stress in rats.

    Science.gov (United States)

    Dahech, Imen; Belghith, Karima Srih; Hamden, Khaled; Feki, Abdelfattah; Belghith, Hafedh; Mejdoub, Hafedh

    2011-12-01

    This study aimed to evaluate the effect of a polysaccharide named levan, which was produced by new isolated bacteria, on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan polysaccharide was given in drinking water for 60 days at a daily dose equivalent to 2%. The oral administration of levan in diabetic rats caused a decrease in glucose level in plasma and an increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in both pancreas and liver. Furthermore, a protective action against hepatic and pancreatic toxicity in diabetic rats was clearly observed. Furthermore, a significant decrease in hepatic and pancreatic indices toxicity was observed, i.e., alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT), lactate deshydrogenases (LDH) activities and the thiobarbituric acid-reactive substances (TBARs). These beneficial effects of levan were confirmed by histological findings in hepatic and pancreatic tissues of diabetic rats. This study demonstrates for the first time that levan is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that administration of levan may be helpful in the prevention of diabetic complications associated with oxidative stress. PMID:21925206

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

    Science.gov (United States)

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

    2014-11-01

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

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

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    C. GAVAN

    2013-07-01

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

  19. 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. PMID:24354928

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

    OpenAIRE

    Maureen Higgs; Erroll Hull; Eugenio Lujan

    2014-01-01

    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...

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

    Science.gov (United States)

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

    2016-08-01

    Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals. PMID:27216768

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

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    Jie Zhao

    2015-11-01

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

  3. 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.

  4. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  6. 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. PMID:22514127

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Hansen, Marianne;

    2014-01-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

  12. 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

  13. 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

  14. 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%. PMID:11308331

  15. 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.

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. PMID:24919144

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Susanne W. Bruun

    2016-01-01

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

  1. Histological Effects of Oral Administration of Artesunate on the Liver in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Dr. Al-Hassan M. Izunya

    2010-07-01

    Full Text Available This experiment was designed to study the histological effects of oral administration of normal anddouble normal doses of artesunate on the histology of the liver in wistar rats. The rats were divided into threegroups (A, B and C of five rats each. A and B served as the treatment groups, while C served as the controlgroup. Group A rats were given 4 mg/kg b.w of artesunate daily for 3 days followed by 2 mg/kg b.w daily fornext for 4 days. Group B rats were given 8 mg/kg2 b.w of artesunate daily for 3 days followed by 4 mg/kg b.wdaily for next 4 days, while group C rats were given only distilled water. The rats were fed with grower's mashpurchased from Edo feeds and Flour M ill Ltd, Ewu, Edo state and were given water ad libitum. On day eightof the experiment, the rats were weighed and sacrificed by cervical dislocation. The livers were carefullydissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after Hand E method showed sinusoidal congestion with cytoplasmic vacuolation (hepatocyte oedema and mildinflammation of the portal tracts. Our study suggests that artesunate at normal dose has a toxic effect on theliver cells and could be a potential hepatotoxic drug. It is therefore recommended that further studies aimedat corroborating these observations be carried out and self-medication with artesunate should be discouraged.

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

    Science.gov (United States)

    Kluk, Anna; Sznitowska, Malgorzata

    2014-01-01

    Modern solid multiparticulate drug forms (minitablets, pellets, granules) can provide the possibility of precise dosing or modified drug release or taste masking for medicines used in children. However, these solid particles require an adequate medium to ease swallowing. The aim of the research was to design a universal semisolid dispersing medium for administration of minitablets and pellets. High viscosity sodium carmellose and carbomer were considered as gelling agents. The hydrogels were prepared with sucrose, glycerol, and potassium sorbate or parabens. Preliminary studies were undertaken to estimate the application properties of the gels under conditions where a medicine is administered to a child. Besides standard tests (viscosity, sedimentation) the following measurements were conducted: gel ductility, mass of the gel removed from a spoon under shaking, ability of the gels to disperse solid particles, and disintegration of minitablets in the gels. The oral hydrogels prepared either with 1.0% and 1.5% carmellose or 0.25% and 0.5% (w/w) carbomer were suitable for dispersing and delivery of minitablets or pellets. Not only viscosity but also ductility was an essential criterion in selecting the best vehicle. The in vivo perceptibility test for pellets and minitablets did not confirm that gels are more advantageous than syrups. PMID:24216119

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2002-09-01

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

  5. The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

    Science.gov (United States)

    Rumpler, M J; Colahan, P; Sams, R A

    2014-02-01

    A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration. PMID:23859819

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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....

  9. [Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

    Science.gov (United States)

    Raschka, C; Koch, H J

    2001-01-01

    We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks. PMID:11878089

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-10-15

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

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

    Science.gov (United States)

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

    2014-01-01

    The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant used for the management of inflammation-related diseases. ROQUETTE Chlorella sp. (RCs) was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered by topical application after scarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopic score with cutaneous application. The microalgae had also efficient effect on healing process and duration of wound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest that administration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions. PMID:24965517

  12. Pharmacokinetics and metabolism study of veratramine in mice after oral administration using LC-MS/MS.

    Science.gov (United States)

    Cong, Yue; Zhang, Jun-Li; Li, Sha-Sha; Shen, Shan; Wang, Jiang-Ying; Cai, Zongwei

    2016-09-01

    A simple and sensitive high-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry (Q-trap-MS) method was developed and validated for the determination of veratramine, the major bioactive and neurotoxic component in Veratrum nigrum L. Veratramine and the internal standard (IS) were separated with a Waters Symmetry C18 column and eluted with a gradient mobile phase system containing acetonitrile and 0.1% aqueous formic acid. The analysis was performed by using positive electrospray ionization mode with multiple reaction monitoring (MRM). Transition ions of m/z 410.2 → 295.2 for veratramine and m/z 426.1 → 113.8 for the IS were monitored. The method was validated with a good linearity in the range of 1-1000 ng/mL and lower limit of quantification of 1 ng/mL. The precision (CV) of intra- and inter-day ranged from 3.92 to 7.29%, while the accuracy (bias) intra- and inter-day were between -4.78 and 1.65%. The recovery, stability and matrix effect were within the acceptable ranges. Five metabolites of veratramine, including four hydroxylated and one sulfated metabolites, were tentatively identified using predictive MRM-information dependent acquisition-enhanced product ion mode (predictive MRM-IDA-EPI). The developed method was successfully applied to the pharmacokinetic and metabolic study of veratramine in mice after oral administration of veratramine. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26972867

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lindinger Michael I

    2007-12-01

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

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

    Science.gov (United States)

    Kersten, E; Barry, A; Klein, S

    2016-03-01

    Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development. PMID:27183705

  17. Metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of oral-administrated berberine

    OpenAIRE

    Gu, Shenghua; Cao, Bei; Sun, Runbin; Tang, Yueqing; Paletta, Janice L.; Wu, Xiao-Lei; Liu, Linsheng; Zha, Weibin; Zhao, Chunyan; Li, Yan; Radlon, Jason M.; Phillip B Hylemon; Zhou, Huiping; Aa, Jiye; Wang, Guangji

    2014-01-01

    Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-...

  18. Oral administration of herbal medicines for the treatment of otitis media with effusion: protocol for a systematic review

    OpenAIRE

    Kim, Yun Hee; Son, Mi Ju; Kim, Young-Eun; Lee, Hye Won; Lee, Myeong Soo

    2014-01-01

    Introduction The purpose of this systematic review is to investigate the efficacy of the oral administration of herbal medicines for otitis media with effusion through analysing trial data. Methods and analysis Electronic searches of the following 11 databases will be performed: MEDLINE, CINAHL, EMBASE, AMED, the Cochrane CENTRAL, 3 Chinese databases (CNKI, Wangfang Data and VIP Information) and 5 Korean databases (KoreaMed, Research Information Service System, Korea Studies Information Syste...

  19. Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats

    OpenAIRE

    Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Ashrafi, Farzaneh

    2013-01-01

    Background Cisplatin (CP) therapy as the most common potent chemotherapeutic process is accompanied by nephrotoxicity. The diabetic state may protect rat kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the glucose level in diabetic animals. Objectives Current study was planned to investigate the effect of oral administration of magnesium supplementation on CP-induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats. Materials and Methods Male...

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

    OpenAIRE

    Hong-Wu Zhang; Jing-Bo Peng; Chang-Yuan Yu; Zhong-Mei Zou; Shu-Qi Li; Zhi-Heng Su; Shu Dong

    2013-01-01

    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 rat...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    PURPOSE: This study evaluated the effect of corticosteroid (CS) administration on edema, analgesia, and neuroregeneration in conjunction with surgical dental extraction, orthognathic surgery, and the risk of developing side effects. MATERIALS AND METHODS: A systematic search of the literature...... was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease...

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

    Indian Academy of Sciences (India)

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

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  4. 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.

  5. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    the conventional antibiotic oxolinic acid. Oral administration of CAP18 to trout did not prevent infection. The proteolytic effect of secretions on the peptide CAP18 in the fish gastrointestinal tract is suggested to account for the inferior effect of oral administration....... disease caused by this pathogen either following i.p. injection or by oral administration (in feed). It was found that injection of CAP18 into juvenile rainbow trout before exposure to Y. ruckeri was associated with lowered mortality compared to non-medicated fish although it was less effective than...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion of...

  8. 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 deter

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

    Pin Marie; Buclin Thierry; Appenzeller Monique; Rothuizen Laura E; Augsburger Marc; Ménétrey Annick; Favrat Bernard; Mangin Patrice; Giroud Christian

    2005-01-01

    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 ad...

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

    Directory of Open Access Journals (Sweden)

    Ibiyeye Yetunde Rukayat

    2012-08-01

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

  12. 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

  13. 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

  14. 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.

  15. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.;

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...... 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. © 1990....

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

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

  18. Low bioavailability of ergotamine tartrate after oral and rectal administration in migraine sufferers.

    OpenAIRE

    Ibraheem, J J; Paalzow, L; Tfelt-Hansen, P

    1983-01-01

    Fifteen migraine patients were administered 2 mg ergotamine tartrate in a partial cross-over design as a single, oral tablet, rectal suppository and rectal solution. Eight of these patients were in a previous investigation given 0.5 mg ergotamine tartrate intravenously. The blood samples were taken up to 54 h after oral and suppository while it was followed for only 3 h after rectal solution. The chemical analysis was performed by applying h.p.l.c. method with a limit of sensitivity of 0.1 ng...

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

    Science.gov (United States)

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

    2008-10-01

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

  20. 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.

  1. Efficacy of oral and intraperitoneal administration of CBMIDA for removing uranium in rats after parenteral injections of depleted uranium

    International Nuclear Information System (INIS)

    The efficacy of oral administration of the chelating agent catechol-3, 6-bis(methyliminodiacetic acid) (CBMIDA) for removing uranium from rats after intraperitoneal (i.p.) and intramuscular (i.m.) injections of depleted uranium (DU) was examined and the results with those by the i.p. injection of CBMIDA were compared. In Experiment 1, after a single i.p. injection of 8 mg kg-1 of DU of rat's body weight, 35 8-week-old male rats were divided into seven groups consisting of five rats each. Three groups were administered with CBMIDA 240, 720 or 1200 mg kg-1 of rat's body weight orally once a day, and three other groups received an i.p. injection of 240, 480 or 720 mg kg-1 CBMIDA for 3 d, starting 30 min after DU injection on the first day. One DU group received no CBMIDA. The remaining five intact rats were used as a control group. Rats were killed 6 d after DU injection. In Experiment 2, the 35 male rats that received a single i.m. injection of 8 mg kg-1 DU were divided into seven groups, and the rats of each group received the same doses of CBMIDA on the same schedules of treatment as those described in Experiment 1. The results obtained in Experiment 1 indicated that orally administered CBMIDA significantly increased the excretion of uranium at doses of 720 and 1200 mg kg-1 and decreased uranium concentrations, particularly in the kidney, at all the doses tested, and the effects were almost equal to those of the i.p. injection. The lack of increases in creatinine and blood urea nitrogen in serum indicated that CBMIDA is efficacious in preventing the renal dysfunction caused by uranium. In Experiment 2, oral administration of CBMIDA significantly increased uranium excretion and significantly decreased uranium concentrations, particularly in the kidneys, at all the doses tested, and the effects were almost equal to those of the i.p. injection. However, these effects of CBMIDA on the i.m.-injected DU were lower than those of the i.p.-injected DU in Experiment 1. These

  2. 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 (poil biodiesel could be chosen as an alternative fuel instead of diesel fuel.

  3. 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...

  4. 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.

  5. Ovine progressive pneumonia virus is transmitted more effectively via aerosol nebulization than oral administration

    Science.gov (United States)

    A new method of experimental infection of ovine progressive pneumonia virus (OPPV), aerosol nebulization (Nb), was compared to intravenous (IV) and oral (PO) methods of experimental infection. Seven month old lambs were given 3.5 × 107 TCID50 of Dubois OPPV LMH19 isolate using IV, PO, or Nb methods ...

  6. Subjective and physiological effects after controlled Sativex and oral THC administration.

    Science.gov (United States)

    Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

    2011-03-01

    Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. PMID:21289620

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nélida Barrueco

    2008-03-01

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

  9. 临床口服药的安全管理%Scurity management of clinical oral administration

    Institute of Scientific and Technical Information of China (English)

    宋美燕; 蔡兰妹; 许丽芳

    2011-01-01

    探讨临床口服用药中的安全隐患及管理对策.从护理部-督导办-护士长三级质控及药剂科定期、不定期对临床口服药应用的检查,以及关于口服药护理不良事件报告中,分析临床口服药存在的安全隐患.从口服药医嘱审核、配置与领取、存放与保管、发药到患者,整个过程的各个环节均存在安全隐患.护理管理者应从严格落实医嘱执行制度及药品管理制度、加强医嘱的审核、强调医护药协调合作、加强护士药物知识培训、加强备用药物管理、加强患者健康教育,提高服药依从性、引进先进仪器,提高工作有效性等方面来提高临床用药安全.%To investigate hidden dangers nd management countermeasures of clinical oral administration The potential safety hidden dangers in clinical oral administration were analyzed through three- level quality control of nursing development,supervision office and head nurse,regular or irregular inspection on clinical oral administration made by pharmacy department,and the adverse nursing incident reports of oral administration.Hidden danger existed in every link of the whole process from medical order examination,drug disposal,storage and dispensation.Nursing managers could improve medication safety by strictly carrying out medical order execution system and drug management system,strengthening prescription examination,doctor-nurse cooperation and nurse training on pharmacological knowledge,giving patients health education to guarantee drug compliance,and introducing advanced instrument to raise work efficiency.

  10. Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

    OpenAIRE

    Supanimit Teekachunhatean; Nisanuch Tosri; Noppamas Rojanasthien; Somdet Srichairatanakool; Chaichan Sangdee

    2013-01-01

    The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receiv...

  11. Comparative study of absorption and distribution of dexamethasone 3H after percutaneous or oral administration in mice and rats

    International Nuclear Information System (INIS)

    Percutaneous absorption of dexamethasone in alcoholic solution in mice and rats was low. Permeability constant measured on mice was included between 1.05 and 1.39.10-5cm/h. Under the site of application, a retention appeared in subcutaneous tissue and skeletal muscles which explained local pharmacological action. In other tissues (plasma, liver, kidney, adrenals and muscles), level of corticoid remained very low. On the contrary after oral administration, dexamethasone was present everywhere, concentration was the highest in liver and kidney

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

    Institute of Scientific and Technical Information of China (English)

    Chang Shan; Liu Yuan; Bo Xiuzhen; Qi Aiju

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

  14. Short-term effects of oral dronedarone administration on cardiac function, blood pressure and electrocardiogram in conscious telemetry dogs.

    Science.gov (United States)

    Saengklub, Nakkawee; Youngblood, Brad; Del Rio, Carlos; Sawangkoon, Suwanakiet; Hamlin, Robert L; Kijtawornrat, Anusak

    2016-07-01

    Dronedarone is a multichannel blocking antiarrhythmic drug that has been used for management of atrial fibrillation in humans, but the data in veterinary medicine are inadequate. The objective of this study was to determine the short-term effects of oral dronedarone on cardiac inotropy and lusitropy, blood pressure and electrocardiogram (ECG) in healthy dogs. A total of 6 beagle dogs were instrumented with telemetry units and sono-micrometry crystals to obtain left ventricular pressure-volume relationship, mean blood pressure (MBP) and ECG. Dogs were given orally dronedarone (20 mg/kg, twice per day) for 7 days. All parameters were obtained hourly at 4-8 hr after the first dose and at 12-, 96- (day 4) and 168-hr (day 7) after dosing. The results showed that dronedarone had no effect on inotropy and lusitropy, while it significantly lengthened PQ interval (P<0.001) and lowered MBP (P<0.05). Dronedarone also tended to reduce cardiac output (P=0.237) and heart rate (P=0.057). These results suggested that short-term effects of oral dronedarone administration at a dose of 20 mg/kg, twice per day, produced negative dromotropy with minimal effect on cardiac function in conscious dogs. PMID:26922916

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

    Science.gov (United States)

    Bykov, V L; Leont'eva, I V

    2011-01-01

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

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

    OpenAIRE

    Smith, Michael; Foster, Jonathan

    2008-01-01

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

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

    OpenAIRE

    Nagelschmitz J; Blunck M; Kraetzschmar J; Ludwig M; Wensing G; Hohlfeld T

    2014-01-01

    J Nagelschmitz,1 M Blunck,1 J Kraetzschmar,1 M Ludwig,1 G Wensing,1 T Hohlfeld2 1Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany; 2Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany Background: The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled...

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

    Directory of Open Access Journals (Sweden)

    Lihan Chen

    2015-05-01

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

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

    Science.gov (United States)

    Brown, A C; Powell, J G; Kegley, E B; Gadberry, M S; Reynolds, J L; Hughes, H D; Carroll, J A; Burdick Sanchez, N C; Thaxton, Y V; Backes, E A; Richeson, J T

    2015-05-01

    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 mg/kg BW), 3) surgical castration at weaning (WNG), or 4) surgical castration at weaning with oral administration of meloxicam (1 mg/kg BW; WMX). A subset of calves (n = 7/treatment group) were selected randomly near birth for blood collection, behavioral analyses, and rectal temperature (RT) records for a 7-d postcastration period on d 0 (birth), 1, 3, and 7, and on d 214 (weaning), 214 + 6 h, 215, 217, 221, and 228. Calf standing and lying activity were monitored from the same subsets by recording x- and y-axis positions of an accelerometer attached to the right metatarsus for 7 d postcastration. Calf BW was recorded throughout the entire production cycle, and carcass data were collected at slaughter. For statistical analyses, bulls left intact at birth were considered a positive control (BUL) for observations that occurred before their treatment application at weaning; likewise, bulls castrated at birth were considered a negative control (STR) during postweaning observations. No difference (P > 0.88) occurred in ADG between treatments throughout the preweaning period (d 0 to 214); however, 56-d postweaning ADG was greatest ( P= 0.02) in STR, intermediate in WMX, and least in WNG. At weaning, haptoglobin (Hp) was greater (P ≤ 0.005) for WNG and WMX compared to STR on d 214+6 h, 215, and 217, and Hp was greater (P = 0.05) in WNG compared to WMX on d 217. Neutrophils increased (P treatments. In this study, surgical castration at weaning, but not near birth, altered the acute phase response, behavior, and growth performance. Oral meloxicam reduced serum Hp and improved ADG briefly when administered to calves castrated at weaning. Oral administration of meloxicam may be efficacious for mitigating some of the stress and inflammation associated

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

    Institute of Scientific and Technical Information of China (English)

    HE Lirong; HE Gang

    2002-01-01

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

  1. 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...... in hepatocytes, indicating that tetrachloroethylene induced DNA damage in the liver. No effect on DNA damage was observed in the kidney. The results are in agreement with carcinogenicity data in mice, in which tetrachloroethylene induced tumours in the liver but not in the kidney, and support that a genotoxic...... mode of action might be involved in liver carcinogenicity in mice. An alternative interpretation of the results conveyed by the Study director at the test facility, involving that tetrachloroethylene did not induce DNA damage in the liver and kidney of mice, is also presented and discussed....

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

    Directory of Open Access Journals (Sweden)

    Yulu Zhou

    2014-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

  4. 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.

  5. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  7. Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

    Science.gov (United States)

    Leary, A; Barthe, L; Clavel, T; Sanchez, C; Oulmi-Castel, M; Paillard, B; Edmond, J M; Brunner, V

    2016-01-01

    Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration. PMID:25989284

  8. 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 PrP(Sc). The results showed a bi-phasic reduction of PrP(Sc) 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 (125)I-PrP(Sc) reached maximal levels by 30 min and 3 hr, respectively, and blood levels were constantly higher than plasma. Upon crossing the GI-tract (125)I-PrP(Sc) became associated to blood cells, suggesting that binding to cells decreased the biological clearance of the agent. Size-exclusion chromatography revealed that oligomeric (125)I-PrP(Sc) were transported from the intestinal tract, and protein misfolding cyclic amplification showed that PrP(Sc) in organs and blood retained the typical prion self-replicating ability. Pharmacokinetic analysis found the oral bioavailability of (125)I-PrP(Sc) to be 33.6%. Interestingly, (125)I-PrP(Sc) 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

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

    Science.gov (United States)

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

    2015-05-01

    N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors. PMID:25069786

  10. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10B/kg, iv + BPA, 15.5 mg 10B/kg, ip; 2. BSH, 34.5 mg 10B/kg, iv + BPA, 31 mg 10B/kg, ip; 3. BSH, 20 mg 10B/kg, iv + BPA, 46.5 mg 10B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with clinical

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

    Science.gov (United States)

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

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max: 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P sports. PMID:25077918

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

    Science.gov (United States)

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

    2016-01-01

    Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg(-1) b.w.), IM (10 mg kg(-1) b.w.), and IV (10 mg kg(-1) b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL(-1), 6.3 h × μg mL(-1), and 6.66 h × μg mL(-1), while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology. PMID:27536243

  13. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

    Directory of Open Access Journals (Sweden)

    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  14. 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 (pbiodiesel groups. Kidney Mg concentration was significantly (pdiesel groups. Kidney Mg concentration was significantly (pdiesel groups. Lung Cd, Co, Cu, Cr, Na, and Zn concentrations were different significantly higher in the control group than in the other groups. Liver Al concentration was different significantly higher in the control group than in the other groups. Liver Ca concentration was significantly (pbiodiesel groups. Serum and lung tissue bioelements 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

  15. Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

    OpenAIRE

    Karschner, EL; Darwin, WD; McMahon, RP; Liu, F; Wright, S; Goodwin, RS; Huestis, MA

    2011-01-01

    Sativex is a cannabis-plant extract delivering nearly 1:1 Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no subs...

  16. 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)

  17. Transabdominal ultrasonography of the small bowel after oral administration of a non-absorbable anechoic solution: Comparison with barium enteroclysis

    International Nuclear Information System (INIS)

    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. Oral administration of royal jelly inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice.

