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Sample records for fasting conditions single-dose

  1. A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

    Science.gov (United States)

    Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

    2009-03-01

    Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

  2. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2014-08-01

    Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

  3. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

  4. Compatibility of the repairable-conditionally repairable, multi-target and linear-quadratic models in converting hypofractionated radiation doses to single doses.

    Science.gov (United States)

    Iwata, Hiromitsu; Matsufuji, Naruhiro; Toshito, Toshiyuki; Akagi, Takashi; Otsuka, Shinya; Shibamoto, Yuta

    2013-03-01

    We investigated the applicability of the repairable-conditionally repairable (RCR) model and the multi-target (MT) model to dose conversion in high-dose-per-fraction radiotherapy in comparison with the linear-quadratic (LQ) model. Cell survival data of V79 and EMT6 single cells receiving single doses of 2-12 Gy or 2 or 3 fractions of 4 or 5 Gy each, and that of V79 spheroids receiving single doses of 5-26 Gy or 2-5 fractions of 5-12 Gy, were analyzed. Single and fractionated doses to actually reduce cell survival to the same level were determined by a colony assay. Single doses used in the experiments and surviving fractions at the doses were substituted into equations of the RCR, MT and LQ models in the calculation software Mathematica, and each parameter coefficient was computed. Thereafter, using the coefficients and the three models, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually-determined equivalent single doses for the hypofractionated doses. The equivalent single doses calculated using the RCR, MT and LQ models tended to be lower than the actually determined equivalent single doses. The LQ model seemed to fit relatively well at doses of 5 Gy or less. At 6 Gy or higher doses, the RCR and MT models seemed to be more reliable than the LQ model. In hypofractionated stereotactic radiotherapy, the LQ model should not be used, and conversion models incorporating the concept of the RCR or MT models, such as the generalized linear-quadratic models, appear to be more suitable.

  5. A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly improves the fasting absorption of EPA and DHA from a single dose of an omega-3 ethyl ester concentrate.

    Science.gov (United States)

    Qin, Yan; Nyheim, Hilde; Haram, Else Marie; Moritz, Joseph M; Hustvedt, Svein Olaf

    2017-10-16

    , respectively. C max was also increased for both EPA and DHA 2.7- to 9.2-fold. PRF-021 is a novel SMEDS formulation of Omega-3-acid EE demonstrating a marked improvement in absorption of a single dose of EPA and DHA EE under fasted conditions. This allows adequate absorption of Omega-3 from the supplement without the requirement of a high-fat meal.

  6. A new single-dose bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae elicits protective immunity and improves growth performance under field conditions.

    Science.gov (United States)

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2016-01-15

    The efficacy of the new single-dose bivalent vaccine of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of co-infection with PCV2 and M. hyopneumoniae. On each farm, a total of 80 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated (n=40) and (ii) unvaccinated (n=40) animals at 3 weeks of age. Protection by the bivalent vaccine helped increase the market weight by 6.2 kg/pig (106.2 kg in vaccinated group vs. 100 kg in unvaccinated group; Phyopneumoniae-specific IFN-γ-SC. Vaccinated animals displayed a reduced PCV2 load in the blood and M. hyopneumoniae load in nasal swabs compared to unvaccinated animals. Vaccination of pigs against PCV2 and M. hyopneumoniae effectively reduced the lung and lymphoid lesion scores compared to unvaccinated animals in all 3 farms. The new bivalent vaccine is very efficacious in controlling PCV2 and M. hyopneumoniae infection based on clinical, immunological, virological, and pathological evaluations under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Comparative Fasting Bioavailability of 2 Different Betahistine Dihydrochloride 24-mg Tablets: A Single- Dose, Randomized-Sequence, Open-Label, 2-Period Crossover Study in Healthy Thai Volunteers

    Directory of Open Access Journals (Sweden)

    Pinpilai Jutasompakorn

    2016-05-01

    Full Text Available Objective: To evaluate the bioequivalence of 24 mg betahistine dihydrochloride tablets between the test product (Stei® and the reference product (Serc® in healthy Thai volunteers. Methods: This was an open-label, randomized sequence, single-dose, two-period crossover study in 24 healthy volunteers. Half of the volunteers received a single dose of test product 24 mg and then reference product 24 mg after a minimum 7-day washout period. The remaining half of volunteers received the reference product first and then the test product with the same washout period. Blood samples were obtained at pre-dose and over 14 hours after dosing. Plasma concentrations of 2-pyridylacetic acid (2-PAA, a major metabolite of betahistine were quantified by using liquid chromatography with tandem mass spectrometry (LC-MS/MS. Tolerability in volunteers were assessed during the study. Results: Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The geometric mean ratios of 2-PAA between the test and reference products were 96.44%, 96.99%, and 94.56% for Cmax, AUC0-t, and AUC0-∞, respectively. These pharmacokinetic parameter values lie within the FDA and European Medicines Agency specified bioequivalence limit (80-125%. No serious adverse events related to the studied drugs were found. Conclusion: It can be concluded that these two betahistine dihydrochloride products were considered bioequivalent.

  8. Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

    Science.gov (United States)

    Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

    2010-11-01

    Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

  9. Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Brown, Jean; Buchanan, William L; Reed, Kenneth; Cooper, Stephen A; Otto, James

    2013-09-01

    Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. We sought to investigate the dose-response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients. All 701 patients from both studies were included in the analysis and safety assessment. FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD

  10. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Science.gov (United States)

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

    2009-10-01

    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  11. Pharmacokinetics and bioequivalence evaluation of two different atorvastatin calcium 10-mg tablets: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy fasted Chinese adult males.

    Science.gov (United States)

    Liu, Yan-Mei; Pu, Hua-Hua; Liu, Gang-Yi; Jia, Jing-Ying; Weng, Li-Ping; Xu, Rong-Jing; Li, Guo-Xiu; Wang, Wei; Zhang, Meng-Qi; Lu, Chuan; Yu, Chen

    2010-07-01

    Atorvastatin calcium is a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor indicated for the prevention of cardiovascular disease and for the treatment of dyslipidemia. Information on the pharmacokinetics of atorvastatin in a Chinese population is lacking, and regulatory requirements necessitate a bioequivalence study for the marketing of a generic product in China. The aim of the present study was to assess the pharmacokinetics and bioequivalence of a test and branded reference formulation of atorvastatin calcium 10-mg tablets in healthy fasted Chinese male volunteers. This was a single-dose, randomized-sequence, open-label, 2-period crossover study with a 2-week washout period between doses. Healthy Chinese males were randomly assigned to receive 20 mg of either the test or reference formulation, and 13 blood samples were obtained over a 48-hour interval. Plasma concentrations of parent atorvastatin and ortho-hydroxy-atorvastatin (primary active metabolite) were simultaneously determined using a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters, including C(max), T(max), t((1/2)), AUC(0-t), and AUC(0-infinity)), were calculated. The 2 formulations were to be considered bioequivalent if 90% CIs for the log transformed ratios of AUC and C(max) of atorvastatin were within the predetermined bioequivalence range (0.80-1.25 for AUC and 0.70-1.43 for C(max)) as established by the State Food and Drug Administration of China. Tolerability was evaluated throughout the study by vital signs monitoring, physical examinations, 12-lead ECGs, and subject interviews on adverse events (AEs). A total of 66 subjects were assessed for inclusion; 20 were excluded prior to study initiation. Of the 46 healthy subjects (mean [SD] age, 24.1 [2.5] years; height, 170.8 [5.1] cm; weight, 64.6 [6.4] kg; body mass index (BMI), 22.1 [1.7] kg/m(2)) who completed the study, 45 subjects (mean [SD] age, 24.1 [2.5] years; height, 171.1 [4

  12. Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

    2013-03-01

    Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

  13. Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: a single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states.

    Science.gov (United States)

    Ahmed, Iman Saad; Aboul-Einien, Mona Hassan; Mohamed, Osama Hussein; Farid, Samar Farghali

    2008-10-02

    The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125 mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.

  14. Single dose regorafenib-induced hypertensive crisis.

    Science.gov (United States)

    Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

    2014-06-01

    Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

  15. Single dose pharmacokinetics of mefloquine in healthy Nigerian ...

    African Journals Online (AJOL)

    Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. Mefloquine 500mg single dose was administered and blood sa mples were collected 11t intervals. Plasma concentrations were determined by RP-HPLC method after sample pretreated step by solid phase extraction ...

  16. single dose pharmacokinetics of mefloquine in healthy nigerian ...

    African Journals Online (AJOL)

    BSN

    Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. Mefloquine 500mg single dose was administered and blood samples were collected. 11t intervals. Plasma concentrations were determined by RP-HPLC method after sample pre- treated step by solid phase extraction ...

  17. single dose pharmacokinetics of mefloquine in healthy nigerian ...

    African Journals Online (AJOL)

    BSN

    University of Jos, Jos Nigeria. Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. ... INTRODUCTION. Mefloquine is a quinolinemethanol antimalarial found to be effective as single dose therapy for all species ..... ·ographic using electron capture. LB. a'"lrl Rcmbo L., (1993).

  18. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

  19. Postprandial triglyceridemia after single dose of alcohol in healthy young men.

    Science.gov (United States)

    Mudráková, E; Poledne, R; Kovář, J

    2013-03-01

    Moderate alcohol consumption provides protection against cardiovascular disease primarily due to increase of HDL-cholesterol. However, it also has some adverse effects on metabolism of triglycerides (TG). Therefore, we addressed the question how a single dose of alcohol affects postprandial lipemia and activities of two enzymes playing a critical role in regulation of triglyceridemia, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). Eight healthy volunteers were given a single dose of alcohol (vodka; 0.6 g of ethanol/kg of body weight) together with a fat load (0.7 g of fat/kg of body weight) in an experimental breakfast or together with dinner 12 h before the experimental breakfast. In comparison to control experiment, alcohol given with breakfast induced increased and prolonged postprandial response of triglyceride-rich lipoproteins (TRL; d Alcohol given in the evening before the experiment increased fasting TG concentration but did not affect changes in TRL and IDL concentrations. LPL activity measured both in vivo using intravenous fat tolerance test and in vitro and HTGL activity were determined at the end of experiments (after 7.5 h of postprandial lipemia study). Neither was affected by a single dose of alcohol. Single dose of alcohol induces immediate and profound changes in metabolism of TRL and IDL. The same dose of alcohol given 12 h before meal does affect baseline TG concentration but not the postprandial changes of triglyceridemia. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Coronary vasodilatory action after a single dose of nicorandil

    NARCIS (Netherlands)

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)

    1988-01-01

    textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive

  1. Rhabdomyolysis induced by a single dose of a statin

    OpenAIRE

    Jamil, S; Iqbal, P

    2004-01-01

    Statins have been shown to cause myotoxicity and rhabdomyolysis. In most cases rhabdomyolysis occurs following the use of these drugs for at least one week. A case of rhabdomyolysis after just a single dose of simvastatin is reported.

  2. Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.

    Science.gov (United States)

    Scallion, Ralph; Moore, Keith A

    2009-10-01

    Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID. The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg. In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day. Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions

  3. Thermoregulation in fasting emperor penguins under natural conditions.

    Science.gov (United States)

    Le Maho, Y; Delclitte, P; Chatonnet, J

    1976-09-01

    Emperor penguins breed during the cold antarctic winter. The males incubate the single egg while fasting for up to 4 mo and losing some 20 kg of their body mass. Fasting captive birds under outdoor conditions lost from 0.145 to 0.434 kg day -1. Mean resting metabolic rate, 49.06 W for 24.8 kg body mass, is 7 and 27%, respectively, higher than predicted from general metabolic equations for birds. Minimal thermal conductance, 1.31 W m-2 degrees C-1, is within the range for other birds. The lower critical temperature is about -10 degrees C; this can be related to large body size (20-40 kg) and to body shape, giving a smaller relative surface area than for other birds. Rigidity of the feathers explains why winds of moderate speed (up to 5 m s-1) have little effect on heat loss. At very low temperatures the behavior of huddling close together is essential in reducing metabolic rate. Without this behavior, survival during the long fast (up to four mo) at winter temperatures would be impossible.

  4. Bioequivalence study of two formulations of flupirtine maleate capsules in healthy male Chinese volunteers under fasting and fed conditions

    Directory of Open Access Journals (Sweden)

    Liu YF

    2017-12-01

    Full Text Available Yanfang Liu, Hua Huo, Zhibo Zhao, Wenli Hu, Yujia Sun, Yunbiao Tang Technical Center for Clinical Pharmacy, Department of Drug Clinical Trail Management Agency, General Hospital of Shenyang Military Area Command, Shenyang, China Aim: This study developed a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine the concentrations of flupirtine and its major active metabolite D-13223 in human plasma in order to assess the bioequivalence (BE of two flupirtine maleate capsules among healthy male Chinese volunteers under fasting and fed conditions. Materials and methods: There were two single-center, randomized, single-dose, open-label, laboratory-blinded, two-period, cross-over studies which included 24 healthy male Chinese volunteers under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 48 h after dosing. The concentrations of flupirtine and its major active metabolite D-13223 in plasma samples were determined by a validated method, that is, high-performance liquid chromatography coupled with a tandem mass spectrometry detector. Pharmacokinetic metrics of area from time zero to the last measurable concentration (AUC0-t, area under the plasma concentration–time curve from administration to infinite time (AUC0-∞, and Cmax were used for BE assessment. Results: Forty-eight healthy volunteers who met the criteria were enrolled and completed the study. According to the observation of vital signs and laboratory measurement, no volunteers had any adverse reactions. Under fasting condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 103.0% (98.1%–108.2% for AUC0-t, 102.9% (98.2%–107.9% for AUC0-∞, and 97.0% (85.9%–109.5% for Cmax. Under fed condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 101.7% (98.4%–105.1% for AUC0-t, 101.6% (98.5%–104.8% for AUC0-∞, and 103.5% (94.7%

  5. Comparative study of analgesic effectiveness of single doses of ...

    African Journals Online (AJOL)

    Method: This study employed the visual analogue scale to measure the effectiveness of single doses of ibuprofen and paracetamol over a six-hour period, following a third molar surgery in a homogenous study population, matched for age, body mass index (BMI) and gender. Alarms were set to remind patients to score pain ...

  6. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  7. Fast beam condition monitor for CMS. Performance and upgrade

    International Nuclear Information System (INIS)

    Leonard, Jessica L.; Bell, Alan; Burtowy, Piotr

    2014-05-01

    The CMS beam and radiation monitoring subsystem BCM1F (Fast Beam Condition Monitor) consists of 8 individual diamond sensors situated around the beam pipe within the pixel detector volume, for the purpose of fast bunch-by-bunch monitoring of beam background and collision products. In addition, effort is ongoing to use BCM1F as an online luminosity monitor. BCM1F will be running whenever there is beam in LHC, and its data acquisition is independent from the data acquisition of the CMS detector, hence it delivers luminosity even when CMS is not taking data. A report is given on the performance of BCM1F during LHC run I, including results of the van der Meer scan and on-line luminosity monitoring done in 2012. In order to match the requirements due to higher luminosity and 25 ns bunch spacing, several changes to the system must be implemented during the upcoming shutdown, including upgraded electronics and precise gain monitoring. First results from Run II preparation are shown.

  8. Fast Beam Condition Monitor for CMS: performance and upgrade

    CERN Document Server

    INSPIRE-00009152; Bell, Alan; Burtowy, Piotr; Dabrowski, Anne; Hempel, Maria; Henschel, Hans; Lange, Wolfgang; Lohmann, Wolfgang; Odell, Nathaniel; Penno, Marek; Pollack, Brian; Przyborowski, Dominik; Ryjov, Vladimir; Stickland, David; Walsh, Roberval; Warzycha, Weronika; Zagozdzinska, Agnieszka

    2014-11-21

    The CMS beam and radiation monitoring subsystem BCM1F (Fast Beam Condition Monitor) consists of 8 individual diamond sensors situated around the beam pipe within the pixel detector volume, for the purpose of fast bunch-by-bunch monitoring of beam background and collision products. In addition, effort is ongoing to use BCM1F as an online luminosity monitor. BCM1F will be running whenever there is beam in LHC, and its data acquisition is independent from the data acquisition of the CMS detector, hence it delivers luminosity even when CMS is not taking data. A report is given on the performance of BCM1F during LHC run I, including results of the van der Meer scan and on-line luminosity monitoring done in 2012. In order to match the requirements due to higher luminosity and 25 ns bunch spacing, several changes to the system must be implemented during the upcoming shutdown, including upgraded electronics and precise gain monitoring. First results from Run II preparation are shown.

  9. Single dose methotrexate therapy: application to interstitial ectopic pregnancy.

    Science.gov (United States)

    Borgatta, L; Burnhill, M; Stubblefield, P

    1998-03-01

    A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2 was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.

  10. Tolerance of the human spinal cord to single dose radiosurgery

    International Nuclear Information System (INIS)

    Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

    2003-01-01

    Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

  11. A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.

    Science.gov (United States)

    Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

    2013-04-01

    To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects. Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC). Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported. The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.

  12. Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2013-08-01

    Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Danang Agung Yunaidi,2 Ronal Simanjuntak,2 Iwan Dwi Santoso,2 Liana W Susanto1 1Dexa Laboratories of Biomolecular Sciences (DLBS, Cikarang, Indonesia; 2Bioavailability and Bioequivalence Laboratory, PT Equilab International, Jakarta, Indonesia Introduction: The present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations. Materials and methods: This study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7, using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week, a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax, time to achieve the Cmax, and the elimination half-life. Results: The geometric mean ratios (90% confidence interval of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52% for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95% for the AUC from time zero to infinity, and 106.71% (93.20%–122.18% for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study. Conclusion: It was concluded that the two candesartan tablet

  13. Role of single dose prophylactic antibiotic in elective caesarean section

    Directory of Open Access Journals (Sweden)

    Hasna Hena Pervin

    2016-08-01

    Full Text Available Background: Maternal morbidity related to infection after caesarean section has been reported to be higher than that of vaginal delivery. The prevention of infection in patients undergoing caesarean section is a major challenge, particularly in hospitals, where there is frequent chance of cross infection due to overcrowding. Objective: The present study was undertaken to see the efficacy of single dose cetriaxone as a prophylaxis in elective caesarean section to prevent postop­erative infection. Methods: This cross sectional study was conducted on 100 patients who underwent elective caesarean section where single dose of Ceftriaxone was used as prophylaxis in the Department of Obstetrics & Gynaecology, Bang­abandhu Sheikh Mujib Medical University Hospital, between January to June 2010. The outcomes measures were post­operative febrile morbidity, wound infe-ction and other infections (urinary tract infection, chest infection. Data were analysed using statistical package for social sciences (SPSS version 11.5.Results: Over one-third (38% patients age group was between 18 -25 years, 56% in between 25 -35 years and 6% were over 35 years old. Nearly half(46% was anemic (haemoglobin< 11 g/dl and 16% was obese (BMI≥28 kg/m2. All the patients were operated by obstetricians of same level. Three per cent patients developed wound infection, 5% developed other infections like UTI and chest infection and 7% had febrile illness. Among the several factors suspected to be associated with post operative complications, preoperative anaemia, long duration of operation (>60 minutes and prolonged hospital stay (>1 week were found to be significantly assocated with postoperative complications.Conclusion: The present study suggests that single dose prophylactic antibiotic ceftriaxone given 1 hour before operation in patients with cesarean section deliveries reduces the chance of postoperative infection to a bare minimum.

  14. Immunogenicity of single dose live attenuated hepatitis a vaccine.

    Science.gov (United States)

    Bhave, Sheila; Bavdekar, Ashish; Sapru, Amita; Bawangade, Seema; Pandit, Anand

    2011-02-01

    A long-term immunogenicity study of a single dose live attenuated H2 strain hepatitis A vaccine is being conducted in healthy Indian children at KEM Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were evaluated for anti-HAV antibodies 30 months post vaccination (2007). Seroprotective antibody levels >20 mIU/mL were demonstrated in 87.8 % subjects with an overall GMT of 92.02 mIU/mL. No hepatitis like illness was recorded in any of the subjects since vaccination.

  15. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    Science.gov (United States)

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

  16. Single-dose radiotherapy for painful bone metastases

    International Nuclear Information System (INIS)

    Kal, H.B.

    1999-01-01

    Background: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. Methods: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare reported therapy schemes which each other for the iso-effect pain relief. Results: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. Conclusion: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief. (orig.) [de

  17. Conditions for substorm onset by the fast reconnection mechanism

    Directory of Open Access Journals (Sweden)

    M. Ugai

    2008-12-01

    Full Text Available The fast reconnection mechanism, involving slow shocks and Alfvénic fast plasma jets, is most responsible for the explosive conversion of magnetic energy associated with geomagnetic substorms and solar flares. In this paper, the spontaneous fast reconnection model is applied to well-known phenomena of substorms. When the east-west width of the tail current sheet becomes 3–4 times larger than its north-south thickness, the fast reconnection mechanism can fully be established, which may lead to substorm onset. The resulting Alfvénic jet can exactly explain, both qualitatively and quantitatively, the in-situ satellite observations of the traveling compression regions (TCRs associated with large-scale plasmoids propagating down the tail. Also, the earthward fast reconnection jet causes drastic magnetic field dipolarization, so that the sheet current ahead of the magnetic loop of closed field lines suddenly turns its direction toward the loop footpoint and a large-scale current wedge is formed according to the growth of field-aligned currents. It is demonstrated that an MHD generator arises ahead of the magnetic loop and drives the current wedge to distinctly enhance the current density in a pair of thin layers of the loop footpoint, giving rise to drastic heating in the form of two ribbons.

  18. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  19. Evaluation of thromboembolic disease using single dose dual phase scintigraphy

    International Nuclear Information System (INIS)

    Sharma, A.R.; Charan, S.; Silva, I.

    2004-01-01

    Introduction: Clinical presentation of thromboembolic disease (TED) is caused by three mechanisms 1) obstruction to venous outflow 2) vascular inflammation and 3) pulmonary emboli. Single Dose (Tc-99m MAA) Dual Phases (Veno-Pulmonary) scintigraphy is theoretically capable of evaluating two of three above mentioned patho-physiological factors. Therefore, a prospective study was designed to explore potential of Single Dose Dual Phase (SDDP) scintigraphy in the evaluation of thromboembolic disease. Materials and methods: Sixty consecutive patients with high clinical likelihood of thromboembolic disease (onset of painful and edematous lower limb, chest pain, shortness of breath, presence of risk factors for DVT, H/o of previous episode of DVT, right ventricular strain on ECHO, hypoxaemia on blood gas analysis), were included in this study. There were 43 men and 17 women (mean age 36 years). They were subjected to single dose dual phase (SDDP) scintigraphy using Tc-99m MAA (4 mci). Firstly venous phase of imaging was obtained with simultaneous injection of Tc-99m MAA diluted in 10 ml normal saline in syringe into superficial veins of dorsum of both feet (large volume continuous flow technique) in whole body acquisition mode on Dual Detectors Gamma Camera; followed by lung perfusion scintigraphy in conventional projections as second phase of study. Venous phase (Venography) was interpreted as per Ziffer's criteria in four venous segments (Unpaired- Inferior Vena Cava, 3 paired - Iliac, Femoral and Popliteal). Interpretation of lung perfusion scan was made as per PIOPED Criteria. Results: Forty-one of sixty patients (67%) showed scintigraphic evidence of venous occlusion (DVT) during venous phase. Out of these, 17 patients eventually had high probability lung scan for pulmonary embolism (29%). None of the patient with negative venous phase (n=19) showed perfusion defects on lung perfusion scan. Venous thrombosis most commonly affected the left lower limb (n=29, 71%). In 5

  20. Nutritional conditioning : The effect of fasting on drug metabolism

    NARCIS (Netherlands)

    Lammers, L.A.

    2018-01-01

    The studies described in this thesis focus on the effect of fasting, as nutritional modulator, on drug metabolism. Drug metabolism varies considerably between and within patients, which may result in treatment failure or, conversely, in untoward side effects. Many factors contribute to the

  1. Effects of sex, age, and fasting conditions on plasma lipidomic profiles of fasted Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Kosuke Saito

    Full Text Available Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female, age (fasted 10 vs. 30 weeks old, and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection, on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting or the time of blood collection (10 AM vs. 4 PM blood collection has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies.

  2. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats.

    Science.gov (United States)

    Sun, Seung-Ho; Park, Sunju; Jeong, Jong-Jin; Lee, Kwang-Ho; Yu, Jun-Sang; Seo, Hyung-Sik; Kwon, Ki-Rok

    2015-06-01

    The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

  3. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Seung-Ho Sun

    2015-06-01

    Full Text Available Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP in Sprague-Dawley (SD rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156. The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group. General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA by using statistical analysis system (SAS, version 9.2. Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

  4. Single dose oral piroxicam for acute postoperative pain

    Science.gov (United States)

    Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

  5. Systematic review and meta-analysis of single-dose and non-single-dose methotrexate protocols in the treatment of ectopic pregnancy.

    Science.gov (United States)

    Yuk, Jin-Sung; Lee, Jung Hun; Park, Won I; Ahn, Hyeong Sik; Kim, Hyun Jung

    2018-02-27

    It remains unclear which methotrexate protocol for the treatment of ectopic pregnancy has a higher success rate or a higher adverse effect rate. To compare the treatment success rates and adverse effect rates of single-dose and non-single-dose (two-dose and multi-dose) methotrexate protocols in the treatment of ectopic pregnancy. Various databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched on July 1, 2017, using search terms including "methotrexate" and "pregnancy." Randomized controlled trials comparing different methotrexate protocols for the treatment of ectopic pregnancy were included. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare treatment success rates and adverse effect rates. The single-dose and non-single-dose protocols had similar success rates (RR 1.00, 95% CI 0.96-1.04; 11 trials, 1121 patients, I 2 =18%). The non-single-dose protocols had a higher adverse effect rate than did the single-dose protocol (RR 0.73, 95% CI 0.59-0.91; nine trials, 934 patients, I 2 =0%). The single-dose methotrexate protocol was the optimal protocol for the medical treatment of ectopic pregnancy. © 2018 International Federation of Gynecology and Obstetrics.

  6. Serial Myocardial Imaging after a Single Dose of Thallium-201

    Directory of Open Access Journals (Sweden)

    Takahiko Kamata

    2014-10-01

    Full Text Available Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise, showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise. Cardiac biomarkers were negative in the clinical course.

  7. Assessment of coverage levels of single dose measles vaccine

    International Nuclear Information System (INIS)

    Tariq, P.

    2003-01-01

    Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)

  8. Single dose intravenous methyl prednisolone versus oral prednisolone in Bell's palsy: A randomized controlled trial

    Science.gov (United States)

    Giri, Prithvi; Garg, Ravindra Kumar; Singh, Maneesh Kumar; Verma, Rajesh; Malhotra, Hardeep Singh; Sharma, Praveen Kumar

    2015-01-01

    Objectives: Corticosteroids have been used in the treatment of Bell's palsy and several other postinfectious neurological conditions. We hypothesized that administration of a single dose of intravenous (IV) methylprednisolone might be an effective alternative to oral prednisolone. Materials and Methods: In this open label, randomized trial, patients with acute Bell's palsy were randomized into two groups. One group received single dose (500 mg) of IV methylprednisolone while the other group received 10 days of oral prednisone. Outcome was assessed at 1 and 3 months with House–Brackmann scale. Results: At 3 months, 93 (79.48%) patients had completely recovered. IV methylprednisolone and oral prednisolone groups had similar recovery rates (80% vs. 78.33%, P > 0.05). Patients with Grade 2 and 3 recovered completely. In patients with Grade 6, the recovery rate was 20%. A better outcome was observed if corticosteroids were administered within 3 days of onset of palsy. Conclusion: Intravenous methylprednisolone and oral prednisolone showed equivalent benefit in patients with acute Bell's palsy. PMID:25878371

  9. Physical Conditions in Ultra-fast Outflows in AGN

    Science.gov (United States)

    Kraemer, S. B.; Tombesi, F.; Bottorff, M. C.

    2018-01-01

    XMM-Newton and Suzaku spectra of Active Galactic Nuclei (AGN) have revealed highly ionized gas, in the form of absorption lines from H-like and He-like Fe. Some of these absorbers, ultra-fast outflows (UFOs), have radial velocities of up to 0.25c. We have undertaken a detailed photoionization study of high-ionization Fe absorbers, both UFOs and non-UFOs, in a sample of AGN observed by XMM-Newton. We find that the heating and cooling processes in UFOs are Compton-dominated, unlike the non-UFOs. Both types are characterized by force multipliers on the order of unity, which suggest that they cannot be radiatively accelerated in sub-Eddington AGN, unless they were much less ionized at their point of origin. However, such highly ionized gas can be accelerated via a magneto-hydrodynamic (MHD) wind. We explore this possibility by applying a cold MHD flow model to the UFO in the well-studied Seyfert galaxy, NGC 4151. We find that the UFO can be accelerated along magnetic streamlines anchored in the accretion disk. In the process, we have been able to constrain the magnetic field strength and the magnetic pressure in the UFO and have determined that the system is not in magnetic/gravitational equipartition. Open questions include the variability of the UFOs and the apparent lack of non-UFOs in UFO sources.

  10. Single dose oral tenoxicam for acute postoperative pain in adults.

    Science.gov (United States)

    Moore, Owen A; McIntyre, Mairead; Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2009-07-08

    Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and is widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral tenoxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. To assess the efficacy of single dose oral tenoxicam in acute postoperative pain, and any associated adverse events. We searched The Cochrane Library (Issue 1, 2009), MEDLINE (March 2009); EMBASE via Ovid (March 2009); the Oxford Pain Relief Database. Randomised, double-blind, placebo-controlled clinical trials of oral tenoxicam for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with tenoxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected. Not one of sixteen studies identified by the searches and examined in detail studied oral tenoxicam in patients with established postoperative pain and therefore no results are available. In the absence of evidence of efficacy for oral tenoxicam in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be

  11. Sibutramine promotes amygdala activity under fasting conditions in obese women.

    Science.gov (United States)

    Oltmanns, Kerstin M; Heldmann, Marcus; Daul, Susanne; Klose, Silke; Rotte, Michael; Schäfer, Michael; Heinze, Hans-Jochen; Münte, Thomas F; Lehnert, Hendrik

    2012-06-01

    Sibutramine, a centrally-acting selective monoamine reuptake inhibitor, has been used as an appetite suppressant drug in obesity. To gain insight into the central nervous actions of sibutramine, brain responses to pictures of food items after sibutramine vs placebo application were assessed by functional magnetic resonance imaging (fMRI) in obese women. In a randomized double-blind crossover design, 10 healthy obese women (BMI 31.8-39.9 kg/m(2)) received 15 mg/d of sibutramine vs placebo for 14 d. Obese participants, and a group of 10 age-matched normal weight controls, viewed pictures of food items and control objects in hungry and satiated states while lying in the MR scanner. The paradigm followed a block design. In obese participants, fMRI measurements were conducted prior and after two weeks of daily sibutramine or placebo administration, whereas control participants were scanned only at one point in time. Upon food item presentation, obese participants showed increased brain activity in areas related to emotional and reward processing, perceptual processing, and cognitive control as compared to normal weight controls. Sibutramine exerted a divergent satiety-dependent effect on amygdala activity in obese participants, increasing activity in the hungry state while decreasing it under conditions of satiation. Our results demonstrate a modulatory influence of sibutramine on amygdala activity in obese women which may underlie the appetite suppressant effects of the drug.

  12. Fornix transection selectively impairs fast learning of conditional visuospatial discriminations.

    Science.gov (United States)

    Kwok, Sze Chai; Buckley, Mark J

    2010-03-01

    As the fornix has previously been implicated in the rapid learning of associations, we hypothesized that fornix transection in macaques would selectively impair the acquisition of rapidly learned conditional visuospatial discrimination problems. Macaque monkeys learned, postoperatively, three sets of concurrent problems of increasing sizes containing 8, 32, and 64 problems, respectively. Each problem consisted of four identical visual stimuli and animals had to learn which stimulus position was rewarded. The lesioned animals made significantly more errors-to-criterion on the smallest set of problems, consistent with the idea that the most rapidly acquired sets would be more vulnerable to fornical damage. Moreover, during the early stages of acquisition across all three sets, fornix transection selectively impeded monkeys' abilities to eliminate nonperseverative errors in correction trials, consistent with an inability to monitor or correct erroneous spatial responses made further back in time than the last trial. Both one-trial learning and an errorless learning (facilitation of performance) were observed in control and fornix lesioned animals but neither were fornix-dependent and overcoming the deleterious effect upon subsequent learning of having made prior errors was also unaffected by fornix transection. The data indicate that the fornix is not important for all forms of new learning; rather it is selectively concerned with the relatively rapid acquisition of spatial and temporal relationships between stimuli and responses.

  13. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies.

    Science.gov (United States)

    Vally, H; Thompson, P J

    2001-10-01

    sensitive and normal asthmatic subjects. Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required.

  14. Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction

    NARCIS (Netherlands)

    Visser, R.; Wind, M.; de Graaf, B.; de Jongh, Franciscus H.C.; van der Palen, Jacobus Adrianus Maria; Thio, B.J.

    2015-01-01

    Objective Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against

  15. Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Bonde, J; Rasmussen, S N

    1992-01-01

    Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

  16. Can Preoperative Intramuscular Single-Dose Dexamethasone Improve Patient-Centered Outcomes Following Third Molar Surgery?

    Science.gov (United States)

    Al-Dajani, Mahmoud

    2017-08-01

    Because of increased attention focused on administering dexamethasone to treat third molar surgical complications, this study investigated the efficacy of single-dose dexamethasone in managing postoperative complications after impacted third molar surgery. Pain intensity and analgesic intake, patients' discomfort, limitation of oral function, and limitation of daily activities were assessed. This triple-blinded split-mouth randomized controlled clinical trial included patients 18 to 30 years old who underwent randomized bilateral extractions of impacted mandibular third molars during 2 consecutive sessions. Each patient was given a single-dose intramuscular injection of dexamethasone (0.1 mg/kg) preoperatively in 1 session and a placebo in the other session. Data were collected daily for 7 postoperative days, and 14 patient-centered outcomes were interpreted. A 2-tailed P value less than .05 was considered significant. All 32 patients (100%) enrolled completed the study. When administered dexamethasone, patients reported less pain (P ≤ .007), took fewer analgesics (P ≤ .002), reported less swelling (P ≤ .007), had less difficulty in eating (P ≤ .024), had less difficulty in enjoying food (P ≤ .005), had less difficulty in speech (P = .043), had less trismus (P = .005), were absent less from school or work (P ≤ .016), and had less disruption of daily activity (P ≤ .042). The differences between the 2 conditions in bleeding, malaise, and sleep disturbance were not significant (P > .05). Prophylactic dexamethasone administered intramuscularly before third molar surgery should be recommended as a safe and effective strategy for decreasing pain and discomfort and enhancing oral functions and daily activities, unless contraindicated. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

    Directory of Open Access Journals (Sweden)

    Flávia de L. Osório

    2015-03-01

    Full Text Available Objectives: Ayahuasca (AYA, a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D, the Montgomery-Åsberg Depression Rating Scale (MADRS, and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS. AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  18. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

    Science.gov (United States)

    Osório, Flávia de L; Sanches, Rafael F; Macedo, Ligia R; Santos, Rafael G dos; Maia-de-Oliveira, João P; Wichert-Ana, Lauro; Araujo, Draulio B de; Riba, Jordi; Crippa, José A; Hallak, Jaime E

    2015-01-01

    Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Open-label trial conducted in an inpatient psychiatric unit. Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  19. Condition for a single bunch high frequency fast blow-up

    International Nuclear Information System (INIS)

    Wang, J.M.; Pellegrini, C.

    1980-01-01

    We study the longitudinal stability of a single particle bunch in a storage ring using Vlasov equation. We show that the Vlasov equation has solutions corresponding to a fast, microwave instability if a condition on the beam current, qualitatively similar to the stability condition for a coasting beam, is satisfied. This condition can be used to define a threshold current, and to discuss its dependence on the longitudinal coupling impedance

  20. FAST

    DEFF Research Database (Denmark)

    Zuidmeer-Jongejan, Laurian; Fernandez-Rivas, Montserrat; Poulsen, Lars K.

    2012-01-01

    ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections...... with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused...... in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold...

  1. Intracellular β2-adrenergic receptor signaling specificity in mouse skeletal muscle in response to single-dose β2-agonist clenbuterol treatment and acute exercise.

    Science.gov (United States)

    Sato, Shogo; Shirato, Ken; Mitsuhashi, Ryosuke; Inoue, Daisuke; Kizaki, Takako; Ohno, Hideki; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-05-01

    The aim of this study was to clarify the intracellular β2-adrenergic receptor signaling specificity in mouse slow-twitch soleus and fast-twitch tibialis anterior (TA) muscles, resulting from single-dose β2-agonist clenbuterol treatment and acute exercise. At 1, 4, and 24 h after single-dose treatment with clenbuterol or after acute running exercise, the soleus and TA muscles were isolated and subjected to analysis. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased after single-dose clenbuterol treatment and acute exercise in the soleus muscle but not in the TA muscle. Although there was no change in the phosphorylation of Akt after acute exercise in either muscle, phosphorylation of Akt in the soleus muscle increased after single-dose clenbuterol treatment, whereas that in the TA muscle remained unchanged. These results suggest that p38 MAPK and Akt pathways play a functional role in the adaptation to clenbuterol treatment and exercise, particularly in slow-twitch muscles.

  2. Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention.

    NARCIS (Netherlands)

    Muro, E.P.; Fillekes, Q.; Kisanga, E.R.; L'homme, R.F.A.; Aitken, S.C.; Mariki, G.; Ven, A.J.A.M. van der; Dolmans, W.M.V.; Schuurman, R.; Walker, A.S.; Gibb, D.M.; Burger, D.M.

    2012-01-01

    BACKGROUND: World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate

  3. Summer student report - Upgrade work for the Fast Beam Condition Monitor at CMS

    CERN Document Server

    Tsrunchev, Peter

    2016-01-01

    Report on summer student internship at CERN. Describes work done towards the replacement of the Fast Beam Conditions Monitor (BCM1F) - activities related to the test beam conducted by the BRIL (Background Radiation Instrumentation and Luminosity) experiment in July 2016, analog opto-hybrids testing and XDAQ development for the uTCA readout system currently under development.

  4. The Orexin Component of Fasting Triggers Memory Processes Underlying Conditioned Food Selection in the Rat

    Science.gov (United States)

    Ferry, Barbara; Duchamp-Viret, Patricia

    2014-01-01

    To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion…

  5. Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke.

    Science.gov (United States)

    Gourab, Krishnaj; Schmit, Brian D; Hornby, T George

    2015-12-01

    To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke. Double-blind, randomized, placebo-controlled crossover trial. Outpatient research setting. Individuals (N=10; 7 men; mean age ± SD, 57±10y) with poststroke hemiplegia of >1 year duration who completed all assessments. Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions. Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30°/s-120°/s) plantarflexor stretch reflexes under passive conditions, and separately during and after 3 superimposed maximal volitional drive to simulate conditions of increased serotonin release. Secondary measures included clinical measures of lower limb coordination and locomotion. SSRI administration significantly increased stretch reflex torques at higher stretch velocities (eg, 90°/s; P=.03), with reflexes at lower velocities enhanced by superimposed voluntary drive (P=.02). No significant improvements were seen in volitional peak torques or in clinical measures of lower limb function (lowest P=.10). Increases in spasticity but not strength or lower limb function were observed with single-dose SSRI administration in individuals with chronic stroke. Further studies should evaluate whether repeated dosing of SSRIs, or as combined with specific interventions, is required to elicit significant benefit of these agents on lower limb function poststroke. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  6. FAST

    Science.gov (United States)

    Nathavitharana, R R; Daru, P; Barrera, A E; Mostofa Kamal, S M; Islam, S; Ul-Alam, M; Sultana, R; Rahman, M; Hossain, Md S; Lederer, P; Hurwitz, S; Chakraborty, K; Kak, N; Tierney, D B; Nardell, E

    2017-09-01

    National Institute of Diseases of the Chest and Hospital, Dhaka; Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Dhaka; and Chittagong Chest Disease Hospital, Chittagong, Bangladesh. To present operational data and discuss the challenges of implementing FAST (Find cases Actively, Separate safely and Treat effectively) as a tuberculosis (TB) transmission control strategy. FAST was implemented sequentially at three hospitals. Using Xpert® MTB/RIF, 733/6028 (12.2%, 95%CI 11.4-13.0) patients were diagnosed with unsuspected TB. Patients with a history of TB who were admitted with other lung diseases had more than twice the odds of being diagnosed with unsuspected TB as those with no history of TB (OR 2.6, 95%CI 2.2-3.0, P stakeholder engagement and laboratory capacity are important for sustainability and scalability.

  7. The influence of food on the pharmacokinetics of amlodipine and losartan after single-dose of its compound tablets in healthy chinese subjects.

    Science.gov (United States)

    Lv, C; Wei, C; Wang, X; Yao, H; Li, R; Wang, B; Guo, R

    2014-05-01

    We aim to identify the effects of food on the pharmacokinetics (PK) of amlodipine, losartan and losartan's active metabolite (EXP3174) after oral administration of the Compound Amlodipine Tablets with single dose in healthy Chinese subjects. 12 subjects took the compounds (10 mg/100 mg, amlodipine/losartan) at the conditions of a high-fat breakfast and an overnight fast with a washout period of 14 days. Plasma samples were obtained at scheduled time, and determined by HPLC-MS/MS for the concentrations of amlodipine and HPLC-MS for the concentrations of losartan and EXP3174, respectively. PK parameters were calculated using Software Drug and Statistics (Version 2.0). When tablets were co-administered with food, there was no significant difference of AUC for amlodipine and losartan, but the AUC of EXP3174 was reduced by 19.1%. Meanwhile, the Cmax of amlodipine, losartan and EXP3174 were reduced by 11.4%, 20.0% and 41.4%, and the Tmax of losartan and EXP3174 were 1.3 and 1.8 h longer, respectively. No significant difference was found at t1/2 following food intake. In conclusion, the Compound Amlodipine Tablets, are affected by food administration by reducing the AUC of EXP3174. It is thus suggested that the Compound Amlodipine Tablets should be administered 1 h before or 2 h after meal. © Georg Thieme Verlag KG Stuttgart · New York.

  8. A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults.

    Science.gov (United States)

    Sikes, Carolyn; Stark, Jeffrey G; McMahen, Russ; Engelking, Dorothy

    2017-11-01

    The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters C max , AUC 0-5 , AUC 5-last , and AUC inf were calculated to determine bioequivalence. Safety was monitored throughout the study. The 90% confidence intervals (CIs) for the log-transformed C max , AUC 0-5 , AUC 5-last , and AUC inf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

  9. Fast Beam Conditions Monitor BCM1F for the CMS Experiment

    CERN Document Server

    Bell, Alan James; Hall-Wilton, R.; Lange, W.; Lohmann, W.; Macpherson, A.; Ohlerich, M.; Rodriguez, N.; Ryjov, V.; Schmidt, R.S.; Stone, R.L.

    2010-01-01

    The CMS Beam Conditions and Radiation Monitoring System, BRM, will support beam tuning, protect the CMS detector from adverse beam conditions, and measure the accumulated dose close to or inside all sub-detectors. It is composed of different sub-systems measuring either the particle flux near the beam pipe with time resolution between nano- and microseconds or the integrated dose over longer time intervals. This paper presents the Fast Beam Conditions Monitor, BCM1F, which is designed for fast flux monitoring measuring both beam halo and collision products. BCM1F is located inside the CMS pixel detector volume close to the beam-pipe. It uses sCVD diamond sensors and radiation hard front-end electronics, along with an analog optical readout of the signals. The commissioning of the system and its successful operation during the first be ams of the LHC are described.

  10. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

    2009-10-07

    Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

  11. The orexin component of fasting triggers memory processes underlying conditioned food selection in the rat.

    Science.gov (United States)

    Ferry, Barbara; Duchamp-Viret, Patricia

    2014-03-14

    To test the selectivity of the orexin A (OXA) system in olfactory sensitivity, the present study compared the effects of fasting and of central infusion of OXA on the memory processes underlying odor-malaise association during the conditioned odor aversion (COA) paradigm. Animals implanted with a cannula in the left ventricle received ICV infusion of OXA or artificial cerebrospinal fluid (ACSF) 1 h before COA acquisition. An additional group of intact rats were food-deprived for 24 h before acquisition. Results showed that the increased olfactory sensitivity induced by fasting and by OXA infusion was accompanied by enhanced COA performance. The present results suggest that fasting-induced central OXA release influenced COA learning by increasing not only olfactory sensitivity, but also the memory processes underlying the odor-malaise association.

  12. Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

    International Nuclear Information System (INIS)

    Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

    1993-01-01

    The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

  13. Comparison of different PADC materials and etching conditions for fast neutron dosimetry

    International Nuclear Information System (INIS)

    Assenmacher, F.; Boschung, M.; Hohmann, E.; Mayer, S.

    2016-01-01

    Etched-track polyallyl diglycol carbonate (PADC) dosemeters have been in use at the Paul Scherrer Institute since 1998 in neutron dosimetry for individual monitoring. In the last years, the availability of PADC materials from different manufacturers has grown, and different etching conditions were proposed, with the intention to improve the quality and overall performance of PADC in individual neutron monitoring. The goal of the present study was to compare the performance of different PADC materials and to investigate the influence of different etching conditions on sensitivity to fast neutrons and lower detection limit. The comparison covers six different PADC materials and eight different etching conditions. (authors)

  14. Efficacy of single dose antihistamine vs. single dose valerian-hops in subjective sleep measures among war refugees: a comparison trial

    Directory of Open Access Journals (Sweden)

    Omar Salem Gammoh

    Full Text Available Abstract Background Many sedatives and anxiolytics are used in single dose or chronically to aid sleep. Clinically important sedatives include valerian-hops and antihistamines as they are used over the counter and are highly accessible and safe agents. Objectives To evaluate and compare a single dose of chlorpheniramine versus valerian-hops combination in modulating subjective sleep measures in insomniac war refugees. Methods Insomnia among refugees was screened using the Insomnia Severity Index (ISI. Insomniac subjects were randomized to received a single dose valerian-hops (320/80 mg (n = 65, or chlorpheneramine (4 mg (n = 50 or placebo (n = 76 two hours prior sleeping. Participants were instructed to complete Leeds Sleep Evaluation Questionnaire (LSEQ, visual analogue scales of anxiety and sedation. Also sleep latency, total hours slept and self-rated improvement were obtained. Results Almost 75% of screened refugees had insomnia. Chlorpheneramine reduced sleep latency and anxiety significantly, however it resulted in poor sleep quality. Valerian-hops group showed marked anxiolysis one hour after dosing, a sleep quality similar to placebo and better than chlorpheneramine, and better alertness compared to placebo. Participants satisfaction was higher with chlorpheneramine and there was no difference in the total hours slept. Discussion Valerian-hops combination may provide better sleep quality than antihistamines.

  15. Plasma anandamide and other N-acylethanolamines are correlated with their corresponding free fatty acid levels under both fasting and non-fasting conditions in women

    Directory of Open Access Journals (Sweden)

    Verhoeckx Kitty CM

    2010-06-01

    Full Text Available Abstract N-acylethanolamines (NAEs, such as anandamide (AEA, are a group of endogenous lipids derived from a fatty acid linked to ethanolamine and have a wide range of biological activities, including regulation of metabolism and food intake. We hypothesized that i NAE plasma levels are associated with levels of total free fatty acids (FFAs and their precursor fatty acid in fasting and non-fasting conditions and ii moderate alcohol consumption alters non-fasting NAE levels. In a fasting and non-fasting study we sampled blood for measurements of specific NAEs and FFAs. In the fasting study blood was drawn after an overnight fast in 22 postmenopausal women. In the non-fasting study blood was sampled before and frequently after a standardized lunch with beer or alcohol-free beer in 19 premenopausal women. Fasting AEA levels correlated with total FFAs (r = 0.84; p N-acylethanolamines and free fatty acids in blood. The trials are registered at ClinicalTrials.gov numbers: NCT00524550 and NCT00652405.

  16. Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines.

    Science.gov (United States)

    Orr, Nadav; Klement, Eyal; Gillis, David; Sela, Tamar; Kayouf, Raid; Derazne, Estela; Grotto, Itamar; Balicer, Ran; Huerta, Michael; Aviram, Lisa; Ambar, Ruhama; Epstein, Yoram; Heled, Yuval; Cohen, Dani

    2006-05-15

    We evaluated in a prospective study the immune response of naïve subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p<0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

  17. A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin

    Directory of Open Access Journals (Sweden)

    Walter B. Junior

    Full Text Available A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002 and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

  18. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2017-05-25

    This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

  19. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

    Directory of Open Access Journals (Sweden)

    Yusuf Kale

    2015-08-01

    Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  20. Effect of Food on the Single-dose Pharmacokinetics and Tolerability of Subutinib and its Active Metabolite in Chinese Healthy Volunteers.

    Science.gov (United States)

    Ding, L-K; Jia, N; Yang, L; Li, J-K; Song, W; Wang, M-H; Wang, C; Gao, X-H; Wen, A-D

    2016-03-01

    The aim of this study is to investigate a food effect on the single-dose pharmacokinetics and tolerability of subutinib maleate capsules in healthy Chinese volunteers. The author evaluated the effect of being under a fasting or fed state at the time of drug intake on the single-dose of subutinib maleate capsules in a randomized, balanced, single-dose, 2-treatment (fasting and fed), 2-period design with a 3-week washout period. The end points were the maximum plasma drug concentration (Cmax) and areas under the plasma-concentration curve (AUC) for 336 h exposure (AUC0-336) and total exposure (AUC0-∞). All volunteers completed the whole study without side effects being observed. For subutinib, Cmax were 6.13 and 5.04 ng·mL(-1), and AUC0-336 were 278.4 and 304.5 h·ng·mL(-1) in the fasting and the fed state, respectively. For active metabolite, Cmax were 0.90 and 0.61 ng·mL(-1), and AUC0-336 were 65.5 and 56.4 h·ng·mL(-1) in the fasting and the fed state, respectively. The authors showed that food intake was associated with a slight increase in AUC values but decrease in Cmax of subutinib, and it was associated with a decrease both in AUC and Cmax of active metabolite. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Increased ophthalmic acid production is supported by amino acid catabolism under fasting conditions in mice.

    Science.gov (United States)

    Kobayashi, Sho; Lee, Jaeyong; Takao, Toshifumi; Fujii, Junichi

    2017-09-23

    Glutathione (GSH) plays pivotal roles in antioxidation and detoxification. The transsulfuration pathway, in conjunction with methionine metabolism, produces equimolar amounts of cysteine (Cys) and 2-oxobutyric acid (2OB). The resulting 2OB is then converted into 2-aminobutyric acid (2AB) by a transaminase and is utilized as a substitute for Cys by the GSH-synthesizing machinery to produce ophthalmic acid (OPT). By establishing a method for simultaneously measuring Cys, GSH, and OPT by liquid chromatography-mass spectrometry, we found that fasting causes an elevation in OPT levels in the liver and blood plasma, even though the levels of Cys and GSH are decreased. Autophagy was activated, but the levels of GSH/OPT-synthesizing enzymes remained unchanged. After 6 h of fasting, the mice were given 1% 2AB and/or 5% glucose in the drinking water for an additional 24 h and the above metabolites analyzed. 2AB administration caused an increase in OPT levels, and, when glucose was co-administered with 2AB, the levels of OPT were elevated further but GSH levels were decreased somewhat. These results suggest that, while Cys is utilized for glyconeogenesis under fasting conditions, reaching levels that were insufficient for the synthesis of GSH, 2OB was preferentially converted to 2AB via amino acid catabolism and was utilized as a building block for OPT. Thus the consumption of Cys and the parallel elevation of 2AB under fasting conditions appeared to force γ-glutamylcysteine synthetase to form γ-glutamyl-2AB, despite the fact that the enzyme has a higher Km value for 2AB than Cys. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

    Science.gov (United States)

    Yamada, Takako; Iida, Tetsuo; Takamine, Satoshi; Hayashi, Noriko; Okuma, Kazuhiro

    2015-01-01

    The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.

  3. Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2003-09-01

    Full Text Available Abstract Background Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. Methods The Cochrane Library (issue 4 2002, EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. Results Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients with placebo (248 patients; the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2. There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients and 2.6 hours for placebo (205 patients. Four other trials used lower doses. Conclusion A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.

  4. Effects of Single Dose Energy Drink on QT and P-Wave Dispersion

    Directory of Open Access Journals (Sweden)

    Huseyin Arinc

    2013-12-01

    Full Text Available INTRODUCTION: Aim of this study is to evaluate the cardiac electrophysiological effects of energy drink (Red Bull on QT and P duration and dispersion on surface electrocardiogram. METHODS: Twenty healthy volunteers older than 17 years of age were included the study. Subjects with a cardiac rhythm except sinus rhythm, history of atrial or ventricular arrhythmia, family history of premature sudden cardiac death, palpitations, T-wave abnormalities, QTc interval greater than 440 milliseconds, or those P-waves and QT intervals unavailable in at least eight ECG leads were excluded. Subjects having insomnia, lactose intolerance, caffeine allergy, recurrent headaches, depression, any psychiatric condition, and history of alcohol or drug abuse, pregnant or lactating women were also excluded from participation. 12 lead ECG was obtained before and after consumption of 250 cc enegry drink. QT and P-wave dispersion was calculated. RESULTS: No significant difference have occurred in heart rate (79 ± 14 vs.81 ±13, p=0.68, systolic pressure (114 ± 14 vs.118 ± 16,p=0.38, diastolic blood pressure (74 ± 12 vs.76 ± 14, p=0.64, QT dispersion (58 ± 12 vs. 57 ± 22, p= 0.785 and P-wave dispersion (37 ± 7 vs. 36 ± 13, p= 0.755 between before and 2 hours after consumption of energy drink. DISCUSSION AND CONCLUSION: Consumption of single dose energy drink doesn't affect QT dispersion and P-wave dispersion, heart rate and blood pressure in healthy adults.

  5. Single Dose Methotrexate in Treatment of Ectopic Pregnancy: Review of 32 Case

    Directory of Open Access Journals (Sweden)

    Aysun Aybatlı

    2011-03-01

    Full Text Available Objective: To evaluate the efficacy of single dose intramuscular methotrexate in the treatment of ectopic pregnancy.Material and Methods: 32 patients who matched the inclusion criteria were enrolled. Success of treatment was defined as a resolution of ectopic pregnancy without performing surgical intervention. The cases in whom the treatment was successful and those that were not were compared for β-hCG values and clinical features.Results: β-hCG at diagnosis averaged 1293.9 mIU/ml. Of the 32 patients who received methotrexate, 26 were successfully treated. 23 patients (71.8% received a single dose of methotrexate, 3 patients (9.3% received an additional dose of methotrexate, 6 patients (18.7% who had failed methotrexate required surgery for cure. The success rate of single-dose methotrexate was 79.3%. Conclusion: Our study shows that single dose systemic methotrexate treatment can be used as an option in unruptured pregnancies.

  6. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... Original Research: Efficacy of single dose of transdermal diclofenac patch. 194. 2012;18(4). South Afr J Anaesth Analg. Introduction. Peripheral tissue injury, as seen in postoperative patients, provokes two kinds of modification in the responsiveness of the nervous system. In peripheral sensitisation, there is ...

  7. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    International Nuclear Information System (INIS)

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A.

    1990-01-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy

  8. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    Energy Technology Data Exchange (ETDEWEB)

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A. (Lahey Clinic Medical Center, Burlington, MA (USA))

    1990-12-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.

  9. The feasibility of repeated left ventricular ejection fraction analysis with sequential single-dose radionuclide ventriculography

    NARCIS (Netherlands)

    van der Vleuten, PA; Slart, RHJA; Tio, RA; van der Horst, ICC; van Veldhuisen, DJ; Dierckx, RA; Zijlstra, F

    Objective Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement

  10. Oral microflora and selection of resistance after a single dose of amoxicillin.

    Science.gov (United States)

    Khalil, D; Hultin, M; Rashid, M U; Lund, B

    2016-11-01

    The study aimed to determine the effects of a single-dose antibiotic prophylaxis on normal oral microflora. A single dose of 2 g amoxicillin was given to 29 healthy volunteers. Saliva was collected before antibiotic administration (day 1), and again on days 2, 5, 10, 17 and 24 and subjected to culturing and antibiotic sensitivity analysis. Twenty-one per cent (6/29) of the individuals carried penicillin-V- and amoxicillin-resistant viridans streptococci before antibiotic administration. After a single dose of amoxicillin there was a significant reduction in Streptococcus salivarius on days 2 and 5, a significant reduction in other viridans streptococci on day 2 and the proportion of viridans streptococci with reduced susceptibility to amoxicillin was significantly increased on days 2 and 5. A single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Single dose of fluoxetine increases muscle activation in chronic stroke patients.

    NARCIS (Netherlands)

    van Genderen, Hanneke Irene; Nijlant, Juliette M.M.; van Putten, Michel Johannes Antonius Maria; Movig, Kris L.L.; IJzerman, Maarten Joost

    2009-01-01

    Objectives: This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. Methods: A crossover, placebo-controlled clinical trial was conducted in 10

  12. Vaginal bleeding following the use of a single dose of 1.5mg ...

    African Journals Online (AJOL)

    Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

  13. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

    NARCIS (Netherlands)

    Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ

    2003-01-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition,

  14. The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

    Science.gov (United States)

    Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

    2017-12-01

    Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

  15. ENDURANCE TRAINING IN FASTING CONDITIONS: BIOLOGICAL ADAPTATIONS AND BODY WEIGHT MANAGEMENT.

    Science.gov (United States)

    Vicente-Salar, Néstor; Urdampilleta Otegui, Aritz; Roche Collado, Enrique

    2015-12-01

    in the majority of sports the athlete is required to achieve optimal conditions both at a muscular and metabolic level as well as in body composition, increasing the lean body mass and maintaining a low body fat mass. In this context, different training protocols have been proposed in order to reduce body fat content, by maximizing fat use instead of glycogen. to verify if the training while fasting favours the use of fatty acids due to the low glycogen levels, allowing an improvement in the performance ant the control of body weight. protocols have been published, differing in time periods and exercise intensity. In addition, several markers ranging from gene expression analysis to determination of circulating parameters have been assessed in order to interpret the results. Discusion: at low intensities of endurance-based exercises, adipose tissue lipolysis and muscle fat oxidation rate seem to be higher in fasting than in fed state. On the other hand, glucose metabolism is adapted in order to save glycogen stores, possibly through gluconeogenesis activation. Finally, it has been observed that protein degradation is mainly downregulated. Only one study analyses changes in body composition after fasting during long periods, thus further work is necessary to demonstrate that this is the best method to control body fat. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  16. 3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

    Science.gov (United States)

    Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

    2014-03-01

    The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo . Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD + couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH ( p = 0.038). No significant change in Fp was found ( p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D

  17. 3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

    Directory of Open Access Journals (Sweden)

    He N. Xu

    2014-03-01

    Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

  18. Fracture of metals samples under conditions of fast heating by intensive X-ray radiation

    Directory of Open Access Journals (Sweden)

    Golubev V.K.

    2012-08-01

    Full Text Available Results on studying the fracture of metals samples in the form of thin disks under fast heating by the X-ray pulse with the complete spectrum are presented in the paper. The samples of such metals as iron, copper, AMg6 aluminum, VT14 titanium, molybdenum, tungsten, cadmium, lead and zinc were tested. The samples were fixed in the special cartridges equipped with the gauges of a mechanical recoil momentum. The cartridges with samples were placed at such distances from the X-ray irradiator where the energy fluxes were 1.38, 0.90 and 0.29kJ/cm2. The irradiating X-ray pulse was about 2 ns in duration. After testing, the depth of material ablation from a sample front surface and the degree and character of its spall damage were determined. The method of metallographic analysis was used for these purposes. Numerical calculations of loading conditions were made with the use of an equation of state taking into account the process of evaporation. The calculated value of maximum negative pressure in the sample at the coordinate corresponding to the formation of spallation zones or spall cracks was conventionally accepted as the material resistance to spall fracture. The comparison of obtained results with the data on the fracture of examined materials in the conditions of fast heating by the X-ray pulse with the hard spectrum and a high-current electron beam was conducted.

  19. Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

    Directory of Open Access Journals (Sweden)

    Mohammad K Moslemi

    2010-11-01

    site infection rates of categories A and B in Group 1 were 0 and two (0.86%, respectively, while those in Group 2 were 0 and five (0.92%, respectively. There was no significant difference in infection rates in terms of remote infection and surgical site infection between Group 1 and Group 2 (P = 0.670. The amounts, as well as the prices, for intravenously administered antibiotics decreased to approximately one quarter.Conclusion: Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy can be recommended as an appropriate method for preventing perioperative infection in urologic surgery. Keywords: surgical site infection, antibiotic prophylaxis, single dose, urologic surgery

  20. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

    OpenAIRE

    Pejčić Zorica; Pokrajac Milena; Jezdimirović Milanka

    2006-01-01

    The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac seru...

  1. Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

    Science.gov (United States)

    Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

    2017-11-01

    Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

  2. Routine β-Human Chorionic Gonadotropin Monitoring for Single-Dose Methotrexate Treatment in Ectopic Pregnancy.

    Science.gov (United States)

    Dai, Yuxin; Zhang, Guorui; Zhu, Lan; Lang, Jinghe; Liu, Zhufeng

    To evaluate an alternative monitoring protocol without day 4 β-human chorionic gonadotropin (β-hCG) measurement for predicting the need for a repeated methotrexate (MTX) dose in patients undergoing single-dose MTX therapy for ectopic pregnancy (EP). Single-center retrospective study (Canadian Task Force classification II-3). University-affiliated hospital. Included in the study were 184 EP patients treated with MTX between January 2009 and December 2016. Single-dose MTX treatment (50 mg/m 2 ). The patients were treated with repeated doses of MTX every 7 days, if necessary, according to Stovall's protocol, or with laparoscopic surgery in cases of tubal rupture. The success of a single-dose of MTX according to the alternative measure was defined as a >50% decrease in the β-hCG level between days 1 and 7 in clinically stable patients. The sensitivity, specificity, false-negative rate, false-positive rate, and attributable risk of this new monitoring measure were calculated and compared with the traditional regimen. The new protocol had a sensitivity and specificity of 100% and 88.7%, respectively, for predicting a required second dose in patients whose day 1 β-hCG levels were <2000 mIU/mL. For patients with day 1 β-hCG level ≥2000 mIU/mL, both monitoring regimens had the same efficiency. The new monitoring model without the day 4 β-hCG measurement may offer both patients and clinicians multiple options to monitor single-dose MTX therapy for selected EP patients, with a comparable clinical efficiency to Stovall's protocol and less expense and follow-up burden to patients. Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

  3. Comparison of post cesarean infection after single dose versus three doses of prophylactic antibiotic regimen

    Directory of Open Access Journals (Sweden)

    Farnaz Mohammadian

    2013-04-01

    Full Text Available Background: Cesarean delivery is a surgical operation which is applied to prevent maternal and fetal complications. Cesarean delivery isn’t without complication and has some complications such as infection. Postoperative infection includes endometritis, wound infection and septic pelvic thrombophlebitis that depend to prophylactic antibiotics and surgical technique. The aim of this study was comparison of post operative infection after single dose and three doses of prophylactic antibiotic regimens. . Material and Methods: This double blind randomized clinical trial was performed on all pregnant women referd to the Vali-Asr Hospital of Zanjan University of Medical Sciences and underwent cesarean delivery during one year from starting study. Participants subsequently were randomized into two groups: A (recieved single dose of prophylactic antibiotic and B (recieved three doses of prophylactic antibiotic. Subjects were checked up for the clinical signs of infection during hospitalization and 10 days after discharge. The results were analyzed by SPSS Software Ver16 and Chi-Square Test. Results: During one year, 146 pregnant women with cesarean delivery entered 2 equal groups (A and B which each group had 73 subjects. During hospitalization after cesarean delivery, 5(6.8% patients of group A and 2(2.7% patients of group B had fever. There was no significant correlation between the two groups. Conclusion: There was no significant correlation between single dose and three doses of prophylactic antibiotic regimens in groups A and B. Therefore, it seems thatthere is no need to use three doses of prophylactic antibiotic for cesarean delivery.Therfore, because of drug resistance and economic loss, single dose of prophylactic antibiotic is recommended for prevention of post cesarean infection

  4. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

    OpenAIRE

    Vally, H; Thompson, P

    2001-01-01

    BACKGROUND—Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose su...