    Science.gov (United States)

    Taniguchi, Yoshifumi; Kohno, Keizo; Inoue, Shin-ichiro; Koya-Miyata, Satomi; Okamoto, Iwao; Arai, Norie; Iwaki, Kanso; Ikeda, Masao; Kurimoto, Masashi

    2003-09-01

    We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression. PMID:12890429

  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. Guaifenesin Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

    Science.gov (United States)

    Thompson, Gary A; Solomon, Gail; Albrecht, Helmut H; Reitberg, Donald P; Guenin, Eric

    2016-07-01

    This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age-based doses of 100-400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo ) and terminal volume of distribution (Vz /F) increased with age. Due to a larger increase in Vz /F than CLo , an increase in terminal exponential half-life was also observed. Allometric scaling indicated no maturation-related changes in CLo and Vz /F. PMID:26632082

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

    Science.gov (United States)

    Ciper, Mesut; Bodmeier, Roland

    2005-10-13

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

  2. PHARMACOKINETIC PROPERTIES OF A SINGLE ADMINISTRATION OF ORAL GABAPENTIN IN THE GREAT HORNED OWL (BUBO VIRGINIANUS).

    Science.gov (United States)

    Yaw, Taylor J; Zaffarano, Bianca A; Gall, Andrew; Olds, June E; Wulf, Larry; Papastavros, Efthimia; Coetzee, Johann F

    2015-09-01

    Gabapentin (1-[aminomethyl] cyclohexane acetic acid) is a γ-aminobutyric acid analogue that has been shown to be efficacious for neuropathic pain control in humans. Plasma gabapentin concentrations >2 μg/ml are considered effective in treating epilepsy in humans and are suggested to provide analgesia for neuropathic pain. This study investigated the pharmacokinetics of a single oral dose of gabapentin suspension (11 mg/kg) in great horned owls ( Bubo virginianus ). Plasma gabapentin concentrations were determined in six healthy birds for 48 hr using high-performance liquid chromatography with mass spectrometric detection. Plasma gabapentin concentrations were estimated by noncompartmental pharmacokinetic analysis. The harmonic mean (±SD) maximum concentration (Cmax), time to maximum concentration (Tmax), and elimination half-life (tv2λZ) for gabapentin (11 mg/kg) were 6.17±0.83 μg/ml, 51.43±5.66 min, and 264.60±69.35 min, respectively. In this study, plasma gabapentin concentrations were maintained above 2 μg/ml for 528 min (8.8 hr), suggesting that gabapentin administered orally every 8 hr may be appropriate in great horned owls. PMID:26352959

  3. 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. PMID:16615665

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

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Ding

    2014-01-01

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

  5. 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.

  6. 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.  

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Sami Ahmad

    2013-01-01

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

  9. The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin.

    OpenAIRE

    Sahai, J; Healy, D P; Stotka, J; Polk, R E

    1993-01-01

    Six healthy male volunteers participated in a two-period, two-treatment study to determine the effect of chronic calcium carbonate administration on ciprofloxacin bioavailability. There was a mean reduction of 40% in Cmax and 43% in AUC when calcium carbonate was administered with ciprofloxacin, compared with ciprofloxacin alone (P < 0.05). There were no changes in either half-life or tmax. It is therefore recommended that patients being treated with ciprofloxacin for serious infections refra...

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

    Science.gov (United States)

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

    2010-03-01

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

  11. Effects of oral administration of caffeine on some physiological parameters and maternal behaviour of sows at farrowing.

    Science.gov (United States)

    Superchi, Paola; Saleri, Roberta; Farina, Elena; Cavalli, Valeria; Riccardi, Enzo; Sabbioni, Alberto

    2016-04-01

    Caffeine has been demonstrated to have a protective effect on neonatal viability of piglets. In order to assess whether caffeine, administered to parturient sows, also affects maternal behaviour, respiratory rate, and dopamine, nitric oxide and serotonin plasma levels, 20 sows, with induced parturition, received orally 27mg/kg of body weight of caffeine (T group; n=10) or not (NT group; n=10), on day 113 of gestation. Treatment did not affect the farrowing length. There were less stillborn piglets in T group than NT group (0.67 vs 2.44; Pbirth was observed. Caffeine did not affect physiological parameters of sows, as the behaviour score of sows laying on belly was reduced (P<0.05). In conclusion, although the present study was carried out with a limited number of sows, administration of caffeine to parturient sows has the potential for reducing the number of stillborn. PMID:27033919

  12. 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.

  13. 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.

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

    Science.gov (United States)

    Bykov, V L; Leont'eva, I V

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  16. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

  17. Oral administration of banana lectin modulates cytokine profile and abundance of T-cell populations in mice.

    Science.gov (United States)

    Sansone, Ana Claudia Miranda Brito; Sansone, Marcelo; Dos Santos Dias, Carlos Tadeu; Oliveira do Nascimento, João Roberto

    2016-08-01

    Banana lectin (BanLec) is a dimeric protein occurring in fruit pulp that modulates immune cell functioning in vitro. In order to assess the immune response in vivo, BanLec from ripe banana (Musa acuminata) fruit was purified and orally given to mice for seven days. The analysis of cytokines in the mice peripheral blood revealed increased IL-10, IL-17 and TNFα, and a reduction of IFNγ and IL-6. In the thymus, an increase of CD4+ and a decrease of CD8+ T-cells were observed after oral administration of BanLec. The modulation of pro- and anti-inflammatory cytokines and T-cells in the peripheral blood and thymus of mice demonstrated the immunomodulatory properties of natural BanLec in vivo. This research brings new data on a protein from a fresh fruit consumed worldwide that may act as an immunomodulator, potentially affecting the host response to infections, immune diseases and cancer. PMID:27106589

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

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    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. 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.

  1. Pharmacokinetic study of enrofloxacin in Nile tilapia (Oreochromis niloticus) after a single oral administration in medicated feed.

    Science.gov (United States)

    Teles, J A; Castello Branco, L C; Del Bianchi, M; Pilarski, F; Reyes, F G R

    2016-04-01

    The objective of this study was to evaluate the disposition kinetics of enrofloxacin (ENR) in the plasma and its distribution in the muscle tissue of Nile tilapia (Oreochromis niloticus) after a single oral dose of 10 mg/kg body weight via medicated feed. The fish were kept at a temperature between 28 and 30 °C. The collection period was between 30 min and 120 h after administration of the drug. The samples were analyzed by high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The ENR was slowly absorbed and eliminated from the plasma (Cmax = 1.24 ± 0.37 μg/mL; Tmax = 8 h; T1/2Ke  = 19.36 h). ENR was efficiently distributed in the muscle tissue and reached maximum values (2.17 ± 0.74 μg/g) after 8 h. Its metabolite, ciprofloxacin (CIP), was detected and quantified in the plasma (0.004 ± 0.005 μg/mL) and muscle (0.01 ± 0.011 μg/g) for up to 48 h. After oral administration, the mean concentration of ENR in the plasma was well above the minimum inhibitory concentrations (MIC50 ) for most bacteria already isolated from fish except for Streptococcus spp. This way the dose used in this study allowed for concentrations in the blood to treat the diseases of tilapia. PMID:26270353

  2. Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.

    Science.gov (United States)

    Duan, Yuwei; Zhang, Baomei; Chu, Lianjun; Tong, Henry Hy; Liu, Weidong; Zhai, Guangxi

    2016-05-01

    The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. PMID:26874910

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat

    International Nuclear Information System (INIS)

    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 both 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 environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled 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. 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. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ∼5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite 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 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics.

  5. 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.

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

    Science.gov (United States)

    Alyoussef, A; Al-Gayyar, M M H

    2016-06-01

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

  7. Distribution, Metabolism and Toxic Effects of Beta-Cypermethrin in Lizards (Eremias argus) Following Oral Administration.

    Science.gov (United States)

    Chen, Li; Xu, Peng; Diao, Jinling; Di, Shanshan; Li, Ruiting; Zhou, Zhiqiang

    2016-04-01

    Beta-cypermethrin (BCYP), a synthetic pyrethriod (PYR) pesticide which is a mixture of the alpha- and theta- cypermethrin, have been reported various toxicological profiles to non-target organisms. But little is known about assimilation, accumulation and toxic effects of BCYP in reptiles. The present study firstly elucidated absorption, tissue distribution, excretion of BCYP in Eremias argus . Treated group were administered orally with BCYP 20mg/kg body weight (bw) dissolved in corn oil. Neurotoxicity was observed at 24h after gavage, and the poisoning symptom ameliorated at 72h. The changes of BCYP concentration depended on degradation time and tissues. Lizards had a strong capacity to eliminate BCYP with different tissue distribution. The tissues concentration of BCYP from high to low were intestine, stomach, heart, kidney, blood, lung, liver and brain. Bimodal phenomena were observed in lung, liver and kidney. These results may be due to the activities of enzymes, circadian rhythm, and enterohepatic circulation in lizards. Based on the results of organ coefficient and histopathology analysis in liver, the liver was confirmed as the main target organ.

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

    Directory of Open Access Journals (Sweden)

    John E. Fincham

    2010-08-01

    Full Text Available Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

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

    Science.gov (United States)

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

    2010-08-01

    Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

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

    Directory of Open Access Journals (Sweden)

    Hannah K. Batchelor

    2015-06-01

    Full Text Available 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.

  12. Transmission of [14C]deoxynivalenol to eggs following oral administration to laying hens

    International Nuclear Information System (INIS)

    Following a single oral dose of [14C]deoxynivalenol (2.2 mg of DON, 2.4 μCi/bird) low levels of residues were transmitted to eggs. Maximum radioactivity, which occurred in the first eggs laid after dosing (within 24 h), amounted to 1.9 μg DON-equivalents/60-g egg (0.087% of dose) levels dropped rapidly in ensuing eggs. During daily consumption of DON, administered in spiked feed over a 12-day period (2.2 mg of DON/bird per day for 6 days followed by 2.2 mg of [14C]DON, 1.5 μCi/bird per day for 6 days), radioactivity levels increased with each subsequent egg laid up until the last exposure to the toxin; maximum levels accounted for 4.2 μg DON-equivalents/60-g egg. Residues quickly declined once the birds were switched to clean feed. Results indicate that although residues appear to accumulate in eggs, levels do not persist once the contaminated source is withdrawn. Preliminary analysis of egg material showed only about 10% of radioactivity present could be identified as the parent toxin, DON

  13. Toxicity of Smokeless Tobacco Extract after 184-Day Repeated Oral Administration in Rats.

    Science.gov (United States)

    Yu, Chenlin; Zhang, Ziteng; Liu, Yangang; Zong, Ying; Chen, Yongchun; Du, Xiuming; Chen, Jikuai; Feng, Shijie; Hu, Jinlian; Cui, Shufang; Lu, Guocai

    2016-03-01

    The use of smokeless tobacco (ST) is growing rapidly and globally. The consumption of ST is associated with an increased risk for developing chronic diseases, such as diabetes, hypercholesterolemia, and myocardial infarction, and has led to many public health problems. It is very important to access the toxicity of ST. This experiment presents data from 184-day toxicology studies in Sprague-Dawley (SD) rats designed to characterize the chronic effects of a smokeless tobacco extract (STE). The control group and treatment groups were matched for a range of nicotine levels. Animals were given STE by oral gavage with doses of 3.75 (low-dose), 7.50 (mid-dose) and 15.00 (high-dose) mg · nicotine/kg body weight/day for 184 days, followed by 30 days for recovery. Variables evaluated included body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights), and histopathology. Decreased body weights and organ weights (heart, liver and kidney) were found in animals in the mid-dose and high-dose groups. STE also showed moderate and reversible toxicity in esophagus, stomach, liver, kidney and lung. PMID:26959038

  14. Toxicity of Smokeless Tobacco Extract after 184-Day Repeated Oral Administration in Rats

    Directory of Open Access Journals (Sweden)

    Chenlin Yu

    2016-03-01

    Full Text Available The use of smokeless tobacco (ST is growing rapidly and globally. The consumption of ST is associated with an increased risk for developing chronic diseases, such as diabetes, hypercholesterolemia, and myocardial infarction, and has led to many public health problems. It is very important to access the toxicity of ST. This experiment presents data from 184-day toxicology studies in Sprague-Dawley (SD rats designed to characterize the chronic effects of a smokeless tobacco extract (STE. The control group and treatment groups were matched for a range of nicotine levels. Animals were given STE by oral gavage with doses of 3.75 (low-dose, 7.50 (mid-dose and 15.00 (high-dose mg·nicotine/kg body weight/day for 184 days, followed by 30 days for recovery. Variables evaluated included body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights, and histopathology. Decreased body weights and organ weights (heart, liver and kidney were found in animals in the mid-dose and high-dose groups. STE also showed moderate and reversible toxicity in esophagus, stomach, liver, kidney and lung.

  15. Disposition and metabolism of glyphosate in the Sprague Dawley rat following oral administration

    International Nuclear Information System (INIS)

    Five groups of male SD rats were administered 14C-labelled glyphosate, (N-[(phosphonomethyl)glycine]) by gavage at a dose level of 10 mg/kg. Animals were killed 2, 6.3, 28, 96 and 168 hours after dosing and the amount of glyphosate-derived material in various organs and excreta were determined. In addition, the metabolic profile in tissues containing > 1% of the administered dose was evaluated. Approximately 93% of the body burden 2 hours after administration was associated with the GI contents and small intestinal tissue. The total body burden 7 days after administration was ∼1% of the dose. Only the kidneys, small intestine, colon, bone, GI contents, residual carcass contained > 1% of the dose 6 hours after administration and the metabolic profiles of these tissues indicated that ∼100% of the body burden was present as unmetabolized parent material. Glyphosate was rapidly eliminated from these tissues with halflives ranging from 20 to 90 hours. A minor metabolite comprising < 0.1% of the dose was detected in the GI contents and colon tissue of 3 animals. Less than 40% of the administered dose was absorbed from the gut and glyphosate was rapidly eliminated from the body with urine and feces being equally important routes of elimination. The whole body halflife was approximately 52 hours. The results from this study indicate that no toxic metabolites of glyphosate were produced, as there was little evidence of metabolism, and essentially 100% of the body burden was parent glyphosate with no significant persistence of accumulated material

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

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    Jezdimirović Milanka

    2012-01-01

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

  17. Toxicokinetics of the mycotoxin ochratoxin A in F 344 rats after oral administration

    International Nuclear Information System (INIS)

    Ochratoxin A (OTA), a mycotoxin produced by several fungi of Aspergillus and Penicillium species, is a nephrotoxin and a renal carcinogen in rodents. This study was performed to investigate the biotransformation and toxicokinetics of this important food contaminant. Male (n = 18) and female (n = 18) F344 rats were administered a single dose of OTA (0.5 mg/kg b.w.) in corn oil by gavage. Animals (n = 3) were sacrificed 24, 48, 72, 96, 672, and 1,344 hours after OTA administration and concentrations of OTA and OTA-metabolites in urine, feces, blood, liver, and kidney were determined by HPLC with fluorescence detection and/or by LC-MS/MS. Recovery of unchanged OTA in urine amounted to 2.1% of dose in males and 5.2% in females within 96 h. In feces, only 5.5% respectively 1.5% of dose were recovered. The major metabolite detected was OTalpha; low concentrations of OTA-glucosides were also present in urine. The maximal blood levels of OTA were observed between 24 and 48 h after administration and were appromixately 4.6 μmol/l in males and 6.0 μmol/l in females. Elimination of OTA from blood followed first-order kinetics with a half-life of approximately 230 h. In liver of both male and female rats, OTA-concentrations were less than 12 pmol/g tissue, with a maximum at 24 h after administration. In contrast, OTA accumulated in the kidneys, reaching a concentration of 480 pmol/g tissue in males 24 h after OTA-administration. Generally, tissue concentrations in males were higher than in females. OTalpha was not detected in liver and kidney tissue of rats administered OTA, and the OTalpha concentrations in blood were low (10-15 nmol/l). The high concentrations of OTA in kidneys of male rats may, in part, explain the organ- and gender-specific toxicity of OTA

  18. 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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  20. Oral administration of Kaempferia parviflora did not disturb male reproduction in rats.

    Science.gov (United States)

    Trisomboon, Hataitip; Tohei, Atsushi; Malaivijitnond, Suchinda; Watanabe, Gen; Taya, Kazuyoshi

    2008-10-01

    To investigate the androgenic effect of Kaempferia parviflora (KP), a Thai herbal plant, adult male rats were randomized into control and KP-treatment groups. Rats were treated orally with water in the control group and with 1,000 mg/kg/day of KP in the treatment group for 45 days. Blood samples were collected on days 10, 20, 30 and 45 for measurement of the serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, progesterone and corticosterone levels. The reproductive and non-reproductive organs were dissected on day 45 and weighed. Mating behavior was also observed on days 20 and 30. Body weight was measured throughout the study period. The results showed that KP induced an increase in body weight compared with the controls. There were no significant differences in the weights of either reproductive (testis, seminal vesicle plus coagulating gland, levator ani muscle plus bulbocarvernosus muscle and glans penis, except the prostate gland) or non-reproductive organs (kidney, adrenal gland and gastracnemius muscle). There were no significant differences in serum levels of either FSH or LH between the two groups. The serum testosterone and progesterone levels were insignificantly lower in the KP group during the first 30 days. The serum corticosterone levels in the KP group were lower than those in the controls throughout the study period and were significantly low on days 20 and 30. There were no significant changes in mating behavior in the rats treated with KP. Although KP affected the body weight and serum corticosterone level, it did not affect mating behavior, reproductive and non-reproductive organ weights or hormones related to the reproductive system in the adult male rats. Therefore, we conclude that the testosterone-like effect of KP did not disturb the hypothalamic-pituitary-testicular axis or male reproduction. PMID:18594126

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

    Science.gov (United States)

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

    2004-07-01

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

  2. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

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    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.

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

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    Prashant Kumar

    Full Text Available Zidovudine (AZT is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50-75% the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano. The nanoparticles (NPs are of 50-60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery.

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

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

  5. Process management of oral medication administration in department of cardiology%心内科实施服药到口流程管理初探

    Institute of Scientific and Technical Information of China (English)

    丁小伟; 王珠琳

    2012-01-01

    Objective To investigate the effects of process management of oral medication administration in department of cardiology. Methods We developed regulations of oral medication administration for patients hospitalized in department of cardiology, assessed administration of oral medicines to patients and nurses' drug dispensing behaviors, carried out process management of oral medication administration, and strengthened supervision and monitoring etc. Results The compliance rate of patients taking oral medicines and patient satisfaction were significantly improved after implement of the process management (P<0. 01 for both). Conclusion Reasonable process management can ensure patients' adherence to oral administration of medicines, and improve safety and therapeutic effect of drugs.%目的 探讨流程管理在确保心内科患者服药到口工作中的实施效果.方法 采用制定心内科患者服药到口常规制度、评估服药与发药状况、实施服药到口流程管理及加强监督力度等方法.结果 实施流程管理前后不同周期患者服药到口率,实施流程管理前后患者满意度比较,差异有统计学意义(均P<0.01).结论 合理的流程管理能确保患者服药到口,保证心内科患者用药安全和治疗效果.

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

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    A Martso

    2008-01-01

    Results. There is evidence that patients tolerate both its sachets and tablets equally well, as confirmed by subjective and objective observations. There are neither marked side effects nor considerable changes in laboratory tests and in the values of vital functions. Diclofenac potassium as early-action tablets (50 and 100 mg exerts a very good analgesic effect in treating migraine since the plasma concentration of the drug peaks on an average of an hour of administration (range 0,33-2 hours and the analgesic effect developed following 60-90 min. Conclusion. By comparing the rate of absorption, it may be concluded that diclofenac potassium as sachets will produce a much rapider analgesic effect. Thus, the high solubility of diclofenac potassium and its very good absorbability (as sachets in particular make the drug a superior analgesic that has a rapid analgesic activity.

  7. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs.

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    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

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

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

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

  9. Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle.

    Science.gov (United States)

    Lanusse, C E; Trudeau, C; Ranjan, S; Prichard, R K

    1991-03-01

    Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2038091

  10. Chronic oral administration of pine bark extract (flavangenol) attenuates brain and liver mRNA expressions of HSPs in heat-exposed chicks.

    Science.gov (United States)

    Yang, Hui; Chowdhury, Vishwajit S; Bahry, Mohammad A; Tran, Phuong V; Do, Phong H; Han, Guofeng; Zhang, Rong; Tagashira, Hideki; Tsubata, Masahito; Furuse, Mitsuhiro

    2016-08-01

    Exposure to a high ambient temperature (HT) can cause heat stress, which has a huge negative impact on physiological functions. Cellular heat-shock response is activated upon exposure to HT for cellular maintenance and adaptation. In addition, antioxidants are used to support physiological functions under HT in a variety of organisms. Flavangenol, an extract of pine bark, is one of the most potent antioxidants with its complex mixture of polyphenols. In the current study, chronic (a single daily oral administration for 14 days) or acute (a single oral administration) oral administration of flavangenol was performed on chicks. Then the chicks were exposed to an acute HT (40±1°C for 3h) to examine the effect of flavangenol on the mRNA expression of heat-shock protein (HSP) in the brain and liver. Rectal temperature, plasma aspartate aminotransferase (AAT), a marker of liver damage, and plasma corticosterone as well as metabolites were also determined. HSP-70 and -90 mRNA expression, rectal temperature, plasma AAT and corticosterone were increased by HT. Interestingly, the chronic, but not the acute, administration of flavangenol caused a declining in the diencephalic mRNA expression of HSP-70 and -90 and plasma AAT in HT-exposed chicks. Moreover, the hepatic mRNA expression of HSP-90 was also significantly decreased by chronic oral administration of flavangenol in HT chicks. These results indicate that chronic, but not acute, oral administration of flavangenol attenuates HSP mRNA expression in the central and peripheral tissues due to its possible role in improving cellular protective functions during heat stress. The flavangenol-dependent decline in plasma AAT further suggests that liver damage induced by heat stress was minimized by flavangenol.

  11. Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

    International Nuclear Information System (INIS)

    Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers. Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans

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

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    Damiana Diniz Rosa

    2014-06-01

    Full Text Available Introduction: Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. Objective: The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Methods: Wistar rats were randomly divided into three groups (n = 6/group: control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose, and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose. Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. Results: The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. Conclusion: These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned.

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Yasha Xu

    2013-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Du Deli; Wang Xinzhong

    2007-01-01

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

  16. 16S ribosomal RNA-based methods to monitor changes in the hindgut bacterial community of piglets after oral administration of Lactobacillus sobrius S1

    NARCIS (Netherlands)

    Su, Y.; Yao, W.; Perez-Gutierrez, O.N.; Smidt, H.; Zhu, W.Y.

    2008-01-01

    16S ribosomal RNA (rRNA) gene based PCR/denaturing gradient gel electrophoresis (DGGE) and real-time PCR were used to monitor the changes in the composition of microbiota in the hindgut of piglets after oral administration of Lactobacillus sobrius S1. Six litters of neonatal piglets were divided ran

  17. Alternative method of oral administration by peanut butter pellet formulation results in target engagement of BACE1 and attenuation of gavage-induced stress responses in mice.

    Science.gov (United States)

    Gonzales, C; Zaleska, M M; Riddell, D R; Atchison, K P; Robshaw, A; Zhou, H; Sukoff Rizzo, S J

    2014-11-01

    Development of novel therapeutic agents aimed at treating neurodegenerative disorders such as Alzheimer's and Parkinson's diseases require chronic and preferentially oral dosing in appropriate preclinical rodent models. Since many of these disease models involve transgenic mice that are frequently aged and fragile, the commonly used oro-gastric gavage method of drug administration often confounds measured outcomes due to repeated stress and high attrition rates caused by esophageal complications. We employed a novel drug formulation in a peanut butter (PB) pellet readily consumed by mice and compared the stress response as measured by plasma corticosterone levels relative to oral administration via traditional gavage. Acute gavage produced significant elevations in plasma corticosterone comparable to those observed in mice subjected to stress-induced hyperthermia. In contrast, corticosterone levels following consumption of PB pellets were similar to levels in naive mice and significantly lower than in mice subjected to traditional gavage. Following sub-chronic administration, corticosterone levels remained significantly higher in mice subjected to gavage, relative to mice administered PB pellets or naive controls. Furthermore, chronic 30day dosing of a BACE inhibitor administered via PB pellets to PSAPP mice resulted in expected plasma drug exposure and Aβ40 lowering consistent with drug treatment demonstrating target engagement. Taken together, this alternative method of oral administration by drug formulated in PB pellets results in the expected pharmacokinetics and pharmacodynamics with attenuated stress levels, and is devoid of the detrimental effects of repetitive oral gavage. PMID:25242810

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

    Directory of Open Access Journals (Sweden)

    Mahy Nicole

    2011-11-01

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

  19. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  20. Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.