  5. The CMS Fast Beams Condition Monitor Backend Electronics based on MicroTCA technology

    CERN Document Server

    Zagozdzinska, Agnieszka Anna

    2016-01-01

    The Fast Beams Condition Monitor (BCM1F), upgraded for LHC Run II, is one sub-system of the Beam Radiation Instrumentation and Luminosity Project of the CMS experiment. It is based on 24 single crystal CVD diamond sensors. Each sensor is metallised with two pads, being read out by a dedicated fast frontend chip produced in 130 nm CMOS technology. Signals for real time monitoring are processed by custom-made back-end electronics to measure separately rates corresponding to LHC collision products, machine induced background and residual activation exploiting different arrival times. The system is built in MicroTCA technology and uses high speed analog-to-digital converters. The data processing module designed for the FPGA allows a distinguishing of collision and machine induced background, both synchronous to the LHC clock, from the residual activation products. In operational modes of high rates, consecutive events, spaced in time by less than 12.5 ns, may partially overlap. Hence, novel signal processing tec...

  6. Acceleration of Solar Energetic Particles at a Fast Traveling Shock in Non-uniform Coronal Conditions

    Science.gov (United States)

    Le Roux, J. A.; Arthur, A. D.

    2017-09-01

    Time-dependent solar energetic particle (SEP) acceleration is investigated at a fast, nearly parallel spherical traveling shock in the strongly non-uniform corona by solving the standard focused transport equation for SEPs and transport equations for parallel propagating Alfvén waves that form a set of coupled equations. This enables the modeling of self-excitation of Alfvén waves in the inertial range by SEPs ahead of the shock and its role in enhancing the efficiency of the diffusive shock acceleration (DSA) of SEPs in a self-regulatory fashion. Preliminary results suggest that, because of the highly non-uniform coronal conditions that the shock encounters, both DSA and wave excitation are highly time-dependent processes. Thus, DSA spectra of SEPs strongly deviate from the simple power-law prediction of standard steady-state DSA theory and initially strong wave excitation weakens rapidly. Consequently, the ability of DSA to produce high energy SEPs in the corona of ∼1 GeV, as observed in the strongest gradual SEP events, appears to be strongly curtailed at a fast nearly parallel shock, but further research is needed before final conclusions can be drawn.

  7. Frequency of wound infection in non-perforated appendicitis with use of single dose perforative antibiotics

    International Nuclear Information System (INIS)

    Ali, K.; Latif, H.; Ahmad, S.

    2015-01-01

    Antibiotics are used both pre and post-operatively in acute appendicitis for preventing wound infection. It has been observed that the routine use of post-operative antibiotics is not necessary in cases of non-perforated appendicitis as only prophylactic antibiotics are sufficient to prevent wound infection. The aim of this study was to see the frequency of wound infection in non-perforated appendicitis with single dose preoperative antibiotics only. Method: This observational study was conducted at the Department of Surgery, Ayub Medical College, Abbottabad from May to November 2014. A total of 121 patients with non-perforated appendicitis were included in the study. Only single dose preoperative antibiotics were used. The patients were followed for wound infection till 8th post-operative day. Results: 121 patients, 56(46.28%) male and 65(53.72%) female were included in the study. The mean age of patients was 27.41 ± 7.12 years with an age range of 18 to 45 years. In the entire series, 7(5.78%) patients developed wound infection. The infection was minor which settled with conservative therapy. Prophylactic antibiotics were found efficacious in 114(94.21%) patients. There was no significant association between wound infection and age and gender. Conclusion: Single dose preoperative antibiotics were found effective in controlling post-operative wound infection without the need of extending the antibiotics to post-operative period in cases of non-perforated appendicitis. (author)

  8. Persistence of Immunity Acquired after a Single Dose of Rubella Vaccine in Japan.

    Science.gov (United States)

    Okafuji, Takao; Okafuji, Teruo; Nakayama, Tetsuo

    2016-05-20

    To date, Takahashi, Matsuura, and TO-336 strains of live-attenuated rubella vaccine have been used in Japan. Japan implemented a single-dose rubella vaccination program until 2006. However, few reports are available on the persistence of immunity after this vaccination program. We collected 276 serum samples from January 2009 to December 2011 at Okafuji Pediatric Clinic and assessed the immune status of these samples against rubella virus during 1-10 years after vaccination with a single dose of Takahashi rubella vaccine. Regional outbreak of rubella did not occur during 1999-2011. The collected serum samples were tested for antibodies against the rubella virus by performing a standard hemagglutination inhibition (HAI) test. Our results showed that all the tested serum samples contained antibodies against the rubella virus 10 years after the vaccination. Geometric mean titer of HAI antibodies was 1:180 and decreased to 1:68 at 10 years after the vaccination. The levels of HAI antibodies decreased logarithmically with time after the vaccination. In conclusion, vaccine-acquired immunity after vaccination with a single dose of live-attenuated Takahashi rubella vaccine was retained for at least 10 years when rubella was under regional control.

  9. Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

    Science.gov (United States)

    Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

    2014-01-01

    The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

  10. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Feras Sendy

    2015-01-01

    Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  11. A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects

    Directory of Open Access Journals (Sweden)

    Ana Amélia Machado DUARTE

    Full Text Available ABSTRACT Objective: The aim of this study was to investigate the acute effect of a single dose of dark chocolate (70% cocoa on blood pressure and heart rate variability. Methods: Thirty-one healthy subjects (aged 18-25 years; both sexes were divided into two groups: 10 subjects in the white chocolate (7.4 g group and 21 in the dark chocolate (10 g group; measurements were performed at the university's physiology lab. An electrocardiogram measured the sympathovagal balance by spectral and symbolic analysis. Results: A single dose of dark chocolate significantly reduced systolic blood pressure and heart rate. After consuming 10 g of dark chocolate, significant increases were observed for heart rate variability, standard deviation of RR intervals standard deviation of all NN intervals, square root of the mean squared differences between adjacent normal RR intervals root mean square of successive differences, and an increase in the high frequency component in absolute values, representing the parasympathetic modulation. Conclusion: In conclusion the importance of our results lies in the magnitude of the response provoked by a single dose of cocoa. Just 10 g of cocoa triggered a significant increase in parasympathetic modulation and heart rate variability. These combined effects can potentially increase life expectancy because a reduction in heart rate variability is associated with several cardiovascular diseases and higher mortality.

  12. Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

    Science.gov (United States)

    Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

    2015-01-01

    The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  13. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

    Science.gov (United States)

    Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

    2017-04-01

    Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

  14. Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

    2016-01-01

    Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

  15. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  16. A Fast Poisson Solver with Periodic Boundary Conditions for GPU Clusters in Various Configurations

    Science.gov (United States)

    Rattermann, Dale Nicholas

    Fast Poisson solvers using the Fast Fourier Transform on uniform grids are especially suited for parallel implementation, making them appropriate for portability on graphical processing unit (GPU) devices. The goal of the following work was to implement, test, and evaluate a fast Poisson solver for periodic boundary conditions for use on a variety of GPU configurations. The solver used in this research was FLASH, an immersed-boundary-based method, which is well suited for complex, time-dependent geometries, has robust adaptive mesh refinement/de-refinement capabilities to capture evolving flow structures, and has been successfully implemented on conventional, parallel supercomputers. However, these solvers are still computationally costly to employ, and the total solver time is dominated by the solution of the pressure Poisson equation using state-of-the-art multigrid methods. FLASH improves the performance of its multigrid solvers by integrating a parallel FFT solver on a uniform grid during a coarse level. This hybrid solver could then be theoretically improved by replacing the highly-parallelizable FFT solver with one that utilizes GPUs, and, thus, was the motivation for my research. In the present work, the CPU-utilizing parallel FFT solver (PFFT) used in the base version of FLASH for solving the Poisson equation on uniform grids has been modified to enable parallel execution on CUDA-enabled GPU devices. New algorithms have been implemented to replace the Poisson solver that decompose the computational domain and send each new block to a GPU for parallel computation. One-dimensional (1-D) decomposition of the computational domain minimizes the amount of network traffic involved in this bandwidth-intensive computation by limiting the amount of all-to-all communication required between processes. Advanced techniques have been incorporated and implemented in a GPU-centric code design, while allowing end users the flexibility of parameter control at runtime in

  17. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

    Directory of Open Access Journals (Sweden)

    Jaydip Ramani

    Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  18. Efficacy of single-dose 500 mg mebendazole in soil-transmitted helminth infections: a review.

    Science.gov (United States)

    Mrus, J; Baeten, B; Engelen, M; Silber, S A

    2018-05-01

    Soil-transmitted helminthiasis (STH) is caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Mebendazole is one of the recommended preventive chemotherapy agents for STH. This review summarizes the efficacy data from 29 studies with single-dose 500 mg mebendazole in STH treatment and compares the results with those of a recently conducted phase 3 study of a 500 mg mebendazole chewable tablet against A. lumbricoides and T. trichiura infections. Studies that reported efficacy results against at least one STH infection were selected from the literature and efficacy data by each STH type were abstracted and pooled. Single-dose 500 mg mebendazole treatment resulted in a cure rate of 92.6% (range: 72.5-100%) for A. lumbricoides, 27.6% (range: 8.4-100%) for T. trichiura and 25.5% (range: 2.9-91.1%) for hookworms. Egg reduction rate for A. lumbricoides was 97.9% (range: 89.8-100%), for T. trichiura it was 72.9% (range: 31.6-93.0%) and for hookworms it was 72.0% (range: -6.5% (denoting an increase in egg count) to 98.3%). Similar results were observed in the studies that were placebo-controlled. In the phase 3 study, the cure rate and egg reduction rate reported was 83.7% and 97.9%, respectively, for A. lumbricoides and 33.9% and 59.7%, respectively, for T. trichiura. In conclusion, single-dose 500 mg mebendazole showed a high cure rate against A. lumbricoides and a substantial reduction in faecal egg count for all STH types. These results are consistent with the recently conducted phase 3 study of a new 500 mg chewable mebendazole tablet.

  19. Treatment of chronic spontaneous urticaria with a single dose of omalizumab: A study of four cases

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Subramaniyan

    2016-01-01

    Full Text Available Background: Chronic spontaneous urticaria (CSU has a detrimental effect on patients′ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7 and Dermatology Life Quality Index (DLQI. Results: A sharp decline in UAS7 and DLQI was documented in 7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

  20. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

    Science.gov (United States)

    Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-02-01

    To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

  1. Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission.

    Science.gov (United States)

    Chi, Benjamin H; Chintu, Namwinga; Cantrell, Ronald A; Kankasa, Chipepo; Kruse, Gina; Mbewe, Felistas; Sinkala, Moses; Smith, Peter J; Stringer, Elizabeth M; Stringer, Jeffrey S A

    2008-06-01

    To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.

  2. Interstitial pregnancy treated with a single-dose of systemic methotrexate: A successful management

    Directory of Open Access Journals (Sweden)

    Serena Corioni

    2015-01-01

    Full Text Available Interstitial pregnancy is an ectopic pregnancy at high hemorrhagic risk. It often poses a diagnostic and therapeutic challenge to the clinician, with a significant risk of morbidity and mortality. It presents a difficult management problem with no absolute standard of care; the most appropriate treatment technique for these pregnancies remains controversial. We describe a case of unruptured interstitial pregnancy successfully treated with a single-dose of systemic methotrexate with subsequent ultrasound and serum beta human chorionic gonadotropin monitoring. Medical management can be a safe and successful option in selected cases that satisfy specific criteria and in women who are able to be monitored after treatment.

  3. Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

    DEFF Research Database (Denmark)

    Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

    2017-01-01

    vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

  4. Application of three-signal regulator for stabilizing fast reactor coolant temperature under emergency conditions

    International Nuclear Information System (INIS)

    Afanas'ev, V.A.; Gryazev, V.M.; Efimov, V.N.; Plyutinskij, V.I.; Tyufyagin, A.N.

    1979-01-01

    A possibility is analyzed for regulating coolant temperature under cram conditions of fart reactors by using signals of inertial thermocouples installed at the reactor outlet to control the coolant flow rate. To improve the regulation quality additional signals on the coolant flow rate and neutron flux are used altogether. The study has been conducted for the BOR-60 reactor. A technique is described for optimization of adjustment parameters of the regulator. Results of transient calculations for power levels of 20 and 60 MW are presented. The control system was tested on the BOR-60 reactor. As the temperature regulator a device was used manufactured on the basis of the RPIB type regulator. The experiments have demonstrated quite satisfactory performance of the control system: temperature deviations at the core outlet did not exceed 17K, and at the reactor outlet - 5K, whereas without the control system - 115 and 25K respectively. High efficiency of the temperature control system enables one to introduce it in fast power reactors

  5. In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions.

    Science.gov (United States)

    Koenigsknecht, Mark J; Baker, Jason R; Wen, Bo; Frances, Ann; Zhang, Huixia; Yu, Alex; Zhao, Ting; Tsume, Yasuhiro; Pai, Manjunath P; Bleske, Barry E; Zhang, Xinyuan; Lionberger, Robert; Lee, Allen; Amidon, Gordon L; Hasler, William L; Sun, Duxin

    2017-12-04

    In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m 2 . Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC 0-24 and C max were lower in fed subjects vs fasted subjects, and T max was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic

  6. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

    NARCIS (Netherlands)

    D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

    2017-01-01

    markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

  7. Single Dose IV Peramivir is Safe and Effective in the Treatment of Pediatric Influenza

    Science.gov (United States)

    Vanchiere, John; Plunkett, Stephanie; Annamalai, Rajasekaran; Julien, Katie; Peterson, James; Goisse, Marcy; Christensen, Shane; Mehta, Priyesh; Coleman, Stephen; Munoz, Flor; Flynt, Amy; Dobo, Sylvia; Nagy, Eniko; Kargl, Deborah; Mathis, Amanda; Collis, Phil; Sheridan, William

    2017-01-01

    Abstract Background Peramivir (PVR) is a potent neuraminidase inhibitor with in vitro activity against all influenza virus subtypes. Previous studies demonstrated the efficacy and safety of PVR as a single dose intravenous (IV) treatment for acute uncomplicated influenza in adults. Methods A phase 3 study compared age-appropriate doses of single dose IV PVR to 5 days of oral oseltamivir (OSE) (4:1 randomization, stratified by age) in pediatric subjects age 0 -17 years within 48 hours of onset of acute uncomplicated influenza. Plasma concentrations of PVR were measured up to 6 hours post dose. Serial viral titers were measured from nasopharyngeal swabs. Severity of influenza signs and symptoms were recorded in a diary. Results 122 subjects were enrolled up to a data cutoff of March 31, 2017 (Coleman, BioCryst Pharmaceuticals: Investigator, Research support; F. Munoz, BioCryst Pharmaceuticals: Investigator, Research support; A. Flynt, BioCryst Pharmaceuticals: Consultant, Consulting fee; S. Dobo, BioCryst Pharmaceuticals: Employee, Salary; E. Nagy, BioCryst Pharmaceuticals: Employee, Salary; D. Kargl, BioCryst Pharmaceuticals: Consultant, Consulting fee; A. Mathis, BioCryst Pharmaceuticals: Employee, Salary; P. Collis, BioCryst Pharmaceuticals: Employee, Salary; W. Sheridan, BioCryst Pharmaceuticals: Employee, Salary

  8. Blood pressure and heart rate effects following a single dose of bitter orange.

    Science.gov (United States)

    Bui, Linda T; Nguyen, DiemThuy T; Ambrose, Peter J

    2006-01-01

    The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p bitter orange versus placebo for hours 2-5 (p bitter orange versus placebo in young, healthy adults.

  9. The effect of a single dose of morphine on muscle fatigue indices in male rats

    Directory of Open Access Journals (Sweden)

    Sedigheh Amiresmaili

    2016-09-01

    Full Text Available Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the  effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water, morphine receiving group, fatigue group (the mice in this group were kept running on  a treadmill . for120 minutes at a rate of 20 meters per minute, and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH and creatine phosphokinase (CPK. Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009. Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009 and CPK (P=0.008. Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK.

  10. Pharmacokinetics of single-dose ceftaroline fosamil in children with cystic fibrosis.

    Science.gov (United States)

    Le, Jennifer; Bradley, John S; Hingtgen, Sara; Skochko, Shannon; Black, Nanette; Jones, Ronald N; Lim, Meerana; Capparelli, Edmund V

    2017-11-01

    Single-dose pharmacokinetics (PK) and safety of ceftaroline fosamil with population pharmacokinetic/pharmacodynamic (PK/PD) modeling for staphylococcal pneumonia was performed in children with CF. Subjects between 6 and 18 years old were evaluated in this phase 1, open-label, single-dose, prospective study using 10 mg/kg (up to 600 mg). Non-compartmental analysis and population-based PK analyses with Monte Carlo simulation (for doses 8-20 mg/kg every 8 h, infused over 1-4 h) were conducted. A total of 20 subjects were enrolled. The median age and weight were 12 yr (range 6.3-17.4) and 38.7 kg (range 17.8-94.3), respectively. A 3-compartment linear model incorporating age and weight provided the best fit for the data. Comparing children 6 to ceftaroline CL compared with published data from non-CF children; greater dosages may be required in children with CF to achieve adequate exposure in the treatment of MRSA pneumonia. Pharmacodynamic-based dosing predicts that dosing should also be based on the patient's MRSA MIC. © 2017 Wiley Periodicals, Inc.

  11. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  12. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    Science.gov (United States)

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Adverse effects of a single dose of gentamicin in adults: a systematic review.

    Science.gov (United States)

    Hayward, Rachel S; Harding, Jan; Molloy, Rob; Land, Lucy; Longcroft-Neal, Kate; Moore, David; Ross, Jonathan D C

    2018-02-01

    To systematically review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, in studies where a comparator was available. A review protocol was developed and registered (PROSPERO: CRD42013003229). Studies were eligible for review if they: recruited participants aged ≥16 years; used gentamicin intramuscularly or intravenously as a single one-off dose; compared gentamicin to another medication or placebo; and monitored adverse events. MEDLINE, EMBASE, Cochrane Library, trial registries, conference proceedings and other relevant databases were searched up to November 2016. Risk of bias was assessed on all included studies. In total, 15 522 records were identified. After removal of duplicates, screening of title/abstracts for relevance and independent selection of full texts by two reviewers, 36 studies were included. Across all the included studies, 24 107 participants received a single one-off dose of gentamicin (doses ranged from 1 mg kg -1 to 480 mg per dose). Acute kidney injury was described in 2520 participants receiving gentamicin. The large majority of cases were reversible. There were no cases of ototoxicity reported in patients receiving gentamicin. A meta-analysis was not performed due to study heterogeneity. A significant number of patients saw a transient rise in creatinine after a single dose of gentamicin at doses up to 480 mg. Persistent renal impairment and other adverse events were relatively rare. © 2017 The British Pharmacological Society.

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

    Science.gov (United States)

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

    2013-06-01

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

  15. Single dose of secnidazole treatment against naturally occuring Giardia duodenalis infection in Sakiz lambs

    Directory of Open Access Journals (Sweden)

    Kerem Ural

    2014-03-01

    Full Text Available Objective. The purposes of this study were to determine whether secnidazole administered at a single dose of 10 mg/kg, orally, lessens or eliminates Giardia cyst shedding, and to validate the benefit of secnidazole treatment on clinical signs and faecal consistency in lambs naturally infected with Giardia duodenalis. Materials and methods. To this extent weaned 12 weeks of age lambs were selected and randomly assigned into two groups based on placebo (group C, n=7 untreated control group or treatment (group S, n=10 lambs treated with a single dose of secnidazole at 10 mg/kg. Results. On days 0 and 10, before and after treatment, respectively, reduction in cyst excretion was determined. The faecal consistency and general health were recorded at each sampling day. Conclusions. During the study there was a high (99.98% reduction in cyst excretion in the secnidazol treatment group compared to the positive control group on day 10, resulting in a significant (p<0.001 reduction, making secnidazole highly effective treatment option.

  16. Effects of single dose intranasal oxytocin on social cognition in schizophrenia.

    Science.gov (United States)

    Davis, Michael C; Lee, Junghee; Horan, William P; Clarke, Angelika D; McGee, Mark R; Green, Michael F; Marder, Stephen R

    2013-07-01

    Deficits in social cognition are common in schizophrenia and predict poor community functioning. Given the current limitations of psychosocial treatments and the lack of pharmacological treatments for social cognitive deficits, the development of novel therapeutic agents could greatly enhance functional recovery in schizophrenia. This study evaluated whether a single dose of intranasal oxytocin acutely improves social cognitive functioning in schizophrenia. Twenty-three male veterans with schizophrenia completed baseline assessments of social cognition that were divided into lower-level (facial affect perception, social perception, detection of lies) and higher-level (detection of sarcasm and deception, empathy) processes. One week later, patients received the same battery after being randomized to a single dose of 40 IU intranasal oxytocin or placebo. Though the groups did not differ significantly on the social cognition composite score, oxytocin improved performance for the higher-level social cognitive tasks (Cohen's d=1.0, p=0.045). Subjects were unable to accurately guess which treatment they had received. The improvements found in higher-level social cognition encourage further studies into the therapeutic potential of oxytocin in schizophrenia. Published by Elsevier B.V.

  17. The Success of the Single-Dose Methotrexate Treatment in an Atypical Heterotopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Serdar Başaranoğlu

    2016-06-01

    Full Text Available Heterotopic pregnancy refers to simultaneous presence of intrauterine and ectopic gestational sacs. Its incidence ex­hibits a rising trend due to the increased use of assisted reproductive technology (ART. This paper aims to present a rare case of tubal and cesarean scar heterotopic pregnancy that occurred following a spontaneous pregnancy. The pa­tient presenting with delayed menstruation and abdominal-inguinal pain was evaluated. Transvaginal ultrasonography revealed a gestational sac located in the scar of a previous cesarean section and in the left tubal region corresponding to a gestational age of 4 weeks and 5 days. The patient was hospitalized and informed about conservative and surgi­cal methods. Then, she was administered a single dose of methotrexate 75 mg intramuscularly. Post-operative period included ultrasonographic and laboratory follow-up. In conclusion, it should be remembered that single-dose systemic methotrexate therapy might constitute an alternative to surgery in unruptured hemodynamically stable cases. J Clin Exp Invest 2016; 7 (2: 200-202

  18. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Effect of Fast Pyrolysis Conditions on the Biomass Solid Residues at High Temperatures (1000-1400°C)

    DEFF Research Database (Denmark)

    Trubetskaya, Anna; Jensen, Anker D.; Jensen, Peter Arendt

    and morphology. Scanning electron microscopy (SEM/EDS), elementary analysis, CAMSIZER XT, ash compositional analysis were applied to characterize the effect of operational conditions on the solid and gas products. Char yield from fast pyrolysis in the DFT setup was 2 to 6 % (daf) lower than in the WMR apparatus...

  20. Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

    Science.gov (United States)

    Vizzotti, C; Pippo, T; Urueña, A; Altuna, J; Palópoli, G; Hernández, M L; Artola, M F; Fernández, H; Orellano, P; Cañero-Velasco, M C; Ciocca, M; Ramonet, M; Diosque, M

    2015-05-07

    Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the

  1. Single Dose Trivalent Vesiculovax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.

    Science.gov (United States)

    Matassov, Demetrius; Mire, Chad E; Latham, Theresa; Geisbert, Joan B; Xu, Rong; Ota-Setlik, Ayuko; Agans, Krystle N; Kobs, Dean J; Wendling, Morgan Q S; Burnaugh, Amanda; Rudge, Thomas L; Sabourin, Carol L; Egan, Michael A; Clarke, David K; Geisbert, Thomas W; Eldridge, John H

    2017-11-15

    Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV , Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were then vaccinated with a single dose of the tri-valent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 post vaccination, a serum IgG response specific for all three GPs was detected in all vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP protein was also detected in a majority of vaccinated macaques. No matter the level of total GP-specific immune response detected post vaccination, all vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against those filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa. IMPORTANCE The West African Ebola Zaire outbreak in 2013 showed that this disease was not only a regional concern, but a worldwide problem and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens like Ebola Sudan and Marburg also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak

  2. Single-dose electron beam irradiation in treatment and prevention of keloids and hypertrophic scars

    International Nuclear Information System (INIS)

    Lo, T.C.M.; Salzman, F.A.; Seckel, B.R.; Wright, K.A.

    1990-01-01

    Low megavolt electron beam irradiation was used on 354 sites in 199 patients at Lahey Clinic either for palliation of symptomatic hypertrophic scars or as post operative irradiation in an attempt to prevent formation or recurrence of hypertrophic scars. Electron energies used ranged from 1.5 to 3.5 MeV. The median age of the 59 male patients was 22 years and of the 140 female patients 35 years. All patients had at least one follow-up visit, and the median follow-up was 35 months. Of the 294 sites treated for the first time, 272 (93 per cent) were irradiated with a single fraction with a skin dose ranging from 2 to 20 Gy. Of the 85 sites in 63 patients without excision of symptomatic hypertrophic scars, single-dose electron beam irradiation was of clinically significant value in only 41 sites (48 per cent). No patients have been treated without surgical excision since 1973. Because of a history of formation of hypertrophic scars elsewhere in the body, 13 patients with 19 incisions were treated prophylactically after operation for other diseases. All sites were irradiated with single doses ranging from 8 to 20 Gy, and hypertrophic scars did not subsequently develop in any patient. Altogether, 119 patients with 174 sites were irradiated after surgical excision of hypertrophic scars to prevent recurrence; 168 sites (97 per cent) received singe-fraction irradiation, and 161 received a dose of 8 Gy greater, up to 15 Gy. No statistically significant differences were observed in complete success rates, ranging from 82 to 90 per cent with doses of 9 Gy or greater. An interval of up to 72h between excision and single-fraction irradiation satisfactorily prevented recurrence, and clinically significant chronic telangiectasia was recorded in only one patient. Postoperative low megavolt electron beam irradiation with a single dose of 9 Gy or greater is highly effective in the prevention of formation recurrence of hypertrophic scars or keloids. (author). 31 refs.; 2 figs.; 4 tabs

  3. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  4. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance.

    Science.gov (United States)

    Lamers, C T J; Ramaekers, J G; Muntjewerff, N D; Sikkema, K L; Samyn, N; Read, N L; Brookhuis, K A; Riedel, W J

    2003-12-01

    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

  5. Deposition of diazepam and its metabolites in hair following a single dose of diazepam

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong

    2017-01-01

    not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam......Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy...... volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide...

  6. Prolonged efficacy of a single dose of the bisphosphonate zoledronic acid.

    Science.gov (United States)

    Brown, Janet E; Ellis, Susan P; Lester, James E; Gutcher, Sandra; Khanna, Tina; Purohit, Om-Prakesh; McCloskey, Eugene; Coleman, Robert E

    2007-09-15

    Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment-induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration. Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was approximately 58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P < 0.001). A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.

  7. Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India

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    Mini S Jacob

    2011-01-01

    Full Text Available Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP provided to delivering HIV seropositive (HIV+ve women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

  8. Study of single dose toxic test of Sweet Bee Venom in Beagle Dogs

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    Hye-Chul, Yoon

    2010-12-01

    Full Text Available Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 ㎎/㎏ body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 ㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 ㎎/㎏ in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

  9. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    Science.gov (United States)

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

    International Nuclear Information System (INIS)

    Brodin, O.; Lennartsson, L.; Nilsson, S.

    1991-01-01

    Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

  11. Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

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    Kaaijk Patricia

    2012-02-01

    Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.

  12. CD36 is indispensable for thermogenesis under conditions of fasting and cold stress

    Energy Technology Data Exchange (ETDEWEB)

    Putri, Mirasari [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Syamsunarno, Mas Rizky A.A. [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Biochemistry, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Jatinangor, West Java 45363 (Indonesia); Iso, Tatsuya, E-mail: isot@gunma-u.ac.jp [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamaguchi, Aiko; Hanaoka, Hirofumi [Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Sunaga, Hiroaki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Koitabashi, Norimichi [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Matsui, Hiroki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamazaki, Chiho; Kameo, Satomi [Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Tsushima, Yoshito [Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); and others

    2015-02-20

    Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36{sup −/−} mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36{sup −/−} mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue {sup 125}I-BMIPP and the glucose analogue {sup 18}F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36{sup −/−} mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36{sup −/−} mice after cold exposure. These findings strongly suggest that CD36{sup −/−} mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation. - Highlights: • We examined the role of CD36 in thermogenesis during cold exposure. • CD36{sup −/−} mice exhibit rapid hypothermia after cold exposure during fasting. • Uptake of fatty acid and glucose is impaired in thermogenic tissues during fasting. • Storage of energy substrates is

  13. Early fasting is long lasting: differences in early nutritional conditions reappear under stressful conditions in adult female zebra finches.

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    E Tobias Krause

    Full Text Available Conditions experienced during early life can have profound effects on individual development and condition in adulthood. Differences in nutritional provisioning in birds during the first month of life can lead to differences in growth, reproductive success and survival. Yet, under natural conditions shorter periods of nutritional stress will be more prevalent. Individuals may respond differently, depending on the period of development during which nutritional stress was experienced. Such differences may surface specifically when poor environmental conditions challenge individuals again as adults. Here, we investigated long term consequences of differences in nutritional conditions experienced during different periods of early development by female zebra finches (Taeniopygia guttata on measures of management and acquisition of body reserves. As nestlings or fledglings, subjects were raised under different nutritional conditions, a low or high quality diet. After subjects reached sexual maturity, we measured their sensitivity to periods of food restriction, their exploration and foraging behaviour as well as adult resting metabolic rate (RMR. During a short period of food restriction, subjects from the poor nutritional conditions had a higher body mass loss than those raised under qualitatively superior nutritional conditions. Moreover, subjects that were raised under poor nutritional conditions were faster to engage in exploratory and foraging behaviour. But RMR did not differ among treatments. These results reveal that early nutritional conditions affect adult exploratory behaviour, a representative personality trait, foraging and adult's physiological condition. As early nutritional conditions are reflected in adult phenotypic plasticity specifically when stressful situations reappear, the results suggest that costs for poor developmental conditions are paid when environmental conditions deteriorate.

  14. Duodenal Sodium/Glucose Cotransporter 1 Expression Under Fasting Conditions Is Associated With Postload Hyperglycemia.

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Suraci, Evelina; Arcidiacono, Gaetano Paride; Cimellaro, Antonio; Mignogna, Chiara; Presta, Ivan; Andreozzi, Francesco; Hribal, Marta Letizia; Perticone, Francesco; Donato, Giuseppe; Luzza, Francesco; Sesti, Giorgio

    2017-11-01

    Type 2 diabetes (T2DM) is associated with a higher intestinal expression of the glucose transporters sodium/glucose cotransporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2). It is currently unsettled whether prediabetes conditions characterized by postprandial hyperglycemia, such as impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) with 1-hour postload glucose ≥155 mg/dL (8.6 mmol/L) (NGT-1h-high) are associated with increased expression of these glucose carriers in the intestine. We evaluated whether duodenal abundance of SGLT-1 and GLUT-2 is augmented in subjects with IGT and NGT-1h-high, in comparison with subjects with NGT and 1-hour postload glucose ˂155 mg/dL (NGT-1h-low). Cross-sectional. A total of 54 individuals underwent an upper gastrointestinal endoscopy. Duodenal SGLT-1 and GLUT-2 protein and messenger RNA levels were assessed by Western blot and reverse transcription polymerase chain reaction, respectively. Of the 54 subjects examined, 18 had NGT-1h-low, 12 had NGT-1h-high, 12 had IGT, and 12 had T2DM. Duodenal SGLT-1 protein and messenger RNA levels were significantly higher in individuals with NGT-1h-high, IGT, or T2DM in comparison with NGT-1h-low subjects. GLUT-2 abundance was higher in individuals with T2DM in comparison with NGT-1h-low subjects; no substantial increase in GLUT-2 expression was observed in NGT-1h-high or IGT individuals. Univariate correlations showed that duodenal SGLT-1 abundance was positively correlated with 1-hour postload plasma glucose levels (r = 0.44; P = 0.003) but not with fasting or 2-hour postload glucose levels. Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion. Copyright © 2017 Endocrine Society

  15. Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

    Science.gov (United States)

    Huang, J; Chen, R; Li, R; Wei, C-M; Yuan, G-Y; Liu, X-Y; Wang, B-J; Guo, R-C

    2012-01-01

    To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent. © Georg Thieme Verlag KG Stuttgart · New York.

  16. The Impact of Oxytocin on Food Intake and Emotion Recognition in Patients with Eating Disorders: A Double Blind Single Dose Within-Subject Cross-Over Design.

    Science.gov (United States)

    Kim, Youl-Ri; Eom, Jin-Sup; Yang, Jae-Won; Kang, Jiwon; Treasure, Janet

    2015-01-01

    Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa (AN) and bulimia nervosa (BN). The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls. A total of 102 women, including 35 patients with anorexia nervosa (AN), 34 patients with bulimia nervosa (BN), and 33 healthy university students of comparable age and intelligence, participated in a double-blind, single dose placebo-controlled cross-over study. A single dose of intranasal administration of oxytocin (40 IU) (or a placebo) was followed by an emotional recognition task and an apple juice drink. Food intake was then recorded for 24 hours post-test. Oxytocin produced no significant change in appetite in the acute or 24 hours free living settings in healthy controls, whereas there was a decrease in calorie consumption over 24 hours in patients with BN. Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN, In patients with AN, oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour. The impact of oxytocin on appetite and social cognition varied between people with AN and BN. A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN. People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls. Those effects of oxytocin were not found in patients with AN. ClinicalTrials.gov KCT00000716.

  17. The Impact of Oxytocin on Food Intake and Emotion Recognition in Patients with Eating Disorders: A Double Blind Single Dose Within-Subject Cross-Over Design

    Science.gov (United States)

    Kim, Youl-Ri; Eom, Jin-Sup; Yang, Jae-Won; Kang, Jiwon; Treasure, Janet

    2015-01-01

    Background and Aim Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa (AN) and bulimia nervosa (BN). The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls. Materials A total of 102 women, including 35 patients with anorexia nervosa (AN), 34 patients with bulimia nervosa (BN), and 33 healthy university students of comparable age and intelligence, participated in a double-blind, single dose placebo-controlled cross-over study. A single dose of intranasal administration of oxytocin (40 IU) (or a placebo) was followed by an emotional recognition task and an apple juice drink. Food intake was then recorded for 24 hours post-test. Results Oxytocin produced no significant change in appetite in the acute or 24 hours free living settings in healthy controls, whereas there was a decrease in calorie consumption over 24 hours in patients with BN. Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN, In patients with AN, oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour. Conclusions The impact of oxytocin on appetite and social cognition varied between people with AN and BN. A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN. People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls. Those effects of oxytocin were not found in patients with AN. Trial Registration ClinicalTrials.gov KCT0000716 PMID:26402337

  18. The Impact of Oxytocin on Food Intake and Emotion Recognition in Patients with Eating Disorders: A Double Blind Single Dose Within-Subject Cross-Over Design.

    Directory of Open Access Journals (Sweden)

    Youl-Ri Kim

    Full Text Available Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa (AN and bulimia nervosa (BN. The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls.A total of 102 women, including 35 patients with anorexia nervosa (AN, 34 patients with bulimia nervosa (BN, and 33 healthy university students of comparable age and intelligence, participated in a double-blind, single dose placebo-controlled cross-over study. A single dose of intranasal administration of oxytocin (40 IU (or a placebo was followed by an emotional recognition task and an apple juice drink. Food intake was then recorded for 24 hours post-test.Oxytocin produced no significant change in appetite in the acute or 24 hours free living settings in healthy controls, whereas there was a decrease in calorie consumption over 24 hours in patients with BN. Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN, In patients with AN, oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour.The impact of oxytocin on appetite and social cognition varied between people with AN and BN. A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN. People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls. Those effects of oxytocin were not found in patients with AN.ClinicalTrials.gov KCT00000716.

  19. Effect of fast pyrolysis conditions on biomass solid residues at high temperatures

    DEFF Research Database (Denmark)

    Trubetskaya, Anna; Jensen, Peter Arendt; Jensen, Anker Degn

    2016-01-01

    % (daf) points lower than in the WMR. During fast pyrolysis pinewood underwent drastic morphological transformations, whereas beechwood and straw samples retained the original porous structure of the parental fuel with slight melting on the surface. The particle size of Danish wheat straw char decreased...

  20. Effect of Fast Pyrolysis Conditions on Structural Transformation and Reactivity of Herbaceous Biomasses at High Temperatures

    DEFF Research Database (Denmark)

    Trubetskaya, Anna; Jensen, Anker D.; Jensen, Peter Arendt

    of organic and inorganic matter on the char structural transformations. The results indicate no influence of the free radicals on char reactivity and burnout. The formation of free radicals in fast pyrolysis is related to the differences in the ash composition, namely presence of K+ ions in the wheat straw...

  1. Effects of food intake on the pharmacokinetic properties of dalcetrapib: findings from three phase I, single-dose crossover studies in healthy volunteers.

    Science.gov (United States)

    Derks, Michael; Kawamura, Hitoshi; Abt, Markus; Meneses-Lorente, Georgina; Phelan, Mary; Ishikawa, Tomohiro

    2011-06-01

    Preclinical studies have reported that the relative bioavailability of dalcetrapib, a modulator of cholesteryl ester transfer protein (CETP) inhibitor activity, was ∼60% higher when administered in the fed state compared with the fasting state. This article reports on 3 studies conducted to assess the effects of food intake, timing of administration with respect to meals, and meal size and content on the relative bioavailability of dalcetrapib in healthy male subjects. Three Phase I studies were performed in healthy subjects: (1) a 2-period crossover study of a single dose of dalcetrapib 900 mg administered in the fed and fasting states (fed versus fasting study [1999]); (2) a 3-period crossover study of a single dose of dalcetrapib 600 mg administered after a light morning meal, a standard evening meal, and a light evening meal (meal timing/size study [2005]); and (3) a 4-period crossover study of a single dose of dalcetrapib 600 mg administered 30 minutes after a high-fat meal or a standard evening meal, and 30 minutes before or 3 hours after the latter (high-fat meal study [2007]). Blood samples for pharmacokinetic analyses (AUC(0-36) or AUC(0-∞), C(max)) were collected up to 36, 144, and 96 hours after study drug administration in the fed versus fasting, meal timing/size, and high-fat meal studies, respectively. CETP activity was measured using a radioisotopic method in the fed versus fasting study and a fluorometric method in the meal timing/size and high-fat meal studies. Tolerability was assessed using monitoring of adverse events, laboratory parameters, vital signs, and ECG. Six men were enrolled in the fed versus fasting study (mean age, 37 years; mean body mass index [BMI], 23.6 kg/m(2)). Dalcetrapib exposure was increased by 64% (AUC(0-36)) and 126% (C(max)) after administration in the fed state. Eighteen men were enrolled in the analysis of the effects of meal timing and size on the properties of dalcetrapib (mean age, 30.5 years; mean BMI, 25.1 kg

  2. Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children.

    Science.gov (United States)

    Madrigal, G; Odio, C M; Mohs, E; Guevara, J; McCracken, G H

    1988-05-01

    One hundred thirty-two children with acute urinary tract infection were randomly assigned to receive trimethoprim-sulfamethoxazole in one dose, two doses daily for 3 days or two doses daily for 7 days. The patient characteristics, etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups. There was no significant difference in bacteriologic cure rates for the single dose regimen (93%) and multidose regimens (96%). The difference in rates of recurrent urinary tract infection between the single dose (20.5%) and 3-day (5.6%) and 7-day (8%) regimens was statistically significant (P = 0.033). A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection.

  3. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765.

  4. Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in Papua New Guinea.

    Science.gov (United States)

    González-Beiras, Camila; Kapa, August; Vall-Mayans, Marti; Paru, Raymond; Gavilán, Sergi; Houinei, Wendy; Bieb, Sibauk; Sanz, Sergi; Martins, Rosario; Mitjà, Oriol

    2017-11-29

    Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU. We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment. We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group, and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR. Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  5. Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

    Science.gov (United States)

    Ehrenpreis, Eli D

    2017-12-01

    Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

  6. Periodic boundary conditions and the error-controlled fast multipole method

    Energy Technology Data Exchange (ETDEWEB)

    Kabadshow, Ivo

    2012-08-22

    The simulation of pairwise interactions in huge particle ensembles is a vital issue in scientific research. Especially the calculation of long-range interactions poses limitations to the system size, since these interactions scale quadratically with the number of particles. Fast summation techniques like the Fast Multipole Method (FMM) can help to reduce the complexity to O(N). This work extends the possible range of applications of the FMM to periodic systems in one, two and three dimensions with one unique approach. Together with a tight error control, this contribution enables the simulation of periodic particle systems for different applications without the need to know and tune the FMM specific parameters. The implemented error control scheme automatically optimizes the parameters to obtain an approximation for the minimal runtime for a given energy error bound.

  7. Influence of fast pyrolysis conditions on yield and structural transformation of biomass chars

    DEFF Research Database (Denmark)

    Trubetskaya, Anna; Jensen, Peter Arendt; Jensen, Anker Degn

    2015-01-01

    Fast pyrolysis of biomass (wood, straw, rice husk) and its major components (cellulose, hemicellulose, lignin) was conducted in a wire mesh reactor. The aim of this study was to understand the influence of temperature (350-1400 ° C), heating rate (10-3000 ° C/s), particle size (0.05-2 mm) and hol......Fast pyrolysis of biomass (wood, straw, rice husk) and its major components (cellulose, hemicellulose, lignin) was conducted in a wire mesh reactor. The aim of this study was to understand the influence of temperature (350-1400 ° C), heating rate (10-3000 ° C/s), particle size (0.05-2 mm...... that the heat treatment temperature had a larger influence on the char yield than the heating rate. Scanning electron microscopy indicated different types of biomass char plasticization influenced by the applied temperatures, heating rates, particle sizes and holding times, except for the rice husk char...

  8. Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

    Directory of Open Access Journals (Sweden)

    Erika Cortez

    2012-01-01

    Full Text Available Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

  9. Fuel pin behavior under slow ramp-type transient-overpower conditions in the CABRI-FAST experiments

    International Nuclear Information System (INIS)

    Fukano, Yoshitaka; Onoda, Yuichi; Sato, Ikken; Charpenel, Jean

    2009-01-01

    In the CABRI-FAST experimental program, four in-pile tests were performed with slow power-ramp-type transient-overpower conditions (called hereafter as 'slow TOP') to study transient fuel pin behavior under inadvertent control rod withdrawal events in liquid metal cooled fast breeder reactors. Annular-pellet fuel pins were used in three tests, while a solid-pellet fuel pin was used in the other test. All of these pins were pre-irradiated in Phenix. The slow TOP test with a solid-pellet fuel pin was realized as a comparatory test against an existing test (E12) in the CABRI-2 program. In the CABRI-FAST test (BCF1), a power ramp rate of 3% Po/s was applied, while in the CABRI-2 test, 1% Po/s was adopted. Moreover, overpower condition was maintained for a few seconds beyond the observed pin failure in the BCF1 test. In spite of the different power ramp rates, evaluated fuel thermal conditions at the observed failure time are quite similar. The continued overpower condition in the BCF1 test resulted in gradual degradation of the pin structure providing information effective for evaluation of various accident scenarios. Three slow TOP tests with the annular fuel in the CABRI-FAST program resulted in no pin failure showing high failure threshold. Based on post-test examination data and a theoretical evaluation, it was concluded that intra-pin free spaces, such as central hole, macroscopic cracks and fuel-cladding gap effectively mitigated fuel cladding mechanical interaction. It was also clarified that cavity pressurization became effective only in case of very large amount of fuel melting. Furthermore, such cavity pressurization was effectively mitigated by a molten-fuel squirting into the upper blanket region pushing the blanket pellets upward. These CABRI FAST slow TOP tests, in combination with the existing CABRI and TREAT tests, provided an extended slow TOP test database with various fuel and transient conditions. (author)

  10. A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

    Science.gov (United States)

    An, Li-Jun; Zhang, Yang; Su, Zheng; Zhang, Xian-Long; Liu, Hai-Lin; Zhang, Zhi-Jie; Hu, Jian-Lin; Li, Shi-Tong

    2017-11-22

    Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

  11. Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

    International Nuclear Information System (INIS)

    Doerr, W.; Kummermehr, J.

    1990-01-01

    Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

  12. Dynamics of the general factor of personality in response to a single dose of caffeine.

    Science.gov (United States)

    Caselles, Antonio; Micó, Joan C; Amigó, Salvador

    2011-11-01

    General Factor of Personality (GFP) research is an emergent field in personality research. This paper uses a theoretical mathematical model to predict the short-term effects of a dose of a stimulant drug on GFP and reports the results of an experiment showing how caffeine achieves this. This study considers the General Factor of Personality Questionnaire (GFPQ) a good psychometric approach to assess GFP. The GFP dynamic mechanism of change is based on the Unique Trait Personality Theory (UTPT). This theory proposes the existence of GFP which occupies the apex of the hierarchy of personality, and extends from an impulsiveness-and-aggressiveness pole (approach tendency) to an anxiety-and-introversion pole (avoidance tendency). An experiment with 25 volunteers was performed. All the participants completed the GFPQ and the Sensation-Seeking Scale list of adjectives from the trait version of MAACL-R (Multiple Affect Adjective Checklist Revised) on an empty stomach. The participants in the experimental group (20) received 330 mg of caffeine. All the participants filled in a state version form with the sensation-seeking adjectives every 4.5 minutes. This study considers that the Sensation-Seeking Scale list of adjectives from the MAACL-R, available in both trait and state versions, is a good psychometric approach to assess GFP. The results show that GFP is modified by a single dose of caffeine in the direction predicted by the UTPT.

  13. Morbid obesity and outcome of ectopic pregnancy following capped single-dose regimen methotrexate.

    Science.gov (United States)

    Hoyos, Luis R; Malik, Mokerrum; Najjar, Marvin; Rodriguez-Kovacs, Javier; Abdallah, Mazen; Vilchez, Gustavo; Awonuga, Awoniyi O

    2017-02-01

    Evaluate whether morbid obesity influenced resolution, number of doses or ultimately surgical management of tubal ectopic pregnancy (TEP) when treated with single-dose regimen methotrexate (SDR-MTX) capped at 100 mg. Retrospective cohort study of patients with a diagnosis of TEP who underwent MTX treatment from 2000 to 2013. Patients were excluded if initial β-hCG ectopic size, embryonic heart tones, decrease of β-hCG, need for additional MTX doses and surgery despite treatment were recorded and compared among the groups. 151 women were included in the study, 89.4% (135/151) non-morbidly obese and 10.6% (16/151) morbidly obese. No differences in age distribution, ethnicity, pre-treatment presence of embryonic heart tones, maximum diameter of ectopic size ≥35 mm and β-hCG ≥5000 mIU/ml were found. Following treatment, the proportion of patients with at least an 80% decrease in their β-hCG levels or need for surgery were similar, however, morbidly obese patients were significantly more likely [11/134 vs. 5/16, OR 5.1 (1.5-17.3, p = 0.015)] to require an additional MTX dose. Among patients with TEP, morbidly obese patients were five times more likely to require an additional dose compared to non-morbidly obese when SDR-MTX capped at 100 mg was used for medical management.

  14. Acute and persistent iatrogenic Cushing's syndrome after a single dose of triamcinolone acetonide.

    Science.gov (United States)

    Iglesias, P; González, J; Díez, J J

    2005-12-01

    Iatrogenic Cushing's syndrome is a well-known adverse effect of glucocorticoids. It usually develops after prolonged exposure to excessive amounts of synthetic glucocorticolds. The development of iatrogenic Cushing's syndrome (ICS) after a single and low dose of synthetic glucocorticoid is an exceptional event. Up to now, only a few number of cases have been associated with triamcinolone acetonide and they have always been related to local administration. We report, for the first time, a patient who developed ICS after a single low dose of parenterally (im) administered triamcinolone acetonide. She was a 45-yr-old woman who referred to us because of cushingoid appearance, whose hormonal determinations were suggestive of secondary adrenal insufficiency. Clinical features were developed one month after the administration of a 40 mg single-dose of im triamcinolone acetonide because of acute laryngitis. Endocrinological evaluation confirmed the hypothalamic-pituitary-adrenal (HPA) axis suppression. Eight months later, cushingoid phenotype had completely disappeared and HPA function had spontaneously recovered. We review clinical features and comment on the possible pathogenic mechanisms of this particular and new form of ICS.

  15. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration.

    Science.gov (United States)

    Hebestreit, Julia M; May, Arne

    2017-01-01

    Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

  16. Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.

    Science.gov (United States)

    Shang, De-Wei; Wang, Zhan-Zhang; Hu, Hai-Tang; Zhang, Yue-Feng; Ni, Xiao-Jia; Lu, Hao-Yang; Zhang, Ming; Hu, Jin-Qing; Qiu, Chang; Peng, Huan; Shen, Ling-Fang; Wen, Yu-Guan

    2018-01-01

    The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUC t ) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about

  17. Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects.

    Science.gov (United States)

    Salem, Isam I; Najib, Naji M

    2012-01-01

    Betamethasone is used for its antiinflammatory and immunosuppressive effects in disorders of many organ systems. However, the pharmacokinetic properties of betamethasone in plasma after intramuscular injection of betamethasone sodium phosphate and betamethasone acetate dual-acting suspension need further investigation. The main aim of this study was to determine the pharmacokinetic parameters of betamethasone, betamethasone acetate, and betamethasone phosphate after the administration of a single intramuscular dose of the dual-acting suspension to healthy human volunteers. Two different studies were conducted in healthy males. Volunteers were judged healthy based on their medical history, physical examination, and laboratory test results. Before confinement, all volunteers were tested for freedom from alcohol and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg of betamethasone acetate was administered by intramuscular injection. Blood sampling covered 48 hours. The plasma samples obtained in the second study were stabilized to enable pharmacokinetic profiling of betamethasone esters. Twenty-four healthy males with mean (SD) age of 27 (6.62) years participated in each study. No incidences of serious adverse events were recorded during the studies. Six mild adverse events were reported in 2 subjects in the second study. One subject suffered from pain at the injection site and insomnia, and another subject complained of heartburn and drowsiness. Betamethasone phosphate appeared to be readily absorbed with a mean AUC(0-t) of 96.01 ng/h/mL and an AUC(0-∞) of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration reached a mean t(½) of 12.92 hours. Betamethasone acetate was not detected in the volunteers' plasma in either study (total of 2208 plasma samples). The observed pharmacokinetic parameters suggested that the acetate ester, and not the

  18. The biological effect of large single doses: a possible role for non-targeted effects in cell inactivation.

    Directory of Open Access Journals (Sweden)

    Marlon R Veldwijk

    Full Text Available BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM. Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4-16.3; P<0.0001 when the density of irradiated cells was increased from 10 to 50×10(3 cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5-15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1-12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5-15 Gy. The dependence of SF on cell numbers at high doses would represent a "cohort effect" in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy.

  19. Quality of life after palliative treatment for oesophageal carcinoma -- a prospective comparison between stent placement and single dose brachytherapy

    NARCIS (Netherlands)

    Homs, Marjolein Y. V.; Essink-Bot, Marie-Louise; Borsboom, Gerard J. J. M.; Steyerberg, Ewout W.; Siersema, Peter D.

    2004-01-01

    Metal stent placement and single dose brachytherapy are commonly used treatment modalities for the palliation of inoperable oesophageal carcinoma. We investigated generic and disease-specific health-related quality of life (HRQoL) after these palliative treatments. Patients with dysphagia from

  20. Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women.

    NARCIS (Netherlands)

    L'homme, R.F.A.; Dijkema, T.; Ven, A.J.A.M. van der; Burger, D.M.

    2006-01-01

    OBJECTIVE: Single-dose nevirapine (SD-NVP) to prevent mother-to-child transmission (MTCT) of HIV is associated with development of NVP resistance, probably because of its long half-life in combination with a low genetic barrier to resistance. The objective of this study was to find enzyme inducers

  1. Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

    NARCIS (Netherlands)

    Mieras, L. (Liesbeth); R. Anthony (Richard); W.H. van Brakel (Wim); Bratschi, M.W. (Martin W.); van den Broek, J. (Jacques); Cambau, E. (Emmanuelle); Cavaliero, A. (Arielle); Kasang, C. (Christa); Perera, G. (Geethal); Reichman, L. (Lee); J.H. Richardus (Jan Hendrik); P. Saunderson (Paul); Steinmann, P. (Peter); Yew, W.W. (Wing Wai)

    2016-01-01

    textabstractPost-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where

  2. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial

    NARCIS (Netherlands)

    Homs, Marjolein Y. V.; Steyerberg, Ewout W.; Eijkenboom, Wilhelmina M. H.; Tilanus, Hugo W.; Stalpers, Lukas J. A.; Bartelsman, Joep F. W. M.; van Lanschot, Jan J. B.; Wijrdeman, Harm K.; Mulder, Chris J. J.; Reinders, Janny G.; Boot, Henk; Aleman, Berthe M. P.; Kuipers, Ernst J.; Siersema, Peter D.

    2004-01-01

    Background Both single-dose brachytherapy and self-expanding metal stent placement are commonly used for palliation of oesophageal obstruction due to inoperable cancer, but their relative merits are unknown. We under-took a randomised trial to compare the outcomes of brachytherapy and stent

  3. Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats

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    Mariana Takaku

    2018-01-01

    Full Text Available Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1α, IL-1β, IL-6, IL-10, and TNF-α. Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH; parecoxib/no hemorrhage (Pcx/NH; placebo/hemorrhage (Plc/H; and parecoxib/hemorrhage (Pcx/H. Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline. Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

  4. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial.

    Science.gov (United States)

    Song, Taejong; Kim, Mi Kyoung; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju

    2016-02-01

    Can a two-dose methotrexate treatment protocol improve the treatment success rate compared with a single-dose protocol in women with an ectopic pregnancy? The two-dose protocol was not superior to the single-dose protocol for the treatment of ectopic pregnancy. Although the two-dose methotrexate protocol for ectopic pregnancy was recently introduced to combine the efficacy and convenience of the fixed multi-dose and single-dose protocols, studies comparing the success rates, treatment satisfaction and acceptability of the single-dose and two-dose treatment protocols for ectopic pregnancy are currently lacking. A randomized trial was conducted on 92 participants with tubal ectopic pregnancy, between May 2013 and April 2015. Patients who were diagnosed with tubal ectopic pregnancy and who elected to undergo systemic methotrexate treatment were randomly assigned to follow either the single-dose (n = 46) or two-dose protocol (n = 46). The primary outcome measure was treatment success without surgical intervention. The secondary outcome measures were the incidence of methotrexate-associated side effects, β-human chorionic gonadotrophin (β-hCG) resolution time, cost of care received and treatment satisfaction. There were no differences in baseline characteristics between the groups. The success rates between the single-dose and two-dose groups did not show a significant difference [82.6 versus 87.0%; relative risk (RR) 0.95; 95% confidence interval (CI) 0.80-1.13]. However, the success rate in a subgroup of participants with a pretreatment β-hCG level of >5000 mIU/ml appeared to be higher in the two-dose group than in the single-dose group (80.0 versus 58.8%), although the difference was not statistically significant. No significant differences in methotrexate-associated side effects, cost or treatment satisfaction were observed between the groups. The two-dose group required a lower number of days for the β-hCG level to decrease to ectopic pregnancy. None. www

  5. Pharmacokinetics and bioequivalence study of aniracetam after single-dose administration in healthy Chinese male volunteers.

    Science.gov (United States)

    Tian, Yuan; Zhang, Jing-Jing; Feng, Shu-Dan; Zhang, Zun-Jian; Chen, Yun

    2008-01-01

    The pharmacokinetics of aniracetam (CAS 72432-10-1) in Chinese healthy male volunteers was investigated for the first time. Twenty male volunteers were enrolled into this open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg (2 x 200 mg/capsule) aniracetam as a test or reference formulation with a 3-day washout period between the two preparations. The plasma concentrations of aniracetam were analyzed by a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters of the test and reference formulations were estimated as follows: The maximum plasma concentrations (Cmax) were 8.75 +/- 7.82 and 8.65 +/- 8.70 ng/mL, Tmax were 0.4 +/- 0.1 and 0.4 +/- 0.1 h, and plasma elimination half-lives (t(1/2)) were 0.47 +/- 0.16 and 0.49 +/- 0.24 h, respectively. The AUC(0-t) values demonstrated nearly identical bioavailability of aniracetam from the examined formulations. AUC(0-2.5) values were 4.53 +/- 6.62 and 4.76 +/- 6.65 ng h/mL, the areas under the plasma concentration-time curve (AUC(0-infinity) were 4.62 +/- 6.66 and 4.85 +/- 6.71 ng h/mL for the test and reference formulation, respectively. No statistical differences were observed for Cmax, and AUC(0-infinity) for aniracetam. The 90% confidence limits calculated for AUC and Cmax of aniracetam were within the standard bioequivalence range (80%-125% for AUC and Cmax). Therefore, the aniracetam test formulation can be regarded as bioequivalent to the aniracetam reference formulation.

  6. Response of CEDIA amphetamines assay after a single dose of bitter orange.

    Science.gov (United States)

    Nguyen, DiemThuy T; Bui, Linda T; Ambrose, Peter J

    2006-04-01

    Bitter orange has recently been substituted as an ingredient in many "ephedra-free" dietary supplements used for weight loss. The primary active ingredient in bitter orange is synephrine. Previous reports have documented false-positive results from ephedrine with urine amphetamine assays. Because of the similarity in chemical structure of ephedrine and synephrine, it is hypothesized that ingestion of a bitter orange supplement may have the potential to cause false-positive results with urine amphetamine assays. The purpose of this study was to determine the response of the CEDIA Amphetamines Assay after ingestion of bitter orange. Six healthy adult male volunteers were administered a single oral dose of Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to 6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post-administration. Additional urine specimens were collected from 1 subject at 9, 12, and 15 hours after administration. All specimens were analyzed by the CEDIA Amphetamines Assay. Urine specific gravity and pH also were measured. All urine specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus, reducing the possibility that the negative results were caused by diluted specimens or reduced excretion of synephrine into alkaline urine. This information will be of value when health care providers or those who interpret drug screens are asked to provide consultation regarding the interference of bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of Nature's Way Bitter Orange was not found to cause a false-positive response to the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

  7. Deposition of diazepam and its metabolites in hair following a single dose of diazepam.

    Science.gov (United States)

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong; Jia, Jingying; Rao, Yulan; Jiang, Fengli; Linnet, Kristian

    2017-01-01

    Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.

  8. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    Science.gov (United States)

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  9. Comparative biodisponibility of a single dose captopril Formulations - doi:10.5020/18061230.2006.p5

    Directory of Open Access Journals (Sweden)

    Aline Kércia Alves Soares

    2012-01-01

    Full Text Available The aim of this study was to evaluate, on human volunteers, the performance of one captopril tablet formulation (Neo-Química Comércio Indústria Ltda against one standard tablet formulation (Capoten® 50mg Bristol-Myers Squibb Brasil S.A.Twenty-four healthy volunteers, as assessed by clinical and laboratory test evaluations, were enrolled in the study. The study was of a two way randomised crossover design comparing both captopril formulations. Plasma samples for determination of captopril were obtained by pre-dose and at frequent intervals for up to 24h post to one of the single dose formulations and were quantified by a validated method employing high-pressure liquid chromatography coupled to mass spectrometry (LCMSMS. The subjects were monitored through-out the study and the formulations were considered to be well tolerated. The maximum reached concentration (Cmax and areas under the curve (AUC0-24h were compared. Captopril Cmax geometric mean ratio was 108.5% (90% IC=101.8-115.7 of Capoten® values. Captopril AUC(0-24h geometric mean ratio was 109.3% (90% CI=102.7-116.3 of Capoten®. Since 90% CI for both Cmax and ratio AUC(0-24h for captopril were within the 80 to 125% interval proposed by both the Food and Drug Administration (FDA and the National Sanitary Surveillance Agency (ANVISA, it is concluded that Captopril Neo- Química was bioequivalent to Capoten® for both the rate and extent of absorption.

  10. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Kim, Yo Han; Choi, Hee Youn; Lim, Hyeong-Seok; Lee, Shi Hyang; Jeon, Hae Sun; Hong, Donghyun; Kim, Seong Su; Choi, Young Kweon; Bae, Kyun-Seop

    2015-01-01

    Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer's disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), or 175 mg/50 cm(2). Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study. The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74-76 hours (~2-4 hours after patch removal), and mean t1/2β was ~63.77-93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%-86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.

  11. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

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    Kwang-Ho Lee

    2015-09-01

    Full Text Available Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP is used. Thus, sweet bee venom (SBV was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal. Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats.

  12. Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation.

    Science.gov (United States)

    Ismi, O; Karabulut, Y Y; Bal, K K; Vayisoglu, Y; Unal, M

    2017-03-01

    Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation. A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation. The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups. Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.

  13. Single-dose Toxicity of ShinYangHur Herbal Acupuncture

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    Eunhye Cha

    2015-06-01

    Full Text Available Objectives: This study was carried out to analyze the single-dose toxicity of ShinYangHur (SYH herbal acupuncture injected into the muscles of Sprague-Dawley (SD rats. Methods: The SYH herbal acupuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, Korea-Good Manufacturing Practice, K-GMP. After the mixing process with sterile distilled water, the pH was controlled to between 7.0 and 7.5. Then, NaCl was added to make a 0.9% isotonic solution by using sterilized equipment. All experiments were conducted at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP. SD rats were chosen for the pilot study. Doses of SYH herbal acupuncture, 0.25, 0.5, and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy was used to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with SYH herbal acupuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  14. Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

    Science.gov (United States)

    Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

    2013-12-01

    Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

  15. Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review

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    McQuay Henry J

    2002-06-01

    Full Text Available Abstract Background Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events. Methods Cochrane Library (issue 4, 2001, Biological Abstracts (March 2002, MEDLINE (March 2002 and PubMed (March 2002 were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected. Results Five included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6. The weighted mean remedication time was 1.9 hours for placebo (126 patients, 7.4 hours for ibuprofen 400 mg (97 patients and 13.6 hours for rofecoxib 50 mg (322 patients. Conclusion Rofecoxib at 2–4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.