    Science.gov (United States)

    Xie, Yuan-Yuan; Wang, Xiu-Ming; Wang, Si-Huan; Wang, Yi-Ming; Tian, Hui-Fang; Yuan, Yong-Sheng; Li, Hong-Yan; Liang, Qiong-Lin; Luo, Guo-An

    2016-07-15

    Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47μgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  2. Hipersensibilidade tuberculínica em crianças menores de um ano de idade vacinadas com BCG oral Tuberculinic hypersensibility among children under one year of life, vaccinated with BCG by oral administration

    Directory of Open Access Journals (Sweden)

    Roberto Brólio

    1977-03-01

    Full Text Available São relatados os resultados da pesquisa da hipersensibilidade tuberculínica pelo PPD, Rt-23,2UT, em crianças menores de um ano de idade, vacinadas anteriormente com BCG oral, pertencentes a uma área do município de São Paulo. Os resultados mostram que para 790 crianças houve 13,0% de reatores fracos e 16,3% de reatores fortes, com um total de 29,3% de reatores. São feitos comentários sobre a vacinação oral e o baixo percentual de reatores encontrados, no controle tuberculínico pós-vacinal, relativamente aos obtidos com o BCG intradérmico.Hypersensibility reaction to tuberculin (PPD RT-23 was studied during five years among children under one year of age, vaccinated with BCG by oral administration, living in an area of city S. Paulo, Brazil. Of 790 children, 13,0% showed a weak reaction and 16.4% showed a strong reaction, totalizing 29.4% reactors. Comparing the results of convertors after BCG vaccination by intradermic administration, this paper shows that a low percentage of children became convertors after being vaccinated with BCG by oral administration.

  3. Early effect of oral administration of omeprazole with mosapride as compared with those of omeprazole alone on the intragastric pH

    Directory of Open Access Journals (Sweden)

    Iida Hiroshi

    2012-03-01

    Full Text Available Abstract Background The ideal medication for acid-related diseases should have a rapid onset of action to promote hemostasis and cause efficient resolution of symptoms. The aim of our study was to comparatively investigate the inhibitory effect on gastric acid secretion of a single oral administration of omeprazole plus mosapride with that of omeprazole alone. Methods Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 hours after a single oral administration of omeprazole 20 mg or that of omeprazole 20 mg plus mosapride 5 mg (the omeprazole being administered one hour after the mosapride. Each administration was separated by a 7-days washout period. Results The average pH during the 6-hour period after administration of omeprazole 20 mg plus mosapride 5 mg was higher than that after administration of omeprazole 20 mg alone (median: 3.22 versus 4.21, respectively; p = 0.0247. Conclusions In H. pylori -negative healthy male subjects, an oral dose of omeprazole 20 mg plus mosapride 5 mg increased the intragastric pH more rapidly than omeprazole 20 mg alone.

  4. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

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

    Institute of Scientific and Technical Information of China (English)

    Hong-yun WANG; Pei HU; Ji JIANG

    2011-01-01

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

  6. The Various Forms of Insulin Secretion Response to the Intravenous and Oral Administration of Glucose in Non-Insulin-Dependent Diabetes Mellitus

    International Nuclear Information System (INIS)

    On the basis of 68 observations on advanced diabetes mellitus (20 cases), latent diabetes with obesity (12 cases), chemical diabetes with subjective symptoms (26 cases) and 10 observations of obesity without diabetes, the authors have analysed the various forms of insulin secretion response to the intravenous and oral administration of glucose. The response appeared to be totally withdrawn in advanced diabetes mellitus although the patients were still capable of responding to stimulation with glucagon. In the two other forms of diabetes described, the response to stimulation by intravenous administration was less marked than in normal subjects. With oral administration, on the other hand, the response was greater, although the insulin secreted in this case appeared ineffective in cases of obesity but effective in conditions without obesity due to the hypoglycaemic effect. (author)

  7. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    Directory of Open Access Journals (Sweden)

    Zhaohui Ge

    2014-01-01

    Full Text Available Pharmacokinetic characters of rhynchophylline (RIN, gastrodin (GAS, and gastrodigenin (p-hydroxybenzyl alcohol, HBA were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT and gouteng (rhynchophylla alkaloids, EPG. At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and Cmax⁡ and AUC0–∞ (P<0.05 were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint.

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

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    Renjie Xu

    2015-04-01

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

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

    Science.gov (United States)

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

    2015-04-28

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

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

    Science.gov (United States)

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

    2015-10-15

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

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

    Science.gov (United States)

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

    2015-11-01

    The aim of this work was to investigate the mucus-permeating properties of poly(ethyleneglycol)-coated nanoparticles prepared from the copolymer of methyl vinyl ether and maleic anhydride (Gantrez® AN) after oral administration in rats. Nanoparticles were "decorated" with PEGs of different molecular masses (PEG2000, PEG6000 and PEG10000) at a PEG-to-polymer ratio of 0.125. All the PEG-coated nanoparticles displayed a mean size of ∼150 nm, slightly negative ζ values and a "brush" conformation as determined from the calculation of the PEG density. For in vivo studies, nanoparticles were labelled with either (99m)Tc or fluorescent tags. Naked nanoparticles displayed a higher ability to interact with the mucosa of the stomach than with the small intestine. However, these interactions were restricted to the mucus layer covering the epithelial surface, as visualised by fluorescence microscopy. On the contrary, PEG-coated nanoparticles moved rapidly to the intestine, as determined by imaging, and, then, were capable to develop important interactions with the mucosa, reaching the surface of the epithelium. These mucus permeating properties were more intense for nanoparticles coated with PEG2000 or PEG6000 than with PEG10000. However, the capability of nanocarriers to develop adhesive interactions within the mucosa decreased when prepared at excessive PEG densities. PMID:25541441

  12. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

    Directory of Open Access Journals (Sweden)

    Anat Frydman-Marom

    Full Text Available An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ play a key role in Alzheimer's disease (AD pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt, which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

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

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    Jia-le He

    2015-01-01

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

  14. The Effect of Oral Administration of dsRNA on Viral Replication and Mortality in Bombus terrestris

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    Niels Piot

    2015-06-01

    Full Text Available Israeli acute paralysis virus (IAPV, a single-stranded RNA virus, has a worldwide distribution and affects honeybees as well as other important pollinators. IAPV infection in honeybees has been successfully repressed by exploiting the RNA interference (RNAi pathway of the insect’s innate immune response with virus-specific double stranded RNA (dsRNA. Here we investigated the effect of IAPV infection in the bumblebee Bombus terrestris and its tissue tropism. B. terrestris is a common pollinator of wild flowers in Europe and is used for biological pollination in agriculture. Infection experiments demonstrated a similar pathology and tissue tropism in bumblebees as reported for honeybees. The effect of oral administration of virus-specific dsRNA was examined and resulted in an effective silencing of the virus, irrespective of the length. Interestingly, we observed that non-specific dsRNA was also efficient against IAPV. However further study is needed to clarify the precise mechanism behind this effect. Finally we believe that our data are indicative of the possibility to use dsRNA for a broad range viral protection in bumblebees.

  15. The Effect of Oral Administration of dsRNA on Viral Replication and Mortality in Bombus terrestris.

    Science.gov (United States)

    Piot, Niels; Snoeck, Simon; Vanlede, Maarten; Smagghe, Guy; Meeus, Ivan

    2015-06-01

    Israeli acute paralysis virus (IAPV), a single-stranded RNA virus, has a worldwide distribution and affects honeybees as well as other important pollinators. IAPV infection in honeybees has been successfully repressed by exploiting the RNA interference (RNAi) pathway of the insect's innate immune response with virus-specific double stranded RNA (dsRNA). Here we investigated the effect of IAPV infection in the bumblebee Bombus terrestris and its tissue tropism. B. terrestris is a common pollinator of wild flowers in Europe and is used for biological pollination in agriculture. Infection experiments demonstrated a similar pathology and tissue tropism in bumblebees as reported for honeybees. The effect of oral administration of virus-specific dsRNA was examined and resulted in an effective silencing of the virus, irrespective of the length. Interestingly, we observed that non-specific dsRNA was also efficient against IAPV. However further study is needed to clarify the precise mechanism behind this effect. Finally we believe that our data are indicative of the possibility to use dsRNA for a broad range viral protection in bumblebees. PMID:26110584

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Indian Academy of Sciences (India)

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

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN- (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

  18. Determination of rhynchophylline and hirsutine in rat plasma by UPLC-MS/MS after oral administration of Uncaria rhynchophylla extract.

    Science.gov (United States)

    Wu, Yu-Tse; Lin, Lie-Chwen; Tsai, Tung-Hu

    2014-03-01

    An ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to concurrently determine rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma was achieved by alkalization and liquid-liquid extraction. The mass transition of precursor ion → product ion pairs were monitored at m/z 385.2 → 160.0 for rhynchophylline, m/z 369.3 → 144.0 for hirsutine and m/z 414.0 → 220.0 for noscapine (internal standard). This method revealed linear relationships from 2.5 to 50 ng/mL (r(2)  > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r(2)  > 0.998) for hirsutine. The limit of quantification values for rhynchophylline and hirsutine in rat plasma were both 2.5 ng/mL. Intra-day and inter-day precisions were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and the accuracy (bias) was 83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal standard. This method was applied successfully to a pharmacokinetic study of rhynchophylline and hirsutine in rats after oral administration. PMID:24122787

  19. Intra-arterial administration of carboplatin plus lower dosage radiation of 60CO as induction treatment in advanced oral cancer

    International Nuclear Information System (INIS)

    Conventional pre-operative chemoradiotherapy often causes severe side effects, which may result in interruption of the treatment and delay of decided operation. Carboplatin (CBDCA) is one of the effective chemotherapeutants for head and neck cancer. We treated 23 patients with advanced oral cancers by a combination of intra-arterial administration of Carboplatin and 60CO radiotherapy. The dosage of Carboplatin was between 20 mg and 35 mg per square meter of body surface. The dosage of external 60CO irradiation was 2 Gy per day and 30 to 60 Gy in total. We evaluated clinical response, toxicity and survival of this therapy of all the patients. Histologic response was also evaluated in some of them. All cancers responded to the regional chemoradiotherapy and demonstrated remission. Two (8%) completed response rate (CR) and 16 (69%) partial response rate (PR) were achieved. The accumulated five-year overall survival rate by Kaplan-Meier method was 73.9%. Fourteen patients (60.8%) showed no evidence of disease (NED) within five years after the therapy. All patients had stomatitis, but most of them were not so severe. The major hematological toxicity was leukopenia, but it was from mild to moderate and reversible. Our study showed that this therapy provided low toxicity, high clinical and histological response rate. (author)

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

    Science.gov (United States)

    NAKAGAWA, Jun; IWASAKI, Tadashi; KODAMA, Hiroshi

    2009-11-01

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

  1. Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

    Science.gov (United States)

    Parayath, Neha N; Nehoff, Hayley; Norton, Samuel E; Highton, Andrew J; Taurin, Sebastien; Kemp, Roslyn A; Greish, Khaled

    2016-01-01

    Oral administration of paclitaxel (PTX), a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid) (SMA). Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg) compared to the commercially available PTX formulation (PTX [Ebewe]). In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe). In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. PMID:27574427

  2. Oral administration of beta-1,3/1,6-glucan to dogs temporally changes total and antigen-specific IgA and IgM

    OpenAIRE

    Stuyven, E; Verdonck, F.; Hoek, I.; Daminet, S.; Duchateau, Luc; Remon, J P; Goddeeris, Bruno; Cox, Eric

    2010-01-01

    The effect of oral administration of beta-1,3/1,6-glucans from Saccharomyces cerevisiae on humoral immunity in domestic dogs is not known. In this study, 15 beagle dogs were orally given MacroGard tablets, which contain 150 mg of this beta-glucan, daily for 4 weeks. At the end of this period, the total serum immunoglobulin A (IgA) level decreased significantly in the group treated with the glucan compared to that in the control group as well as compared to the concentrations before supplement...

  3. Oral Administration of β-1,3/1,6-Glucan to Dogs Temporally Changes Total and Antigen-Specific IgA and IgM▿

    OpenAIRE

    Stuyven, E; Verdonck, F.; Hoek, I.; Daminet, S.; Duchateau, L.; Remon, J P; Goddeeris, B M; Cox, E

    2009-01-01

    The effect of oral administration of β-1,3/1,6-glucans from Saccharomyces cerevisiae on humoral immunity in domestic dogs is not known. In this study, 15 beagle dogs were orally given MacroGard tablets, which contain 150 mg of this β-glucan, daily for 4 weeks. At the end of this period, the total serum immunoglobulin A (IgA) level decreased significantly in the group treated with the glucan compared to that in the control group as well as compared to the concentrations before supplementation....

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

    Science.gov (United States)

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

    2016-05-01

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

  5. Effects of long-term administration of cancer-promoting substances on oral subepithelial mast cells in the rat.

    Science.gov (United States)

    Sand, L; Hilliges, M; Larsson, P A; Wallstrom, M; Hirsch, J M

    2002-01-01

    The role of oral subepithelial mast cells in the defence against tumours is a matter of controversy. The effect of established and suggested carcinogens, such as the carcinogen 4-nitroquinoline-N-oxide (4-NQO) and Herpes simplex virus type 1 (HSV-1), in combination with oral snuff on lower lip subepithelial mast cells (MC) was studied in rats. The rats were exposed to prolonged use of oral snuff. The test substances were administered in a surgically created canal in the lower lip of the rats. There were 15 rats in each test group and 10 rats in the control group. The amount of countable subepithelial mast cells decreased significantly when the rat oral mucosa was exposed to the oral carcinogen 4-NQO but the effect of oral snuff and HSV-1 infection was weak. Our findings suggest that mast cells play a role in immunological cell defence against chemical carcinogens. Further studies are needed to clarify the mechanisms. PMID:12529973

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

    Wang, Yao-Nan; Wang, Hong-Jie; Yang, Jian; Xin, Shao-Kun; Han, Ling-Yu; Zhao, Hai-Yu; Han, Shu-Yan; Gao, Bo; Hu, Hao; Hu, Yuan-Jia; Bian, Bao-Lin; Si, Nan

    2016-01-01

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

  8. Pharmacokinetics of amoxicillin after oral administration in recently weaned piglets with experimentally induced Escherichia coli subtype O149 : F4 diarrhea

    DEFF Research Database (Denmark)

    Jensen, G.M.; Lykkesfeldt, J.; Frydendahl, K.;

    2004-01-01

    Objective-To measure the effect of Escherichia coli subtype 0149:F4-induced diarrhea on the pharmacokinetics of orally administered amoxicillin in affected piglets relative to that of uninfected piglets. Animals-22 healthy 4-week-old recently weaned Danish crossbred piglets. Procedure-12 piglets...... were orally inoculated through gastric intubation with 10(9) CFUs of an E coli 0149:F4 strain and responded by developing diarrhea 12 to 16 hours later. Piglets were dosed with amoxicillin trihydrate solution (20 mg/kg) by gastric intubation. A control group of 10 age-matched piglets without signs of...... diarrhea was dosed similarly. Blood samples were obtained before amoxicillin administration and at 0.5, 1, 1.5, 2, 3, 6, 12, and 24 hours after amoxicillin administration. The plasma concentration of amoxicillin was analyzed by high-performance liquid chromatography. Results-A significant 39% decrease in...

  9. Implications of In-Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 3. Oral Drug Products.

    Science.gov (United States)

    Allain, Leonardo; Baertschi, Steven W; Clapham, David; Foti, Chris; Lantaff, Wendy M; Reed, Robert A; Templeton, Allen C; Tønnesen, Hanne Hjorth

    2016-05-01

    The ICH Q1B guidance and additional clarifying manuscripts provide the essential information needed to conduct photostability testing for pharmaceutical drug products in the context of manufacturing, packaging, and storage. As the previous 2 papers in this series highlight for drug products administered by injection (part 1) and drug products administered via topical application (part 2), there remains a paucity of guidance and methodological approaches to conducting photostability testing to ensure effective product administration. Part 3 in the series is presented here to provide a similar approach and commentary for photostability testing for oral drug products. The approach taken, as was done previously, is to examine "worst case" photoexposure scenarios in combination with ICH-defined light sources to derive a set of practical experimental approaches to support the safe and effective administration of photosensitive oral drug products. PMID:27056630

  10. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

    OpenAIRE

    Zipeng Gong; Ying Chen; Ruijie Zhang; Yinghan Wang; Yan Guo; Qing Yang; Haixian Zhang; Yu Dong; Xiaogang Weng; Shuangrong Gao; Xiaoxin Zhu

    2014-01-01

    In the present study, post inflammation irritable bowel syndrome (PI-IBS) rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg) to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different poi...

  11. Safety and Pharmacokinetics of Abacavir (1592U89) following Oral Administration of Escalating Single Doses in Human Immunodeficiency Virus Type 1-Infected Adults

    OpenAIRE

    Kumar, Princy N.; Sweet, Donna E.; McDowell, James A.; Symonds, William; Lou, Yu; Hetherington, Seth; LaFon, Stephen

    1999-01-01

    Abacavir (1592U89) is a nucleoside analog reverse transcriptase inhibitor that has been demonstrated to have selective activity against human immunodeficiency virus (HIV) in vitro and favorable safety profiles in mice and monkeys. A phase I study was conducted to evaluate the safety and pharmacokinetics of abacavir following oral administration of single escalating doses (100, 300, 600, 900, and 1,200 mg) to HIV-infected adults. In this double-blind, placebo-controlled study, subjects with ba...

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

    Institute of Scientific and Technical Information of China (English)

    段国玉

    2002-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王小平; 张宇; 粟文娟; 王珊珊; 王英

    2009-01-01

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

  14. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method.

    Science.gov (United States)

    Ge, Zhaohui; Xie, Yuanyuan; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0-∞ (P Uncaria and Gastrodia elata as a classic "herb pair" has been verified from the pharmacokinetic viewpoint. PMID:25610474

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

    Science.gov (United States)

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

    2014-12-01

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

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

    OpenAIRE

    Nélida Barrueco; Cecilia Martínez Fernández-Llamazares; Esther Durán; María Teresa Martínez Marín; Cristina Relaño García

    2008-01-01

    Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio acti...

  17. Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response

    OpenAIRE

    De Costa, Anna-Maria A.; Justis, Danielle N.; Schuyler, Corinne A.; M. Rita I. Young

    2012-01-01

    The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions tha...

  18. Effect of oral administration of Propionibacterium acnes on growth performance, DTH response and anti-OVA titers in goat kids

    Directory of Open Access Journals (Sweden)

    Luis Miguel Ferrer

    2013-01-01

    Full Text Available Immunostimulants are susbstances that stimuli the response of effector cells to activate the immune response such as antigen uptake, cytokine release or antibody response. These substances can increase resistence to infection by different types of microorganisms, reducing dependence of antibiotics used in livestock animals. Recent reports have demonstrated the positive effect of Propionibacterium acnes (P. acnes to control animal diseases. In this study, we evaluated the effect of the non-specific immunostimulant P. acnes on immunological functions and growth performance in goat kids. Twenty five goat kids served as control group (A and another 25 animals received P. acnes being the experimental group (B. Kids were challenged with ovalbumin (OVA to assess humoral immunity. To assess in vivo cell immunity, delayed type hypersensitivity (DTH test with phytohemagglutinin (PHA was used, clinical signs and body weight were recorded each week until 9 weeks of age when the experiment ended. Blood samples were obtained to analyze serum proteins fractions and anti-OVA specific antibodies. No clinical signs of disease and no differences (p>0.05 on body weight between groups were recorded (7.32±0.81 kg in group A, 7.13±0.65 kg in group B. Goat kids from group B had more total protein (59.8±5g/l and albumin levels (32.8±3.3g/l than goat kids from group A (56.6±5.7 g/l, 29.6±3.9 g/l respectively (p<0.05. DTH response in goat kids from group B on day 42 was higher (p<0.05 than group A. At day 63, goat kids from group receiving P. acnes had higher percentage (85.4 of anti-OVA IgM titers (p<0.05 than control group (57.7. In conclusion, the results showed that oral administration of P. acnes to goat kids improved some aspects of the immune system of the animals and it could be used to control goat diseases.

  19. Evaluation of the radioprotective Effect of the co-oral Administration of Vitamin B12 with Vitamin c on some Haematological and Biochemical Alterations in Male Albino Rats

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the prophylactic efficacy of co-oral administration of vitamin B12 with vitamin C against radiation induced haematological and biochemical alterations in male albino rats. Male albino rats were divided into six groups (n=8). Group 1: rats were kept as control, Group 2; rats received orally vita-min B12 (2000μgkg-1). Group 3; rats received Vitamin B12 with Vitamin C (500mgkg-1). Group 4; rats whole body exposed to 7Gy of gamma rays. Group 5; rats received vitamin B12 for 21 successive days before irradiation. Group 6; rats received Vitamin B12 with Vitamin C for 21 successive days before irradiation. Animals were sacrificed the third day post irradiation. The oral administration of Vitamin B12 with or with-out Vitamin C enhanced the recovery from radiation-induced haemopoietic injury and some biochemical changes demonstrated by a significant increase (p0.05>) of WBCs, RBCs and Platelets count, Hb content, Hct%, serum erythropoietin and iron levels and a significant reduction (p0.05>) of serum homocysteine level (Hcy), creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to their respective values in irradiated rats. Improvement of oxidative stress in heart and spleen tissues denoted by a significant decrease in lipid peroxidation (MDA) and a significant increase in glutathione (GSH) content was recorded also. The co-oral administration of vitamin B12 with vitamin C has no effect on the prophylactic efficacy of vitamin B12

  20. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    Science.gov (United States)

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  1. Effect of daily administration of oral etoposide for patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent radiation therapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to explore the effect of daily administration of oral etoposide(25mg) for patients with stage III NSCLC treated with concurrent radiation therapy. Planned endpoints were response, survival and toxicities. Material and Methods: Between (8(92)) and (9(95)), 37 stage III NSCLC patients were randomized to daily oral etoposide(25mg) with concurrent radiation therapy group(ERT) in 21 and radiation therapy alone group(RT) in 16. Etoposide was administered in the morning throughout radiation therapy. Median total irradiated dose, fraction size and time were 61.9Gy, 34.2 fractions and 48.8 days, respectively. Results: TO Monovariate survival analysis between ERT and RT showed no significant difference(p=0.10), but multivariate analysis confirmed that administration of oral etoposide is independent prognostic factor (p=0.009), together with T factor and N factor. Conclusion: ERT was better in local response but poorer in survival than RT. We concluded that complications of ERT was severe enough to cause death in some patients. We should design some methods to decrease these complications to make use of good local response acquired with ERT

  2. In Situ Lipidization as a New Approach for the Design of a Self Microemulsifying Drug Delivery System (SMEDDS) of Doxorubicin Hydrochloride for Oral Administration.