  16. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

    International Nuclear Information System (INIS)

    Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

    1998-01-01

    Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. SINGLE-DOSE CEFAZOLIN PROPHYLAXIS IN ELECTIVE LSCS- A PROSPECTIVE OBSERVATIONAL STUDY

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    Mannasseril Antony Kunjamma

    2017-10-01

    Full Text Available BACKGROUND Surgical site infections are the most common nosocomial infections. Postoperative complications, especially surgical site infections can double the length of time a patient stays in hospital and increase the cost of healthcare. Antibiotic prophylaxis before surgery has evolved over last twenty years and is definitely valuable to reduce postoperative wound infection. Obstetric surgeries are considered as clean contaminated wounds where antibiotic prophylaxis has proven beneficial in preventing postoperative complications, antibiotic resistance and economic burden. But, in countries like India, even a large group of obstetricians are reluctant to follow it. Hence, this study was conducted. The aim of the study is to study the effectiveness of single-dose cefazolin prophylaxis in preventing postoperative complications in patients undergoing elective cesarean compared to postoperative antibiotics. MATERIALS AND METHODS This was a prospective observational study conducted in the Department of Obstetrics and Gynaecology, Medical College, Kottayam, from January 2014-December 2014. After obtaining permission from the hospital ethical committee for research, hundred patients undergoing elective cesarean in our hospital were selected for the study using strict inclusion and exclusion criteria of which fifty patients received injection cefazolin 2g intravenously one hour before surgery. Remaining fifty patients who were matched for age, parity and body mass index were given cefotaxime and metronidazole pre and postoperatively. All these patients were followed up postoperatively for complications, antibiotic change and duration of hospital stay. Statistical analysis done using suitable software. RESULTS Complications were comparable in those receiving prophylactic cefazolin and those receiving postoperative antibiotics. Both groups required antibiotic change for complications. Patients requiring prolonged hospital stay was comparable in both the

  18. Fast electron accumulation and its mechanism in a harmonic trap under ultrahigh vacuum conditions

    International Nuclear Information System (INIS)

    Mohamed, T.; Imao, H.; Mohri, A.; Oshima, N.; Yamazaki, Y.

    2011-01-01

    We present here a fast and efficient electron accumulation in a multiring trap (MRT) in a superconducting solenoid of 5 T. More than 10 10 electrons were accumulated within a fraction of a second for an electron beam in the range of 10 -7 A. The MRT was installed in a cryogenic bore tube cooled down to ∼10 K. Electron accumulation as a function of various parameters such as the beam intensity, the MRT depth, and the MRT length was studied. We succeeded in extracting a consistent picture of the electron accumulation mechanisms, which consist of interactions of the incoming electron beam with the reflected beam and with the electrons trapped in the MRT.

  19. Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions.

    Science.gov (United States)

    Al-Numani, Dina; Scarsi, Claudia; Ducharme, Murray P

    2016-02-01

    To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.

  20. Fast access to the CMS detector condition data employing HTML5 technologies

    International Nuclear Information System (INIS)

    Pierro, Giuseppe Antonio; Cavallari, Francesca; Di Guida, Salvatore; Innocente, Vincenzo

    2011-01-01

    This paper focuses on using HTML version 5 (HTML5) for accessing condition data for the CMS experiment, evaluating the benefits and risks posed by the use of this technology. According to the authors of HTML5, this technology attempts to solve issues found in previous iterations of HTML and addresses the needs of web applications, an area previously not adequately covered by HTML. We demonstrate that employing HTML5 brings important benefits in terms of access performance to the CMS condition data. The combined use of web storage and web sockets allows increasing the performance and reducing the costs in term of computation power, memory usage and network bandwidth for client and server. Above all, the web workers allow creating different scripts that can be executed using multi-thread mode, exploiting multi-core microprocessors. Web workers have been employed in order to substantially decrease the web page rendering time to display the condition data stored in the CMS condition database.

  1. Mapping the intermediate digestion phases of human healthy intestinal contents from distal ileum and caecum at fasted and fed state conditions

    DEFF Research Database (Denmark)

    Tran, Thuy; Fatouros, Dimitrios G; Vertzoni, Maria

    2017-01-01

    collected from distal ileum and caecum of two healthy volunteers under fasted and fed state conditions. KEY FINDINGS: In samples collected both in the fasted and fed states, Cryo-TEM study revealed the presence of large spherical unilamellar and occasionally bi-lamellar and oligolamellar vesicles...

  2. Pelvic rotation torque during fast-pitch softball hitting under three ball height conditions.

    Science.gov (United States)

    Iino, Yoichi; Fukushima, Atsushi; Kojima, Takeji

    2014-08-01

    The purpose of this study was to investigate the relevance of hip joint angles to the production of the pelvic rotation torque in fast-pitch softball hitting and to examine the effect of ball height on this production. Thirteen advanced female softball players hit stationary balls at three different heights: high, middle, and low. The pelvic rotation torque, defined as the torque acting on the pelvis through the hip joints about the pelvic superior-inferior axis, was determined from the kinematic and force plate data using inverse dynamics. Irrespective of the ball heights, the rear hip extension, rear hip external rotation, front hip adduction, and front hip flexion torques contributed to the production of pelvic rotation torque. Although the contributions of the adduction and external rotation torques at each hip joint were significantly different among the ball heights, the contributions of the front and rear hip joint torques were similar among the three ball heights owing to cancelation of the two torque components. The timings of the peaks of the hip joint torque components were significantly different, suggesting that softball hitters may need to adjust the timings of the torque exertions fairly precisely to rotate the upper body effectively.

  3. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-03-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Hyeong-Seok Lim,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Donghyun Hong,2 Seong Su Kim,2 Young Kweon Choi,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea; 2iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea Background: Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer’s disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Methods: Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, or 175 mg/50 cm2. Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch were assessed throughout the study. Results: The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax and the area under the curve (AUC increased in a dose-proportional manner. Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal, and mean t1/2ß was ~63.77–93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%–86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. Conclusion: The donepezil patch

  4. [Single dose toxicity studies of calcipotriol (MC903) in rats and dogs].

    Science.gov (United States)

    Imaizumi, T; Tsuruta, M; Kitagaki, T; Ono, M; Shirakawa, K; Nagata, M; Konishi, R

    1996-07-01

    A single dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, administered subcutaneously (s.c.) and percutaneously (p.c.) was studied in Slc:SD rats (s.c. and p.c.) and beagle dogs (s.c.). The LD50 values of MC903 were as follows: rats, 2.19 mg/kg in males and 2.51 mg/kg in females by s.c., and more than 15 mg/kg in both sexes by p.c.; dogs, more than 1.5 mg/kg in males by p.c. No sexual difference was noted in LD50 values of rats. Death of rats was observed from 1 to 3 days after administration by both routes. Dead animals showed decreases in body weight and locomotor activity, reddish tear, abnormal gait and dirty hair by both routes. Furthermore, dead animals administered by s.c. showed salivation, nasal discharge, piloerection, ptosis, diarrhea, urorrhea, nasal and vaginal bleeding, subnormal temperature, loose stool, cyanosis, irregular and deep respirations, clonic and tonic convulsions. Survival of rats showed similar signs to those of dead animals except for nasal discharge, nasal and vaginal bleeding, cyanosis, agonal respiration and convulsion. Discoloration of the kidney, white patch of the heart and a dilatation of the stomach wall were observed on macroscopic examinations. No mortalities were observed in dogs which showed vomiting, conjunctival congestion, circumoral and auricular reddenings, periblepharal purplish reddening, decreases in locomotor activity and defecation, emaciation, eye discharge, skin desquamation of treated area and an increase in respiration. On macroscopic examination, desquamation of the skin, reddening of the circumoral mucosa, pale gray yellow striations in renal tubules of the cortex and discoloration of the thyroid were observed. Histopathological findings revealed epidermal thickening with parakeratosis, fibrocytes, hypertrophy and hypersecretion of the sebaceous and sweat glands, formation of epitheloid glanulomas and infiltration of neutrophils in the subcutaneous tissues. Furthermore, moderate calcium

  5. Use and knowledge of single dose activated charcoal: A survey of Australian doctors.

    Science.gov (United States)

    Corcoran, Gabriela; Chan, Betty; Chiew, Angela

    2016-10-01

    The use of single dose activated charcoal (SDAC) as a means of gastric decontamination is declining. The present study examined the potential use of SDAC in common overdose scenarios by Australian emergency doctors, compared with clinical toxicologists and current guidelines. We conducted a cross-sectional survey of emergency doctors and toxicologists on the use of SDAC. The survey covered demographic data, education and previous use of SDAC and six clinical scenarios. The scenarios selected included agents not bound to SDAC, sustained-release preparations and ingestions at varying time points. Statistical calculations were performed using Fisher's exact test. There were 397 emergency doctors and 20 toxicologists who responded to the survey. Seventy-one per cent (n = 280/397) of emergency doctors indicated they had received some education on decontamination. Eighty-three per cent (n = 331/397) had administered SDAC during their medical career, 29% (n = 117/397) within the past year. There was a significant difference in responses between emergency doctors and toxicologists in two scenarios; a toxic paracetamol ingestion presenting within 1 h (P = 0.009) and verapamil ingestion in a 3 year old boy (P = 0.001). Toxicologists were more likely to administer SDAC in these scenarios, 89% (n = 16/18) and 88% (n = 15/17), respectively, compared with 52% (n = 197/381) and 43% (n = 158/371) of emergency doctors. Our study showed that there is a significant variation in the use of SDAC between toxicologists and emergency doctors in some scenarios. Clinical toxicologists are more likely to administer SDAC in certain overdose settings. It is essential to provide education on the benefits versus actual risks of SDAC in acute poisoning so that doctors will understand when to administer SDAC or seek further advice. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  6. The CMS fast beams condition monitor back-end electronics based on MicroTCA technology: status and development

    Science.gov (United States)

    Zagozdzinska, Agnieszka A.; Dabrowski, Anne E.; Pozniak, Krzysztof T.

    2015-09-01

    The Fast Beams Condition Monitor (BCM1F), upgraded for LHC Run II, is used to measure the online luminosity and machine induced background for the CMS experiment. The detector consists of 24 single-crystal CVD diamond sensors that are read out with a custom fast front-end chip fabricated in 130 nm CMOS technology. Since the signals from the sensors are used for real time monitoring of the LHC conditions they are processed by dedicated back-end electronics to measure separately rates corresponding to LHC collision products, machine induced background and residual activation exploiting different arrival times. The system is built in MicroTCA technology and uses high speed analog-to-digital converters. In operational modes of high rates, consecutive events, spaced in time by less than 12.5 ns, may cause partially overlapping events. Hence, novel signal processing techniques are deployed to resolve overlapping peaks. The high accuracy qualification of the signals is crucial to determine the luminosity and the machine induced background rates for the CMS experiment and the LHC.

  7. New Findings on New York City's Conditional Cash Transfer Program. Fast Focus. No. 18-2013

    Science.gov (United States)

    Riccio, James A.

    2013-01-01

    The Earned Income Tax Credit (EITC) and Temporary Assistance for Needy Families (TANF) are long-standing policies that link cash assistance to low-income families to work effort. A new policy being tested in New York City adopts this "conditional cash transfer" principle and extends it to a broader set of family efforts to build their…

  8. Fast Transient Thermal Analysis of Non-Fourier Heat Conduction Using Tikhonov Well-Conditioned Asymptotic Waveform Evaluation

    Directory of Open Access Journals (Sweden)

    Sohel Rana

    2014-01-01

    Full Text Available Non-Fourier heat conduction model with dual phase lag wave-diffusion model was analyzed by using well-conditioned asymptotic wave evaluation (WCAWE and finite element method (FEM. The non-Fourier heat conduction has been investigated where the maximum likelihood (ML and Tikhonov regularization technique were used successfully to predict the accurate and stable temperature responses without the loss of initial nonlinear/high frequency response. To reduce the increased computational time by Tikhonov WCAWE using ML (TWCAWE-ML, another well-conditioned scheme, called mass effect (ME T-WCAWE, is introduced. TWCAWE with ME (TWCAWE-ME showed more stable and accurate temperature spectrum in comparison to asymptotic wave evaluation (AWE and also partial Pade AWE without sacrificing the computational time. However, the TWCAWE-ML remains as the most stable and hence accurate model to analyze the fast transient thermal analysis of non-Fourier heat conduction model.

  9. Performance of the Fast Beam Conditions Monitor BCM1F of CMS in the first running periods of LHC

    CERN Document Server

    Schmidt, R S; Castro, E; Hall-Wilton, R; Hempel, M; Lange, W; Lohmann, W; Muller, S; Ryjov, V; Stickland, D; Walsh, R

    2011-01-01

    The Beam Conditions and Radiation Monitoring System, BRM, is implemented in CMS to protect the detector and provide an interface to the LHC. Seven sub-systems monitor beam conditions and the radiation level inside the detector on different time scales. They detect adverse beam conditions, facilitate beam tuning close to CMS, and measure the doses accumulated in different detector components. Data are taken and analysed independently of the CMS data acquisition, displayed in the control room, and provide inputs to the trigger system and the LHC operators. In case of beam conditions dangerous to the CMS detector, a beam abort is induced. The Fast Beam Conditions Monitor, BCM1F, is a flux counter close to the beam pipe inside the tracker volume. It uses single-crystal CVD diamond sensors, radiation-hard FE electronics, and optical signal transmission to measure the beam halo as well as collision products bunch by bunch. The system has been operational during the initiatory runs of LHC in September 2008. It works...

  10. Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.

    Science.gov (United States)

    Gerrits, Mireille G F; Schnabel, Peter G; Post, Teun M; Peeters, Pierre A M

    2013-02-01

    The pharmacokinetics of the monophasic oral contraceptive nomegestrol acetate (NOMAC) plus 17β-estradiol (E(2)) were investigated after a single dose and multiple dosing. NOMAC/E2 (2.5 mg/1.5 mg) was administered daily to healthy women (18-50 years, n=23) for 24 days; blood samples for pharmacokinetic analysis were obtained on Day 24 and again, after a 10-day pill-free interval, on Day 35 after a single dose. NOMAC reached steady state after 5 days with mean ±standard deviation (SD) trough NOMAC concentration (C(av)) of 4.4±1.4 ng/mL. On Day 24, mean±SD peak NOMAC concentration (Cmax, 12.3±3.5 ng/mL) was reached in mean 1.5 h (t(max)); the mean±SD elimination half-life (t(½)) was 45.9±15.3 h. After a single dose, NOMAC mean±SD C(max) was 7.2±2.0 ng/mL and mean±SD t(½) was 41.9±16.2 h. On Day 24, E2 mean±SD C(av) was 50.3±25.7 pg/mL; mean±SD Cmax was 86.0±51.3 pg/mL. After a single dose, mean±SD E2 Cmax was 253±179 pg/mL. These data demonstrate that NOMAC/E2 has a pharmacokinetic profile consistent with once-daily dosing. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Single-dose methotrexate treatment for ectopic pregnancy and pregnancy of unknown location and progesterone as a predictor of success.

    Science.gov (United States)

    Wu, Joyce; Ludlow, Joanne P; De Vries, Bradley; Black, Kirsten; Beale, Philip

    2014-10-01

    The use of single-dose intramuscular administration of methotrexate in the treatment of ectopic pregnancies (EP) is a well-established practice. This study evaluates its use at a novel dose of 40 mg/m(2) body surface area (BSA). To evaluate the efficacy and safety of single-dose methotrexate treatment 40 mg/m(2) for tubal EP and persistent pregnancies of unknown location (PUL) and determine whether serum progesterone is a predictor of treatment success. Retrospective cohort study of patients receiving intramuscular methotrexate 40 mg/m(2) for the treatment of EP or PUL at Royal Prince Alfred Hospital over five years. One hundred and eighteen women received single-dose methotrexate with an overall success of 84%. Surgical intervention was needed in 16.6%. Pretreatment beta-hCG level and ectopic diagnosis were independent variables predictive of the need for surgery (P = 0.003 and 0.02, respectively). Serum progesterone level was not predictive of the need for a second dose or surgery. The sensitivity and specificity at pretreatment beta-hCG of 1202 IU/L were 84% and 74%, respectively. Commonly reported side effects included nausea, abdominal pain and heavy vaginal bleeding. Significant treatment-related adverse effects were rare. Single-dose IM methotrexate at a novel dose of 40 mg/m(2) is a safe and effective treatment for selected EP and persistent PUL. The risk of surgery was positively correlated to serum beta-hCG level and the diagnosis of EP. Progesterone was not a risk factor for surgery. Further studies are required to confirm the efficacy of this dose regimen and explore the safety of expectant management as an alternative to methotrexate treatment. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  12. Experimental loop for fast neutron fuels under normal, abnormal, transient and emergency conditions

    International Nuclear Information System (INIS)

    Bauge, M.; Colomez, G.; Marfaing, R.J.; Mourain, M.

    1976-01-01

    Within the scope of safety experiments on power reactor fuels, an experimental loop is described which can, by reduction of the flow, flush the sodium joint of vented mixed carbide fuel elements and allow the study of the resulting phenomena. With the help of the annex laboratories at OSIRIS, the control test can be analyzed and followed, with special attention to the study of the migration of fission products inside and outside the fuel. This apparatus can, of course, also be used for testing the fuels under normal and abnormal working conditions [fr

  13. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  14. Fast Curing Bio-Based Phenolic Resins via Lignin Demethylated under Mild Reaction Condition

    Directory of Open Access Journals (Sweden)

    Jiongjiong Li

    2017-09-01

    Full Text Available Demethylation technique has been used to enhance lignin reactivity for preparation of phenolic resins. However, the demethylation efficiency and the demethylated lignin (DL reactivity were still unsatisfactory. To improve the demethylation efficiency, alkali lignin was demethylated under different mild conditions using sodium sulfite as a catalyst. Lignin and DL were characterized by 1H-NMR (nuclear magnetic resonance and Fourier transform infrared (FT-IR spectroscopy to determine the demethylation mechanism. With the demethylation of lignin, the methoxyl group content decreased from 1.93 m mol/g to 1.09 m mol/g, and the phenolic hydroxyl group content increased from 0.56 m mol/g to 0.82 m mol/g. These results revealed that methoxyl groups were attacked by SO32−, and some methoxyl groups were converted to phenolic hydroxyl groups by a nucleophilic substitution reaction, generating DL with high reactivity. The chemical properties of lignin-based phenolic resins were studied by 13C-NMR and FT-IR spectroscopy, and their physical properties were also investigated. The results indicated that lignin-based phenolic resins exhibited faster curing rate and shorter gel time. In addition, the bonding strength increased from 0.92 MPa to 1.07 MPa, and the formaldehyde emission decreased from 0.58 mg/L to 0.22 mg/L after lignin demethylated at the optimum condition.

  15. Single dose IOERT versus whole breast irradiation. Cosmetic results in breast-conserving therapy

    Energy Technology Data Exchange (ETDEWEB)

    Struikmans, Henk [Medical Centre Haaglanden, Radiotherapy Centre West, The Hague (Netherlands); Leiden University Medical Centre, Department of Radiotherapy, Leiden (Netherlands); Snijders, Malou; Mast, Mirjam E.; Fisscher, Ursula; Petoukhova, Anna; Koper, Peter [Medical Centre Haaglanden, Radiotherapy Centre West, The Hague (Netherlands); Franssen, Jan-Huib; Speijer, Gabrielle [HAGA Medical Centre, Department of Radiotherapy, The Hague (Netherlands); Immink, Marcelle J. [Reinier de Graaf Medical Centre, Department of Radiotherapy, Delft (Netherlands); Leiden University Medical Centre, Department of Radiotherapy, Leiden (Netherlands); Marinelli, Andreas [Medical Centre Haaglanden, Department of Surgery, The Hague (Netherlands); Merkus, Jos [HAGA Medical Centre, Department of Surgery, The Hague (Netherlands)

    2016-10-15

    Scarce data are available about the cosmetic result of single dose intraoperative electron radiotherapy (IOERT) in breast-conserving radiotherapy. We included 71 breast cancer patients. Breast-conserving surgery and sentinel node procedure had started almost 3 years earlier. Subsequently, 26 patients were treated with IOERT and 45 patients received postoperative whole breast irradiation (WBI). For both groups we determined seven dimensionless asymmetry features. We compared the subjectively and the objectively derived cosmetic scores with each other. For four asymmetry features we noted significantly smaller differences for patients treated with IOERT when compared to those treated with WBI: relative breast contour difference, relative breast area difference and relative breast overlap difference. After correcting for excision volume a significant difference was noticed also for relative lower breast contour. For the IOERT group the cosmetic scores ''excellent or good'' as determined by each patient and one physician were 88 and 96 %, respectively. When the overall cosmetic scores for patients treated with IOERT and WBI were compared to those of the objectively derived scores, there was a fair level of agreement. For patients treated with IOERT we noted less asymmetry and high rates of ''good or excellent'' subjectively derived cosmetic scores. The level of agreement between the subjectively and the objectively derived cosmetic scores was limited. Due to the small sample size and the design of the study no definitive conclusions can be drawn. (orig.) [German] Es sind nur wenige Daten zum kosmetischen Ergebnis nach alleiniger intraoperativer Radiotherapie mittels Elektronen (IOERT) in der brusterhaltenden Behandlung verfuegbar. In einer komparativen Kohortenanalyse wurden 71 Brustkrebspatientinnen eingeschlossen. Ihre brusterhaltende Operation mit Sentinel-Lymphknotenverfahren begann 3 Jahre vorher. Im Anschluss erhielten 26

  16. Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2015-07-14

    There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific benefits are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations, and when tested in the same and different trials. Adding caffeine to analgesics also increases the number of people obtaining good pain relief. Combinations of ibuprofen and caffeine are available without prescription in some parts of the world. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 1 February 2015. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either ibuprofen plus caffeine or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. We identified five randomised, double-blind studies with 1501 participants, but

  17. Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.

    Science.gov (United States)

    Tye, Charlotte; Johnson, Katherine A; Kelly, Simon P; Asherson, Philip; Kuntsi, Jonna; Ashwood, Karen L; Azadi, Bahare; Bolton, Patrick; McLoughlin, Gráinne

    2016-12-01

    Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders. Children with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four-choice RT task with slow-baseline and fast-incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD-RT), coefficient of variation (CV) and ex-Gaussian distribution measures of Mu, Sigma and Tau. In the slow-baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD-only and ASD + ADHD demonstrated increased MRT, SD-RT, CV and Tau compared to TDC and ASD-only. Importantly, greater improvement in MRT, SD-RT and Tau was demonstrated in ADHD and ASD + ADHD from slow-baseline to fast-incentive conditions compared to TDC and ASD-only. Slower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder-specific and disorder-convergent aetiological pathways. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for

  18. FULL GPU Implementation of Lattice-Boltzmann Methods with Immersed Boundary Conditions for Fast Fluid Simulations

    Directory of Open Access Journals (Sweden)

    G Boroni

    2017-03-01

    Full Text Available Lattice Boltzmann Method (LBM has shown great potential in fluid simulations, but performance issues and difficulties to manage complex boundary conditions have hindered a wider application. The upcoming of Graphic Processing Units (GPU Computing offered a possible solution for the performance issue, and methods like the Immersed Boundary (IB algorithm proved to be a flexible solution to boundaries. Unfortunately, the implicit IB algorithm makes the LBM implementation in GPU a non-trivial task. This work presents a fully parallel GPU implementation of LBM in combination with IB. The fluid-boundary interaction is implemented via GPU kernels, using execution configurations and data structures specifically designed to accelerate each code execution. Simulations were validated against experimental and analytical data showing good agreement and improving the computational time. Substantial reductions of calculation rates were achieved, lowering down the required time to execute the same model in a CPU to about two magnitude orders.

  19. Black Tea Lowers Blood Pressure and Wave Reflections in Fasted and Postprandial Conditions in Hypertensive Patients: A Randomised Study

    Directory of Open Access Journals (Sweden)

    Davide Grassi

    2015-02-01

    Full Text Available Hypertension and arterial stiffening are independent predictors of cardiovascular mortality. Flavonoids may exert some vascular protection. We investigated the effects of black tea on blood pressure (BP and wave reflections before and after fat load in hypertensives. According to a randomized, double-blind, controlled, cross-over design, 19 patients were assigned to consume black tea (129 mg flavonoids or placebo twice a day for eight days (13 day wash-out period. Digital volume pulse and BP were measured before and 1, 2, 3 and 4 h after tea consumption. Measurements were performed in a fasted state and after a fat load. Compared to placebo, reflection index and stiffness index decreased after tea consumption (p < 0.0001. Fat challenge increased wave reflection, which was counteracted by tea consumption (p < 0.0001. Black tea decreased systolic and diastolic BP (−3.2 mmHg, p < 0.005 and −2.6 mmHg, p < 0.0001; respectively and prevented BP increase after a fat load (p < 0.0001. Black tea consumption lowers wave reflections and BP in the fasting state, and during the challenging haemodynamic conditions after a fat load in hypertensives. Considering lipemia-induced impairment of arterial function may occur frequently during the day, our findings suggest regular consumption of black tea may be relevant for cardiovascular protection.

  20. Intercomparison of fast response commercial gas analysers for nitrous oxide flux measurements under field conditions

    Science.gov (United States)

    Rannik, Ü.; Haapanala, S.; Shurpali, N. J.; Mammarella, I.; Lind, S.; Hyvönen, N.; Peltola, O.; Zahniser, M.; Martikainen, P. J.; Vesala, T.

    2015-01-01

    Four gas analysers capable of measuring nitrous oxide (N2O) concentration at a response time necessary for eddy covariance flux measurements were operated from spring until winter 2011 over a field cultivated with reed canary grass (RCG, Phalaris arundinacea, L.), a perennial bioenergy crop in eastern Finland. The instruments were TGA100A (Campbell Scientific Inc.), CW-TILDAS-CS (Aerodyne Research Inc.), N2O / CO-23d (Los Gatos Research Inc.) and QC-TILDAS-76-CS (Aerodyne Research Inc.). The period with high emissions, lasting for about 2 weeks after fertilization in late May, was characterized by an up to 2 orders of magnitude higher emission, whereas during the rest of the campaign the N2O fluxes were small, from 0.01 to 1 nmol m-2 s-1. Two instruments, CW-TILDAS-CS and N2O / CO-23d, determined the N2O exchange with minor systematic difference throughout the campaign, when operated simultaneously. TGA100A produced the cumulatively highest N2O estimates (with 29% higher values during the period when all instruments were operational). QC-TILDAS-76-CS obtained 36% lower fluxes than CW-TILDAS-CS during the first period, including the emission episode, whereas the correspondence with other instruments during the rest of the campaign was good. The reasons for systematic differences were not identified, suggesting further need for detailed evaluation of instrument performance under field conditions with emphasis on stability, calibration and any other factors that can systematically affect the accuracy of flux measurements. The instrument CW-TILDAS-CS was characterized by the lowest noise level (with a standard deviation of around 0.12 ppb at 10 Hz sampling rate) as compared to N2O / CO-23d and QC-TILDAS-76-CS (around 0.50 ppb) and TGA100A (around 2 ppb). We identified that for all instruments except CW-TILDAS-CS the random error due to instrumental noise was an important source of uncertainty at the 30 min averaging level and the total stochastic error was frequently

  1. Doubling the single-dose infusion rate of tocilizumab in rheumatoid arthritis is safe and efficacious

    DEFF Research Database (Denmark)

    Lindegaard, H M; Johansen, P; Gröndal, G

    2016-01-01

    OBJECTIVES: To investigate the impact of enhanced infusion rate of tocilizumab on the occurrence of infusion reactions, overall safety, and efficacy in rheumatoid arthritis (RA). METHOD: We conducted a 24-week multicentre, open-label, randomized parallel group study comparing adverse event (AE......) and effect profiles following tocilizumab IV 8 mg/kg every 4 weeks over 31 min vs. standard 60-min infusions in patients with RA and an inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-α inhibitors. RESULTS: A total of 47 patients were...... enrolled in the study and randomized to fast infusions (n = 25) and controls (n = 22). Incidences of infusion reactions were similar between the two groups, neither of them leading to withdrawal. Likewise, the incidence of additional AEs did not differ between the treatment arms. Two serious adverse events...

  2. Evaluation of the Ross fast solution of Richards' equation in unfavourable conditions for standard finite element methods

    International Nuclear Information System (INIS)

    Crevoisier, D.; Voltz, M.; Chanzy, A.

    2009-01-01

    Ross [Ross PJ. Modeling soil water and solute transport - fast, simplified numerical solutions. Agron J 2003;95:1352-61] developed a fast, simplified method for solving Richards' equation. This non-iterative 1D approach, using Brooks and Corey [Brooks RH, Corey AT. Hydraulic properties of porous media. Hydrol. papers, Colorado St. Univ., Fort Collins: 1964] hydraulic functions, allows a significant reduction in computing time while maintaining the accuracy of the results. The first aim of this work is to confirm these results in a more extensive set of problems, including those that would lead to serious numerical difficulties for the standard numerical method. The second aim is to validate a generalisation of the Ross method to other mathematical representations of hydraulic functions. The Ross method is compared with the standard finite element model, Hydrus-1D [Simunek J, Sejna M, Van Genuchten MTh. The HYDRUS-1D and HYDRUS-2D codes for estimating unsaturated soil hydraulic and solutes transport parameters. Agron Abstr 357; 1999]. Computing time, accuracy of results and robustness of numerical schemes are monitored in 1D simulations involving different types of homogeneous soils, grids and hydrological conditions. The Ross method associated with modified Van Genuchten hydraulic functions [Vogel T, Cislerova M. On the reliability of unsaturated hydraulic conductivity calculated from the moisture retention curve. Transport Porous Media 1988:3:1-15] proves in every tested scenario to be more robust numerically, and the compromise of computing time/accuracy is seen to be particularly improved on coarse grids. Ross method run from 1.25 to 14 times faster than Hydrus-1D. (authors)

  3. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    Science.gov (United States)

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

  4. Predicting factors of medical treatment success with single dose methotrexate in tubal ectopic pregnancy: a retrospective study

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    Fariba Mirbolouk

    2015-06-01

    Full Text Available Background: Nowadays, The first step in treatment of ectopic pregnancy (EP is medical treatment. Medical treatment with methotrexate (MTX for EP is safe and effective method without the risks associated with the surgical procedure. But there are controversies between studies for which patients will respond better to medical treatment. Objective: The aim of the present study was to investigate the predictive factors of success or failure of treatment of EP with single dose MTX. Materials and Methods: In this retrospective study, records of 370 patients who were treated for tubal EP with single dose of MTX were reviewed during four years. Patients were divided into two groups; the first group or “success group” are the patients who were successfully treated with MTX. The second group or “failure group” consist the patients who did not respond to the MTX therapy. The week of gestation, size and location of EP and β-hCG level were compared between groups. Results: Of 370 patients, 285 (77.1% were successfully treated with MTX. 85 patients (22.9% required surgery after a mean of 5.4 (range 2-15 days. Day-1 beta- human chorionic gonadotropin (β-hCG and fall in β-hCG between day 1 and day 4 were the best predictors for single dose MTX treatment success. The cutoff value of initial β-hCG with the success treatment results was found to be 1375 IU/mL there was no statistical difference between groups about week of gestation, size and location of EP. Conclusion: The results showed that patients who have β-hCG levels below 1375 and the number of cases with decreasing β-hCG level on day 4 are the good candidates for medical treatment.

  5. Single-dose ethanol administration activates the hypothalamic-pituitary-adrenal axis: exploration of the mechanism of action.