    Science.gov (United States)

    Derajram M Benival, M; Devarajan, Padma V

    2015-05-01

    The present paper reports in situ lipidization as a novel approach for the design of Dox-self microemulsifying drug delivery system (SMEDDS). Dox-aerosol OT (AOT) ion pair complex (lipidized Dox), exhibited high log P value of 1.74, indicating lipophilic nature. The lipidized Dox revealed good solubility but limited stability in various oils. Rapid complex formation of Dox with AOT dissolved in oils, and the high partitioning of lipidized Dox (-90%) into the oily phase presented in situ lipidization as a strategy to overcome the limited chemical stability of lipidized Dox. SMEDDS was prepared by mixing the lipidizing agent AOT, the surfactant α-Tocopheryl-Polyethyleneglycol-1 000-Succinate (TPGS) and Capmul as the oil. Dox was suspended in the SMEDDS to obtain Dox-SMEDDS. Dox-SMEDDS on aqueous dilution, resulted in a microemulsion with globule size 196 ± 16.56 nm, and revealed slow release of Dox. Oral bioavailability study in rats revealed a 420% enhancement from Dox-SMEDDS compared to Dox solution. Dox-SMEDDS and control group revealed comparable superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in heart and kidneys suggesting safety of the Dox-SMEDDS. Efficacy study (tumor size reduction) in fibrosarcoma mouse model suggested Dox-SMEDDS as a promising oral delivery system for the treatment of cancer. In situ lipidization of Dox in SMEDDS presents a novel approach for the design of an orally bioavailable and promising formulation of Dox for oral administration. PMID:26390522

  3. On the validity of setting breakpoint minimum inhibition concentrations at one quarter of the plasma concentration achieved following oral administration of oxytetracycline

    DEFF Research Database (Denmark)

    Coyne, R.; Samuelsen, O.; Bergh, Ø.;

    2004-01-01

    that the therapy was probably beneficial. Thus, the data obtained in this work suggest that the application of the 4:1 ratio is not a valid method of generating meaningful breakpoint MIC values. Published values for the MIC of OTC against A. salmonicida and the plasma concentrations achieved after oral...... administration of OTC medicated feed were applied to investigate the validity of the application of the 4:1 ratio. Breakpoints generated by the application of this ratio to these data would suggest that OTC could never have had any value in combating A. salmonicida infections. As this conclusion is contrary...... to experience, it is argued that examination of the published data reinforces the conclusion that the 4:1 ratio has little value in the oral therapy of fish disease....

  4. Oral administration of heat-inactivated Mycobacterium bovis reduces the response of farmed red deer to avian and bovine tuberculin.

    Science.gov (United States)

    López, Vladimir; González-Barrio, David; Lima-Barbero, José Francisco; Ortiz, José Antonio; Domínguez, Lucas; Juste, Ramón; Garrido, Joseba M; Sevilla, Iker A; Alberdi, Pilar; de la Fuente, José; Gortázar, Christian

    2016-04-01

    Orally delivered mycobacterial antigens may not sensitize the immunized animals causing a positive tuberculin skin test response. As the first step to address this critical issue, we characterized the response of farmed red deer (Cervus elaphus) to orally delivered heat-inactivated Mycobacterium bovis. Thirty-two adult red deer hinds from a farm known to be free of tuberculosis (TB) were randomly assigned to two different treatment groups, immunized (n=24) and control (n=8). Immunized hinds were dosed orally with 2ml of PBS containing 6×10(6) heat-inactivated M. bovis. The mean skin test response of immunized deer to both avian purified protein derivative (aPPD) and bovine PPD (bPPD) was consistently lower in immunized than in control hinds. One year after immunization, immunized hinds had a significant reduction in the skin test response to aPPD and in the ELISA antibody levels against both aPPD and bPPD (24-36% reduction; Ptest response to phytohaemagglutinin, or in the ELISA antibody levels against the M. bovis specific antigen MPB70. The mRNA levels for C3, IFN-γ and IL-1β and serum protein levels for IFN-γ and IL-1β did not vary between immunized and control deer. However, serum C3 protein levels were significantly higher (P=0.001) in immunized than in control deer six months after immunization. These results confirm that oral heat-inactivated M. bovis does not sensitize farmed red deer and therefore does not cause false-positive responses in the tuberculin skin test. The absence of sensitization in orally immunized deer opens the possibility of testing the vaccine in deer and possibly other ruminants without the risk of causing false-positive reactions in TB-tests. This study also provided the first evidence that orally-delivered inactivated mycobacterial antigens elicit some kind of immune response in a ruminant. PMID:27032499

  5. The effect of food composition on serum testosterone levels after oral administration of Andriol® Testocaps®

    OpenAIRE

    Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul

    2007-01-01

    Objective Andriol® Testocaps® is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. Design An open-label, single-centre, four-way crossover study. With a washout period of 6–7 days, 80 mg TU was administered in the morning 5 mi...

  6. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

    Directory of Open Access Journals (Sweden)

    Efrosini S Katsanou

    Full Text Available Chios mastic gum (CMG, a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE, at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD. The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE.

  7. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

    Science.gov (United States)

    Katsanou, Efrosini S; Kyriakopoulou, Katerina; Emmanouil, Christina; Fokialakis, Nikolas; Skaltsounis, Alexios-Leandros; Machera, Kyriaki

    2014-01-01

    Chios mastic gum (CMG), a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE), at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD). The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE. PMID:24950217

  8. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.

    Directory of Open Access Journals (Sweden)

    Mayuka Nakajima

    Full Text Available Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83 once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.

  9. Toxicological Evaluation of Oral Administration of Phoenix dactylifera L. Fruit Extract on the Histology of the Liver and Kidney of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Abel Nosereme Agbon

    2014-06-01

    Full Text Available Various parts of Phoenix dactylifera (date palm are used in traditional medicine to treat various disorders such as fever, abdominal troubles, etc., in different parts of the world. A preliminary phytochemical screening of the aqueous fruit extract of Phoenix dactylifera (AFPD revealed the presence of alkaloids, tannins, saponins, flavonoids and carbohydrates. This study was designed to investigate the effects of oral administration of AFPD on the histology of the liver and kidney in Wistar rats. Thirty-nine Wistar rats were divided into two groups-control (three rats and treatment (thirty-six rats. The animals in experimental group were further categorised for two phase study (eighteen rats divided into three groups; six rats/group for each phase. In the first phase, the three groups (A, B and C were administered AFPD (10, 100 and 1000 mg/kg, oral, respectively. In the second phase, the three groups (D, E and F were administered AFPD (1600, 2900 and 5000 mg/kg, oral, respectively. In both phases, after 24 h of AFPD administration, three rats of the six in each group were sacrificed and the other three sacrificed after 21 days. Histopathological examinations of liver and kidney sections of the experimental animals were compared with the control. No mortality or signs of toxicity was observed in the experimental animals upon administration of AFPD, even at doses as high as 5000 mg/kg, which was confirmed by mild pathological changes with remarkable recovery after 21 days. This result demonstrates that the LD50 of AFPD is greater than 5000 mg/kg and is relatively safe.

  10. Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

    Science.gov (United States)

    Timchalk, C; Finco, D R; Quast, J F

    1997-03-01

    The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey

  11. Protection and systemic translocation of siRNA following oral administration of chitosan/siRNA nanoparticles

    DEFF Research Database (Denmark)

    Gonzalez, Borja Ballarin; Dagnæs-Hansen, Frederik; Fenton, Robert A.;

    2013-01-01

    hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ...

  12. Effect of administration of oral contraceptives on the synthesis and breakdown of myofibrillar proteins in young women

    DEFF Research Database (Denmark)

    Hansen, M; Langberg, H.; Holm, Lars;

    2011-01-01

    Oral contraceptive (OC) treatment has an inhibiting effect on protein synthesis in tendon and muscle connective tissue. We aimed to investigate whether OC influence myofibrillar protein turnover in young women. OC-users (24±2 years; Lindynette® n=7, Cilest® n=4) and non-OC-users (controls, 24±4 y...

  13. Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Christensen, N J; Sørensen, T I;

    1991-01-01

    Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 8...

  14. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Badoud, F; Boccard, J; Schweizer, C; Pralong, F; Saugy, M; Baume, N

    2013-11-01

    The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the

  15. Oral administration of O-2 lean, an anti-obesity herbal composition increased 5-HT metabolism, decreased food intake and body weight in overweight rats

    International Nuclear Information System (INIS)

    Feeding behavior is complex processes controlled by the neruroendocrine system.5-HT play an important role in regulation of energy balance by suppressing food intake. Depletion of brain serotonin increase feeding behavior and develop obesity. Many serotoninergic compounds are available in market for the management of body weight. 02-Lean is an anti-obesity herbal formulation prepared by combination of different herbs. Oral administration of aqueous suspension of 02-Lean caused a significant decrease in body weight, food intake, and increase in whole brain 5-HT 5HIAA, tryptophan and plasma tryptophan in over weight rats treated with 0.096g/2ml 02-Lean in comparison to control group. (author)

  16. Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model

    OpenAIRE

    Lopamudra Haldar; Gandhi, D.N.

    2016-01-01

    Aim: To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. Materials and Methods: An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1) was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2) and (T3) groups received spore biomass of Bacillus coagulans B...

  17. Augmentation of the antibody response of Atlantic salmon by oral administration of alginate-encapsulated IPNV antigens.

    Directory of Open Access Journals (Sweden)

    Lihan Chen

    Full Text Available The objective of the present study was to assess the effect of alginate-encapsulated infectious pancreatic necrosis virus antigens in inducing the immune response of Atlantic salmon as booster vaccines. One year after intraperitoneal injection with an oil-adjuvanted vaccine, post-smolts were orally boosted either by 1 alginate-encapsulated IPNV antigens (ENCAP; 2 soluble antigens (UNENCAP or 3 untreated feed (control. This was done twice, seven weeks apart. Sampling was done twice, firstly at 7 weeks post 1st oral boost and the 2nd, at 4 weeks after the 2nd oral boost. Samples included serum, head kidney, spleen and hindgut. Serum antibodies were analyzed by ELISA while tissues were used to assess the expression of IgM, IgT, CD4, GATA3, FOXP3, TGF-β and IL-10 genes by quantitative PCR. Compared to controls, fish fed with ENCAP had a significant increase (p<0.04 in serum antibodies following the 1st boost but not after the 2nd boost. This coincided with significant up-regulation of CD4 and GATA3 genes. In contrast, serum antibodies in the UNENCAP group decreased both after the 1st and 2nd oral boosts. This was associated with significant up-regulation of FOXP3, TGF-β and IL-10 genes. The expression of IgT was not induced in the hindgut after the 1st oral boost but was significantly up-regulated following the 2nd one. CD4 and GATA3 mRNA expressions exhibited a similar pattern to IgT in the hindgut. IgM mRNA expression on the other hand was not differentially regulated at any of the times examined. Our findings suggest that 1 Parenteral prime with oil-adjuvanted vaccines followed by oral boost with ENCAP results in augmentation of the systemic immune response; 2 Symmetrical prime and boost (mucosal with ENCAP results in augmentation of mucosal immune response and 3 Symmetrical priming and boosting (mucosal with soluble antigens results in the induction of systemic immune tolerance.

  18. Oral administration of heat-inactivated Mycobacterium bovis reduces the response of farmed red deer to avian and bovine tuberculin.

    Science.gov (United States)

    López, Vladimir; González-Barrio, David; Lima-Barbero, José Francisco; Ortiz, José Antonio; Domínguez, Lucas; Juste, Ramón; Garrido, Joseba M; Sevilla, Iker A; Alberdi, Pilar; de la Fuente, José; Gortázar, Christian

    2016-04-01

    Orally delivered mycobacterial antigens may not sensitize the immunized animals causing a positive tuberculin skin test response. As the first step to address this critical issue, we characterized the response of farmed red deer (Cervus elaphus) to orally delivered heat-inactivated Mycobacterium bovis. Thirty-two adult red deer hinds from a farm known to be free of tuberculosis (TB) were randomly assigned to two different treatment groups, immunized (n=24) and control (n=8). Immunized hinds were dosed orally with 2 ml of PBS containing 6 × 10(6) heat-inactivated M. bovis. The mean skin test response of immunized deer to both avian purified protein derivative (aPPD) and bovine PPD (bPPD) was consistently lower in immunized than in control hinds. One year after immunization, immunized hinds had a significant reduction in the skin test response to aPPD and in the ELISA antibody levels against both aPPD and bPPD (24-36% reduction; P<0.05). By contrast, no significant change was observed in the skin test response to phytohaemagglutinin, or in the ELISA antibody levels against the M. bovis specific antigen MPB70. The mRNA levels for C3, IFN-γ and IL-1β and serum protein levels for IFN-γ and IL-1β did not vary between immunized and control deer. However, serum C3 protein levels were significantly higher (P=0.001) in immunized than in control deer six months after immunization. These results confirm that oral heat-inactivated M. bovis does not sensitize farmed red deer and therefore does not cause false-positive responses in the tuberculin skin test. The absence of sensitization in orally immunized deer opens the possibility of testing the vaccine in deer and possibly other ruminants without the risk of causing false-positive reactions in TB-tests. This study also provided the first evidence that orally-delivered inactivated mycobacterial antigens elicit some kind of immune response in a ruminant.

  19. Sodium borocaptate (BSH) for Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model: boron biodistribution at 9 post administration time-points

    International Nuclear Information System (INIS)

    The therapeutic success of Boron Neutron Capture Therapy (BNCT) depends centrally on boron concentration in tumor and healthy tissue. We previously demonstrated the therapeutic efficacy of boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) as boron carriers for BNCT in the hamster cheek pouch oral cancer model. Given the clinical relevance of sodium mercaptoundecahydro-closo-dodecaborate (BSH) as a boron carrier, the aim of the present study was to expand the ongoing BSH biodistribution studies in the hamster cheek pouch oral cancer model. In particular, we studied 3 additional post-administration time-points and increased the sample size corresponding to the time-points evaluated previously, to select more accurately the post-administration time at which neutron irradiation would potentially confer the greatest therapeutic advantage. BSH was dissolved in saline solution in anaerobic conditions to avoid the formation of the dimer BSSB and its oxides which are toxic. The solution was injected intravenously at a dose of 50 mg 10 B/kg (88 mg BSH / kg). Different groups of animals were killed humanely at 7, 8, and 10 h after administration of BSH. The sample size corresponding to the time-points 3, 4, 6, 9 and 12 h was increased. Samples of blood, tumor, precancerous tissue, normal pouch tissue, cheek mucosa, parotid gland, palate, skin, tongue, spinal cord marrow, brain, liver, kidney, spleen and lung were processed for boron measurement by Optic Emission Spectroscopy (ICP-OES). Boron concentration in tumor peaked to 24-34 ppm, 3-10 h post-administration of BSH, with a spread in values that resembled that previously reported in other experimental models and human subjects. The boron concentration ratios tumor/normal pouch tissue and tumor/blood ranged from 1.3 to 1.8. No selective tumor uptake was observed at any of the time points evaluated. The times post-administration of BSH that would be therapeutically most useful would be 5, 7 and 9 h. The

  20. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

    Science.gov (United States)

    Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

    2015-08-01

    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. PMID:26117186

  1. Evaluation of renal function following administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP) in animals submitted to oral intoxication with uranyl nitrate

    International Nuclear Information System (INIS)

    Workers involved in the processes of extraction, purification and manufacture of uranium of nuclear plants are occupationally exposed to both natural and enriched uranium. Several chelating agents (TIRON, EDTA, BAI, etc.) have been tested in terms of their capacity to sequester uranium before it reaches its target organs. Our laboratory has studied a first generation biphosphonate, ethane-1-hydroxy-1,1-biphosphonate (EHBP). We have shown that treatment with EHBP induces survival rates of 75% and 100% in adult and suckling rats respectively intoxicated with an intraperitoneal injection of uranyl nitrate. There are no data available to date on the renal function following treatment with EBHP to counteract the toxic effects of an oral lethal dose of uranyl nitrate. The aim of the present study was to assay creatininemia and uremia as end-points to assess renal function. The results obtained reveal that the alterations in renal function induced by oral uranyl nitrate intoxication can be reduced at 48 hours and reverted at 14 days by subcutaneous or oral administration of EHBP. (author)

  2. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shannon D Shields

    Full Text Available Cerebellar symptoms significantly diminish quality of life in patients with multiple sclerosis (MS. We previously showed that sodium channel Nav1.8, although normally restricted to peripheral somatosensory neurons, is upregulated in the cerebellum in MS, and that Nav1.8 expression is linked to ataxia and MS-like symptoms in mice. Furthermore, intracerebroventricular administration of the Nav1.8 blocker A-803467 temporarily reversed electrophysiological and behavioral manifestations of disease in a mouse MS model; unfortunately A-803467 is not orally bioavailable, diminishing the potential for translation to human patients. In the present study, we assessed the effect of per os (p.o. dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE model. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders.

  3. Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

    International Nuclear Information System (INIS)

    Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy. - Highlights: • We study the biodistribution of BPA+BSH for BNCT in experimental oral cancer. • The 3 BPA+BSH protocols assayed are potentially therapeutic. • Different proportions of B compounds with different CBE factors will affect response

  4. Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

    Institute of Scientific and Technical Information of China (English)

    罗维丹; 邬成霖

    2001-01-01

    @@ Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

  5. Effects of Oral Administration of Non-genotoxic Hepato-hypertrophic Compounds on Metabolic Potency of Rat Liver

    OpenAIRE

    Fang, Xing; Nunoshiba, Tatsuo; Yoshida, Midori; Nishikawa, Akiyoshi; Nemoto, Kiyomitsu; Degawa, Masakuni; Arimoto, Sakae; Okamoto, Keinosuke; Takahashi, Eizo; Negishi, Tomoe

    2014-01-01

    It remains uncertain why non-genotoxic compounds that result in liver hypertrophy cause liver tumors. In an effort to resolve this issue, we examined whether liver post-mitochondrial fraction (S9) prepared from rats treated with non-genotoxic compounds affected the genotoxicity of pro-mutagens. Known hepatotoxic compounds, such as piperonyl butoxide (PBO), decabromodiphenyl ether (DBDE), beta-naphthoflavone (BNF), indole-3-carbinol (I3C) and acetaminophen (AA), were orally administered to mal...

  6. Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas-liquid chromatography.

    Science.gov (United States)

    Morrison, P J; Bradbrook, I D; Rogers, H J

    1979-01-01

    1 A gas chromatographic assay for the estimation of therapeutic concentrations of cinnarizine in plasma is described. 2 Cinnarizine (75 mg) was administered orally to twelve healthy subjects in the form of capsules and tablets on two separate occasions. No difference was found in the plasma levels or absorption of cinnarizine from these formulations. 3 The mean plasma elimination half-life of cinnarizine was 3.24 h. PMID:444354

  7. Detection and Quantification of Flavobacterium psychrophilum-Specific Bacteriophages In Vivo in Rainbow Trout upon Oral Administration: Implications for Disease Control in Aquaculture

    Science.gov (United States)

    Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias; Lauritsen, Anne H.

    2014-01-01

    The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods—bath, oral intubation into the stomach, and phage-coated feed—with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼105 PFU mg intestine−1 and ∼103 PFU mg spleen−1 within the first 24 h following the bath and ∼107 PFU mg intestine−1 and ∼104 PFU mg spleen−1 within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼104 PFU mg intestine−1 and ∼101 PFU mg spleen−1 were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60% survival

  8. Detection and quantification of Flavobacterium psychrophilum-specific bacteriophages in vivo in rainbow trout upon oral administration: implications for disease control in aquaculture.

    Science.gov (United States)

    Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias; Lauritsen, Anne H; Madsen, Lone

    2014-12-01

    The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods-bath, oral intubation into the stomach, and phage-coated feed-with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10(5) PFU mg intestine(-1) and ∼10(3) PFU mg spleen(-1) within the first 24 h following the bath and ∼10(7) PFU mg intestine(-1) and ∼10(4) PFU mg spleen(-1) within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10(4) PFU mg intestine(-1) and ∼10(1) PFU mg spleen(-1) were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60

  9. Oral Administration of Faecalibacterium prausnitzii Decreased the Incidence of Severe Diarrhea and Related Mortality Rate and Increased Weight Gain in Preweaned Dairy Heifers

    Science.gov (United States)

    Foditsch, Carla; Pereira, Richard Van Vleck; Ganda, Erika Korzune; Gomez, Marilia Souza; Marques, Eduardo Carvalho; Santin, Thiago; Bicalho, Rodrigo Carvalho

    2015-01-01

    Probiotics are a promising alternative to improve food animal productivity and health. However, scientific evidence that specific microbes can be used to benefit animal health and performance is limited. The objective of this study was to evaluate the effects of administering a live culture of Faecalibacterium prausnitzii to newborn dairy calves on subsequent growth, health, and fecal microbiome. Initially, a safety trial was conducted using 30 newborn bull calves to assess potential adverse effects of the oral and rectal administration of F. prausnitzii to neonatal calves. No adverse reactions, such as increased body temperature or heart and respiratory rates, were observed after the administration of the treatments. All calves survived the experimental period, and there was no difference in fecal consistency score, attitude, appetite or dehydration between the treatment groups. The rectal route was not an efficient practice while the oral route ensures that the full dose is administered to the treated calves. Subsequently, a randomized field trial was completed in a commercial farm with preweaned calves. A total of 554 Holstein heifers were assigned to one of two treatment groups: treated calves (FPTRT) and non-treated calves (control). Treated calves received two oral doses of F. prausnitzii, one at treatment assignment (1st week) and another one week later. The FPTRT group presented significantly lower incidence of severe diarrhea (3.1%) compared with the control group (6.8%). Treated calves also had lower mortality rate associated with severe diarrhea (1.5%) compared to control calves (4.4%). Furthermore, FPTRT calves gained significantly more weight, 4.4 kg over the preweaning period, than controls calves. The relative abundance of F. prausnitzii in the fecal microbiota was significantly higher in the 3rd and 5th weeks of life of FPTRT calves than of the control calves, as revealed by sequencing of the 16S rRNA gene. Our findings showed that oral

  10. Oral Administration of Faecalibacterium prausnitzii Decreased the Incidence of Severe Diarrhea and Related Mortality Rate and Increased Weight Gain in Preweaned Dairy Heifers.

    Directory of Open Access Journals (Sweden)

    Carla Foditsch

    Full Text Available Probiotics are a promising alternative to improve food animal productivity and health. However, scientific evidence that specific microbes can be used to benefit animal health and performance is limited. The objective of this study was to evaluate the effects of administering a live culture of Faecalibacterium prausnitzii to newborn dairy calves on subsequent growth, health, and fecal microbiome. Initially, a safety trial was conducted using 30 newborn bull calves to assess potential adverse effects of the oral and rectal administration of F. prausnitzii to neonatal calves. No adverse reactions, such as increased body temperature or heart and respiratory rates, were observed after the administration of the treatments. All calves survived the experimental period, and there was no difference in fecal consistency score, attitude, appetite or dehydration between the treatment groups. The rectal route was not an efficient practice while the oral route ensures that the full dose is administered to the treated calves. Subsequently, a randomized field trial was completed in a commercial farm with preweaned calves. A total of 554 Holstein heifers were assigned to one of two treatment groups: treated calves (FPTRT and non-treated calves (control. Treated calves received two oral doses of F. prausnitzii, one at treatment assignment (1st week and another one week later. The FPTRT group presented significantly lower incidence of severe diarrhea (3.1% compared with the control group (6.8%. Treated calves also had lower mortality rate associated with severe diarrhea (1.5% compared to control calves (4.4%. Furthermore, FPTRT calves gained significantly more weight, 4.4 kg over the preweaning period, than controls calves. The relative abundance of F. prausnitzii in the fecal microbiota was significantly higher in the 3rd and 5th weeks of life of FPTRT calves than of the control calves, as revealed by sequencing of the 16S rRNA gene. Our findings showed that oral

  11. HPLC method for comparative study on tissue distribution in rat after oral administration of salvianolic acid B and phenolic acids from Salvia miltiorrhiza.