    Science.gov (United States)

    Thiagarajan, A B; Mefford, I N; Eskay, R L

    1989-10-01

    Activation of the hypothalamic-pituitary-adrenal axis (HPAA) by single-dose ethanol administration, which achieved moderately high blood ethanol levels, was explored in naive rats in order to determine the mechanism of ethanol's activation of the stress axis. Adult male rats received a single dose (3.2 g/kg body weight-1 of a 12% solution of ethanol in physiological saline. The plasma concentration of immunoreactive (ir) adrenocorticotropic hormone (ACTH), beta-endorphin (BE) and corticosterone (CS) was determined by radioimmunoassay, whereas, plasma concentrations of epinephrine (E) and norepinephrine (NE) were quantified following reverse-phase liquid chromatographic separation and amperometric detection. Ethanol induced maximal plasma ACTH levels within minutes, which declined toward basal levels by 60 min, whereas, plasma concentration of CS rose rapidly and remained elevated at 60 min. Plasma ACTH and CS levels in saline-treated control animals did not vary significantly at any time point. Consistent with co-release of ACTH from corticotrophs, the plasma concentration of ir-BE increased 5-fold at 15 min and declined towards basal levels at 60 min after-ethanol challenge. Plasma E increased 10- to 20-fold as compared to saline controls or preinjection levels and returned to preinjection levels by 90 min, in a manner similar to ethanol-induced changes in proopiomelanocortin-derived peptides and CS. Removal of the adrenal medulla and thus the source of E prior to ethanol administration, did not attenuate activation of the HPAA. Passive immunoneutralization of arginine vasopressin (AVP), using a high-titer AVP antiserum and a protocol which was found to block ether-induced ACTH secretion by 40% in adult male rats, failed to even partially block ethanol-induced ACTH or CS secretion. The results of this study indicate that neither adrenal medulla-derived E nor AVP are significant regulators or coregulators of corticotroph secretions following a moderately high

  6. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    International Nuclear Information System (INIS)

    Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

    2013-01-01

    Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

  7. Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis.

    Science.gov (United States)

    Ito, Shin; Yasuda, Mitsuru; Hatazaki, Kyoko; Mizutani, Kosuke; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

    2016-09-01

    We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability. We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients. The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3. A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Cost-effectiveness of a chemoprophylactic intervention with single dose rifampicin in contacts of new leprosy patients.

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    Willemijn J Idema

    Full Text Available BACKGROUND: With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR for contacts as chemoprophylactic intervention in the control of leprosy. METHODS: We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER between the standard multidrug therapy (MDT program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case. FINDINGS: Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214, slightly less cost-effective in next door neighbours (ICER $497 and least cost-effective among household contacts (ICER $856. CONCLUSION: Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.

  9. Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate vaccine in pediatric and adolescent oncology patients.

    Science.gov (United States)

    Hung, Te-Yu; Kotecha, Rishi S; Blyth, Christopher C; Steed, Sarah K; Thornton, Ruth B; Ryan, Anne L; Cole, Catherine H; Richmond, Peter C

    2017-11-01

    Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer. A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks after the administration of single-dose PCV13. Serotype-specific immunoglobulin G antibody titers were measured, and titers ≥0.35 μg/mL were considered protective. Solicited side effects were recorded in a 7-day diary after vaccination. Eighty-five children were recruited. At baseline, ≤50% had protective antibody titers against Streptococcus pneumoniae for 10 serotypes in the AIT group and for 8 serotypes in the CIT group. Postvaccination, ≥70% had protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups, respectively. Both groups had comparable responses to PCV7 serotypes, whereas a significantly higher proportion in the CIT group achieved protective antibody titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%). A single-dose of PCV13 is safe and immunogenic in children diagnosed with cancer. All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure. The current data support the recommendation for an additional dose of PCV13 after the completion of immunosuppressive therapy to provide additional protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

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    Jan Susilo

    2011-08-01

    Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

  11. Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    Full Text Available Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms.To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK, which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A. ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A. ceylanicum hookworm burdens from infected hamsters, in the process eliminating hookworm egg shedding in feces and protecting infected hamsters from blood loss. Anthelmintic activity is increased about 3-fold, eliminating >97% of the parasites with a single 3 mg dose (∼30 mg/kg, by incorporating a simple formulation to help prevent digestion in the acidic stomach of the host mammal.These studies advance the development of Cry5B protein as a potent, safe single-dose anthelmintic for hookworm therapy and make available the information of how

  12. Angiotensin Converting Enzyme Inhibitors Mitigate Collagen Synthesis Induced by a Single Dose of Radiation to the Whole Thorax

    OpenAIRE

    Kma, Lakhan; Gao, Feng; Fish, Brian L.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2012-01-01

    Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradi...

  13. A dramatic response to a single dose of infliximab in a patient with prolonged pustular psoriasis derived from inverse psoriasis.

    Science.gov (United States)

    Li, Mengmeng; Dai, Weiwei; Yan, Wei; Liu, Yuanzhen; Wang, Lian; Li, Wei

    2017-07-01

    We report a case of a 25-year-old Chinese man with an exceptionally prolonged history of pustular psoriasis derived from inverse psoriasis who was unsatisfied with conventional treatment and was successfully treated with a single dose of infliximab without noticeable adverse effects. No recurrence or flaring was observed after 3 months of follow-up. This case illustrates that infliximab may be an effective and safe therapeutic option for patients with refractory pustular psoriasis derived from inverse psoriasis. © 2017 Wiley Periodicals, Inc.

  14. Seropositivity among Korean Young Adults Approximately 2 Years after a Single-Dose Vaccination against Hepatitis A Virus.

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    Yeong-Jun Song

    Full Text Available We previously observed 80.7% seropositivity and a significant interaction between gender and hepatitis A virus (HAV vaccine type (Havrix vs. Epaxal on the seropositivity approximately 11 months after single-dose HAV vaccinations in Korean young adults. Our objective was to evaluate seropositivity approximately 2 years after a single-dose HAV vaccination and the influence of demographic characteristics on seropositivity, including the interaction between gender and vaccine type. Seronegative medical school students were randomly vaccinated with Havrix or Epaxal. Based on a total serum anti-HAV antibody titer cutoff of 20 IU/mL, 338 participants (76.0% of the 445 vaccinees were seropositive 20-25 months after a single-dose HAV vaccination. The seropositive rates were similar after vaccination with Havrix (77.0% and Epaxal (74.9%. Univariate analysis indicated that female (p = 0.052 and less obese (p < 0.001 participants had a higher seropositive rate, whereas other characteristics such as age, alcohol use, smoking history, vaccine type, and follow-up duration were not associated with seropositivity. Multivariate analysis indicated that women (p = 0.026 and participants with moderate alcohol use (p < 0.001 showed significantly higher seropositive rates than men and participants with no or low alcohol use, respectively. The seropositive rates after vaccination with Havrix and Epaxal were 70.9% and 67.5% in men and 87.7% and 91.3% in women, respectively (p for interaction = 0.304. Compared with the seropositive rate approximately 11 months after vaccination, the seropositive rate decreased substantially only in men in the Havrix group (11.0% points, and consequently, the interaction between gender and vaccine type disappeared while seropositivity remained high (87.7% and 91.3% in Havrix and Epaxal groups, respectively among women approximately 2 years after vaccination. Further studies are needed to assess whether the seropositive rate would be

  15. Effects of short-term fasting on stress physiology, body condition, and locomotor activity in wintering male white-crowned sparrows.

    Science.gov (United States)

    Krause, Jesse S; Pérez, Jonathan H; Meddle, Simone L; Wingfield, John C

    2017-08-01

    For wild free-living animals the availability of food resources can be greatly affected by environmental perturbations such as weather events. In response to environmental perturbations, animals activate the hypothalamic-pituitary-adrenal (HPA) axis to adjust physiology and behavior. The literature asserts that during weather events food intake declines leading to changes in HPA axis activity, as measured by both baseline and stress-induced glucocorticoid concentrations. Here we investigated how body condition, locomotor activity, and stress physiology were affected by varying lengths of a fast (1, 2, 6, and 24h; similar to that experienced by free-living birds) compared to when food was provided ad libitum in captive wintering male white-crowned sparrows, Zonotrichia leucophrys gambelii, exposed to a short day photoperiod. Baseline corticosterone concentrations were increased for all fasting durations but were highest in 6 and 24h fasted birds. Stress-induced corticosterone was elevated in 1h fasted birds with a trend for the 2h of fast; no other differences were found. Baseline corticosterone concentrations were negatively related to both total fat scores and body mass. All birds lost body mass regardless of fast length but birds fasted for 24h lost the most. Fat scores declined in the 6 and 24h groups, and no measureable changes were detected in pectoralis muscle profile. Locomotor activity was increased over the entire period in which food was removed regardless of fasting duration. Together this suggests that reduced food availability is responsible, at least in part, for the rapid elevation both baseline corticosterone under any duration of fast and stress-induced concentrations during short-term fasts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Seed storage at elevated partial pressure of oxygen, a fast method for analysing seed ageing under dry conditions.

    Science.gov (United States)

    Groot, S P C; Surki, A A; de Vos, R C H; Kodde, J

    2012-11-01

    Despite differences in physiology between dry and relative moist seeds, seed ageing tests most often use a temperature and seed moisture level that are higher than during dry storage used in commercial practice and gene banks. This study aimed to test whether seed ageing under dry conditions can be accelerated by storing under high-pressure oxygen. methods: Dry barley (Hordeum vulgare), cabbage (Brassica oleracea), lettuce (Lactuca sativa) and soybean (Glycine max) seeds were stored between 2 and 7 weeks in steel tanks under 18 MPa partial pressure of oxygen. Storage under high-pressure nitrogen gas or under ambient air pressure served as controls. The method was compared with storage at 45 °C after equilibration at 85 % relative humidity and long-term storage at the laboratory bench. Germination behaviour, seedling morphology and tocopherol levels were assessed. The ageing of the dry seeds was indeed accelerated by storing under high-pressure oxygen. The morphological ageing symptoms of the stored seeds resembled those observed after ageing under long-term dry storage conditions. Barley appeared more tolerant of this storage treatment compared with lettuce and soybean. Less-mature harvested cabbage seeds were more sensitive, as was the case for primed compared with non-primed lettuce seeds. Under high-pressure oxygen storage the tocopherol levels of dry seeds decreased, in a linear way with the decline in seed germination, but remained unchanged in seeds deteriorated during storage at 45 °C after equilibration at 85 % RH. Seed storage under high-pressure oxygen offers a novel and relatively fast method to study the physiology and biochemistry of seed ageing at different seed moisture levels and temperatures, including those that are representative of the dry storage conditions as used in gene banks and commercial practice.

  17. Seed storage at elevated partial pressure of oxygen, a fast method for analysing seed ageing under dry conditions

    Science.gov (United States)

    Groot, S. P. C.; Surki, A. A.; de Vos, R. C. H.; Kodde, J.

    2012-01-01

    Background and Aims Despite differences in physiology between dry and relative moist seeds, seed ageing tests most often use a temperature and seed moisture level that are higher than during dry storage used in commercial practice and gene banks. This study aimed to test whether seed ageing under dry conditions can be accelerated by storing under high-pressure oxygen. Methods Dry barley (Hordeum vulgare), cabbage (Brassica oleracea), lettuce (Lactuca sativa) and soybean (Glycine max) seeds were stored between 2 and 7 weeks in steel tanks under 18 MPa partial pressure of oxygen. Storage under high-pressure nitrogen gas or under ambient air pressure served as controls. The method was compared with storage at 45 °C after equilibration at 85 % relative humidity and long-term storage at the laboratory bench. Germination behaviour, seedling morphology and tocopherol levels were assessed. Key Results The ageing of the dry seeds was indeed accelerated by storing under high-pressure oxygen. The morphological ageing symptoms of the stored seeds resembled those observed after ageing under long-term dry storage conditions. Barley appeared more tolerant of this storage treatment compared with lettuce and soybean. Less-mature harvested cabbage seeds were more sensitive, as was the case for primed compared with non-primed lettuce seeds. Under high-pressure oxygen storage the tocopherol levels of dry seeds decreased, in a linear way with the decline in seed germination, but remained unchanged in seeds deteriorated during storage at 45 °C after equilibration at 85 % RH. Conclusions Seed storage under high-pressure oxygen offers a novel and relatively fast method to study the physiology and biochemistry of seed ageing at different seed moisture levels and temperatures, including those that are representative of the dry storage conditions as used in gene banks and commercial practice. PMID:22967856

  18. Impact of single dose intravenous tranexamic acid on peri-operative blood transfusion requirements in burn patients: A prospective, randomized trial

    Directory of Open Access Journals (Sweden)

    Nidhi Bhatia

    2017-07-01

    Conclusions: Preoperative administration of a single dose of tranexamic acid significantly reduces blood loss during debridement of burn wounds and skin graft harvesting surgeries without increasing the risk of untoward side-effects or complications.

  19. Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial.

    NARCIS (Netherlands)

    Hamza, O.J.M.; Matee, M.I.N.; Bruggemann, R.J.M.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Lee, H.A.L. van der; Verweij, P.E.; Ven, A.J.A.M. van der

    2008-01-01

    BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for

  20. Single-dose methotrexate injection for treatment of ectopic pregnancy in women with relatively low levels of human chorionic gonadotropin.

    Science.gov (United States)

    Krissi, Haim; Peled, Yoav; Eitan, Ram; Bishara, Amani; Goldchmit, Chen; Ben-Haroush, Avi

    2013-05-01

    To evaluate potential risk factors at admission for failed single-dose methotrexate injection in women with ectopic pregnancy. File review of a tertiary medical center in Israel yielded 102 consecutive patients with ectopic pregnancy initially treated with single-dose methotrexate. Overall successful treatment was defined as normalization of human chorionic gonadotropin (hCG) levels after the first or second injection. The mean pretreatment hCG level for the whole cohort was 2350 ± 2955 mIU/mL (median, 1187 mIU/mL; 90th percentile, 5000 mIU/mL). Resolution of ectopic pregnancy was achieved after a single injection in 76/102 (74.5%) women and after a second dose in 16/21 (76.2%) women. The remaining 10 (9.8%) patients were treated surgically after the first (5/76) or the second (5/26) dose. The overall success rate for methotrexate treatment was 90.2%. On multivariate stepwise logistic analysis, fetal cardiac activity was an independent predictor of a failed first methotrexate injection, and presence of a yolk sac and mass size were independent predictors of overall methotrexate failure and need for secondary surgery. In patients with ectopic pregnancy and relatively low levels of serum hCG, the most important predictors of overall failure of methotrexate injection were the presence of a yolk sac and mass size. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Single dose oral azithromycin versus seven day doxycycline in the treatment of non-gonococcal mucopurulent endocervicitis.

    Science.gov (United States)

    Sendağ, F; Terek, C; Tuncay, G; Ozkinay, E; Güven, M

    2000-02-01

    The aim of this study was to compare single dose oral azithromycin versus seven-day doxycycline in the treatment of non-gonococcal mucopurulent cervicitis (MPC). One hundred and thirty-one women with non-gonococcal MPC were enrolled in a prospective-randomised study to compare the efficacy and safety of a single oral dose of 1 g azithromycin and a seven-day course of 100 mg doxycycline twice daily. Clinical examination and culture samples for Chlamydia trachomatis and other microorganisms were performed before and approximately 14 days after starting the treatment. Of the 131 women recruited (67 in the azithromycin group and 64 in the doxycycline group), Ureaplasma urealyticum was isolated from 21 (16%); Chlamydia trachomatis from 15 (11.5%); and Mycoplasma hominis from 3 (2.3%) of the patients at the initial examination. The eradication rate of baseline culture-positive cases at the follow-up visit in the azithromycin group was 71.4%, and 77.3% in the doxycycline group. There was no statistically significant difference in efficacy between the single dose azithromycin and seven-day course of doxycycline in the treatment of culture-positive cases. Azithromycin 1 g appears to be an effective and safe alternative to doxycycline for the treatment of non-gonococcal MPC.

  2. Effect of Low-Dose (Single-Dose Magnesium Sulfate on Postoperative Analgesia in Hysterectomy Patients Receiving Balanced General Anesthesia

    Directory of Open Access Journals (Sweden)

    Arman Taheri

    2015-01-01

    Full Text Available Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH pain relief under balanced general anesthesia. Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20 and normal saline (N=20 groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1 in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS at 0, 6, 12, and 24 hours after the surgeries. Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05. Pethidine requirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001. Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.

  3. Single dose metrifonate or praziquantel treatment in Kenyan children. I. Effects on Schistosoma haematobium, hookworm, hemoglobin levels, splenomegaly, and hepatomegaly.

    Science.gov (United States)

    Stephenson, L S; Kinoti, S N; Latham, M C; Kurz, K M; Kyobe, J

    1989-10-01

    The relationships between S. haematobium, hookworm, malaria, hemoglobin level, splenomegaly, and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia, S. haematobium, and hookworm are common and malaria is holoendemic. Children with light to moderate S. haematobium infection were examined (Exam 1), assigned at random to groups receiving placebo (PL, n = 104), metrifonate (MT, n = 103, dose 10 mg/kg body weight) or praziquantel (PR, n = 105, dose 40 mg/kg body weight), treated, and examined 8 months later (Exam 2). At Exam 2, 62% of the MT group still passed S. haematobium eggs vs. 13% in the PR group. Egg reduction rates were substantial in both groups, but greater in the PR group; geometric mean egg counts in both groups were very low. Prevalence and intensity in the PL group had not changed between exams. Hookworm egg counts were significantly reduced in the MT group (59% egg reduction rate); malarial infection had increased in all 3 groups, presumably due to the long rainy season between exams. Hookworm egg count was the most significant predictor of initial hemoglobin level, followed by S. haematobium egg count and presence of malarial infection. Treatment with a single dose of MT or PR can produce substantial decreases in S. haematobium infection 8 months later.

  4. A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

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    Salah H. Al Janaby

    2017-02-01

    Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

  5. Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.

    Science.gov (United States)

    Chi, Benjamin H; Ellis, Giovanina M; Chintu, Namwinga; Cantrell, Ronald A; Sinkala, Moses; Aldrovandi, Grace M; Warrier, Ranjit; Mbewe, Felistas; Nakamura, Kyle; Stringer, Elizabeth M; Frenkel, Lisa M; Stringer, Jeffrey S A

    2009-11-01

    A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.

  6. Interaction between single-dose Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus vaccines on dually infected pigs.

    Science.gov (United States)

    Park, Su-Jin; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee

    2014-06-01

    The objective of this study was to determine the effects of Mycoplasma hyopneumoniae and/or porcine reproductive and respiratory syndrome virus (PRRSV) vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. The M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas the PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimes; vaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Implications of soil heterogeneity on growth performance of fast-growing trees under marginal site conditions - an ecophysiological perspective

    Science.gov (United States)

    Veste, Maik; Halke, Christian; Schmitt, Dieter; Mantovani, Dario; Zimmermann, Reiner; Küppers, Manfred; Freese, Dirk

    2017-04-01

    The integration of fast-growing trees and hedgerows has been proposed in order to improve the environmental performance of agricultural systems and to provide woody biomass for bioenergy. Due to the current increase of bioenergy, strong interests are emerging to use marginal lands for short-rotation forestry. Especially in Lower Lusatia (Brandenburg, Germany) large areas of reclaimed post-mining sites are available for the cultivation of short-rotation coppies and agroforesty systems. The dumped overburden material has little or no recent soil organic matter, low nutrient content and low water holding capacity. Our study aim was to evaluate the effects of small-scale spatial and temporal variations of edaphic conditions on plant water relations, photosynthesis and biomass production of black locust (Robinia pseudoacacia) and poplar (Populus spp.) on marginal lands. Particularly, on dumped soils in the post-mining area, due to the adverse edaphic conditions, the stem growth was drastically reduced during summer drought below the critical pre-dawn water potential value of -0.5 MPa. But also on agricultural fields soil depth and soil water availability are the key factors determining the biomass production of poplar and black locust. A reduction of soil N availability as a result of low soil nitrogen content or drought induce nodulation and biological nitrogen fixation (BNF) in Robinia in order to sustain the required nitrogen amounts for plant growth. In our experiment the nodule biomass increased in combination with a decrease of the δ15N values of the leaves under extreme drought stress. Under field conditions the percentage of nitrogen derived from the atmosphere in black locust varies 63% - 83% and emphasized the importance of nitrogen fixations for tree growth on marginal lands. Our investigation under different edaphic conditions and soil water availabilities showed clearly the ecophysiological and morphological plasticity of the investigated tree species and

  8. Oral contraception does not alter single dose saquinavir pharmacokinetics in women

    Science.gov (United States)

    Fröhlich, Margit; Burhenne, Jürgen; Martin-Facklam, Meret; Weiss, Johanna; von Wolff, Michael; Strowitzki, Thomas; Walter-Sack, Ingeborg; Haefeli, Walter E

    2004-01-01

    Aims Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. Methods Saquinavir was administered in a hard gelatin capsule formulation (Invirase®) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. Results Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17β-estradiol by −23.4 pg ml−1 (57%, 95%CI: −76% to −37.4%); progesterone by −0.25 ng ml−1 (33%, 95%CI: −45.3% to −21.5%); follicle-stimulating hormone by −4.06 U l−1 (82%, 95%CI: −96.5% to −67.7%); and luteinizing hormone by −3.49 U l−1 (74%, 95%CI: −93 to −54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l−1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. Conclusions There

  9. A comparative bioavailability study of two ibuprofen formulations after single-dose administration in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Metta S.S. Wiria

    2007-09-01

    Full Text Available This study was aimed to investigate the bioequivalence of ibuprofen 125 mg suppository formulation (Ibukal®, test formulation from PT. Kalbe Farma, Tbk., Jakarta and the ibuprofen suppository comparative formulation (Proris®, from PT. Pharos Indonesia, Jakarta in 12 healthy volunteers. The pharmacokinetic parameters used in this study were the area under the concentration-time curve from time zero to hour 10 (AUC0-t, the area under the concentration-time curve from time zero to infinite (AUC0-inf, the maximum concentration (Cmax, and the time needed to reach the maximum concentration (tmax. The study was designed as a random cross-over fashion, single-blinded which included 12 healthy adult volunteers. The volunteers were fasted overnight and in the morning they received a suppository of the test drug (Ibukal® or a suppository of the comparative drug (Proris®. Blood samples were withdrawn on hour 0 (control, 20 min; 40 min; 1; 1.5; 2; 2.5; 3; 4; 6; 8; and 10 time points after the administration of the drug. Following a wash-out period of 1 week, this procedure was repeated using the other drug. The serum concentration of the drug was determined by means of high-performance liquid chromatography with ultraviolet detection. The results of the study showed that, the mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the test drug were, respectively, 28.59(3.37 μg.h.mL-1, 30.47(3.56 μg.h.mL-1, 8.24(1.44 μg/mL, and 1.33(0.44 h. The mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the comparative drug were, respectively, 28.13(8.14 μg.h.mL-1, 30.56(8.05 μg.h.mL-1, 8.27(2.88 μg/mL, and 1.79(0.33 h. The geometric means ratio of the test to the comparative drug were 104.38% (CI 90%: 90.38-120.54% for AUC0-t, 101.97% (CI 90%: 89.51-116.16% for AUC0-inf, and 104.02% (CI 90%: 85.73-126.16% for Cmax. There was no side effect of the drug detected in this study. From the results we can conclude that the 125 mg of ibuprofen suppository of PT Kalbe Farma

  10. Cafeteria diet overfeeding in young male rats impairs the adaptive response to fed/fasted conditions and increases adiposity independent of body weight.

    Science.gov (United States)

    Castro, H; Pomar, C A; Picó, C; Sánchez, J; Palou, A

    2015-03-01

    We analyzed the effects of a short exposure to a cafeteria diet during early infancy in rats on their metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis. Ten-day-old male pups were fed a control or a cafeteria diet for 12 days and then killed under ad libitum feeding conditions or 12 h fasting. The expression of key genes related to energy metabolism in liver, retroperitoneal white adipose tissue (WAT) and hypothalamus were analyzed. Despite no differences in body weight, cafeteria-fed animals had almost double the fat mass of control rats. They also showed higher food intake, higher leptinemia and altered hypothalamic expression of Neuropetide Y, suggesting a dysfunction in the control of food intake. Unlike controls, cafeteria-fed animals did not decrease WAT expression of Pparg, sterol regulatory element binding transcription factor 1 or Cidea under fasting conditions, and displayed lower Pnpla2 expression than controls. In liver, compared with controls, cafeteria animals presented: (i) lower expression of genes related with fatty acid uptake and lipogenesis under ad libitum-fed conditions; (ii) higher expression of fatty acid oxidation-related genes and glucokinase under fasting conditions; (iii) greater expression of leptin and insulin receptors; and higher protein levels of insulin receptor and the pAMPK/AMPK ratio. A short period of exposure to a cafeteria diet in early infancy in rat pups is enough to disturb the metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis, particularly in WAT, and hence induces an exacerbated body fat accumulation and increased metabolic risk, with no apparent effects on body weight.

  11. An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.

    Directory of Open Access Journals (Sweden)

    Cameron B Williams

    Full Text Available The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1 reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8. No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

  12. Bioequivalence of lamotrigine 50-mg tablets in healthy male volunteers: a randomized, single-dose, 2-period, 2-sequence crossover study.

    Science.gov (United States)

    Perez-Lloret, S; Olmos, L; de Mena, F; Pieczanski, P; Rodriguez Moncalvo, J J

    2012-10-01

    OBEJCTIVE: To compare the bioavailability of two 50-mg lamotrigine dispersible tablet formulations (Epilepax®, Ivax-TEVA Argentina Laboratories, Argentina, as a test formulation, and Lamictal®, GlaxoSmithKline, UK, as a reference formulation) in 24 healthy male volunteers. This study was a randomized, 2-period, 2-sequence crossover design that was open for subjects and investigators, but blind for the bioanalytical lab. Serum samples were obtained over a 120-h interval. A 9-day wash-out period was allowed between treatments. The concentrations of lamotrigine were analyzed by high-performance liquid chromatography followed by ultraviolet-visible detection. Lamotrigine time-concentrations curves were obtained and the following pharmacokinetic parameters were calculated: AUC0-t, AUC0-inf and Cmax. Bioequivalence was declared if the 90% confidence interval (CI) of the mean test/reference ratios for AUC0-t, AUC0-inf and Cmax were within 80.00-125.00%. The geometric mean and respective 90% CI of test/reference percent ratios were 100.83% (92.53-107.88%) for AUC0-t, 99.91% (93.79-108.40%) for AUC0-inf, and 95.62% (90.91-100.57%) for Cmax. No serious adverse events were observed. 1 patient reported a mild rash following the administration of each formulation. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in this sample of fasting healthy volunteers. These results suggest that bioequivalence studies evaluating 50-mg doses of Lamotrigine are feasible and recommended, since such doses may minimize the risk of severe rash or Stevens-Johnson Syndrome. This study was registered at the Argentinean Clinical Trials National Registry (www.anmat.gov.ar), No 1666/2008. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Investigating the condition of medical counseling and some of clinical aspects for fasting in holy month of Ramadan from the perspective of diabetic and hypertensive patients

    Directory of Open Access Journals (Sweden)

    Ahmad Mahmoudian

    2015-06-01

    Full Text Available Introduction: Although fasting has many benefits for health, it can be dangerous for patients. So it is necessary that physicians have adequate information about clinical aspects of fasting and they should advice patients. Therefore in this study we analyses the condition of physicians counseling about fasting from the perspective of patients. Methods:In this descriptive analytical cross-sectional study, patients with diabetes and hypertension who were going to doctors in Isfahan in holy month of Ramadan of 2012 and 2013 completed the questionnaires. A valid self-regulation questionnaire including patient`s satisfaction from the quality of physicians counseling about fasting (In the area of education, evaluation of the patient condition, communication /relationship with patients, caring for diseases in holy Ramadan and the incidence of symptoms in fasting had been used with  = 0.76. The patients completed the questionnaire after visit. The data was analyzed by Independent t-test, chi-square, Regression, one-way ANOVA in the19 spss software. Results: 285 patients, 199(69.8% female and 86(30.2% male, were selected. The mean satisfaction score of counseling was 70.50 ±13.23. The highest score (75.36±14.16 was referred to counseling of physician, and the least score (66.09±18.84 to patient assessment by physician. Mean score of Patients' satisfaction of specialists was higher than of general practitioner (p-value

  14. Accurate evaluation of fast threshold voltage shift for SiC MOS devices under various gate bias stress conditions

    Science.gov (United States)

    Sometani, Mitsuru; Okamoto, Mitsuo; Hatakeyama, Tetsuo; Iwahashi, Yohei; Hayashi, Mariko; Okamoto, Dai; Yano, Hiroshi; Harada, Shinsuke; Yonezawa, Yoshiyuki; Okumura, Hajime

    2018-04-01

    We investigated methods of measuring the threshold voltage (V th) shift of 4H-silicon carbide (SiC) metal–oxide–semiconductor field-effect transistors (MOSFETs) under positive DC, negative DC, and AC gate bias stresses. A fast measurement method for V th shift under both positive and negative DC stresses revealed the existence of an extremely large V th shift in the short-stress-time region. We then examined the effect of fast V th shifts on drain current (I d) changes within a pulse under AC operation. The fast V th shifts were suppressed by nitridation. However, the I d change within one pulse occurred even in commercially available SiC MOSFETs. The correlation between I d changes within one pulse and V th shifts measured by a conventional method is weak. Thus, a fast and in situ measurement method is indispensable for the accurate evaluation of I d changes under AC operation.

  15. Cellular and humoral responses in liver of cattle and buffaloes infected with a single dose of Fasciola gigantica.

    Science.gov (United States)

    Molina, Elizabeth C; Skerratt, Lee F

    2005-07-15

    The cellular components of the hepatic inflammatory infiltrate in cattle and buffaloes infected with a single dose of 1000 Fasciola gigantica were analysed by immunohistochemistry and histology. T and B lymphocytes, plasma cells, eosinophils and mast cells were present in the hepatic lesions. It is proposed that both cellular and humoral immune responses were induced in the liver of cattle and buffaloes during infection with F. gigantica probably by antigens released by the developing flukes and by damage caused by the flukes during their migration in the liver. The local T cell response differed between these animals, with the response decreasing after 3 weeks post-infection in cattle in contrast to a gradually increasing response in buffaloes. Difference in the T cell response between cattle and buffaloes may be related to their differences in resistance and resilience to infection with F. gigantica.

  16. A Systematic Review on Effect of Single-Dose Preoperative Antibiotics at Surgical Osteotomy Extraction of Lower Third Molars

    DEFF Research Database (Denmark)

    Marcussen, Karoline Brørup; Laulund, Anne Sofie; Jørgensen, Henrik L

    2016-01-01

    PURPOSE: We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar...... surgical extraction implying osteotomy. MATERIALS AND METHODS: The Medline, Cochrane Library, and Embase databases were searched for RCTs until August 2015. The primary outcome measure was postoperative inflammatory reactions, with a subgroup analysis of surgical site infection (SSI) and alveolar osteitis.......08 to 0.45; P = .0002). A meta-analysis of 5 trials showed that 2 g of preoperative oral amoxicillin was able to reduce the incidence of SSI and the difference was statistically significant (OR = 0.22; 95% CI, 0.08 to 0.59; P = .002). Seven trials reported on alveolar osteitis, 6 studies on oral use, 2...

  17. Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

    Science.gov (United States)

    Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

    2018-03-15

    Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV

  18. Bixin and norbixin in human plasma: determination and study of the absorption of a single dose of Annatto food color.

    Science.gov (United States)

    Levy, L W; Regalado, E; Navarrete, S; Watkins, R H

    1997-09-01

    A procedure was developed for the detection and determination of bixin and norbixin in human plasma by reversed-phase HPLC with a sensitivity limit of 5 micrograms l-1. A group of seven volunteers ingested a single dose of 1 ml of a commercial Annatto Food Color (16 mg of cis-bixin in soybean oil). The presence of bixin (cis and trans) and norbixin (cis and trans) was demonstrated in the plasma at average levels of 11.6, 10.1, 2.8 and 0 micrograms l-1 of bixin and 48, 58, 53 and 29 micrograms l-1 of norbixin after 2, 4, 6 and 8 h, respectively. Considerable individual variations were observed. Complete plasma clearance generally occurred for bixin by 8 h and for norbixin by 24 h after ingestion of cis-bixin.