    Science.gov (United States)

    Xu, Man; Fu, Gang; Qiao, Xue; Wu, Wan-Ying; Guo, Hui; Liu, Ai-Hua; Sun, Jiang-Hao; Guo, De-An

    2007-10-01

    A sensitive and selective high-performance liquid chromatography method was developed and validated to determine the prototype of salvianolic acid B and the metabolites of phenolic acids (protocatechuic acid, vanillic acid and ferulic acid) in rat tissues after oral administration of total phenolic acids and salvianolic acid B extracted from the roots of Salvia miltiorrhiza, respectively. The tissue samples were treated with a simple liquid-liquid extraction prior to HPLC. Analysis of the extract was performed on a reverse-phase C(18) column with a mobile phase consisting of acetonitrile and 0.05% trifluoracetic acid. The calibration curves for the four phenolic acids were linear in the given concentration ranges. The intra-day and inter-day relative standard deviations in the measurement of quality control samples were less than 10% and the accuracies were in the range of 88-115%. The average recoveries of all the tissues ranged from 78.0 to 111.8%. This method was successfully applied to evaluate the distribution of the four phenolic acids in rat tissues after oral administration of total phenolic acids of Salvia miltiorrhiza or salvianolic acid B and the possible metabolic pathway was illustrated. PMID:17549679

  12. Hydrolysis is the dominating in vivo metabolism pathway for arctigenin: identification of novel metabolites of arctigenin by LC/MS/MS after oral administration in rats.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2013-04-01

    The phenylpropanoid dibenzylbutyrolactone lignan arctigenin, a key component found in Arctium lappa, or burdock, has been reported with a variety of therapeutic effects including anticancer, anti-inflammation, and antivirus effects. Using LC/MS/MS, three novel metabolites of arctigenin, namely, arctigenic acid, arctigenin-4-O'-glucuronide, and 4-O-demethylarctigenin were identified after oral administration of arctigenin in rats for the first time. Another potential metabolite of arctigenin, arctigenin-4'-O-sulfate, was identified in vitro but not in vivo. Structure of arctigenic acid, the major metabolite of arctigenin, was confirmed by 13C-NMR and 1H-NMR. Rapid hydrolysis in plasma was identified as the major metabolic pathway of arctigenin after its oral administration, with Vmax, Km, and Clint in rat plasma determined to be 2.21 ± 0.12 nmol/min/mg, 89.12 ± 9.44 µM, and 24.74 µL/min/mg, respectively. Paraoxonase 1 was further confirmed to be the enzyme responsible for arctigenin hydrolysis, with Vmax, Km, and Clint determined to be 55.39 ± 1.49 nmol/min/mg, 300.3 ± 10.86 µM, and 184.45 µL/min/mg, respectively. PMID:23519790

  13. Ultra-performance liquid-chromatography with tandem mass spectrometry for rapid analysis of pharmacokinetics, biodistribution and excretion of schisandrin after oral administration of Shengmaisan.

    Science.gov (United States)

    Lu, Sheng-Wen; Zhang, Ai-Hua; Sun, Hui; Yan, Guang-Li; Han, Ying; Wu, Xiu-Hong; Wang, Xi-Jun

    2013-12-01

    This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component-schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC-MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/z 415.22 → 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half-life (T1/2 ) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin was recovered in feces and was not detected in urine.

  14. Cloud point extraction-HPLC method for the determination and pharmacokinetic study of aristolochic acids in rat plasma after oral administration of Aristolochiae Fructus.

    Science.gov (United States)

    Ren, Gang; Huang, Qun; Wu, Jiangang; Yuan, Jinbin; Yang, Gaihong; Yan, Zhihong; Yao, Shouzhuo

    2014-03-15

    Based on cloud-point extraction (CPE), a high performance liquid chromatography method (HPLC) was developed and validated for the determination of aristolochic acids (AAs) in rat plasma after oral administration of Aristolochiae Fructus (AF). Non-ionic surfactant Genapol X-080, an environmentally friendly solvent, was used for the micelle-mediated extraction. Various influencing factors on CPE process were investigated and optimized. AAs were extracted from rat plasma after adding 1ml of 4.5% (v/v) surfactant in the presence of 0.2mol/l HCl and 20mg NaCl, and the incubation temperature and time were 50°C and 10min, respectively. Base-line separation was obtained for the AAs in rat plasma with the optimized chromatography conditions. The detection limits (LOD) reached downward 10ng/ml. The intra-day and inter-day precisions were less than 7.8%, the accuracies were within ±5.5%, and the average recovery factors were in the range of 94.5-105.4%. In comparison with liquid-liquid extraction, the CPE method has a considerable LOD and higher recoveries. The proposed CPE-HPLC method was specific, sensitive and reliable, and could be an effective tool for the determination of AAs in biological matrixes. With the method the pharmacokinetics of AAs were investigated successfully after oral administration of AF by rats.

  15. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi.

    Directory of Open Access Journals (Sweden)

    Joana N Rocha

    Full Text Available There is currently no licensed vaccine that protects foals against Rhodococcus equi-induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8 were vaccinated by gavaging with eBeam-inactivated R. equi at ages 2, 7, and 14 days, or gavaged with equal volume of saline solution (n = 4, and subsequently infected intrabronchially with live, virulent R. equi at age 21 days. The proportion of vaccinated foals that developed pneumonia following challenge was similar among the vaccinated (7/8; 88% and unvaccinated foals (3/4; 75%. This vaccination regimen did not appear to be strongly immunogenic in foals. Alternative dosing regimens or routes of administration need further investigation and may prove to be immunogenic and protective.

  16. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi

    Science.gov (United States)

    Rocha, Joana N.; Cohen, Noah D.; Bordin, Angela I.; Brake, Courtney N.; Giguère, Steeve; Coleman, Michelle C.; Alaniz, Robert C.; Lawhon, Sara D.; Mwangi, Waithaka; Pillai, Suresh D.

    2016-01-01

    There is currently no licensed vaccine that protects foals against Rhodococcus equi–induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam)-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8) were vaccinated by gavaging with eBeam-inactivated R. equi at ages 2, 7, and 14 days, or gavaged with equal volume of saline solution (n = 4), and subsequently infected intrabronchially with live, virulent R. equi at age 21 days. The proportion of vaccinated foals that developed pneumonia following challenge was similar among the vaccinated (7/8; 88%) and unvaccinated foals (3/4; 75%). This vaccination regimen did not appear to be strongly immunogenic in foals. Alternative dosing regimens or routes of administration need further investigation and may prove to be immunogenic and protective. PMID:26828865

  17. Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells.

    Science.gov (United States)

    Adar, T; Ben Ya'acov, A; Lalazar, G; Lichtenstein, Y; Nahman, D; Mizrahi, M; Wong, V; Muller, B; Rawlin, G; Ilan, Y

    2012-02-01

    Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH. PMID:22236001

  18. Effect of submucosal or oral administration of prednisolone on postoperative sequelae following surgical extraction of impacted mandibular third molar: A randomized controlled study

    Directory of Open Access Journals (Sweden)

    Adebayo Aremu Ibikunle

    2016-01-01

    Full Text Available Background: The aim of the study was to evaluate the effect of preoperatively administered submucosal and oral prednisolone on postoperative pain, facial swelling, and trismus following third molar surgery. Patients and Methods: This was a randomized controlled trial in which subjects were randomly distributed into three groups. Group A consisted of subjects who received 40 mg oral prednisolone; Group B consisted of subjects who received 40 mg submucosal injection of prednisolone while Group C consisted of subjects who did not receive prednisolone. Each group had 62 subjects. Measurements for facial width/facial swelling, pain, and mouth opening were recorded preoperatively and postoperatively. The postoperative evaluation points were postoperative days 1, 3, and 7. These measurements were compared with the preoperative values both within and among the groups. Results: Most of the subjects were in their third decade of life. A considerable increase in the mean postoperative values for pain, facial width and trismus was observed. Notably, subjects who did not receive prednisolone showed comparatively higher values for the measured parameters throughout the postoperative evaluation period. Subjects who received submucosal injection of prednisolone showed overall lower values compared to those who received oral prednisolone. Conclusion: The results of this study indicate that the administration of prednisolone has a significantly beneficial effect in ameliorating the postoperative sequelae of the third molar surgery. In addition, the effect of submucosally injected prednisolone is comparable to the orally administered prednisolone; indeed it shows superiority to the latter in a number of dimensions. Submucosal injection of prednisolone offers a simple, effective, easy, safe, and minimally invasive option to existing therapeutic methods of reducing these postoperative sequelae.

  19. Hidratación oral continua o a dosis fraccionadas en niños deshidratados por diarrea aguda Oral rehydration in continuous administration or in fractionated doses in dehydrated children with acute diarrhea

    Directory of Open Access Journals (Sweden)

    Felipe Mota-Hernández

    2002-01-01

    Full Text Available Objetivo. Evaluar la seguridad y efectividad de dos técnicas de hidratación oral. Material y métodos. Ensayo clínico aleatorio, hecho en el Servicio de Hidratación Oral del Hospital Infantil de México, Federico Gómez, entre septiembre de 1998 y junio de 1999. Cuarenta pacientes deshidratados por diarrea aguda, menores de cinco años, recibieron suero oral ad libitum (grupo AL y otros cuarenta lo recibieron en dosis fraccionada (grupo DF. Las características clínicas fueron similares en ambos grupos. Los resultados se presentan como promedio y desviación estándar o mediana, según la distribución de frecuencias simples y relativas. Resultados. El promedio de gasto fecal en el grupo AL fue 11.0±7.5 g/kg/h y en el grupo DF 7.1±7.4 (p=0.03. La ingesta de suero, el tiempo de hidratación y la diuresis promedio, fueron similares entre ambos grupos (p>0.05. Seis pacientes del grupo AL y cinco del DF tuvieron gasto fecal alto (>10 g/kg/hora, mejorando con la administración de atole de arroz. Un paciente del grupo AL y dos pacientes del DF tuvieron vómitos persistentes, mejorando con gastroclisis. Ningún paciente requirió rehidratación intravenosa. Conclusiones. Estos resultados sugieren que la administración de suero oral ad libitum, bajo supervisión, es tan segura y efectiva como la técnica de dosis fraccionada para el tratamiento de niños deshidratados por diarrea aguda.Objective. To evaluate the safety and effectiveness of two oral rehydration techniques. Material and Methods. A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS ad libitum (AL group; another forty patients received ORS in fractionated doses (FD group. Clinical characteristics were similar in both groups. Results are presented as

  20. Pharmacokinetics, efficacy prediction indexes, and residue depletion of ribavirin in Atlantic salmon's (Salmo salar) muscle after oral administration in feed.

    Science.gov (United States)

    San Martín, B; Muñoz, R; Cornejo, J; Martínez, M A; Araya-Jordán, C; Maddaleno, A; Anadón, A

    2016-08-01

    Ribavirin is an antiviral used in human medicine, but it has not been authorized for use in veterinary medicine although it is effective against infectious salmon anemia (ISA) virus, between others. In this study, we present a pharmacokinetic profile of ribavirin in Atlantic salmon (Salmo salar), efficacy prediction indexes, and the measure of its withdrawal time. To determine the pharmacokinetic profile, fishes were orally administered with a single ribavirin dose of 1.6 mg/kg bw, and then, plasma concentrations were measured at different times. From the time-vs.-concentration curve, Cmax = 413.57 ng/mL, Tmax  = 6.96 h, AUC = 21394.01 μg·h/mL, t1/2  = 81.61 h, and K10  = 0.0421/h were obtained. Ribavirin reached adequate concentrations during the pharmacokinetic study, with prediction indexes of Cmax /IC50  = 20.7, AUC/IC50  = 1069.7, and T>IC50  = 71 h, where IC is the inhibitory concentration 50%. For ribavirin depletion study, fishes were orally administered with a dairy dose of 1.6 mg/kg bw during 10 days. Concentrations were measured on edible tissue on different days post-treatment. A linear regression of the time vs. concentration was conducted, obtaining a withdrawal time of 1966 °C days. Results obtained reveal that the dose of 1.6 mg/kg bw orally administered is effective for ISA virus, originating a reasonable withdrawal period within the productive schedules of Atlantic salmon. PMID:26960624

  1. Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

    Energy Technology Data Exchange (ETDEWEB)

    D.W. Nigg; William Bauer; Various Others

    2014-06-01

    Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.

  2. Tissue depletion of azaperone and its metabolite azaperol after oral administration of azaperone in food-producing pigs

    Directory of Open Access Journals (Sweden)

    N. Mestorino

    2013-01-01

    Full Text Available Azaperona es un tranquilizante de tipo butirofenona usado en ganado porcino. Los cerdos son particularmente sensibles al estrés durante el manejo y transporte al matadero. La azaperona es parcialmente metabolizada in vivo a azaperol, un metabolito con actividad farmacológica. Las concentraciones altas y persistentes de azaperona y azaperol en el lugar de inyección contraindican el uso de azaperona por vía intramuscular para el transporte de cerdos de producción de carne al matadero; el uso oral podría ser una alternativa para evitar residuos en el lugar de inyección. El presente estudio determinó la depleción en los tejidos de azaperona y su metabolito azaperol después de la administración oral de la formulación Stresnil®. Cerdos machos (30-45 kg de peso corporal fueron tratados con Stresnil® (dosis oral única de 4 mg azaperona/kg de peso corporal y se sacrificaron 6, 24 y 48 horas después de la administración. De cada animal se obtuvo músculo, piel + grasa, hígado y riñón. Azaperona y azaperol se analizaron por HPLC tras la extracción en fase sólida. Las concentraciones de azaperona más azaperol en todos los tejidos analizados no superaron el Límite Máximo de Residuos (LMR establecidos por la Unión Europea (100 mg / kg en el músculo, el hígado, los riñones y la piel + grasa en ningún momento del muestreo. Como consecuencia, según los resultados obtenidos en el presente estudio, los tejidos comestibles de los cerdos tratados por vía oral con 4 mg/kg de azaperona, 6 horas antes al sacrificio, podrían ser aceptables para garantizar la seguridad de los consumidores. Sin embargo, se estimó un tiempo de espera de cero horas por análisis de regresión lineal.

  3. Attenuation of Biochemical Parameters in Streptozotocin-induced Diabetic Rats by Oral Administration of Extracts and Fractions of Cephalotaxus sinensis

    OpenAIRE

    Saeed, Muhammad K.; Deng, Yulin; Dai, Rongji

    2007-01-01

    Cephalotaxus sinensis (C. sinensis) large size, evergreen tree common in China and utilized for numerous effective pharmacological applications in Chinese traditional medicine. The hepato-renal effects of C. sinensis were evaluated in vivo using Streptozotocin (STZ)-induced diabetic rats as an tentative model. Animals were orally treated with 80% EtOH extract (aq.EE), H2O extract (WtE) and ethylacetate (EaF)/butanol fractions (BtF) of C. sinensis (200 mg/kg, b.w.) for 28 days whereas control ...

  4. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses. PMID:25274606

  5. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice.

    Science.gov (United States)

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg((-1)) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg((-1)) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  6. Dietary geraniol by oral or enema administration strongly reduces dysbiosis and systemic inflammation in dextran sulphate sodium-treated mice.

    Directory of Open Access Journals (Sweden)

    Luigia eDe Fazio

    2016-03-01

    Full Text Available (Trans-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH, is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulphate sodium (DSS-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120mg kg(-1 body weight, starting six days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg(-1 dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2 expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  7. Human radiation studies: Remembering the early years. Oral history of Donner Lab Administrator Baird G. Whaley, August 15, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Baird G. Whaley, Donner Lab Administrator, was interviewed by representatives of US DOE Office of Human Radiation Experiments (OHRE). The purpose of the interview was to capture the remembrances of Mr. Whaley concerning what he could relate on activities at the Donner Lab that pertain to the OHRE responsibilities. Following a brief biographical sketch, Mr. Whaley relates his experiences in administration at the LAB including funding activities, staffing concerns, intralaboraory politics, and remembrances of John Lawrence, John Gofman, Cornelius Tobias, Jim Born, Alex Margolis, B.V.A. Low- Beer, and Ed Alpen. Further patient care procedures for Donner Clinic Research Programs were discussed.

  8. Human radiation studies: Remembering the early years. Oral history of Donner Lab Administrator Baird G. Whaley, August 15, 1994

    International Nuclear Information System (INIS)

    Baird G. Whaley, Donner Lab Administrator, was interviewed by representatives of US DOE Office of Human Radiation Experiments (OHRE). The purpose of the interview was to capture the remembrances of Mr. Whaley concerning what he could relate on activities at the Donner Lab that pertain to the OHRE responsibilities. Following a brief biographical sketch, Mr. Whaley relates his experiences in administration at the LAB including funding activities, staffing concerns, intralaboraory politics, and remembrances of John Lawrence, John Gofman, Cornelius Tobias, Jim Born, Alex Margolis, B.V.A. Low- Beer, and Ed Alpen. Further patient care procedures for Donner Clinic Research Programs were discussed

  9. Effect of intravenous or oral sodium chlorate administration on the fecal shedding of Escherichia coli in sheep

    Science.gov (United States)

    The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 +/- 2.5 kg) were administered 150 mg NaClO3 per kg BW by gavage or i.v. infusion in a cross-over design with sal...

  10. COMPARISON OF THE LUNG ADENOMA RESPONSE IN STRAIN A/J MICE AFTER INTRAPERITONEAL AND ORAL ADMINISTRATION OF CARCINOGENS

    Science.gov (United States)

    This study was undertaken to compare the ability of a series of compounds from different chemical classes to induce lung tumors in strain A/J mice after either ip or po administration. 3-Methylcholanthrene, benzo(a)pyrene, urethan, diethylnitrosamine, ethylnitrosourea, and dimeth...

  11. A pharmacokinetic and residual study of sulfadiazine/trimethoprim in mandarin fish (Siniperca chuatsi) with single- and multiple-dose oral administrations.

    Science.gov (United States)

    Wang, W; Luo, L; Xiao, H; Zhang, R; Deng, Y; Tan, A; Jiang, L

    2016-06-01

    A pharmacokinetic and tissue residue study of sulfadiazine combined with trimethoprim (SDZ/TMP = 5/1) was conducted in Siniperca chuatsi after single- (120 mg/kg) or multiple-dose (an initial dose of 120 mg/kg followed by a 5-day consecutive dose of 60 mg/kg) oral administrations at 28 °C. The absorption half-life (t1/2α ), elimination half-life (t1/2β ), volume of distribution (Vd /F), and the total body clearance (ClB /F) for SDZ and TMP were 4.3 ± 1.7 to 6.3 ± 1.8 h and 2.4 ± 1.0 to 3.9 ± 0.9 h, 25.9 ± 4.5 to 53.0 ± 5.6 h and 11.8 ± 3.5 to 17.1 ± 3.4 h, 2.34 ± 0.78 to 3.67 ± 0.99 L/kg and 0.39 ± 0.01 to 1.33 ± 0.57 L/kg, and 0.03 ± 0.01 to 0.06 ± 0.01 L/kg·h and 0.02 ± 0.01 to 0.05 ± 0.01 L/kg·h, respectively, after the single dose. The elimination half-life (t1/2β ) and mean residue time (MRT) for SDZ and TMP were 68.8 ± 7.8 to 139.8 ± 12.3 h and 34.0 ± 5.5 to 56.1 ± 6.8 h, and 99.3 ± 6.1 to 201.7 ± 11.5 h and 49.1 ± 3.5 to 81.0 ± 5.1 h, respectively, after the multiple-dose administration. The daily oral SDZ/TMP administration might cause a high tissue concentration and long t1/2β , thereby affecting antibacterial activity. The withdrawal time for this oral SDZ/TMP formulation (according to the accepted guidelines in Europe for maximum residue limits, sulfonamides, and <0.05 mg/kg for TMP) should not be <36 days for fish. PMID:26669806

  12. 品管圈活动在口腔肿瘤术后口腔护理管理中的应用%Application of quality control circle on oral administration after oral cancer surgery

    Institute of Scientific and Technical Information of China (English)

    杨雄涛; 陈世容; 杨青; 赵家凤

    2015-01-01

    目的:探讨品管圈活动在口腔肿瘤术后口腔护理管理中的应用效果。方法成立品管圈活动小组,确立以“降低口腔肿瘤术后口腔感染发生率”为活动主题,进行现状调查,设立目标,从人、物、法3个方面查找原因,经过要因论证,确定主要因素,提出并落实有效的对策。选择2011年12月—2012年8月口腔肿瘤术后患者104例为活动前组,2012年9月—2013年5月口腔肿瘤术后患者107例为活动后组,通过自行设计的问卷调查患者的主观感觉、护士的评估和口腔分泌物细菌培养,比较实施前后患者口腔感染情况和护士操作技能改善情况。结果活动后口腔感染发生率为8.41%,活动前为18.27%,差异有统计学意义(χ2=4.453,P<0.05);口腔肿瘤术后患者口腔舒适度高于活动前,差异有统计学意义(χ2=47.766,P<0.01);活动后发生口臭11例,活动前为27例,差异有统计学意义(χ2=8.783,P<0.01);品管圈活动后护士口腔护理理论考核与技能操作成绩分别为(93.07±3.55),(94.27±3.58)分,高于活动前的(84.56±2.78),(86.01±4.55)分,差异有统计学意义(t 值分别为-7.782,-5.882;P<0.01)。结论品管圈活动为患者提供了清洁、舒适的口腔护理服务,提高了护士护理技能水平,降低了口腔炎症的发生。%Objective To discuss the effect of quality control circle activities in the oral administration process after oral cancer surgery. Methods The QCC was established and built up the theme of‘The decrease of the incidence of wound infection in the mouth after oral cancer surgery’ to investigate current status, set goals, and find the case from people, objects and rules. All information collected had been analyzed and demonstrated to confirm the main factors, and the corresponding measure was made out and implemented. A total of 104 oral cancer patients had been chosen before QCC establishment as control group during December 2011 to August 2012

  13. Toxicity effect of sub-chronic oral administration of class bitters® - a polyherbal formula on serum electrolytes and hematological indices in male Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Kingsley C. Patrick-Iwuanyanwu

    2015-11-01

    Full Text Available The indiscriminate administration of readyto- use herbal formulations has become a major concern due to their potential health risk. The study investigated the effect of class bitters® (CB - a polyherbal formula prepared with Mondia whitei, Khaya senegalensis, Capparis erythrocarpus, Thoningia sanguinea and Xylopia aethiopica on serum electrolytes and hematological parameters in male Wistar albino rats. Two doses (500 and 1000 mg kg–1 of the polyherbal drugs were administered orally to male Wistar albino rats for a period of 9 weeks. The results showed that administration of 500 and 1000 mg kg–1 body weight of CB recorded a marked increase in the levels of sodium and chlorum when compared with control. However, there was a marked reduction in the levels of potassium and hydrogen carbonate. The results of the study also showed a significant (P≤0.05 decrease in the level of hematological parameters such as hemoglobin (Hb, packed cell volume (PCV, red blood cells (RBCs and platelets levels in the male Wistar albino rats, when compared with control. The marked decrease in Hb, PCV, RBCs and platelets concentrations observed in experimental rats in this study suggest that CB may have an adverse effect on erythropoiesis. These observations therefore showed that long-term administration of CB might cause renal disease and anemia.

  14. Prophylaxis of tumor through oral administration of IL-12 GM-CSF gene carried by live attenuated salmonella

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A live attenuated AraA- autotrophic mutant of Salmonella typhimurium (SL3261) was used as carrier for eukaryotic expression vectors EGFPN1, pCMVmIL-12, pCMVhIL-12, pCMVmGM-CSF and pCMVhGM-CSF and was administered orally to BALB/c and C57BL/6 mice. After 6 weeks, these mice were challenged with 4T1 and Lewis tumor cells respectively. GFP expression and gene integrati-on could be detected in mice's livers, spleens, intestines, kidneys and tumors. The serum level of cytokines increased significantly in treated mice, so did the ratio of , which resulted in the tumor regression and prolongation of the survival time of those mice. These researches laid an experimental foundation for the tumor gene therapy using live attenuated salmonella.

  15. Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Christensen, N J; Sørensen, T I;

    1991-01-01

    Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80......-mg dose of propranolol. Baseline azygos and renal venous norepinephrine levels were significantly higher than arterial norepinephrine levels (+20%, p less than 0.005; and +28%, p less than 0.001, respectively). Hepatic venous norepinephrine and all venous epinephrine values were below the arterial...... values (all p less than 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p less than 0.01; and +93%, p less than 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p less than 0.01), whereas...

  16. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    Science.gov (United States)

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells. PMID:21554106

  17. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    Science.gov (United States)

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.

  18. SURVEY OF SHORT-TERM ORAL CORTICOSTEROID ADMINISTRATION BY ORTHOPAEDIC PHYSICIANS IN COLLEGE AND HIGH SCHOOL ATHLETES

    Directory of Open Access Journals (Sweden)

    Albert W. Pearsall IV

    2009-03-01

    Full Text Available The use of oral corticosteroid (OCS drugs is advocated because of their potent anti-inflammatory effects. They also possess many potential adverse effects. No study has assessed physician prescribing practices of OCS therapy in high school (HS or college (COL athletes. This paper reports the prescribing patterns of sports medicine physicians who used short-term OCS therapy and to describe associated complications in HS and COL athletes within a 24- month period. An internet link to a descriptive epidemiology survey was included in an e-mail to all members of the Arthroscopy Association of North America and the American Orthopaedic Society for Sports Medicine. Descriptive statistics and correlation analysis were used to examine responses. Total response rate was 32% (615/1,928. Sixty-six percent of the physicians indicated prescribing OCS to both groups of athletes, while 29% reported prescribing OCS to COL athletes and 5% to HS athletes for musculoskeletal injuries. Physicians who prescribed multiple OCS regimens to the same athlete within the same season (P = 0.01 and physicians who prescribed OCS to the skeletally immature athlete (P = 0.009 reported more complications than other physicians. Among the 412 physicians who did not prescribe OCS in the treatment of athletic induced musculoskeletal injury, 251 (61% cited a risk of developing medical complications as the primary reason for avoiding use. The reported number of medical complications was low with no cases of avascular necrosis reported for the 2-year recall period. Orthopaedic surgeons who treated athletic induced musculoskeletal injuries with a short-term course of oral corticosteroids reported that high school and college athletes benefited with few medical complications

  19. Investigation of hospital oral administration at night among elderly inpatients%老年住院患者夜间给药安全的调查

    Institute of Scientific and Technical Information of China (English)

    王云文; 姜国珍; 梁淑芹; 郭爱青; 丁梅; 徐玲芳

    2015-01-01

    Objective To ensure the safety of oral administration at night among elderly inpatients. Methods By the purposive sampling method, a total of 165 clinical nurses and 274 elderly patients were selected as sample. Elderly patients received nocturnal tracking and 165 nurses underwent survey questionnaire, that investigate risk factors for night safety of oral-administration. Results For circumstances of night oral medicine administration among 165 nurses, the rate of medicine inspection was highest (90. 9%), while the implementation rate of putting medicine into mouth was lowest (33. 3%). Drug regimen and administration time of elderly patients had positive correlation with the implantation level of putting medicine in the mouth by nurses (r=0.407, 0. 335;P < 0. 05). The compliance and posture of medication administration had positive correlation with medicine knowledge education to patients by nurses (r=0. 380, 0. 429;P<0. 05), and the adverse reactions of patients was positively correlated with nurses observed after taking the drug (r=0. 464,P<0. 05). Conclusions We should focus on guiding elderly patients to take medicine correctly and compliance of medicine order, and carry out the training of comprehensive drug knowledge for nurses to decrease the risks of night medicine administration.%目的:了解老年住院患者夜间药物服用情况及其影响因素,减少给药差错的发生。方法采用目的抽样方法,选择三级医院临床一线护士165名和老年患者274例为调查对象,通过对老年患者夜间跟踪调查及护理人员问卷调查,对结果进行Spearman相关性分析,了解影响口服药发放安全的风险因素。结果165名护士夜间安全给药执行情况,发药查对严格执行率最高,占90.9%,发药到口严格执行率最低,占33.3%。患者服用方式、服用时间与护士发药到口执行程度呈正相关( r值分别为0.407,0.335;P<0.05);患者遵医行为、服药姿势与护士对药物知识宣

  20. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice

    OpenAIRE

    ORIKASA, Shuzo; NABESHIMA, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (109 CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of ky...

  1. Endogenous and xenobiotic metabolite profiling of liver extracts from SCID and chimeric humanized mice following repeated oral administration of troglitazone.

    Science.gov (United States)

    Barnes, Alan J; Baker, David R; Hobby, Kirsten; Ashton, Simon; Michopoulos, Filippos; Spagou, Konstantina; Loftus, Neil J; Wilson, Ian D

    2014-01-01

    1. Metabonomic analysis, via a combination of untargeted and targeted liquid chromatography-mass spectrometry (LC-MS) and untargeted (1)H NMR spectroscopy-based metabolite profiling, was performed on aqueous (AQ) and organic liver extracts from control (SCID) and chimeric humanized (PXB) mice dosed with troglitazone at 0, 300 and 600 mg/kg/day for seven days. 2. LC-MS analysis of AQ liver extracts showed a more "human-like" profile for troglitazone metabolites for PXB, compared with SCID, mice. 3. LC-MS detected differences in endogenous metabolites, particularly lipid species in dosed mice, including elevated triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB compared with SCID mouse liver extracts. Following drug administration changes in the relative proportions of the ions for various unsaturated fatty acids were observed for both types of mouse, some of which were specific to PXB or SCID mice. 4.  (1)H NMR spectroscopy revealed that AQ PXB mouse liver extracts had elevated amounts of inosine, fumarate, creatine, aspartate, trimethylamine N-oxide, glycerophosphocholine, phosphocholine, choline, glutamine, glutamate, acetate, alanine and lactate relative to SCID mice and decreased histidine, glycogen, α- and β-glucose, taurine, and glutathione. Increased uracil and tyrosine concentrations were detected for PXB mice on troglitazone administration. 5. Metabonomic profiling thus showed clear differences between humanized and SCID mice, including after administration of troglitazone. PMID:24350779

  2. The antioxidant status and oxidative stability of muscle from lambs receiving oral administration of Artemisia herba alba and Rosmarinus officinalis essential oils.

    Science.gov (United States)

    Aouadi, Dorra; Luciano, Giuseppe; Vasta, Valentina; Nasri, Saida; Brogna, Daniela M R; Abidi, Sourour; Priolo, Alessandro; Salem, Hichem Ben

    2014-06-01

    The effect of the dietary supplementation to lambs of essential oils (EOs) from rosemary (Rosmarinus officinalis) and artemisia (Artemisia herba alba) on the antioxidant status of muscle and on meat oxidative stability was studied. Eighteen Barbarine lambs were divided into 3 groups and for 95days received oat hay and concentrates. One group (C) was not supplemented, while the other two groups received 400mg/kg of EOs from rosemary (R400) or artemisia (A400). Both EOs possessed antioxidant properties and their oral administration improved the reducing and radical scavenging capacity of the muscle compared to the C treatment (P<0.01). Nevertheless, supplementing EOs did not exert protection against lipid oxidation and did not affect the colour stability in meat over 7days of aerobic storage. PMID:24583334

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

    Directory of Open Access Journals (Sweden)

    Menghua Liu

    2015-03-01

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

  4. Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs.

    Science.gov (United States)

    Bidgood, T L; Papich, M G

    2005-08-01

    Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.

  5. Effects of oral powder electrolyte administration on packed cell volume, plasma chemistry parameters, and incidence of colic in horses participating in a 6-day 162-km trail ride.

    Science.gov (United States)

    Walker, Wade T; Callan, Robert J; Hill, Ashley E; Tisher, Kelly B

    2014-08-01

    This study evaluated the effects of administering oral powder electrolytes on packed cell volume (PCV), plasma chemistry parameters, and incidence of colic in horses participating on a 6-day 162-km trail ride in which water was not offered ad libitum. Twenty-three horses received grain with powder electrolytes daily while 19 control horses received grain only. Horses were ridden approximately 32 km a day at a walk or trot. Packed cell volume and plasma chemistry parameters were analyzed daily. Episodes of colic were diagnosed and treated by a veterinarian unaware of treatment group allocation. Blood parameters and incidence of colic were compared between treatment groups. Electrolyte administration did not alter PCV or plasma chemistry parameters compared to controls. The incidence of colic was significantly higher in treated horses (P = 0.05). Oral powder electrolytes did not enhance hydration status or electrolyte homeostasis and may be associated with colic in horses participating on long distance trail rides similar to this model. PMID:25082992

  6. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    Science.gov (United States)

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging. PMID:27045316

  7. Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Argiles, J.; Herrera, E.

    1989-02-01

    Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.

  8. Stereoselective urinary excretion of S-(-)- and R-(+)-propranolol glucuronide following oral administration of RS-propranolol in Chinese Han subjects

    Institute of Scientific and Technical Information of China (English)

    Lian-Jun Luan; Qing Shao; Jian-Yin Ma; Su Zeng

    2005-01-01

    AIM: To study the stereoselectivity of phase Ⅱglucuronidation metabolism of side-chain propranolol in Chinese Hah population.METHODS: Sixteen adult Chinese Hah volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC.RESULTS: The mean values of kwere 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7±2.46% and 7.68±1.60% for S-(-)- and R-(+)-propranolol glucuronide,respectively. The results showed the elimination rate constant kof S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide.CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.

  9. HPLC-MS/MS analysis of a traditional Chinese medical formulation of Bu-Yang-Huan-Wu-Tang and its pharmacokinetics after oral administration to rats.

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    Lee-Hsin Shaw

    Full Text Available Bu-yang-huan-wu-tang (BYHWT is one of the most popular formulated traditional Chinese medicine prescriptions, and is widely for prevention of ischemic cardio-cerebral vascular diseases and stroke-induced disability. A specific high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS has been developed and validated for simultaneous quantification of the nine main bioactive components, i.e., astragaloside I, astragaloside II, astragaloside IV, formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside, ligustilide and paeoniflorin in rat plasma after oral administration of BYHWT extract. This method was applied to investigate the pharmacokinetics in conscious and freely moving rats. No significant matrix effects were observed. The overall analytical procedure was rapid and reproducible, which makes it suitable for quantitative analysis of a large number of samples. Among them, three astragalosides and four isoflavones in A. membranaceus, ligustilide in Radix Angelicae Sinensis and Rhizoma Ligustici Chuanxiong and paeoniflorin in Radix Paeoniae Rubra were identified. This developed method was then successfully applied to pharmacokinetic studies of the nine bioactive constituents after oral administration of BYHWT extracts in rats. The pharmacokinetic data demonstrated that astragaloside I, astragaloside II, astragaloside IV and ligustilide presented the phenomenon of double peaks. The other herbal ingredients of formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside and paeoniflorin appeared together in a single and plateau absorption phase. These phenomenona suggest that these components may have multiple absorption sites, regulation of enterohepatic circulation or the gastric emptying rate, or there is ingredient-ingredient interaction. These pharmacokinetic results provide a constructive contribution to better understand the absorption mechanism of BYHWT and to support additional clinical evaluation.

  10. Comparison of diclofenac-emulgel local application with oral ibuprofen administration for the treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules

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    J Zacher

    2007-01-01

    Full Text Available Objective. To assess efficacy and tolerability of diclofenac-emulgel local application in comparison with oral ibuprofen administration for the treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules. Material and methods. 321 pts were randomized into two groups. Diclofenac-emulgel (active drug and placebo ibuprofen tablets were administered in one of them, placebo diclofenac-emulgel and ibuprofen tablets (active drug — in the other. Diclofenac was administered as 10 cm strip locally 4 times a day and 400 mg of ibuprofen were given 3 times a day. Frequency of improvement was used as the main outcome measure. Improvement was registered if pain on 100 mm visual analog scale decreased at least by 40%. Disease activity, pain at rest, pain at movement, morning stiffness, grip strength and quality of life were used as additional outcome measures. Results. To the end of treatment according to 5% lower equivalency limit local therapy was at least as effective as oral administration of ibuprofen (p=0,007. Administration of both treatment methods provided also comparable improvement of all additional outcome measures. Both treatment methods showed good tolerability but more pts with receiving ibuprofen experienced serious adverse events than those using diclofenac (9 and 4 pts respectively. There was also similar proportion of pts prematurely withdrawn due to side effects (n=21: 5 (3% from them received diclofenac and 16 (10% - ibuprofen. Similar ratio of adverse events attributed to study treatment was revealed. Such events were present in 2 pts using diclofenac and in 13 (8,3% receiving ibuprofen. Most of these events applied to gastrointestinal tract (in 1 pt using diclofenac and in 8 pts receiving ibuprofen. Conclusion. Local treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules with diclofenac is at least as effective as systemic administration of ibuprofen

  11. Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enterica serovar Typhimurium infection in mice

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    Perdigón Gabriela

    2011-08-01

    Full Text Available Abstract Background Diarrheal infections caused by Salmonella, are one of the major causes of childhood morbidity and mortality in developing countries. Salmonella causes various diseases that range from mild gastroenteritis to enteric fever, depending on the serovar involved, infective dose, species, age and immune status of the host. Probiotics are proposed as an attractive alternative possibility in the prevention against this pathogen infection. Previously we demonstrated that continuous Lactobacillus casei CRL 431 administration to BALB/c mice before and after challenge with Salmonella enterica serovar Typhimurium (S. Typhimurium decreased the severity of Salmonella infection. The aim of the present work was to deep into the knowledge about how this probiotic bacterium exerts its effect, by assessing its impact on the expression and secretion of pro-inflammatory (TNFα, IFNγ and anti-inflammatory (IL-10 cytokines in the inductor and effector sites of the gut immune response, and analyzing toll-like receptor (TLR2, TLR4, TLR5 and TLR9 expressions in both healthy and infected mice. Results Probiotic administration to healthy mice increased the expression of TLR2, TLR4 and TLR9 and improved the production and secretion of TNFα, IFNγ and IL-10 in the inductor sites of the gut immune response (Peyer's patches. Post infection, the continuous probiotic administration, before and after Salmonella challenge, protected the host by modulating the inflammatory response, mainly in the immune effector site of the gut, decreasing TNFα and increasing IFNγ, IL-6 and IL-10 production in the lamina propria of the small intestine. Conclusions The oral administration of L. casei CRL 431 induces variations in the cytokine profile and in the TLRs expression previous and also after the challenge with S. Typhimurium. These changes show some of the immune mechanisms implicated in the protective effect of this probiotic strain against S. Typhimurium, providing

  12. Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

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    Hyun-moon Back

    2015-01-01

    Full Text Available KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life and Tmax of matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively. Cmax and AUCinf of matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

  13. Significant mucosal sIgA production after a single oral or parenteral administration using in vivo CD40 targeting in the chicken.

    Science.gov (United States)

    Chou, Wen-Ko; Chen, Chang-Hsin; Vuong, Christine N; Abi-Ghanem, Daad; Waghela, Suryakant D; Mwangi, Waithaka; Bielke, Lisa R; Hargis, Billy M; Berghman, Luc R

    2016-10-01

    Many pathogens enter the host through mucosal surfaces and spread rapidly via the circulation. The most effective way to prevent disease is to establish mucosal and systemic immunity against the pathogen. However, current vaccination programs in poultry industry require repeated administrations of live-attenuated virus or large amounts (10 to 100μg) of antigen together with adjuvant to induce specific secretory IgA immune responses at the mucosal effector sites. In the present study, we show that a single administration of 0.4μg of oligopeptide complexed with an agonistic anti-chicken CD40 (chCD40) monoclonal antibody (Mab) effectively targets antigen-presenting cells of the bird's mucosa-associated lymphoid tissue in vivo, and induces peptide-specific secretory IgA (sIgA) in the trachea 7days post administration. Anti-chCD40 Mab-peptide complex was administered once to four-week old male Leghorns via various mucosal routes (orally, via cloacal drinking, or oculo-nasally) or via subcutaneous (s.c.) immunization. Immunization through any of the three mucosal induction routes induced significant peptide-specific mucosal sIgA responses 7 and 14days after immunization. Interestingly, s.c. injection of the complex also induced mucosal sIgA. Our data suggest in vivo targeting of CD40 as a potential adjuvant platform, particularly for the purpose of enhancing and speeding up mucosal vaccine responses in chickens, and potentially other food animals. This is the first study able to elicit specific sIgA immune responses in remote mucosal sites with a single administration of only 0.4μg of antigen. PMID:27663378

  14. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. PMID:25006518

  15. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

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    Jennifer L. Cornish

    2012-09-01

    Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  16. Growth performance and oxidative damage in kidney induced by oral administration of Cr(III) in chicken.

    Science.gov (United States)

    Liu, Yanhan; Liu, Cun; Cheng, Jia; Fan, Wentao; Zhang, Xiao; Liu, Jianzhu

    2015-11-01

    This study aimed to evaluate the effects of adding chromic chloride (CrCl3) in the drinking water of chickens. Hyland brown male chickens were randomly divided into four groups. Three groups orally received 1/2 LD50, 1/4 LD50, and 1/8 LD50 CrCl3mgkg(-1) body weight daily for 42d. The fourth group was treated with water. The chickens were sacrificed at 14, 28, and 42d post-treatment. The renal injury was examined through histological analysis, and kidney mass was determined. The effects on growth performance were assessed by measuring the weight of the body, chest muscles, and leg muscles. Oxidative damage was evaluated by determining the antioxidant defense levels in kidney homogenates. The body weight and the weight of tissues gained time-dependently, but significantly decreased compared with those in the control group (Pkidney compared with those in the control groups. Whereas, administering Cr(3+) reduced the activities of superoxide dismutase, catalase, glutathione peroxidase, and total an-tioxidant capacity compared with those in the control group (Pkidney dose- and time-dependently.

  17. Liquid chromatography tandem mass spectrometry identification of proanthocyanidins in rat plasma after oral administration of grape seed extract

    Science.gov (United States)

    Prasain, Jeevan K.; Peng, Ning; Dai, Yanying; Moore, Ray; Arabshahi, Alireza; Wilson, Landon; Barnes, Stephen; Wyss, J. Michael; Kim, Helen; Watts, Ray L.

    2009-01-01

    Proanthocyanidin rich plant extracts derived from grape seed extract (GSE), hawthorn and cranberry are on markets for their preventive effects against cardiovascular diseases and uroinfections in woman. However, the importance of these health beneficial effects of these botanicals remains elusive due to incomplete understanding of uptake, metabolism and bioavailability of proanthocyanidins in vivo. In the present study rats were given GSE orally (300 mg/kg, twice a day) and blood and urine were collected over a 24 h period. Monomeric catechins and their methylated metabolites, and proanthocyanidins up to trimers were detected in blood samples treated with GSE using LC-MS/MS operating in the multiple reaction monitoring (MRM) mode. A new tetramethylated metabolite of dimeric proanthocyanidin (m/z 633) in GSE-treated urine was tentatively identified. Using LC-MS/MS, (+)-catechin and (−)-epicatechin were identified in the brain conclusively. These data suggested that GSE catechins cross the blood brain barrier and may be responsible for the neuroprotective effects of GSE. PMID:19095430

  18. Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration.

    Science.gov (United States)

    Shah, Mansi K; Madan, Parshotam; Lin, Senshang

    2014-06-01

    Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P-188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161 nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and enteric-coated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability. PMID:23697916

  19. Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals.

    Science.gov (United States)

    Kameswara Rao, B; Giri, R; Kesavulu, M M; Apparao, C

    2001-01-01

    The effect of administration of different doses of Pterocarpus santalinus L. bark extracts in normal and diabetic rats, on blood glucose levels was evaluated in this study. Among the three fractions (aqueous, ethanol and hexane), ethanolic fraction at the dose of 0.25 g/kg body weight showed maximum antihyperglycemic activity. The same dose did not cause any hypoglycemic activity in normal rats. The results were compared with the diabetic rats treated with glibenclamide and the antihyperglycemic activity of ethanolic extract of PS bark at the dose of 0.25 g/kg b.w. was found to be more effective than that of glibenclamide. PMID:11137350

  20. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

    Science.gov (United States)

    Orikasa, Shuzo; Nabeshima, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-Zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan. These results suggest the potential of BB536 for supplemental treatment of the symptoms of schizophrenia. PMID:27508116

  1. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

    Science.gov (United States)

    Orikasa, Shuzo; Nabeshima, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-Zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan. These results suggest the potential of BB536 for supplemental treatment of the symptoms of schizophrenia.

  2. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation.

    Science.gov (United States)

    López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  3. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Science.gov (United States)

    Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  4. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Science.gov (United States)

    Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  5. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    Gabriela López-Armas

    2016-01-01

    Full Text Available Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1 control, (2 REMSD, (3 melatonin (10 mg/kg plus REMSD, (4 melatonin and intraperitoneal luzindole (once a day at 5 mg/kg plus REMSD, and (5 luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P<0.021. The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  6. Oral administration of French maritime pine bark extract (Flavangenol® improves clinical symptoms in photoaged facial skin

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    Furumura M

    2012-07-01

    Full Text Available Minao Furumura,1,2 Noriko Sato,1 Nobutaka Kusaba,3 Kinya Takagaki,3 Juichiro Nakayama11Department of Dermatology, Fukuoka University School of Medicine, Fukuoka, 2Department of Dermatology, Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology, Fukuoka, 3Toyo Shinyaku Co Ltd, Tosu City, Saga, JapanBackground: French maritime pine bark extract (PBE has gained popularity as a dietary supplement in the treatment of various diseases due to its polyphenol-rich ingredients. Oligometric proanthocyanidins (OPCs, a class of bioflavonoid complexes, are enriched in French maritime PBE and have antioxidant and anti-inflammatory activity. Previous studies have suggested that French maritime PBE helps reduce ultraviolet radiation damage to the skin and may protect human facial skin from symptoms of photoaging. To evaluate the clinical efficacy of French maritime PBE in the improvement of photodamaged facial skin, we conducted a randomized trial of oral supplementation with PBE.Methods: One hundred and twelve women with mild to moderate photoaging of the skin were randomized to either a 12-week open trial regimen of 100 mg PBE supplementation once daily or to a parallel-group trial regimen of 40 mg PBE supplementation once daily.Results: A significant decrease in clinical grading of skin photoaging scores was observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation regimens. A significant reduction in the pigmentation of age spots was also demonstrated utilizing skin color measurements.Conclusion: Clinically significant improvement in photodamaged skin could be achieved with PBE. Our findings confirm the efficacy and safety of PBE.Keywords: polyphenols, pine bark extract, skin photoaging, antioxidants, antiaging

  7. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    International Nuclear Information System (INIS)

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg-1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  8. Antioxidant Activity of Oral Administration of Rosmarinus Officinalis Leaves Extract on Rat's Hippocampus which Exposed to 6-Hydroxydopamine

    Directory of Open Access Journals (Sweden)

    Arashpour Rasoul

    2016-01-01

    Full Text Available Carnosic acid, a diterpene of Rosemarinus officinalis leaves extract (RE, has potent antioxidant activity in vitro. The dopaminergic connection of substantia nigra pars compacta to the hippocampus might be affected by oxidative stress which caused cognitive impairment observed in the early phase of Parkinson's disease (PD. Adult male Wistar rats were lesioned bilaterally by intra-nigral injection of 6-OHDA, and divided into six groups: four groups that orally given RE containing 40% of carnosic acid, at doses of 25, 50 and 100 mg/kg (treated rats and distilled water (H2O, once daily for a period of 14 days before and after the injury. There were also two another groups as control rats which injected by normal saline and untreated lesion group. The injured animals were evaluated for their spatial memory performance by Morris Water Maze test. Lesioned rats showed significant increase in escape latency, as compared with control group. Two weeks after injury, tissue samples were collected from the hippocampus. Levels of catalase (CAT, glutathione peroxidase (GPX and superoxide dismutase (SOD, malondialdehyde (MDA and reactive oxygen species (ROS were determined. There were significant increase of SOD, GPX and CAT enzymes activities in RE50 treated group as compared to lesioned rats. We found a significant decrease of ROS in RE50 treated group as compared to Lesioned rats. These findings provide evidence that 50 mg/kg of RE decreased oxidative damage of the hippocampus induced by 6-OHDA and serve as potential candidate for the treatment of PD.