  19. Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

    Science.gov (United States)

    Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

    2017-12-01

    African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

  20. Coordinated Hard Sphere Mixture (CHaSM): A fast approximate model for oxide and silicate melts at extreme conditions

    Science.gov (United States)

    Wolf, A. S.; Asimow, P. D.; Stevenson, D. J.

    2015-12-01

    Recent first-principles calculations (e.g. Stixrude, 2009; de Koker, 2013), shock-wave experiments (Mosenfelder, 2009), and diamond-anvil cell investigations (Sanloup, 2013) indicate that silicate melts undergo complex structural evolution at high pressure. The observed increase in cation-coordination (e.g. Karki, 2006; 2007) induces higher compressibilities and lower adiabatic thermal gradients in melts as compared with their solid counterparts. These properties are crucial for understanding the evolution of impact-generated magma oceans, which are dominated by the poorly understood behavior of silicates at mantle pressures and temperatures (e.g. Stixrude et al. 2009). Probing these conditions is difficult for both theory and experiment, especially given the large compositional space (MgO-SiO2-FeO-Al2O3-etc). We develop a new model to understand and predict the behavior of oxide and silicate melts at extreme P-T conditions (Wolf et al., 2015). The Coordinated Hard Sphere Mixture (CHaSM) extends the Hard Sphere mixture model, accounting for the range of coordination states for each cation in the liquid. Using approximate analytic expressions for the hard sphere model, this fast statistical method compliments classical and first-principles methods, providing accurate thermodynamic and structural property predictions for melts. This framework is applied to the MgO system, where model parameters are trained on a collection of crystal polymorphs, producing realistic predictions of coordination evolution and the equation of state of MgO melt over a wide P-T range. Typical Mg-coordination numbers are predicted to evolve continuously from 5.25 (0 GPa) to 8.5 (250 GPa), comparing favorably with first-principles Molecular Dynamics (MD) simulations. We begin extending the model to a simplified mantle chemistry using empirical potentials (generally accurate over moderate pressure ranges, consuming classical MD calculations. This approach also sheds light on the universality

  1. Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch.

    Science.gov (United States)

    Lin, Yu; Zou, Yanye; Lin, Jialiang; Zhang, Tao; Deng, Jie

    2013-08-01

    1. A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson's disease. Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration. 2. A total of 18 minipigs were randomly divided into three groups (six animals for each group). A single dose of 1 mg rasagiline tablet was orally administrated to one group. Meanwhile, single dose of 1.25 and 2.5 mg (2 and 4 cm(2)) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively. The pharmacokinetic parameters such as plasma half-life (t1/2), time to peak plasma-concentration (Tmax), mean residence time (MRT), area under the curve (AUC(0-t)) were significantly (p rasagiline (1.25 mg patch: 11.8 ± 6.5 h, 2.5 mg patch: 12.5 ± 4.7 h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1 mg tablet: 4.7 ± 2.5 h). The dose-normalized relative bioavailability of rasagiline patch in minipig were 178.5% and 156.4%, respectively, for 1.25 and 2.5 mg patches compared with 1 mg rasagiline tablet. The prolonged t1/2 and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.

  2. Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR.

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    Phonepasong Ayé Soukhathammavong

    2012-01-01

    Full Text Available BACKGROUND: Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH infections. We assessed the efficacy of single oral doses of albendazole (400 mg and mebendazole (500 mg for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. METHODOLOGY: We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples were randomly assigned to albendazole (n=100 and mebendazole (n=100. Cure rate (CR; percentage of children who became egg-negative after treatment, and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. PRINCIPAL FINDINGS: Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01, and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively and moderate ERRs (82.1% and 78.2%, respectively. CONCLUSIONS/SIGNIFICANCE: Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN29126001.

  3. Serum β-hCG levels post-treatment of ectopic pregnancy with a single dose of intramuscular methotrexate.

    Science.gov (United States)

    Hadinata, Ignatius E; Doyle, Lex W; Thompson, Derrick; Reti, Leslie

    2015-04-01

    The cytotoxic management of ectopic pregnancy using a single dose of intramuscular methotrexate injection has been well established as effective for a select number of women with unruptured tubal ectopic pregnancy where there are minimal symptoms. The purpose of this study was to create centile curves of serum β-hCG levels following successful treatment with a single dose of 50 mg/m(2) of intramuscular methotrexate to treat ectopic pregnancy. Data were retrieved from women treated at the Royal Women's Hospital for ectopic pregnancy between 2006 and 2012. Only women with minimal symptoms, initial serum β-hCG ≤5000 IU/L and ectopic mass size of ≤35 mm on ultrasound were included. Two hundred and fifty-three cases of ectopic pregnancy were analysed. Initial β-hCG of women in the study ranged from 18 to 3995 IU/L with a median of 497 (25th to 75th centiles; 222-1160) IU/L. The median levels of β-hCG levels at day 4, 7 and 14 postmethotrexate injection were 73.8, 47.2 and 10.4% of the initial β-hCG level, respectively. The 90th centiles of β-hCG levels at day 4, 7 and 14 were 124.7, 93.8 and 40.0% of initial β-hCG level, respectively. Whilst no comparison with those unsuccessfully treated was made, pending further validation studies, the use of these curves may reduce the reliance on specialist units and streamline care for many women with ectopic pregnancy, such as those whose β-hCG regress in line with centile values without crossing a certain threshold. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  4. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

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    Gårevik Nina

    2012-03-01

    Full Text Available Abstract Background Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR. There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR. Methods 39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2. Results The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007. This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively. Conclusion Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.

  5. Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

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    Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

    2017-05-01

    Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

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

    Science.gov (United States)

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

    2016-12-01

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

  7. [Effect of supplementation with a single dose of vitamin D in children with cerebral palsy. Preliminary randomised controlled study].

    Science.gov (United States)

    Le Roy, Catalina; Meier, Martina; Witting, Scarlett; Pérez-Bravo, Francisco; Solano, Carlos; Castillo-Durán, Carlos

    2015-01-01

    Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bed-ridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient+deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P=.07). A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. A Pilot Study on Single-dose Toxicity Testing of Hominis placenta Pharmacopuncture in Sprague-Dawley Rats

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    Yoo-Hwan Lee

    2015-06-01

    Full Text Available Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea, an institution authorized to perform non clinical studies, under the regulations of Good Laboratory Practice (GLP. SD rats were chosen for the pilot study. Doses of Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hominis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.

  9. High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

    Science.gov (United States)

    Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

    2011-04-13

    The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

  10. Exploring surface landscapes with molecules: rotationally induced diffraction of H2on LiF(001) under fast grazing incidence conditions.

    Science.gov (United States)

    Del Cueto, M; Muzas, A S; Somers, M F; Kroes, G J; Díaz, C; Martín, F

    2017-06-28

    Atomic diffraction by surfaces under fast grazing incidence conditions has been used for almost a decade to characterize surface properties with more accuracy than with more traditional atomic diffraction methods. From six-dimensional solutions of the time-dependent Schrödinger equation, we show that diffraction of H 2 molecules under fast grazing incidence conditions could be even more informative for the characterization of ionic surfaces, due to the large anisotropic electrostatic interaction between the quadrupole moment of the molecule and the electric field created by the ionic crystal. Using the LiF(001) surface as a benchmark, we show that fast grazing incidence diffraction of H 2 strongly depends on the initial rotational state of the molecule, while rotationally inelastic processes are irrelevant. We demonstrate that, as a result of the anisotropy of the impinging projectile, initial rotational excitation leads to an increase in intensity of high-order diffraction peaks at incidence directions that satisfy precise symmetry constraints, thus providing a more detailed information on the surface characteristics than that obtained from low-order atomic diffraction peaks under fast grazing incidence conditions. As quadrupole-ion surface potentials are expected to accurately represent the interaction between H 2 and any surface with a marked ionic character, our analysis should be of general applicability to any of such surfaces. Finally, we show that a density functional theory description of the molecule-ion surface potential catches the main features observed experimentally.

  11. A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

    Science.gov (United States)

    Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

    2015-07-31

    Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy.

    Science.gov (United States)

    Kim, Junhwan; Jung, Young Mi; Lee, Da Yong; Jee, Byung Chul

    2017-01-01

    To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis. Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group ( P >0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group. We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L.

  13. Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

    2014-01-01

    Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

  14. Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate After Single-dose Administration in Healthy Korean Male Subjects.

    Science.gov (United States)

    Kim, Yun; Kim, Anhye; Lee, SeungHwan; Choi, Sung-Hak; Lee, Dae Young; Song, Ji-Su; Lee, Howard; Jang, In-Jin; Yu, Kyung-Sang

    2017-09-01

    Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant Staphylococcus aureus. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects. A block-randomized, double-blind, placebo-controlled, single-dose study was conducted in 3 groups (200, 400, and 600 mg; 10 subjects in each group). In the second part of the study, subjects from the 200-mg group received administration orally and intravenously (1-hour infusion) via 2-way crossover for the evaluation of absolute bioavailability. There was a 7-day washout period between treatments in the absolute bioavailability part of the study. Serial blood samples for PK analysis were collected for up to 72 hours. Tolerability was assessed by analysis of adverse events. Thirty healthy Korean subjects completed the study and were included in the PK and tolerability analyses. Tedizolid phosphate was rapidly converted into tedizolid. After a single oral dose, the T max of tedizolid was observed to be 1.5 to 2.5 hours, and the plasma concentration-time curve of tedizolid showed a 2-phase elimination pattern, with a half-life of ~11 hours. Dose-dependent increases were observed in the AUC last value (29,441-78,062 μg · h/L) and in the C max value ( 2679-6980 μg/L) with the administration of tedizolid phosphate 200 to 600 mg PO. The absolute bioavailability of tedizolid was 95.2% (90% CI, 92.7%-97.8%) in the 200-mg administration group. There were no serious adverse events or clinically significant changes in the

  15. Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug - Drug Interaction Studies.

    Science.gov (United States)

    Litou, Chara; Vertzoni, Maria; Goumas, Constantinos; Vasdekis, Vassilis; Xu, Wei; Kesisoglou, Filippos; Reppas, Christos

    2016-06-01

    Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults. Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am. Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen. Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

  16. Long-Term Cognitive Functioning in Single-Dose Total-Body Gamma-Irradiated Rhesus Monkeys (Macaca mulatta)

    Science.gov (United States)

    Hanbury, David B.; Peiffer, Ann M.; Dugan, Greg; Andrews, Rachel N.; Cline, J. Mark

    2016-01-01

    In this study, the effects of a potentially lethal radiation exposure on the brain for long-term cognitive sequelae were investigated using Rhesus macaques (Macaca mulatta) adopted from other facilities after analysis of acute radiation response via the Centers for Medical Countermeasures against Radiation (CMCR) network. Fifty-nine animals were given the opportunity to participate in cognitive cage-side testing. The animals that received single-dose gamma irradiation were significantly less likely to engage in cognitive testing than the controls, suggesting that irradiated animals may have differences in cognitive ability. Five irradiated (6.75–8.05 Gy) and three naïve control animals self-selected, were extensively trained and administered a simple visual discrimination with reversal (SVD+R) task 2–3 times per week for 11–18 months. Each session consisted of 30 trials in which the animals were required to choose the correct visual stimulus for a food reward. After the initial presentation, the stimulus that signaled the presence of food was twice reversed once the animal reached criterion (90% accuracy across four consecutive sessions). While the limited sample size precluded definitive statistical analysis, irradiated animals took longer to reach the criterion subsequent to reversal than did control animals, suggesting a relative deficiency in cognitive flexibility. These results provide preliminary data supporting the potential use of a nonhuman primate model to study radiation-induced, late-delayed cognitive deficits. PMID:27740889

  17. Single dose of diclofenac or meloxicam for control of pain, facial swelling, and trismus in oral surgery.

    Science.gov (United States)

    Orozco-Solís, Mariana; García-Ávalos, Yazmín; Pichardo-Ramírez, Celeste; Tobías-Azúa, Francisco; Zapata-Morales, Juan-Ramón; Aragon-Martínez, Othoniel-Hugo; Isiordia-Espinoza, Mario-Alberto

    2016-01-01

    Postoperative pain associated with removal of mandibular third molars has been documented from moderate to severe during the first 24 hours after surgery, with pain peaking between 6 and 8 hours when a conventional local anesthetic is used. Dental pain is largely inflammatory, and evidence-based medicine has shown that nonsteroidal anti-inflammatory drugs are the best analgesics for dental pain. The aim of this study was to compare the analgesic, anti-inflammatory and anti-trismus effect of a single dose of diclofenac and meloxicam after mandibular third molar extraction. A total of 36 patients were randomized into two treatment groups, each with 18 patients, using a series of random numbers: Group A, was administered 100 mg of diclofenac; and Group B, 15 mg of meloxicam. Drugs were administered orally 1 hour prior to surgery. We evaluated pain intensity, analgesic consumption, swelling, as well as trismus. The results of this study showed that patients receiving 15 mg of meloxicam had less postoperative pain (P=0.04) and better aperture than those receiving 100 mg of diclofenac (P=0.03). The meloxicam group presented less swelling than diclofenac group; however, significant statistical differences were not observed. Data of this double-blind, randomized, parallel-group clinical trial demonstrated that patients receiving 15 mg of preoperative meloxicam had a better postoperative analgesia and anti-trismus effect compared with who were given 100 mg of diclofenac after third molar extractions.

  18. Pharmacokinetics and effect on the corrected QT interval of single-dose escitalopram in healthy elderly compared with younger adults.

    Science.gov (United States)

    Chung, Hyewon; Kim, Anhye; Lim, Kyoung Soo; Park, Sang-In; Yu, Kyung-Sang; Yoon, Seo Hyun; Cho, Joo-Youn; Chung, Jae-Yong

    2017-01-01

    Escitalopram is the (S)-enantiomer of citalopram that has a potential QT prolonging effect. In this study, 12 healthy elderly individuals received a single oral dose of escitalopram (20 mg), and their pharmacokinetics and QT effect data were compared with data from 33 younger adults obtained in a previous study. Serial blood samples for pharmacokinetic analysis were collected and ECG was performed up to 48 h postdose. The elderly and younger adults showed similar pharmacokinetic profiles. The geometric mean ratios (90% confidence interval) of the elderly compared with the younger adults were 1.02 (0.89-1.17) and 1.01 (0.86-1.17) for the maximum plasma concentration and area under the concentration-time curve, respectively. The mean baseline-adjusted QT (dQT) time profiles were similar and the mean values of maximum dQT were not significantly different between the elderly and the younger adults. The linear mixed-effect model indicated a weak but positive relationship between the escitalopram concentration and dQT, with an estimated coefficient of concentration of 0.43-0.54. In conclusion, the pharmacokinetics and QT effect of a single dose of escitalopram observed in the elderly without comorbidities and younger adults were generally similar.

  19. Pharmacokinetics and egg residues after oral administration of a single dose of meloxicam in domestic chickens (Gallus domesticus).

    Science.gov (United States)

    Souza, Marcy J; Bergman, Joan B; White, Molly S; Gordon, Kristen I; Gerhardt, Lillian E; Cox, Sherry K

    2017-08-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam in domestic hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg). ANIMALS 8 healthy adult White Leghorn hens. PROCEDURES Hens were administered 1 mg of meloxicam/kg PO once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma, egg whites (albumen), and egg yolks were analyzed by high-performance liquid chromatography. RESULTS The half-life, maximum concentration, and time to maximum concentration of meloxicam in plasma samples were 2.8 hours, 7.21 μg/mL, and 2 hours, respectively. Following meloxicam administration, the drug was not detected after 4 days in egg whites and after 8 days in egg yolks. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that meloxicam administered at a dose of 1 mg/kg PO in chickens appears to maintain plasma concentrations equivalent to those reported to be therapeutic for humans for 12 hours. The egg residue data may be used to aid establishment of appropriate drug withdrawal time recommendations.

  20. Single-dose oral fluconazole versus topical clotrimazole in patients with pityriasis versicolor: A double-blind randomized controlled trial.

    Science.gov (United States)

    Dehghan, Mohammad; Akbari, Negin; Alborzi, Nazila; Sadani, Somayeh; Keshtkar, Abas A

    2010-08-01

    This study was designed to compare the therapeutic effects of topical clotrimazole and systemic fluconazole in pityriasis versicolor. A double-blind randomized controlled trial was carried out in the dermatological clinic of Gorgan, northern Iran, between April 2006 and May 2007. All consecutive patients with pityriasis versicolor were included and randomly divided into two groups. In the first group (G1), patients underwent treatment with a single dose of fluconazole capsule (400 mg) and placebo cream. In the second group (G2), patients underwent treatment with clotrimazole cream (twice daily) and placebo capsule. The course of treatment was 2 weeks. All subjects were re-evaluated 2, 4 and 12 weeks after the end of the therapeutic course. After 2 weeks, the rate of complete resolution of disease was significantly higher in G2 than G1 (49.1% vs 30%). After 4 weeks, 41 patients (81.2%) of G1 and 52 patients (94.9%) of G2 showed complete resolution. After 12 weeks, 46 patients (92%) in G1 and 45 patients (81.8%) in G2 showed complete resolution. Recurrence rate in G1 and G2 were 6% and 18.2%, respectively. No complications were seen in either group. In this study, clinical response at week 4 was greater in the clotrimazole group than the fluconazole group. Recurrence at week 12 after treatment was less with oral fluconazole than clotrimazole cream. So, for better evaluation, more studies need to be done.

  1. Fate of [14C] warfarin in guinea-pigs: effect of a concomitant single dose of salicylate

    International Nuclear Information System (INIS)

    Wong, L.T.; Solomonraj, G.; Thomas, B.H.

    1978-01-01

    When a single dose of sodium salicylate (177.8 mg kg -1 , by mouth) was given with [ 14 C] warfarin (1 mg kg -1 , i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14 C for 6 h. At 1 h, salicylate increased the distribution of 14 C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14 C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14 C in the first 5 h after salicylate and a decrease in 14 C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [ 14 C] warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin. (author)

  2. Effect of a single dose of low-level laser therapy on spontaneous and chewing pain caused by elastomeric separators.

    Science.gov (United States)

    Qamruddin, Irfan; Alam, Mohammad Khursheed; Fida, Mubassar; Khan, Asma Gul

    2016-01-01

    The aim of this study was to see the effect of a single dose of low-level laser therapy on spontaneous and chewing pain after the placement of elastomeric separators. Eighty-eight patients were randomly selected for this single-blind study. Elastomeric separators were placed mesial and distal to the permanent first molars in all quadrants. Both arches were divided into experimental and control sides. The experimental sides were treated with low-level laser therapy on 3 points on the buccal mucosa for 20 seconds each, with a 940-nm gallium-aluminum-arsenic diode laser on continuous mode and power set at 200 mW. The other side received placebo laser therapy without turning on the laser. A numeric rating scale was used to assess the intensity of spontaneous and chewing pain for the next 7 days. The independent sample t test and repeated-measures analysis of variance with the post hoc Tukey test was used to analyze the results. Significant differences were found in spontaneous and chewing pain among both groups (P low-level laser therapy can be an efficient modality to reduce the postoperative pain associated with the placement of elastomeric separators. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  3. The impact of salpingectomy and single-dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy.

    Science.gov (United States)

    Sahin, Cagdas; Taylan, Enes; Akdemir, Ali; Ozgurel, Banu; Taskıran, Dilek; Ergenoglu, Ahmet M

    2016-10-01

    To investigate the effects of salpingectomy and methotrexate treatments on ovarian reserve in ectopic pregnancy. In this prospective study, a total of 131 patients with ectopic pregnancy were divided into 3 groups of methotrexate (MTX) only (Group-1, n: 55), salpingectomy only (Group-2, n: 61), and salpingectomy following MTX (Group-3, n: 15). Pretreatment and post-treatment anti-Müllerian hormone (AMH) levels were evaluated. Significant differences in AMH levels were detected between group 1 and group 2 (2.52±1.28 vs. 1.96±1.66, p=0.043), and group 1 and group 3 (2.52±1.28 vs. 1.77±0.76, p=0.035) at one month postoperative. However, these differences disappeared at the 3rd postoperative month. When AMH levels were compared within the same group, postoperative one month AMH levels were significantly lower than the preoperative AMH levels only in group 3 (p=0.03). However, this difference also disappeared at the 3rd postoperative month. Systemic single-dose methotrexate treatment, unilateral salpingectomy, and salpingectomy following methotrexate administration in ectopic pregnancy were reassuring based on pretreatment and post-treatment AMH levels. Current medical and surgical treatment approaches do not have an obvious negative effect on ovarian reserve. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    2014-01-01

    Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

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

    Science.gov (United States)

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

    2012-08-01

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

  6. A Pilot Study on Single-dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Ilhong Son

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze single dose toxicity and the lethal dose of Scolopendrid Pharmacopuncture in rats. Methods:All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered to the experimental group, and 1.0 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results:No deaths or abnormalities occurred in any of the groups. No significant changes in the weight, hematological parameters or clinical chemistry were noted between the control group and the experimental group. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion:The above findings suggest Scolopendrid Pharmacopuncture is a relatively safe to use for treatment. Further studies on the subject should be conducted to yield more concrete evidence.

  7. [Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

    Science.gov (United States)

    Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

    2014-03-01

    To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

  8. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

    Science.gov (United States)

    Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-10-01

    Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

  9. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

    Science.gov (United States)

    Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-01-01

    Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

  10. Leprosy Post-Exposure Prophylaxis (LPEP) programme: Study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

    NARCIS (Netherlands)

    Barth-Jaeggi, T. (Tanja); Steinmann, P. (Peter); Mieras, L. (Liesbeth); W.H. van Brakel (Wim); J.H. Richardus (Jan Hendrik); Tiwari, A. (Anuj); Bratschi, M. (Martin); Cavaliero, A. (Arielle); Vander Plaetse, B. (Bart); Mirza, F. (Fareed); Aerts, A. (Ann)

    2016-01-01

    textabstractIntroduction: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose

  11. Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Motokazu Kato

    2010-01-01

    Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations.

  12. The effect of single dose versus two doses of praziquantel on Schistosoma haematobium infection and pathology among school-aged children in Mali

    DEFF Research Database (Denmark)

    Sacko, M.; Magnussen, Pascal; Traoré, M.

    2009-01-01

    The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled interventi...

  13. Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years.

    Science.gov (United States)

    Negredo, E; Bonjoch, A; Pérez-Álvarez, N; Ornelas, A; Puig, J; Herrero, C; Estany, C; del Río, L; di Gregorio, S; Echeverría, P; Clotet, B

    2015-08-01

    Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96. The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients. © 2015 British HIV Association.

  14. SiC-based neutron detector in quasi-realistic working conditions: efficiency and stability at room and high temperature under fast neutron irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Ferone, Raffaello; Issa, Fatima; Ottaviani, Laurent; Biondo, Stephane; Vervisch, Vanessa [IM2NP, UMR CNRS 7334, Aix-Marseille University, Case 231,13397 Marseille Cedex 20, (France); Szalkai, Dora; Klix, Axel [KIT- Karlsruhe Institute of Technology, Institute of Neutron Physics and Reactor Technology Karlsruhe 76344, (Germany); Vermeeren, Ludo [SCK-CEN, Boeretang 200, B-2400 Mol, (Belgium); Saenger, Richard [Schlumberger, Clamart, (France); Lyoussi, Abadallah [CEA, DEN, Departement d' Etudes des Reacteurs, Service de Physique Experimentale, Laboratoire Dosimetrie Capteurs Instrumentation, 13108 Saint-Paul-lez-Durance, (France)

    2015-07-01

    In the framework of the European I SMART project, we have designed and made new SiC-based nuclear radiation detectors able to operate in harsh environments and to detect both fast and thermal neutrons. In this paper, we report experimental results of fast neutron irradiation campaign at high temperature (106 deg. C) in quasi-realistic working conditions. Our device does not suffer from high temperature, and spectra do show strong stability, preserving features. These experiments, as well as others in progress, show the I SMART SiC-based device skills to operate in harsh environments, whereas other materials would strongly suffer from degradation. Work is still demanded to test our device at higher temperatures and to enhance efficiency in order to make our device fully exploitable from an industrial point of view. (authors)

  15. Pharmacokinetics of a single dose of voriconazole administered orally with and without food to red-tailed hawks (Buteo jamaicensus).

    Science.gov (United States)

    Parsley, Ruth A; Tell, Lisa A; Gehring, Ronette

    2017-04-01

    OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.

  16. Blood-spinal cord barrier function and morphometry after single doses of x-rays in rat spinal cord

    International Nuclear Information System (INIS)

    Stewart, Patricia A.; Vinters, Harry V.; Wong, C. Shun

    1995-01-01

    Purpose: The effects of irradiation on blood-spinal cord barrier (BSCB) function and ultrastructure were evaluated using a rat spinal cord model. Methods and Materials: Rats received a single dose of 25 Gy to the cervical spinal cord (C2-T2). At various times following irradiation and before the onset of paralysis, BSCB function was assessed using horseradish peroxidase (HRP) as a vascular tracer, and barrier-related structural changes in the capillaries were evaluated using morphometric techniques. Results: Focal extravasation of HRP was seen at 93 days after irradiation, and extensive extravasation was apparent by 114 days in white matter, but not in gray matter. At 93 days, pathologic changes apparent by light microscopy were very minor in the white matter of the irradiated segment. By 107 days, myelin beading, Wallerian degeneration, edema, and histiocytes were apparent in white matter, and these features became increasingly prominent over the following weeks. No noteworthy changes were seen in gray matter at these times. Electron microscopic examination showed that, during the first 93 days following irradiation, more than half of the endothelial cells in white matter had disappeared (p < 0.05). In terms of the putative vascular pores, no abnormalities in endothelial junctions (the presumed small pore) were found, but there was an increase in the density of endothelial vesicles (a putative form of the large pore) in irradiated white matter (p < 0.001), but not in gray matter. Pericytes, thought to act as a second line of defence in the blood-brain barrier, increased in size but not in number in the irradiated white matter of the spinal cord. Conclusion: We suggest that radiation damage to endothelial cells, which form the BSCB prior to the onset of neurological deficit, may play an important role in the pathogenesis of white matter necrosis

  17. Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

    Science.gov (United States)

    Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

    2011-06-15

    Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

  18. Single dose CpG immunization protects against a heterosubtypic challenge and generates antigen specific memory T cells

    Directory of Open Access Journals (Sweden)

    Alexander eVogel

    2015-06-01

    Full Text Available Despite extensive research, influenza A virus (IAV remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains such as H5N1 and pandemic H1N1 highlight the need for universal, cross-protective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated x31 (H3N2 reduced viral titers and partially protected mice from a heterosubtypic challenge with a lethal dose of PR8 (H1N1. Early after immunization, vaccinated mice showed increased innate immune activation with high levels of MHCII and CD86 expression on dendritic cells in both the draining lymph nodes and lungs. Three days after immunization, CD4 and CD8 cells in the lung upregulated CD69, suggesting that activated lymphocytes are present at the site of vaccine administration. The ensuing effector Th1 responses were capable of producing multiple cytokines and were present at least 30 days after immunization. Furthermore, functional memory responses were observed, as antigen specific IFN-γ+ and GrB+ cells were detected early after lethal infection. Together, this work provides evidence for using pattern recognition receptor agonists as a mucosal vaccine platform for inducing robust T cell responses capable of protecting against heterologous IAV challenges.

  19. Design and statistical considerations for studies evaluating the efficacy of a single dose of the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H

    2018-05-01

    Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.

  20. Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections.

    Science.gov (United States)

    Dey, Sudipta Kumar; Das, Amal Kanti; Sen, Sumit; Hazra, Avijit

    2015-01-01

    Uncomplicated skin and skin structure infections (uSSSIs) are a common clinical problem. Majority are caused by staphylococci and streptococci. Different oral antibiotics are used for uSSSI, with comparable efficacy but varying treatment duration, cost, and adverse event profile. Azithromycin is used in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g dose of the drug would produce a response in uSSSI comparable to conventional dosing. We conducted a parallel group, open-label, randomized, controlled trial (CTRI/2015/07/005969) with subjects of either sex, ≥12 years of age, presenting with uSSSI to the dermatology outpatient department. One group (n = 146) received 2 g single supervised dose while the other (n = 146) received conventional dose of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8. Complete clinical cure implied complete healing of lesions, without residual signs or symptoms, within 7 days. High cure rate was observed in both arms (97.97% and 98.63%, respectively) along with noticeable improvement in symptom profile from baseline but without statistically significant difference between groups. However, excellent adherence (defined as no tablets missed) was better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable between groups with the majority of adverse events encountered being gastrointestinal in nature and mild. Single 2 g azithromycin dose achieved the same result as conventional azithromycin dosing in uSSSI with comparable tolerability but with the advantage of assured adherence. This dose can, therefore, be recommended as an alternative and administration supervised if feasible.

  1. Single-dose protection against Plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron A.

    Science.gov (United States)

    Sridhar, S; Reyes-Sandoval, A; Draper, S J; Moore, A C; Gilbert, S C; Gao, G P; Wilson, J M; Hill, A V S

    2008-04-01

    Human adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigen Plasmodium berghei circumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8(+) T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.

  2. Nitrogen-13 glutamate uptake and perfusion in Walker 256 carcinosarcoma before and after single-dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, W.H.; Helus, F.; Layer, K.; Panzer, M.; Hoever, K.H.O.; Ostertag, H.

    1986-10-01

    Nitrogen-13 (13N) glutamate uptake was recorded in 18 anesthetized rats, both before and at least once after intervention. Each investigation was immediately followed by imaging of blood flow distribution using (11C)butanol. All animals had Walker 256 carcinosarcoma implants in one hind leg. Tumors were locally irradiated with a dose of 800 rad in 14 rats; in four rats, the vasoactive substance 5-hydroxytryptamine (5-HT) was administered. Prior to interventions, the (13N)glutamate tumor-to-muscle uptake showed a linear correlation with blood flow close to identity (y = 0.117 + 0.915x, r = 0.97). After irradiation, a discordant pattern was observed: blood flow tended to increase, while (13N)glutamate tumor-to-muscle uptake dropped from 4.30 +/- 0.66 (s.e.m.) to 3.06 +/- 0.36 (p less than 0.005) during 30 min and attained 4.04 +/- 0.67 2 days later. If (13N)glutamate tumor-to-muscle uptake was related to that of (11C) butanol in each individual animal, this index dropped from 0.93 +/- 0.03 (s.e.m.) to 0.62 +/- 0.04 (p less than 0.001) 30 min after irradiation and attained 0.90 +/- 0.09 after 2 days. In animals treated with 5-HT, (13N)glutamate and (11C)butanol showed a parallel drop from 6.60 +/- 0.84 to 2.10 +/- 0.60 (p less than 0.05) and from 6.8 +/- 0.78 to 2.08 +/- 0.74 (p less than 0.05), respectively. Thus, single-dose irradiation causes (13N)glutamate uptake to be uncoupled with respect to flow, while (13N)glutamate uptake in untreated tumors is flow-limited and responds together with flow on vasomotion.