  9. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Science.gov (United States)

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  10. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  11. Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

    Directory of Open Access Journals (Sweden)

    Neuza Mariko Aymoto Hassimotto

    2013-01-01

    Full Text Available Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF extracted from wild mulberry and the cyanidin-3-glucoside (C3G, the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg in mice. In each trial, AF and C3G (4 mg/100 g/animal were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P<0.05. In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P<0.05. Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

  12. Mensuration of cardioangiopulmonary indices by radiocardiogram before and after the verapamil oral administration in subjects with chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Twenty subjects with chronic obstructive pulmonary disease were studied. The diagnosis was obtained from the history, clinical evaluation, pulmonary radiography, pulmonary and hepatic scintigraphies and spirometry. About 360 mg of verapamil was administered daily, every eight hours for ten days. Before and after drug administration, the arterial pressures, the spirometric measurements and nine cardiac roentgenographic indexes were measured. Vital capacity increased in all cases, but did not reach the normal levels. These data suggest that the effect of verapamil on the pulmonary circulation brought benefits to the subjects. This occurred either by direct pulmonary vasodilation, or by bronchodilation, reducing hypoxia. In all cases, the pulmonary resistance was diminished. Finally, verapamil seems to be a drug with real benefits in subjects with chronic obstructive pulmonary disease and we advise a continuation of the studies. (author)

  13. UP-REGULATION OF HEPATIC RECEPTOR FOR GROWTH HORMONE IN THE FLOUNDER (PARALICHTHYS OLIVACEUS) AFTER ORAL ADMINISTRATION WITH EXOGENOUS GH

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The iodination efficiency of salmon GH(Sgh) was 38.82%,using a modification of the chloramine-T method. The specific activity of the 125I-Sgh was about 40 μCi/μg protein. The results of binding assay showed a single class of high affinity and low-capacity binding site in flounder liver. Long-term administration with exogenous GH can induce the up-regulation of hepatic GH receptor in total binding capacity though there was no significant difference of association constant among any groups. Considering that there was no significant difference in capacity of free binding sites of livers from control and experimental fish, this result also indicated that the liver from experimental fish, compared to that from control fish, had more occupied binding sites.

  14. The Effect of Chronic Oral Administration of Withania Somnifera Root on Learning and Memory in Diabetic Rats Using Passive Avoidance Test

    Directory of Open Access Journals (Sweden)

    M. Roghani

    2006-07-01

    Full Text Available Introduction & Objective: Diabetes mellitus (especially type I is accompanied with disturbances in learning, memory, and cognitive skills in the human society and experimental animals. Considering the potential anti-diabetic effect of the medicinal plant Withania somnifera (ashwagandha and the augmenting effect of its consumption on the memory and mental health, this study was conducted to evaluate the effect of chronic oral administration of ashwagandha root on learning and memory in diabetic rats using passive avoidance test. Materials & Methods: For this purpose, male Wistar diabetic rats were randomly divided into control, ashwagandha-treated control, diabetic, and ashwagandha-treated diabetic groups. Ashwagandha treatment continued for 1 to 2 months. For induction of diabetes, streptozotocin was injected i.p. at a single dose of 60 mg/kg. Serum glucose level was determined before the study and at 4th and 8th weeks after the experiment. In addition, for evaluation of learning and memory, initial latency (IL and step-through latency (STL were determined after 1 and 2 months using passive avoidance test. Results: It was found that one- and two-month administration of ashwagandha root at a weight ratio of 1/15 has not any significant hypoglycemic effect in treated control and diabetic groups. Furthermore, there was a significant increase (p<0.05 in IL in diabetic and ashwagandha-treated diabetic groups after two months compared to control group. In this respect, there was no significant difference between diabetic and ashwagandha-treated diabetic groups. In addition, STL significantly increased in ashwagandha-treated control group after 1 (p<0.01 and 2 (p<0.05 month in comparison to control group. On the other hand, STL significantly decreased (p<0.05 in diabetic group and significantly increased (p<0.05 in ashwagandha-treated diabetic group as compared to control group after two months. Conclusion: In summary, chronic oral administration of

  15. Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir.

    Science.gov (United States)

    Sebbag, Lionel; Thomasy, Sara M; Woodward, Andrew P; Knych, Heather K; Maggs, David J

    2016-08-01

    OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus. PMID:27463546

  16. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    Science.gov (United States)

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  17. Quantitation of enniatins in biological samples of Wistar rats after oral administration by LC-MS/MS.

    Science.gov (United States)

    Escrivá, Laura; Font, Guillermina; Manyes, Lara

    2015-01-01

    The emerging Fusarium mycotoxins enniatins (ENNs) have diverse biological properties, mainly due to their ionophoric activity, and represent a potential risk to human and animal health since they are commonly found in food and feed. In vivo toxicity studies are scarce and limited to the major mycotoxins. Until now, any method for the simultaneous analysis of these compounds in plasma, serum and feces from rat has been reported. A method for the extraction and determination of ENNs A, A1, B and B1 from Wistar rat samples by liquid chromatography tandem mass spectrometry has been developed. The method was successfully validated with satisfactory recoveries (70-106%), good intraday (rat samples that were administered a mixture of ENNs containing 1.19, 2.16, 1.03 and 1.41 mg/kg body weight of ENN A, A1, B and B1, respectively. Blood, urine and feces samples collected every 2 h during the 8-h duration of the experiment were analyzed. The administered dose of the mixture of ENNs did not cause observable adverse effects on the animals. ENNs concentrations detected in serum and urine were below LOQs. The four ENNs were detected in feces reaching the maximum concentration at 6 h after administration.

  18. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus- indica mucilage

    Institute of Scientific and Technical Information of China (English)

    Ricardo Vázquez-Ramírez; Marisela Olguín-Martínez; Carlos Kubli-Garfias; Rolando Hernández-Mu(n)oz

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats.METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined.Histological studies of gastric samples from the experimental groups were included.RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes.Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect.The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes.CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids,mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  19. Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after oral administration in fermented oatmeal gruel. A pilot study.

    Science.gov (United States)

    Stjernquist-Desatnik, A; Warfving, H; Johansson, M L

    2000-01-01

    The occurrence of Lactobacillus plantarum DSM 9843 on tonsillar scrapings was studied after single-dose administration. Six healthy volunteers gargled 100 ml of fermented oatmeal gruel containing 2 x 10(11) colony forming units (cfu) of Lb. plantarum DSM 9843 for 2 min and then swallowed it. Two healthy volunteers drank 50 ml fermented oatmeal gruel (containing 1 x 10(11) cfu of Lb. plantarum DSM 9843) mixed with 50 ml fruit juice, and in another experiment, 5 ml fermented oatmeal gruel (containing 1 x 10(10) cfu of Lb. plantarum DSM 9843) mixed with 95 ml fruit juice. Lb. plantarum DSM 9843 were found in tonsillar scrapings 4-8 h after intake of 2 x 10(11) cfu, for 5-8 h after intake of 1 x 10(11) cfu, and finally up to 4 h after intake of 1 x 10(10) cfu. On electron microscopy micrographs, short rod-shaped bacteria were visible 1 h after intake of the fermented oatmeal gruel, but not 2 h after intake. The results suggest that Lb. plantarum DSM 9843 possess an ability to adhere to tonsillar cells.

  20. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation.

    Science.gov (United States)

    López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  1. Oral administration of Bifidobacterim bifidum for modulating microflora, acid and bile resistance, and physiological indices in mice.

    Science.gov (United States)

    Wang, Bao-Gui; Xu, Hai-Bo; Wei, Hua; Zeng, Zhe-Ling; Xu, Feng

    2015-02-01

    Bifidobacteria are generally acknowledged as major gut microflora used as probiotics, which promote human health. In this study, the effects of the administration of Bifidobacterim bifidum on modulating gastrointestinal (GI) tract microflora, acid and bile resistance, and physiological indices in BALB/c mice were investigated. Results showed that B. bifidum can significantly improve the ecosystem of the GI tract by increasing the amount of probiotics and reducing the populations of pathogenic bacteria, as measured by plate count and real-time PCR. After exposure to simulated GI tract conditions, the growth of gut microflora in the B. bifidum group was higher than that in the control group when incubated for 12 h in MRS or nutrient broth adjusted to pH 2.0 or 3.0 or in the presence of a concentration of bile salt (0.45% m/v). The blood biochemical index was examined, and the physiological effect of the cell-free extract of gut microflora was evaluated by measuring the activity of various enzymes, including α-glucosidases, esterase, and lactate dehydrogenase. This study suggested that a B. bifidum strain can stabilize blood sugar, lower cholesterol levels in serum, and improve metabolic activity. Moreover, B. bifidum was a promising enhancer of microbial diversity in mouse intestine and played a vital role in human physiological processes, which can benefit the health of a host.

  2. A small scale study on the effects of oral administration of the β-glucan produced by Aureobasidium pullulans on milk quality and cytokine expressions of Holstein cows, and on bacterial flora in the intestines of Japanese black calves

    Directory of Open Access Journals (Sweden)

    Uchiyama Hirofumi

    2012-06-01

    Full Text Available Abstract Background The β–(1 → 3,(1 → 6-D-glucan extracellularly produced by Aureobasidium pullulans exhibits immunomodulatory activity, and is used for health supplements. To examine the effects of oral administration of the β–(1 → 3,(1 → 6-D-glucan to domestic animals, a small scale study was conducted using Holstein cows and newborn Japanese Black calves. Findings Holstein cows of which somatic cell count was less than 3 x 105/ml were orally administered with or without the β-(1 → 3,(1 → 6-D-glucan-enriched A. pullulans cultured fluid (AP-CF for 3 months, and the properties of milk and serum cytokine expression were monitored. Somatic cell counts were not significantly changed by oral administration of AP-CF, whereas the concentration of solid non fat in the milk tended to increase in the AP-CF administered cows. The results of cytokine expression analysis in the serum using ELISA indicate that the expressions of tumor necrosis factor-α (TNF-α and interleukin (IL-6 in all cows which were orally administered with AP-CF became slightly lower than that of control cows after the two-month treatment. On the other hand, IL-8 expression tended to indicate a moderately higher level in all treated cows after the three-month administration of AP-CF in comparison with that of the control cows. Peripartum Japanese Black beef cows and their newborn calves were orally administered with AP-CF, and bacterial flora in the intestines of the calves were analyzed by T-RFLP (terminal restriction fragment length polymorphism. The results suggest that bacterial flora are tendentiously changed by oral administration of AP-CF. Conclusions Our data indicated the possibility that oral administration of the β–(1 → 3,(1 → 6-D- glucan produced by A. pullulans affects cytokine expressions in the serum of Holstein cows, and influences bacterial flora in the intestines of Japanese Black calves. The findings may be

  3. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B. [Massachusetts General Hospital, Harvard Medical School, Dept. of Dermatology, Boston, MA (United States); Cuevas, J. [Hospital Universitario de Guadalajara, Dept. of Pathology, Guadalajara (Spain); Villarrubia, V.G. [I.F. Cantabria SA, Medical Dept., Immunology Sect., Madrid (Spain)

    1997-12-31

    Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8{+-}0.59 times and MPD increased 2.75{+-}0.5 and 6.8{+-}1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au). 50 refs.

  4. Orally co-administrated oleo-gum resin of Commiphora myrrha decreases the bioavailability of cyclosporine A in rats.

    Science.gov (United States)

    Al-Jenoobi, F I; Alam, M A; Al-Mohizea, A M; Ahad, A; Raish, M

    2015-08-01

    Cyclosporine A is a narrow therapeutic indexed immunosuppressant used after organ transplantation. Several herbs have been reported to alter its pharmacokinetics. Myrrh, dried oleogum resin obtained from Commiphora myrrha (Burseraceae) has been used for many common ailments. The present study was carried out to investigate the effect of myrrh on the pharmacokinetics of cyclosporine A. The rats of the control group received 60 mg/kg, p.o. cyclosporine A, and blood samples were collected at predetermined time intervals. Rats of the test group were treated with an aqueous suspension of myrrh (380 mg/kg p.o.) for eight days and on 8th day a single dose of cyclosporine A was administered to the treated group after 1 h of myrrh administration. Blood samples were drawn at predetermined time points and the drug was analyzed in whole blood by using H-Class UPLC-TQD. Pharmacokinetic profiles of control and test group were compared. Statistically significant differences were observed between the pharmacokinetic parameters of control and treated groups. In the myrrh treated group, the AUC(0-t) and C(max) of cyclosporine A was decreased by about 45% and 48%, respectively. The time to reach maximum concentration (T(max)) remained almost unchanged in both groups. Results indicated that the bioavailability of cyclosporine A was reduced by about 45% when co-administered with myrrh. This observation suggests that concurrent consumption of myrrh and cyclosporine A should be avoided. To confirm the clinical relevance of these findings, P-gp and CYP3A based molecular investigations can be performed along with a well-planned clinical study.

  5. In vivo pharmacokinetic comparisons of ferulic acid and puerarin after oral administration of monomer, medicinal substance aqueous extract and Nao-De-Sheng to rats

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    Zhen Ouyang

    2012-01-01

    Full Text Available Background: Nao-De-Sheng decoction (NDS, a traditional Chinese medicine (TCM prescription containing Radix puerariae lobatae, Floscarthami, Radix et Rhizoma Notoginseng, Rhizoma chuanxiong and Fructus crataegi, is effective in the treatment of cerebral arteriosclerosis, ischemic cerebral stroke and apoplexy linger effect. Ferulic acid and puerarin are the main absorbed effective ingredients of NDS. Objective: To assess the affection of other components in medical material and compound recipe compatibility on the pharmacokinetics of ferulaic acid and puerarin, of ferulic acid from the monomer Rhizoma chuanxiong aqueous extract and NDS were studied. And pharmacokinetics comparisons of puerarin from the monomer Radix puerariae extract and NDS decoction were investigated simultaneously. Materials and Methods: At respective different time points after oral administration of the monomer, medicinal substance aqueous extract and NDS at the same dose in rats, plasma concentrations of ferulic acid and puerarin in rats were determined by RP-HPLC, and the main pharmacokinetic parameters were estimated with 3P97 software. Results: The plasma concentration-time curves of ferulaic acid and puerarin were both best fitted with a two-compartment model. AUC 0−t, AUC 0→∞ , Tmax , and Cmax of ferulic acid in the monomer and NDS decoction were increased significantly (P < 0.05 compared with that in Rhizoma chuanxiong aqueous extract. And statistically significant increase (P < 0.05 in pharmacokinetic parameters of puerarin including AUC 0−t, AUC 0→∞ , CL, Tmax and Cmax were obtained after oral administration of puerarin monomer compared with Radix puerariae extract. Although the changes of AUC 0−t, AUC 0→∞ and CL had no statistically significant, Cmax of puerarin in NDS was increased remarkably (P < 0.05 compared with that in single puerarin. Conclusions: Some ingredients of Rhizoma chuanxiong and Radix puerariae may be suggested to remarkably

  6. 家兔对乙酰氨基酚口服给药的药代动力学研究%Pharmacokinetics of Paracetamol Oral Administration in Rabbits

    Institute of Scientific and Technical Information of China (English)

    杨朝令; 李仲娟; 石金舟; 汪宏良; 向环英

    2013-01-01

    Objective To compare the absorption curve after oral administration of Paracetamol in pure powder and tablets in rabbits,and discuss the characteristics of Paracetamol pharmacokinetics. Methods Plasma concentration of Paracetamol in rabbits was determined by colorimetry method. The main pharmacokinetic parameters of Paracetamol were analyzed by 3p87 software. Results The standard curves (R2=0.9914) and absorption curves of pills solution and the pure powder of Paracetamol were the same.The absorption peak appeared in 15min,but the tablet was significantly lower than the pure powder.The main pharmacokinetic parameters of Paracetamol were as follows C0 (93.6 ±1.56)mg/L,V (2.72±0.32)h, t1/2(3.62±0.33)h and AUC(490.7±134.6) mg/h/L. Conclusion Oral administration of Paracetamol is rapidly absorbed in the body in line with single-compartment model dynamics.%目的 通过比较对乙酰氨基酚标准品与片剂在家兔体内的吸收曲线,探讨口服给药后对乙酰氨基酚在家兔体内的药物动力学特征.方法 比色法测出对乙酰氨基酚的血药浓度,采用3P87软件计算对乙酰氨基酚的药物动力学参数.结果 对乙酰氨基酚标准品的标准曲线R2=0.9914;口服药片对乙酰氨基酚15 min达峰.药物动力学参数为Co(93.6±1.56)mg/L,V(2.72±0.32)h,t1/2(3.62±0.33)h,AUC (490.7±134.6)mg/h/L,与标准品比较差异无统计学意义.结论 片剂对乙酰氨基酚口服给药吸收迅速,在家兔体内符合单室模型动力学特性.

  7. Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model

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    Lopamudra Haldar

    2016-07-01

    Full Text Available Aim: To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. Materials and Methods: An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1 was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2 and (T3 groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4 was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. Results: The rats those (T2 and T3 received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (p<0.01 in fecal coliform counts and increase (p<0.05 in both fecal lactobacilli and Bacillus spore counts as compared to the control group (T4 and the group fed only skim milk (T1. In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. Conclusions: This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

  8. Oral Administration of Polymyxin B Modulates the Activity of Lipooligosaccharide E. coli B against Lung Metastases in Murine Tumor Models.

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    Jagoda Kicielińska

    Full Text Available Polymyxin B (PmB belongs to the group of cyclic peptide antibiotics, which neutralize the activity of LPS by binding to lipid A. The aim of this study was to analyze the effect of PmB on the biological activity of lipooligosaccharide (LOS E. coli B,rough form of LPS in vitro and in experimental metastasis models.Cultures of murine macrophage J774A.1 cells and murine bone marrow-derived dendritic cells (BM-DC stimulated in vitro with LOS and supplemented with PmB demonstrated a decrease in inflammatory cytokine production (IL-6, IL-10, TNF-α and down-regulation of CD40, CD80, CD86 and MHC class II molecule expression. Additionally, PmB suspended in drinking water was given to the C57BL/6 mice seven or five days prior to the intravenous injection of B16 or LLC cells and intraperitoneal application of LOS. This strategy of PmB administration was continued throughout the duration of the experiments (29 or 21 days. In B16 model, statistically significant decrease in the number of metastases in mice treated with PmB and LOS (p<0.01 was found on the 14th day of the experiments, whereas the most intensive changes in surface-antigen expression and ex vivo production of IL-6, IL-1β and TNF-α by peritoneal cells were observed 7 days earlier. By contrast, antigen expression and ex vivo production of IL-6, IL-10, IFN-γ by splenocytes remained relatively high and stable. Statistically significant decrease in LLC metastases number was observed after the application of LOS (p<0.01 and in the group of mice preconditioned by PmB and subsequently treated with LOS (LOS + PmB, p<0.01.In conclusion, prolonged in vivo application of PmB was not able to neutralize the LOS-induced immune cell activity but its presence in the organism of treated mice was important in modulation of the LOS-mediated response against the development of metastases.

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

    International Nuclear Information System (INIS)

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

  10. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

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    Zipeng Gong

    2014-01-01

    Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  11. Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation.

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    Hyun-Su Lee

    Full Text Available Atopic dermatitis (AD is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

  12. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

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    Yosuke Kikuchi

    Full Text Available The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  13. Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation.

    Science.gov (United States)

    Lee, Hyun-Su; Choi, Eun-Ju; Lee, Kyung-Sik; Kim, Hye-Ran; Na, Bo-Ra; Kwon, Min-Sung; Jeong, Gil-Saeng; Choi, Hyun Gyu; Choi, Eun Young; Jun, Chang-Duk

    2016-01-01

    Atopic dermatitis (AD) is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA) isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production. PMID:26959360

  14. Effect on morphology, oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination.

    Science.gov (United States)

    Lv, Yingjun; Liu, Zhijun; Tian, Yujie; Chen, Hongbo

    2013-03-01

    Cases of pet poisoning and infant renal calculus have attracted much attention to the toxicity of melamine and its derivatives, such as cyanuric acid. Although individually melamine and cyanuric acid have low toxicity, their simultaneous presence can cause severe damage. Little is known about their adverse effects on the reproductive system. In this study, mice were orally administrated 1, 5 or 25 mg/kg/d of both melamine and cyanuric acid for 13 weeks. Lethargy, rough hair, and reduction of food and water intake and of body and testis weight were found after exposure to the combination, and pathological changes were found in the morphology of the testes, such as disruption of the seminiferous tubule structure, decrease of the spermatogenic cell series and coagulation necrosis. Total antioxidant capacity and superoxide dismutase activities and glutathione concentration was lower and malondialdehyde concentration was higher than in control mice. The activities of malate dehydrogenase, lactate dehydrogenase and Na(+)/K(+)-ATPase were also lower in combination treated mice than in control mice. These results indicate that the combined exposure to both melamine and cyanuric acid damaged testes in mice by either a direct or indirect effect, which may be related to renal failure and secondary anorexia. Oxidative stress and lower energy production levels both contributed to the testicular damage.

  15. LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets.

    Science.gov (United States)

    Cheng, Minlu; Liu, Ruijuan; Wu, Yao; Gu, Pan; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2016-01-25

    An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4 mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients>0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063 ng/mL to 2.034 ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ± 15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72 h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose. PMID:26519688

  16. LC/MS/MS determination and pharmacokinetic study of iridoid glycosides monotropein and deacetylasperulosidic acid isomers in rat plasma after oral administration of Morinda officinalis extract.

    Science.gov (United States)

    Li, Chunmin; Dong, Jian; Tian, Jingchang; Deng, Zhipeng; Song, Xiujing

    2016-02-01

    Morinda officinalis is a famous traditional Chinese medicine containing iridoid glycoside compounds, such as monotropein and deacetylasperulosidic acid. The aim of the study was to develop a novel and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of the two isomeric iridoid glycosides and then evaluate their pharmacokinetic properties in rats. Selected-reaction monitoring mode was employed for quantification of two analytes in rat plasma. The calibration curves were linear over their respective concentration range with correlation coefficient >0.995 for both analytes. Precision for monotropein and deacetylasperulosidic acid ranged from 2.5 to 11.9% relative standard deviation, and the accuracy of two analytes was -2.0-3.7 and -6.4-10.7% relative error, respectively. This method was successfully applied in pharmacokinetic study after oral administration of M. officinalis extract in rats. The results provided a basis for further research on the bioactivity of M. officinalis. PMID:26053360

  17. Oral administration of two probiotic strains, Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711, enhances the intestinal function of healthy adults.

    Science.gov (United States)

    Olivares, Mónica; Díaz-Ropero, M A Paz; Gómez, Nuria; Lara-Villoslada, Federico; Sierra, Saleta; Maldonado, Juan Antonio; Martín, Rocío; López-Huertas, Eduardo; Rodríguez, Juan Miguel; Xaus, Jordi

    2006-03-15

    Modifications in gastrointestinal parameters, intestinal colonization and tolerance are some of the main goals claimed for probiotics. However, although healthy people are the common target for these new functional food products, the number of clinical trials analysing the effects of probiotics in gastrointestinal parameters of healthy subjects is very scarce. A randomized, double blind, placebo-controlled human clinical trial involving 30 healthy adults was performed to investigate the effect of a fermented product containing two probiotic strains, Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711, on several blood and fecal parameters, most of them related to the host intestinal function. The volunteers were randomly distributed into two groups, one receiving a standard yogurt and the other a similar dairy fermented product in which the Lactobacillus delbreuckii subsp. bulgaricus yogurt strain had been replaced by a combination of the probiotic strains L. gasseri CECT5714 and L. coryniformis CECT5711. The volunteers that received the probiotic strains reported no adverse effects and the strains could be isolated from their feces at a relatively high level. In fact, the concentration of fecal lactic acid bacteria significantly increased in the probiotic group. Additionally, the oral administration of the probiotic strains led to an improvement of parameters such as the production of short chain fatty acids, the fecal moisture and the frequency and volume of the stools. As a result, the volunteers assigned to the probiotic group perceived a clear improvement in their intestinal habits. The study revealed that probiotics may exert a positive effect on healthy adults.

  18. Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism.

    Science.gov (United States)

    Khan, Husain Y; Zubair, Haseeb; Ullah, Mohd F; Ahmad, Aamir; Hadi, Sheikh M

    2011-12-01

    To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

  19. Activation of Cellular Immunity in Herpes Simplex Virus Type 1-Infected Mice by the Oral Administration of Aqueous Extract of Moringa oleifera Lam. Leaves.

    Science.gov (United States)

    Kurokawa, Masahiko; Wadhwani, Ashish; Kai, Hisahiro; Hidaka, Muneaki; Yoshida, Hiroki; Sugita, Chihiro; Watanabe, Wataru; Matsuno, Koji; Hagiwara, Akinori

    2016-05-01

    Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti-herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV-1) infection model. AqMOL (300 mg/kg) was administered orally to HSV-1-infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed-type hypersensitivity (DTH) reaction to inactivated HSV-1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice at 4 days post-infection. AqMOL administration was effective in elevating the ratio of CD11b(+) and CD49b(+) subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV-1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26814058

  20. Modifications in rat testicular morphology and increases in IFN-gamma serum levels by the oral administration of subtoxic doses of mercuric chloride.

    Science.gov (United States)

    Penna, Salvador; Pocino, Marisol; Marval, Maria Josefina; Lloreta, José; Gallardo, Luis; Vila, Joan

    2009-01-01

    Mercury induces structural and functional damage in several organs, however the effects of subtoxic doses of the metal on the male reproductive system are not well defined. In order to analyze testicular and epididymal morphological alterations and changes in IL-4 or IFN-gamma serum levels, adult male Sprague-Dawley rats received 0.01, 0.05 or 0.1 microg/ml of mercuric chloride (HgCl(2)) in deionized water for 1 to 7 months by oral route. Controls received deionized water alone. Twenty rats, separated in four groups of five animals each, were used per time of exposure. Progressive degenerative lesions consisting of lack of germ cell cohesion and desquamation, arrest at spermatocyte stage and hypospermatogenesis were observed in seminiferous epithelium by light and electron microscopy. Leydig cells showed cytoplasmic vacuolation and nuclear signs of cell death. Loss of peritubular cell aggregation was evidenced in the epididymis. Mercury accumulation was detected in both organs by mass spectroscopy. Rats showed enhanced IFN-gamma serum levels as compared to controls but only reached significance after 7 months of mercury administration. Subtoxic doses of inorganic mercury could lead to reproductive and immunological alterations. The results demonstrate that sublethal concentrations of mercuric chloride are enough to induce morphological and ultrastructural modifications in male reproductive organs. These contribute to functional alterations of spermatogenesis with arrest at spermatocyte stage, hypospermatogenesis and possibly impaired steroidogenesis which together could affect male fertility. PMID:19462287

  1. Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Desai D

    2016-01-01

    Full Text Available Diti Desai,1–4 Neeraj Prabhakar,2 Veronika Mamaeva,3,5 Didem Şen Karaman,2,4 Iris AK Lähdeniemi,1,6 Cecilia Sahlgren,3,7,* Jessica M Rosenholm,2,4,* Diana M Toivola1,6,* 1Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 2Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 3Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; 4Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 5Department of Clinical Science, University of Bergen, Bergen, Norway; 6Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; 7Department of Biomedical Engineering, Technical University of Eindhoven, Eindhoven, the Netherlands *These authors contributed equally to this work Abstract: Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol (PEG, poly(ethylene imine (PEI, and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs thus remained intact in vivo

  2. Analysis of the toxicity and histopathology induced by the oral administration of Pseudanabaena galeata and Geitlerinema splendidum (cyanobacteria) extracts to mice.

    Science.gov (United States)

    Rangel, Marisa; Martins, Joyce C G; Garcia, Angélica Nunes; Conserva, Geanne A A; Costa-Neves, Adriana; Sant'Anna, Célia Leite; de Carvalho, Luciana Retz

    2014-01-22

    Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the

  3. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria Extracts to Mice

    Directory of Open Access Journals (Sweden)

    Marisa Rangel

    2014-01-01

    Full Text Available Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt of the Institute of Botany of Brazil, the acetic acid extracts (AE of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia

  4. Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.

    Science.gov (United States)

    Kim, Eun Ji; Shin, Minjeong; Park, Heesook; Hong, Ji Eun; Shin, Hyun-Kyung; Kim, Jongdai; Kwon, Dae Young; Park, Jung Han Yoon

    2009-12-01

    3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties. In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer. PMID:19864400

  5. Simultaneous Determination of Eight Alkaloids in Rat Plasma by UHPLC-MS/MS after Oral Administration of Coptis deltoidea C. Y. Cheng et Hsiao and Coptis chinensis Franch.

    Science.gov (United States)

    Liu, Lu; Wang, Zhi-Bin; Song, Yang; Yang, Jing; Wu, Li-Jun; Yang, Bing-You; Wang, Qiu-Hong; Wang, Li-Qian; Wang, Ru-Xuan; Yang, Chun-Juan

    2016-01-01

    A ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight alkaloids: tetrahydropalmatine (A); palmatine (B); magnoflorine (C); columbamine (D); berberine (E); worenine (F); berberrubine (G) and coptisine (H) in rat plasma, which are the active components in Coptis deltoidea C. Y. cheng et Hsiao (CCY) and Coptis chinensis Franch (CF). The chromatographic separation of analytes was successfully achieved on an Agilent SB-C18 column (1.8 µm, 150 mm × 2.1 mm) using a programme with a mobile phase consisting of acetonitrile and water containing 0.3% acetic acid at a flow rate of 0.25 mL/min. The analytes were detected with a triple quadrupole tandem MS in multiple reaction monitoring (MRM) mode and an electrospray ionization (ESI) source in positive mode. The validated method showed good linearity over a wide concentration range (r² > 0.991), and lower limits of quantification (LLOQ) less than 1.1 ng/mL for all analytes, and matrix effects ranged from 85.2% to 106.8%. The mean extraction recoveries were no less than 86.4%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The method validation results demonstrated that the proposed method was sensitive, specific, and reliable, which could lay a foundation for the pharmacokinetic study of eight analytes after oral administration of CCY and CF in subsequent studies. PMID:27428938

  6. Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

    Science.gov (United States)

    Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

    2016-01-01

    Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

  7. Simultaneous determination of five bioactive secolignans in rat plasma by LC-MS/MS for pharmacokinetic studies following oral administration of Peperomia dindygulensis Miq. extract.

    Science.gov (United States)

    Wang, Xin-zhi; Liang, Jing-yu; Wen, Hong-mei; Shan, Chen-xiao; Liu, Rui

    2014-01-01

    A rapid and sensitive ultra fast performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of five bioactive secolignans in Peperomia dindygulensis extract, including peperomin A, peperomin B, peperomin C, 4″-hydroxypeperomin B and 4″-hydroxypeperomin C in rat plasma. Arctigenin was used as the internal standard. The separation was performed on an Innovation™ Polar-RP C18 column by a gradient elution within a runtime of 7min. The mobile phase consisted of A (methanol) and B (0.1% formic acid in water) at a flow rate of 0.4mL/min. The detection was accomplished by using positive ion TurboIonSpray ionization in multiple reaction monitoring mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.9972. The lower limits of quantification were 1.1ng/mL for peperomin A, 1.24ng/mL for peperomin B, 1.02ng/mL for peperomin C, 1.91ng/mL for 4″-hydroxypeperomin B and 1.27ng/mL for 4″-hydroxypeperomin C. The intra- and inter-day precision (RSD%) was within 15% and the accuracy (RE%) ranged from -11.7% to 10.3%. This simple and sensitive method was fully validated and successfully applied to the pharmacokinetic study of peperomin A, peperomin B, peperomin C, 4″-hydroxypeperomin B and 4″-hydroxypeperomin C in rat plasma after oral administration of P. dindygulensis extract. PMID:24295907

  8. Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013).

    Science.gov (United States)

    Thomasy, Sara M; Shull, Olivia; Outerbridge, Catherine A; Lim, Christine C; Freeman, Kate S; Strom, Ann R; Kass, Philip H; Maggs, David J

    2016-09-01

    OBJECTIVE To evaluate outcomes for cats treated with orally administered famciclovir 3 times/d for clinical signs attributed to naturally occurring feline herpesvirus type 1 (FHV-1) infection and to assess variables related to owner satisfaction with the treatment. DESIGN Retrospective case series. ANIMALS 59 client-owned cats. PROCEDURES Medical records were reviewed to identify cats treated for presumed FHV-1 infection from 2006 through 2013 with ≥ 1 follow-up visit. Signalment, duration of clinical signs, prior treatment, examination findings, diagnostic test results, concurrent treatments, and outcome data were recorded. Owners were asked to complete a survey regarding patient- and treatment-related variables. Data were compared between cats that received low (approx 40 mg/kg [18 mg/lb]) and high (approx 90 mg/kg [41 mg/lb]) doses of famciclovir, PO, 3 times/d. RESULTS Patient age ranged from 0.03 to 16 years. Conjunctivitis (51/59 [86%]), keratitis (51 [86%]), blepharitis (19 [32%]), nasal discharge or sneezing (10 [17%]), and dermatitis (4 [7%]) were common findings. Clinical improvement was subjectively graded as marked in 30 (51%) cats, mild in 20 (34%), and nonapparent in 9 (15%). Median time to improvement was significantly shorter, and degree of improvement was significantly greater in the highdose group than in the low-dose group. Adverse effects potentially attributable to famciclovir administration were reported for 10 cats. On the basis of survey responses, most (29/32 [91%]) owners were satisfied with their cat's treatment. CONCLUSIONS AND CLINICAL RELEVANCE Famciclovir at the prescribed dosages was associated with improved clinical signs in cats with presumed FHV-1 infection, and few adverse effects were attributed to the treatment. Further studies are needed to assess whether a famciclovir dosage of 90 versus 40 mg/kg, PO, 3 times/d would result in increased efficacy and shorter treatment time. PMID:27556267

  9. Pharmacokinetics of Active Components of Yokukansan, a Traditional Japanese Herbal Medicine after a Single Oral Administration to Healthy Japanese Volunteers: A Cross-Over, Randomized Study

    Science.gov (United States)

    Kitagawa, Hiroyuki; Munekage, Masaya; Ichikawa, Kengo; Fukudome, Ian; Munekage, Eri; Takezaki, Yuka; Matsumoto, Takashi; Igarashi, Yasushi; Hanyu, Haruo; Hanazaki, Kazuhiro

    2015-01-01

    Context Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia. Objective To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers. Design, Setting, and Participants A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012. Interventions Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period. Main Outcome Measure Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE). Results The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650–1.98 ng/mL and 0.138–0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975–1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72–1.95 h for GM and 2.47–3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7–108 ng/mL, 8.00–8.01 h, and 9.39–12.3 h, respectively. Conclusion We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS. Trial Registration Japan Pharmaceutical Information Center JAPIC CTI-121811 PMID:26151135

  10. The anti emetic effect of oral administration of ondansetron or granisetron in macacus cynomolgus exposed to mixed neutron-gamma irradiation; Effet antiemetique de l`ondansetron ou du granisetron administres oralement chez le macaque soumis a une irradiation mixte neutron-gamma

    Energy Technology Data Exchange (ETDEWEB)

    Martin, C.; Roman, V.; Martin, S.; Janodet, D.; Fatome, M. [Centre de Recherches du Service de Sante des Armees, 38 - La Tronche (France)

    1995-10-01

    Nausea and vomiting are the most often observed symptoms in the course of the early radiation syndrome. Their prevention has long been difficult because of the low effectiveness and side-effects of most antiemetics. There is a clear evidence that 5HT{sub 3} receptor antagonists such as ondansetron and granisetron are highly effective to prevent radiation-induced emesis without any side-effect. We studied the prophylactic effectiveness of their oral administration to macacus cynomolgus, for mixed neutron-gamma whole-body exposure, tat high dose rates. Doses of 4 mg of ondansetron or 1 mg of granisetron were administered before, or after, or both before and after irradiation. The treatment was effective when administered both before and after radiation exposure. It was significant but incomplete if administered once. Post-irradiation administration is interesting, particularly in case of accident. Both antiemetic drugs were well tolerated. Their effectiveness and tolerance are apparently comparable. The 5HT{sub 3} receptor antagonists represent a much improved treatment for radiation-induced nausea and vomiting by completely inhibiting emesis, if administered before and after irradiation. Unwanted sedation and extra-pyramidal side-effects, usually associated with the clinical use of D{sub 2} receptor antagonists, were not observed. (authors). 40 refs., 5 tabs.

  11. 口服橄榄油治疗脑卒中后便秘52例疗效观察%Constipation after oral administration of olive oil and 52 cases of stroke treatment efficacy

    Institute of Scientific and Technical Information of China (English)

    安莉; 甄景; 王杏微; 王钧

    2011-01-01

    Objective: To observe the olive oil for the treatment of constipation in patients with stroke. Methods: 52 cases of stroke in patients with constipation after oral administration of olive oil and constipation treatment of stroke, observed in patients with defecation. Results: 52 cases of stroke in patients with constipation after oral administration of olive oil, a marked improvement in bowel movements, the effective rate of 90. T%. Conclusion: After oral administration of olive oil for constipation have a better stroke treatment.%目的:观察橄榄油对脑卒中患者便秘的治疗效果.方法:对52例脑卒中便秘患者采用口服橄榄油治疗卒中后便秘,观察患者的排使情况.结果:52例脑卒中便秘患者经口服橄榄油后,排使情况明显改善,有效率为90.4%.结论:口服橄榄油对脑卒中后便秘有较好的治疗作用.

  12. Nursing Care of Patients with Constipation After Stroke by Oral Administration of Olive Oil%脑卒中便秘患者口服橄榄油后的治疗护理观察

    Institute of Scientific and Technical Information of China (English)

    杜媛媛

    2016-01-01

    Objective: To observe the olive oil for the treatment of constipation in patients with stroke. Methods: 52 cases of stroke in patients with constipation after oral administration of olive oil and constipation treatment of stroke, observed in patients with defecation. Results: 52 cases of stroke in patients with constipation after oral administration of olive oil, a marked improve-ment in bowel movements, the effective rate of 90.4%. Conclusion: After oral administration of olive oil for constipation have a better stroke treatment.%目的:观察脑卒中患者便秘口服橄榄油的治疗护理效果。方法:对200例脑卒中便秘患者采用口服橄榄油治疗卒中后便秘,观察患者的排便情况。结果:200例脑卒中便秘患者经口服橄榄油后,排便情况明显改善,有效率为95%。结论:脑卒中患者便秘口服橄榄油后有较好的治疗护理作用,在临床上值得推广。

  13. Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Amalia E Yanni

    2008-04-01

    Full Text Available Amalia E Yanni1, Eleutherios Margaritis2, Nikolaos Liarakos2, Alkisti Pantopoulou2, Maria Poulakou2, Maria Kostakis2, Despoina Perrea2, Alkis Kostakis31Department of Science of Dietetics and Nutrition, Harokopio University of Athens, Athens, Greece, 2Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, 32nd Department of Propedeutic Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceObjective: To study the effect of oral administration of a nitric oxide (NO donor L-arginine (L-Arg, a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME and an inhibitor of xanthine oxidase, allopurinol (Allo, on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R in rats.Methods: Male Wistar rats received per os L-Arg (800 mg/kg or L-NAME (50 mg/kg or Allo (100 mg/kg 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1, L-NAME(IR1 and Allo(IR1 respectively or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8, L-NAME(IR8 and Allo(IR8 respectively. There was one group underwent 1 hr occlusion (I, a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1, a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8 and a last group that served as control (C. Serum NO concentration and catalase activity were measured.Results: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1 groups compared with group C but not in L-NAME(IR1 and Allo(IR1 group. Catalase activity was enhanced in L-NAME(IR1 group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8, L-NAME(IR8 and Allo(IR8 compared with control while catalase activity did not show significant difference in any group.Conclusions: The results of the

  14. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

    International Nuclear Information System (INIS)

    Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au)

  15. Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age

    OpenAIRE

    Stensson, Malin; Koch, G; Coric, S.; Abrahamsson, T. R.; Jenmalm, M. C.; Birkhed, D.; Wendt, Lill-Kari

    2014-01-01

    The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and ...

  16. Oral Cancer

    Science.gov (United States)

    ... TMJ Disorders Oral Cancer Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer ... Puts Someone at Risk? Possible Signs & Symptoms Early Detection About Oral Cancer Oral cancer includes cancers of ...

  17. Nitroglicerina transdérmica versus nifedipina oral para inibição do trabalho de parto prematuro: ensaio clínico randomizado Transdermal nitroglycerin versus oral nifedipine administration for tocolysis: a randomized clinical trial

    OpenAIRE

    Melania Maria Ramos de Amorim; Luis André Marinho Lippo; Aurélio Antônio Ribeiro Costa; Isabela Cristina Coutinho; Alex Sandro Rolland Souza

    2009-01-01

    OBJETIVO: comparar a efetividade da nitroglicerina transdérmica com a nifedipina oral na inibição do trabalho de parto prematuro. MÉTODOS: foi realizado um ensaio clínico com 50 mulheres em trabalho de parto prematuro, randomizadas em dois grupos, 24 para nifedipina oral (20 mg) e 26 para nitroglicerina transdérmica (patch 10 mg). Foram selecionadas as pacientes com gestação única, entre a 24ª e 34ª semanas e diagnóstico de trabalho de parto prematuro. Foram excluídas pacientes com malformaçõ...

  18. Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine

    Directory of Open Access Journals (Sweden)

    Rahman Md

    2012-07-01

    Full Text Available Abstract Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α and chicken interleukin-18 (chIL-18 as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.

  19. Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12

    Directory of Open Access Journals (Sweden)

    Sanz-Cuesta Teresa

    2012-05-01

    Full Text Available Abstract Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain, and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm. Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml, adherence to treatment, quality of life (EuroQoL-5D questionnaire, patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The results of this study should help establish

  20. Oral administration of a fusion protein between the cholera toxin B subunit and the 42-amino acid isoform of amyloid-β peptide produced in silkworm pupae protects against Alzheimer's disease in mice.

    Directory of Open Access Journals (Sweden)

    Si Li

    Full Text Available A key molecule in the pathogenesis of Alzheimer's disease (AD is a 42-amino acid isoform of the amyloid-β peptide (Aβ42, which is the most toxic element of senile plaques. In this study, to develop an edible, safe, low-cost vaccine for AD, a cholera toxin B subunit (CTB-Aβ42 fusion protein was successfully expressed in silkworm pupae. We tested the silkworm pupae-derived oral vaccination containing CTB-Aβ42 in a transgenic mouse model of AD. Anti-Aβ42 antibodies were induced in these mice, leading to a decreased Aβ deposition in the brain. We also found that the oral administration of the silk worm pupae vaccine improved the memory and cognition of mice, as assessed using a water maze test. These results suggest that the new edible CTB-Aβ42 silkworm pupae-derived vaccine has potential clinical application in the prevention of AD.

  1. Occurrence of specific influenza antibodies in saliva and nasal secretion of monkeys (Macacus rhesus) after oral administration of influenza vaccine inactivated by gamma rays

    International Nuclear Information System (INIS)

    Antibodies in nasal secretion and saliva were measured in 10 Macacus rhesus wich had been immunized orally with a 60Co-gamma-inactivated influenza vaccine. Prior to immunization monkeys had no detectable antibodies against hemagglutinin (HA) and neuraminidase, resp. in sera or secretions. Oral immunization using intraoesophageal tubing, induced the occurrence of both antiobodies in pilocarpine-stimulated secretions within 28 days but not in sera. 6 monkeys reacted with increasing HA antibodies in nasal secretions and 10 monkeys with increasing neuraminidase antibodies. Salivary HA antibodies occurred in 8 of 10 and neuraminidase antibodies in 9 of 10 animals. In most cases antibodies occurred in both secretions simultaneously. These results demonstrate the stimulation of antibodies specific to influenza in the respiratory tract of monkeys after oral immunization with an inactivated vaccine, for the first time. (author)

  2. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

    Directory of Open Access Journals (Sweden)

    Mizrahi M

    2012-12-01

    Full Text Available Meir Mizrahi,1 Yehudit Shabat,1 Ami Ben Ya'acov,1 Gadi Lalazar,1 Tomer Adar,1 Victor Wong,2 Brian Muller,2 Grant Rawlin,2 Yaron Ilan11Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel; 2Immuron Limited, North Melbourne, AustraliaBackground: Nonalcoholic steatohepatitis (NASH is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia, containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH.Methods: In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days.Results: Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT and homeostatic model assessment insulin resistance (HOMA scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1, adiponectin and T regulatory cells.Conclusion: Hyperimmune colostrum alleviates NASH.Keywords: NASH, anti-LPS, diabetes, adipokines, regulatory T cells

  3. A rapid and safe plasmid isolation method for efficient engineering of recombinant lactobacilli expressing immunogenic or tolerogenic epitopes for oral administration

    NARCIS (Netherlands)

    Maassen, C.B.M.

    1999-01-01

    Recombinant lactobacilli are being developed which can be used as expression and delivery vectors of heterologous antigens in oral vaccination and other therapeutic applications. Because most Lactobacillus strains do not accept ligation mixtures, sufficiently pure plasmid DNA needs to be isolated fr