  3. Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Kim, Yo Han; Hong, Donghyun; Kim, Seong Su; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2015-08-01

    We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model. This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates. Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), and 175 mg/50 cm(2) were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm(2) and 175 mg/50 cm(2) every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations. A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm(2) or 175 mg/50 cm(2) patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

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

    Science.gov (United States)

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

    2013-03-01

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

  5. A single dose of sodium nitrate does not improve oral glucose tolerance in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Cermak, Naomi M; Hansen, Dominique; Kouw, Imre W K; van Dijk, Jan-Willem; Blackwell, Jamie R; Jones, Andrew M; Gibala, Martin J; van Loon, Luc J C

    2015-08-01

    Dietary nitrate (NO3(-)) supplementation has been proposed as an emerging treatment strategy for type 2 diabetes. We hypothesized that ingestion of a single bolus of dietary NO3(-) ingestion improves oral glucose tolerance in patients with type 2 diabetes. Seventeen men with type 2 diabetes (glycated hemoglobin, 7.3% ± 0.2%) participated in a randomized crossover experiment. The subjects ingested a glucose beverage 2.5 hours after consumption of either sodium NO3(-) (0.15 mmol NaNO3(-) · kg(-1)) or a placebo solution. Venous blood samples were collected before ingestion of the glucose beverage and every 30 minutes thereafter during a 2-hour period to assess postprandial plasma glucose and insulin concentrations. The results show that plasma NO3(-) and nitrite levels were increased after NaNO3(-) as opposed to placebo ingestion (treatment-effect, P = .001). Despite the elevated plasma NO3(-) and nitrite levels, ingestion of NaNO3(-) did not attenuate the postprandial rise in plasma glucose and insulin concentrations (time × treatment interaction, P = .41 for glucose, P = .93 for insulin). Despite the lack of effect on oral glucose tolerance, basal plasma glucose concentrations measured 2.5 hours after NaNO3(-) ingestion were lower when compared with the placebo treatment (7.5 ± 0.4 vs 8.3 ± 0.4 mmol/L, respectively; P = .04). We conclude that ingestion of a single dose of dietary NO3(-) does not improve subsequent oral glucose tolerance in patients with type 2 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax.

    Science.gov (United States)

    Kma, Lakhan; Gao, Feng; Fish, Brian L; Moulder, John E; Jacobs, Elizabeth R; Medhora, Meetha

    2012-01-01

    Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradiation. Rats that survived acute pneumonitis (at 6-12 weeks) were evaluated monthly for synthesis of lung collagen. Other endpoints included breathing rate, wet to dry lung weight ratio, and analysis of lung structure. Treatment with captopril (145-207 mg/m(2)/day) or enalapril (19-28 mg/m(2)/day), but not fosinopril (19-28 mg/m(2)/day), decreased morbidity from acute pneumonitis. Lung collagen in the surviving irradiated rats was increased over that of controls by 7 months after irradiation. This increase in collagen synthesis was not observed in rats treated with any of the three ACE inhibitors. Analysis of the lung morphology at 7 months supports the efficacy of ACE inhibitors against radiation-induced fibrosis. The effectiveness of fosinopril against fibrosis, but not against acute pneumonitis, suggests that pulmonary fibrosis may not be a simple consequence of injury during acute pneumonitis. In summary, three structurally-different ACE inhibitors mitigate the increase in collagen synthesis 7 months following irradiation of the whole thorax and do so, even when therapy is started one week after irradiation.

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

    Science.gov (United States)

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

    2017-03-01

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

  8. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study.

    Science.gov (United States)

    Wiebe, Sabrina; Schnell, David; Külzer, Raimund; Gansser, Dietmar; Weber, Anne; Wallenstein, Gudrun; Halabi, Atef; Conrad, Anja; Wind, Sven

    2017-06-01

    Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30-59 mL/min/1.73 m 2 and 15-29 mL/min/1.73 m 2 , respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC last ) and maximum plasma concentration (C max ) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUC last and C max , was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUC last for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3-213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28-39 % for moderate impairment, 34-42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.

  9. Single-Dose and Fractionated Irradiation Promote Initiation and Progression of Atherosclerosis and Induce an Inflammatory Plaque Phenotype in ApoE-/- Mice

    International Nuclear Information System (INIS)

    Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

    2008-01-01

    Purpose: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE -/- mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype. Methods and Materials: ApoE -/- mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examinated for presence of atherosclerotic lesions, plaque size, and phenotype. Results: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy. Conclusions: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE -/- mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype

  10. Ontogenetic timing as a condition-dependent life history trait: High-condition males develop quickly, peak early, and age fast.

    Science.gov (United States)

    Hooper, Amy K; Spagopoulou, Foteini; Wylde, Zachariah; Maklakov, Alexei A; Bonduriansky, Russell

    2017-03-01

    Within-population variation in ageing remains poorly understood. In males, condition-dependent investment in secondary sexual traits may incur costs that limit ability to invest in somatic maintenance. Moreover, males often express morphological and behavioral secondary sexual traits simultaneously, but the relative effects on ageing of investment in these traits remain unclear. We investigated the condition dependence of male life history in the neriid fly Telostylinus angusticollis. Using a fully factorial design, we manipulated male early-life condition by varying nutrient content of the larval diet and, subsequently, manipulated opportunity for adult males to interact with rival males. We found that high-condition males developed more quickly and reached their reproductive peak earlier in life, but also experienced faster reproductive ageing and died sooner than low-condition males. By contrast, interactions with rival males reduced male lifespan but did not affect male reproductive ageing. High-condition in early life is therefore associated with rapid ageing in T. angusticollis males, even in the absence of damaging male-male interactions. Our results show that abundant resources during the juvenile phase are used to expedite growth and development and enhance early-life reproductive performance at the expense of late-life performance and survival, demonstrating a clear link between male condition and ageing. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  11. Study on liquid-metal MHD power generation system with two-phase natural circulation. Applicability to fast reactor conditions

    International Nuclear Information System (INIS)

    Saito, Masaki

    2000-03-01

    Feasibility study of the liquid-metal MHD power generation system combined with the high-density two-phase natural circulation has been performed for the applicability to the simple, autonomic energy conversion system of the liquid-metal cooled fast reactor. The present system has many promising aspects not only in the energy conversion process, but also in safety and economical improvements of the liquid-metal cooled fast reactor. For example, the high cycle efficiency can be expected because of the similarity of the present cycle to the Ericsson cycle. Sodium-Water Interaction problem can be excluded by proper combination of the working fluids. As the economical feature, the present system is so simple that the liquid-metal main circular pump, the steam turbine generator, and even the steam generator can be excluded if the thermodynamic working fluid is injected directly into the high temperature liquid metal MHD working fluid. In addition, the present system has the potential to be applied to various heat sources including solar energy because of the high flexibility of the operation temperature. In the present paper, as the first step of the feasibility study, the cycle analyses were performed to examine the effects of the main system parameters on the fundamental characteristics of the system. It is found that the cycle efficiency of the present system is enough competitive with that of the conventional steam turbine system. It is, however, found that the cycle efficiency depends strongly on the gas-liquid slip ratio in the two-phase flow channel. As the conclusions, it is recommended to perform experimental study to obtain the fundamental data, such as the gas-liquid slip ratio in the high-density liquid-metal two-phase natural circulation. (author)

  12. SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

    Science.gov (United States)

    Tulloch, Simon J; Zhang, Yuxin; McLean, Angus; Wolf, Kathleen N

    2002-11-01

    To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.

  13. Scattering of H(D) from LiF(1 0 0) under fast grazing incidence conditions: To what extent is classical dynamics a useful tool?

    Energy Technology Data Exchange (ETDEWEB)

    Muzas, A.S. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Martín, F. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-nanociencia), Cantoblanco, 28049 Madrid (Spain); Díaz, C., E-mail: cristina.diaz@uam.es [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain)

    2015-07-01

    Diffraction experiments of atoms and molecules under fast grazing incidence conditions have opened a new field in surface science. This experimental effort calls for complementary theoretical studies, which would allow a detailed analysis of experimental data. Here, we have analyzed the ability of classical dynamics simulations to reproduce experimental results. To perform this study, a DFT (density functional theory) based potential energy surface, describing the interaction between a H atom and a LiF(1 0 0) surface, has been computed. Diffraction probabilities have been simulated by means of a classical binning method. Our results have been found to be in qualitative good agreement with recent experimental measurements.

  14. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  15. Misonidazole cytotoxicity in vivo: a comparison of large single doses with smaller doses and extended contact of the drug with tumor cells

    International Nuclear Information System (INIS)

    Conroy, P.J.; Sutherland, R.M.; Passalacqua, W.

    1980-01-01

    Experiments were performed to determine the kinetics and magnitude of misonidazole cytotoxicity in EMT6/Ro tumors using an in vivo-in vitro clonogenicity assay. A comparison was made between the cytotoxic effects of large single doses with smaller doses of misonidazole administered ip and those produced on extended contact of the drug with tumor cells using a continuous iv drug infusion system. After a single ip dose of 1 mg/g, cytotoxicity was maximum at 18 to 24 h; by 72 h the clonogenic cells per tumor had returned to control levels. The maximum cytotoxicity was greater (a decrease of 10 times) if the animals were kept at 37 0 C compared with ambient conditions (a decrease of 4.5 times) where the body temperature would decrease due to the drug. A dose-response curve performed with the animals at 37 0 C showed no significant cytotoxicity at 18 h after single ip doses of 0.5 mg/g or less. Other experiments were carried out at 37 0 C using a drug continuous infusion system. Two profiles were studied: (a) continuous constant rate infusion over 3 days of constant serum and tumor levels of both 100 and 200 μg/ml and (b) continuous variable rate infusion where the maximum serum levels reached 80 or 200 μg/ml after 2 to 4 h and decayed with a half-life of 12 h as in humans. Significant cytotoxicity was obtained under both of these conditions. Maximum cytotoxicity occurred at about 24 h in both types of experiments and amounted to decreases of clonogenic tumor cells of 4.5 and 7 times for 100 and 200 μg/ml, respectively, after constant rate infusion and 2 to 4 times for 80 and 200 μg/ml, respectively, after variable rate infusion. Because of the relatively rapid recovery in the number of clonogenic tumor cells by 72 h, the cytotoxic effects were not reflected as changes in tumor size even when the animals were maintained at 37 0 C

  16. Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration.

    Science.gov (United States)

    McBride, John W; Dias, Nicola; Cameron, David; Offord, Robin E; Hartley, Oliver; Boyd, Peter; Kett, Vicky L; Malcolm, R Karl

    2017-10-01

    5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES following single-dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24-mg/ml), intermediate (6.18-mg/ml), and high (32.0-mg/ml; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability, and in vitro release testing. Following vaginal gel administration to sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue, and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behavior, with the high-concentration gels exhibiting a greater viscosity and cohesive structure than the intermediate- and low-concentration gels. In in vitro release testing, >90% 5P12-RANTES was released from the low- and intermediate-concentration gels after 72 h. For the high-concentration gel, ∼50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilization and/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, vaginal tissue, and serum increased in a dose-dependent manner. The highest concentrations were measured in vaginal fluid (10 5 to 10 7 ng/ml), followed by vaginal tissue (10 4 to 10 6 ng/ml). Both of these concentration ranges are several orders of magnitude above the reported half-maximal inhibitory concentrations. The lowest concentration was measured in serum (<10 2 ng/ml). The 5P12-RANTES pharmacokinetic data are similar to those reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's potency at picomolar concentrations, its strong barrier to resistance, and the full protection that it was observed to provide in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as

  17. Columns and optimum gradient conditions for fast second-dimension separations in comprehensive two-dimensional liquid chromatography.

    Science.gov (United States)

    Hájek, Tomáš; Jandera, Pavel

    2012-07-01

    Gradient elution provides significantly higher peak capacity in comparison to the isocratic elution mode, hence it is very useful in online comprehensive two-dimensional liquid chromatography (LC). We compared suitability of five commercial core-shell columns and one monolithic column for fast gradients in the second LC dimension, where the time of separation is strictly limited by the fraction cycle time. In two-dimensional reversed-phase systems with partially correlated retention, the resolution, the peak capacity, and the regularity of coverage of the second-dimension retention space can be improved by appropriate adjusting the gradient time and the gradient range to suit the sample properties. We developed a new strategy for adjusting the gradient mobile phase composition range in the second-dimension, employing the retention data of representative sample standards characterizing the sample properties, which can be calibrated using the reference alkylbenzene series. Optimized second-dimension gradients with single-step or segmented profiles covering two or more fraction ranges, employed for the separation of subsequent fractions from the first-dimension, improve significantly the resolution, the separation time, and the regularity of coverage of the two-dimensional retention plane. The approach was applied to the two-dimensional comprehensive separation of phenolic acids and flavonoid compounds occurring as natural antioxidants. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

    2015-01-01

    randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...... medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...

  19. Double-blind double-dummy crossover comparison of the effect of a single dose of cimetidine and trithiozine on gastric secretion.

    Science.gov (United States)

    Procacciante, F; Benvenuti, C; Citone, G; Montesani, C; Ribotta, G

    1980-01-01

    Twelve patients with duodenal ulcer were admitted to a double-blind double-dummy single dose study in which the H2-receptor antagonist effect of Cimetidine and the activity of Trithiozine, endowed with an unknown mechanism, on gastric acid secretion were compared. For the balanced incomplete block design each patient received two out of four treatments. The single doses tested were 200 and 400 mg of both drugs. Cimetidine reduced all the parameters investigated, while Trithiozine increased basal acid output and acid concentration and did not affect maximal and peak acid output, basal and maximal volume and maximal acid concentration. The multiple range comparison between mean adjusted differences of the four doses were significantly in favour of Cimetidine, except for PAO, basal volume and basal acid concentration, despite the remarkable percent difference between Cimetidine and Trithiozine. In this study, Cimetidine confirmed its inhibitory properties, and Trithiozine did not appear to be an antisecretory agent.

  20. Fast “Feast/Famine” Cycles for Studying Microbial Physiology Under Dynamic Conditions : A Case Study with Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Suarez-Mendez, C.A.; Sousa, A.; Heijnen, J.J.; Wahl, S.A.

    2014-01-01

    Microorganisms are constantly exposed to rapidly changing conditions, under natural as well as industrial production scale environments, especially due to large-scale substrate mixing limitations. In this work, we present an experimental approach based on a dynamic feast/famine regime (400 s) that

  1. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    Science.gov (United States)

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  2. Pharmacokinetics of Solithromycin (CEM-101) after Single or Multiple Oral Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult Subjects▿

    OpenAIRE

    Still, J. Gordon; Schranz, Jennifer; Degenhardt, Thorsten P.; Scott, Drusilla; Fernandes, Prabhavathi; Gutierrez, Maria J.; Clark, Kay

    2011-01-01

    The pharmacokinetics of orally administered solithromycin (CEM-101), a novel fluoroketolide, were evaluated in healthy subjects in three phase 1 studies. In two randomized, double-blinded, placebo-controlled studies, escalating single oral doses of solithromycin (50 to 1,600 mg) or seven oral daily doses (200 to 600 mg) of solithromycin were administered. A third study evaluated the effects of food on the bioavailability of single oral doses (400 mg) of solithromycin. Following single doses, ...

  3. Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen.

    Science.gov (United States)

    Yıldırım, Aysegul; Cırık, Derya Akdağ; Altay, Metin; Gelisen, Orhan

    2015-06-01

    To investigate the predictive factors for the requirement of additional doses of methotrexate in women with ectopic pregnancy treated with single-dose methotrexate regimen. This retrospective cohort study was conducted on women treated with single-dose methotrexate regimen for ectopic pregnancy at a tertiary referral center. Control group included the patients who were treated only with a single dose of methotrexate (n = 131) and study group included the patients who need a second dose or third dose methotrexate (n = 76). The sonographic variables such as size of the ectopic mass, the endometrial thickness and biochemical variables were analyzed via Chi square and student t test. Logistic regression analysis used to determine independent predictors of the additional dose requirement. The size of the ectopic mass and the endometrial thickness were similar in both groups. However, all human chorionic gonadotropin values on day 1, 4 and 7 were significantly higher in study group than the control group (p = 0.0001). Logistic regression analysis revealed that the human chorionic gonadotropin changes between day 1 and 4 is a predictive factor for requirement of additional doses of methotrexate (area under curve: 0.763, p 22% reduction from day 1 to 4. Less than 22% reduction in human chorionic gonadotropin levels from day 1 to 4 can be used as a predictive factor for the requirement of an additional dose of methotrexate in single-dose regimen. This cutoff value can be used for patients to inform about the probable longer resolution time and refer to alternative treatment modalities such as two-dose, multiple-dose regimens or surgery.

  4. Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial.

    Science.gov (United States)

    Fillekes, Quirine; Muro, Eva P; Chunda, Catherine; Aitken, Susan; Kisanga, Elton R; Kankasa, Chipepo; Thomason, Margaret J; Gibb, Diana M; Walker, A Sarah; Burger, David M

    2013-11-01

    To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women. In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antiretroviral (ARV)-naive pregnant women ≥18 years old from Zambia and Tanzania and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group. Primary endpoints were the pharmacokinetics of and resistance to nevirapine. Thirty-five and 37 women were allocated to the control and intervention groups, with median (IQR) ages of 27 (23-31) and 27 (23-33) years, respectively. Twenty-three and 23 women had detectable nevirapine levels at delivery and subsequent samples in the control and the intervention groups, respectively. Geometric mean (GM) (95% CI) plasma levels of nevirapine at delivery were 1.02 (0.58-1.78) mg/L and 1.14 (0.70-1.86) mg/L in the control and intervention groups, respectively (P = 0.76). One week after delivery, 0/23 (0%) and 15/22 (68%) control and intervention mothers, respectively, had undetectable levels of nevirapine ( 0.28). Adding 7 days of an enzyme inducer to single-dose nevirapine to prevent mother-to-child transmission of HIV significantly reduced subtherapeutic nevirapine levels by shortening the half-life of nevirapine. As prolonged subtherapeutic nevirapine dosage leads to the emergence of resistance, single-dose nevirapine could be used with phenytoin as an alternative if other ARVs were unavailable.

  5. Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China

    International Nuclear Information System (INIS)

    Tian Jia-he; Zhang Jin-ming; He Yi-jie; Hou Qing-tian; Oyang Qiao-hong; Wang Jian-min; Chuan Ling

    1999-01-01

    A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with 153 Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician's Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29±14.47 and 20.13±13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54±25.90 to 71.67±26.53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5 x 10 9 /l) and platelet (nadir 6.0 x 10 10 /l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, 153 Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of

  6. Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

    2017-03-01

    The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

  7. Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.

    Science.gov (United States)

    Jablonka, Eric M; Lamelas, Andreas M; Kim, Julie N; Molina, Bianca; Molina, Nathan; Okwali, Michelle; Samson, William; Sultan, Mark R; Dayan, Joseph H; Smith, Mark L

    2017-08-01

    Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. Therapeutic, III.

  8. Cost-effectiveness of single-dose tamsulosin and dutasteride combination therapy compared with tamsulosin monotherapy in patients with benign prostatic hyperplasia in the UK.

    Science.gov (United States)

    Walker, Anna; Doyle, Scott; Posnett, John; Hunjan, Manjit

    2013-09-01

    To estimate the long-term cost-effectiveness of single-dose dutasteride/tamsulosin combination therapy as a first-line treatment for benign prostatic hyperplasia (BPH) from the perspective of the UK National Health Service (NHS). A Markov state transition model was developed to estimate healthcare costs and patient outcomes, measured by quality-adjusted life years (QALYs), for patients aged ≥50 years with diagnosed BPH and moderate to severe symptoms. Costs and outcomes were estimated for two treatment comparators: oral, daily, single-dose combination therapy (dutasteride 0.5 mg + tamsulosin 0.4 mg), and oral daily tamsulosin (0.4 mg) over a period up to 25 years. The efficacy of comparators was taken from results of the Combination of Avodart and Tamsulosin (CombAT) trial. Cumulative discounted costs per patient were higher with combination therapy than with tamsulosin, but QALYs were also higher. After 25 years, the incremental cost-effectiveness ratio for combination therapy was £12,219, well within the threshold range (£20,000-£30,000 per QALY) typically applied in the NHS. Probabilistic sensitivity analysis showed that the probability of combination therapy being cost-effective given the threshold range is between 78% and 88%. Single-dose combination dutasteride/tamsulosin therapy has a high probability of being cost-effective in comparison to tamsulosin monotherapy in the UK's NHS. © 2013 BJU International.

  9. Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

    Science.gov (United States)

    Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

    2016-11-01

    Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1

    Science.gov (United States)

    Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Kagaayi, Joseph; Kizza, Allan; Pillay, Visva; Laeyendecker, Oliver; Reynolds, Steven J.; Eshleman, Susan H.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.

    2009-01-01

    Background Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4+ T cells, potentially complicating future treatment. Methods Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4+ T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. PMID:19338474

  11. Fast-Growing Energy Crops Grown In Conditions Of Slovakia In The Context Of The EU Energy Policy

    Directory of Open Access Journals (Sweden)

    Jureková Zuzana

    2015-05-01

    Full Text Available The energy-efficient low-carbon EU economy (known as the 20-20-20 sets fundamental objectives in reducing greenhouse gas emissions (20%, increasing the share of renewable energy sources (20% and saving primary energy consumption (20%. The objectives are incorporated in the National Renewable Energy Action Plans (NREAPs. Slovakia has to increase the share of renewable energy sources (RES by 14% in its energy mix by 2020. Currently, the most widely used RES are water and solar energy, biomass and biogas. Our country has suitable ecological conditions for growing the so called energy crops in lowland and upland areas. So far, however, there is a lack of science-based information on the potential production of biomass in different soil-ecological and climatic conditions of the Slovak Republic. Our experimental research is focused on quantification of biomass production of various willow (genus Salix, poplar (genus Populus and silvergrass (Miscanthus sinensis varieties grown in ecological conditions of southern Slovakia. We evaluated the biomass production of the studied crops. The results were evaluated in terms of the EU call (2013: to obtain more energy while reducing inputs and negative environmental impacts.

  12. Fast sampling under process conditions and after new start-up in the steam-water cycle of power plant

    Energy Technology Data Exchange (ETDEWEB)

    Maughan, E.V. [College of Knowledge, Duisburg (Germany); Hoerig, A. [Dr. Leye GmbH (Germany); Leleux, K.H.; Leye, W.

    2007-11-15

    Acid (''cation'') conductivity is used throughout the power industry by manufacturers of steam-driven plants, utility operators and supporting organisations (e.g. the VGB) in specifications, guidelines and standards to quantify steam quality. Although this measured quantity is non-specific and cannot identify any single contaminant, it remains nevertheless a good indication of the steam quality being fed to the turbine. Since the acid conductivity is measured after a strong cation resin exchanger, any changes in flow can upset the measured result, even if flow is discontinued for a short period of time. In addition the presence of dissolved carbon dioxide, found mainly under start-up conditions, will strongly influence the measurement and mask the presence of more harmful ionic contaminants, which have been implicated in the corrosion of materials of construction in the plant cycle. This presentation describes a method to maintain the integrity of the cation exchanger resin even under upset flow conditions and a device for the rapid removal of dissolved carbon dioxide (degassed acid conductivity) to eliminate this nuisance contaminant, which would otherwise unnecessarily delay the return of the steam turbine to service, owing to elevated acid conductivity values. In addition a device to remove transported corrosion products (particularly present during start-up conditions), thus preventing ''blinding'' of on-line sensors and contamination of the analysers, is also presented. (orig.)

  13. Radiation-induced heart disease due to intrathonacic tumor radiotherapy of a single dose to the rabbits' heart

    International Nuclear Information System (INIS)

    Zhou Weibing; Feng Yan; Chen Jiayi; Luo Quanyong

    2007-01-01

    found in rabbits heart irradiated in clinical related single dose ranging from 0 to 18 Gy, which suggests that the incidence of acute RIHD is lower in thoracic tumor radiotherapy. Yet, we must bear in mind, if the dose is more than or equal to 22 Gy, severe heart damage may occur. The dose to the heart should be kept minimum. ECG is an useful method to detect the RIHD. Further research on the validity of heart SPECT( 99 Tc m -MIBI) is necessary, and important. There are no positive findings of the 99 Tc m -HL91 and 99m Tc-Annexin V used as SPECT agents to test the RIHD. (authors)

  14. Single-dose, randomized crossover comparisons of different-strength imatinib mesylate formulations in healthy Korean male subjects.

    Science.gov (United States)

    Kim, Kyoung-Ah; Park, Shin Jung; Kim, Chin; Park, Ji-Young

    2013-10-01

    Imatinib mesylate is used to treat chronic myeloid leukemia and advanced gastrointestinal stromal tumors. The purpose of this study was to compare the pharmacokinetics of 2 different strengths of the imatinib formulation containing 100 mg (reference) and 400 mg (test) to satisfy the regulatory requirement for marketing. A single-center, randomized, single-dose, open-label, 2-period, 2-sequence, comparative crossover study with a 14-day washout period was conducted in 30 healthy male volunteers. Plasma samples for the drug analysis were collected up to 72 hours after drug treatment. Participants received either the reference (4 tablets of 100-mg imatinib) or the test (1 tablet of 400-mg imatinib) formulation during the first period and the alternative formulation during the second period. The safety profiles and tolerability of the 2 formulations were also assessed based on physical examinations, laboratory tests, a 12-lead ECG, and vital signs. Thirty participants were initially enrolled; their mean (SD) age, height, weight, and body mass index were 24.9 (2.0) years (range, 23-30 years), 174 (5) cm (range, 164-185 cm), 69.9 (2.0) kg (range, 54.1-87.4 kg), and 23.0 (2.0) kg/m(2) (range, 18.5-26.9 kg/m(2)); 28 healthy participants completed both treatment periods. Two subjects did not complete the study because they withdrew consent for personal reasons. The observed mean (SD) Cmax, AUC0-last, and AUC0-∞ values for the reference formulation were 1792 (357) ng/mL, 28,485 (6274) ng · h/mL, and 29,079 (6371) ng · h/mL, respectively. Corresponding values for the test formulation were 1710 (312) ng/mL, 27,222 (4624) ng · h/mL , and 27,872 (4751) ng · h/mL. The geometric mean ratios (90% CIs) between the 2 formulations at the 400-mg dose of imatinib were 0.9579 (0.9054-1.0136) for Cmax, 0.9652 (0.9174-1.0155) for AUC0-last, and 0.9679 (0.9203-1.0179) for AUC0-∞, respectively. During the study period, 6 adverse events (3 for the reference and 3 for the test

  15. The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.

    Science.gov (United States)

    Hämmerle, Sibylle P; Mindeholm, Linda; Launonen, Aino; Kiese, Beate; Loeffler, Rolf; Harfst, Evita; Azria, Moise; Arnold, Michel; John, Markus R

    2012-04-01

    Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients. In this single-center, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women. 16 subjects were randomized to receive 4 single doses out of 6 different treatments: placebo, teriparatide 20 μg sc, or 1, 2.5, 5 or 10 mg of oral PTH134 formulated with 200 mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive 4 out of 6 different treatments: placebo, teriparatide 20 μg sc, or 2.5 or 5 mg of oral PTH134 formulated with either 100 or 200 mg 5-CNAC. Doses were given ≥6 days apart. All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1-34 disappeared from blood faster after oral than after sc administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of sc teriparatide 20 μg (Forsteo®). Mean+/-SD hPTH134 Cmax values were, respectively, 74+/-59, 138+/-101, 717+/-496, and 1624+/-1579 pg/mL for 1, 2.5, 5, and 10 mg doses of this peptide administered with 200 mg 5-CNAC; while mean+/-SD AUC (0-last) values were, respectively, 30+/-40, 62+/-69, 320+/-269, and 627+/-633 h*pg/mL. The corresponding estimates for teriparatide 20 μg sc were 149+/-35 for Cmax and 236+/-58 for AUC (0-last) Ionized calcium remained within normal limits in all treatment groups except for 3 isolated events. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH

  16. Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

    Science.gov (United States)

    Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

    2008-04-01

    Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

  17. A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

    Science.gov (United States)

    Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

    2016-10-17

    We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

  18. Increased bioavailability of celecoxib under fed versus fasted conditions is determined by postprandial bile secretion as demonstrated in a dynamic gastrointestinal model.

    Science.gov (United States)

    Lyng, Eric; Havenaar, Robert; Shastri, Prathap; Hetsco, Lucy; Vick, Andrew; Sagartz, John

    2016-08-01

    The objective of this study was to utilize physiologically relevant dynamic dissolution testing with the TNO intestinal model (TIM-1) in vitro gastrointestinal model to investigate the bioaccessibility of celecoxib. A single 200-mg dose of celecoxib was evaluated under average adult human physiological conditions simulated in the TIM-1 system. The in vitro data were compared with the clinically established pharmacokinetic data. When expressed as a percent of drug that progresses from the duodenum to the jejunum and ileum compartments (bioaccessible sites), the study demonstrated a 2-fold increase in the total bioaccessibility for celecoxib when co-administered with a high-fat meal as opposed to co-administration with a glass of water (fasted conditions). That increase in bioaccessibility was similar to a 1.2 to 1.6-fold increase in systemic exposure in adults and children following co-administration with a high-fat meal when compared to the exposure measured when celecoxib was co-administered with only water. Following that comparison, the flexibility of the TIM-1 system was used to more specifically investigate individual parameters of gastrointestinal conditions, such as the rate of bile secretion (emptying of the bile bladder) that accompanies high-fat meal consumption. We demonstrated that increased bile secretion after co-administration of a high-fat meal played a more important role in the increased celecoxib bioaccessibility than did the food matrix. This indicates that in humans without a bile bladder the exposure of celecoxib administered with food might be as low as under fasted state.

  19. A New Integrated Lab-on-a-Chip System for Fast Dynamic Study of Mammalian Cells under Physiological Conditions in Bioreactor

    Directory of Open Access Journals (Sweden)

    An-Ping Zeng

    2013-05-01

    Full Text Available For the quantitative analysis of cellular metabolism and its dynamics it is essential to achieve rapid sampling, fast quenching of metabolism and the removal of extracellular metabolites. Common manual sample preparation methods and protocols for cells are time-consuming and often lead to the loss of physiological conditions. In this work, we present a microchip-bioreactor setup which provides an integrated and rapid sample preparation of mammalian cells. The lab-on-a-chip system consists of five connected units that allow sample treatment, mixing and incubation of the cells, followed by cell separation and simultaneous exchange of media within seconds. This microsystem is directly integrated into a bioreactor for mammalian cell cultivation. By applying overpressure (2 bar onto the bioreactor, this setup allows pulsation free, defined, fast, and continuous sampling. Experiments evince that Chinese Hamster Ovary cells (CHO-K1 can be separated from the culture broth and transferred into a new medium efficiently. Furthermore, this setup permits the treatment of cells for a defined time (9 s or 18 s which can be utilized for pulse experiments, quenching of cell metabolism, and/or another defined chemical treatment. Proof of concept experiments were performed using glutamine containing medium for pulse experiments. Continuous sampling of cells showed a high reproducibility over a period of 18 h.

  20. Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: Effect of feeding and dose proportionality.

    Science.gov (United States)

    Akabane, R; Sato, T; Sakatani, A; Miyagawa, Y; Tazaki, H; Takemura, N

    2018-01-19

    Basic information related to the pharmacokinetics of sildenafil in dogs is scarce. This study aimed to describe the pharmacokinetic properties of oral sildenafil and determine the effect of feeding and dose proportionality. The effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated using a crossover study with six dogs. In addition, the dose proportionality of sildenafil ranging 1-4 mg/kg was evaluated using five dogs in the fasted states. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil administrations were well tolerated in all studies. Feeding reduced the area under the curve extrapolated to infinity (AUC inf ) and the maximum plasma concentration (C max ) significantly. The elimination half-life (T 1/2 ) did not differ between the fasted and the fed states. For dose proportionality, nonproportional increases in AUC inf and C max at 1-4 mg/kg doses were detected by a power model analysis. © 2018 John Wiley & Sons Ltd.

  1. Differential pharmacokinetics of diclofenac potassium for oral solution vs immediate-release tablets from a randomized trial: effect of fed and fasting conditions.

    Science.gov (United States)

    Chen, Cuiping; Bujanover, Shay; Kareht, Stephanie; Rapoport, Alan M

    2015-02-01

    analyzed for diclofenac concentrations. Pharmacokinetic parameters, including peak concentration (Cmax ), time to Cmax (tmax ), area under the concentration-time curve (AUC) from time 0 to last measurable concentration (AUCt ), and extrapolation to infinity (AUC∞ ) were obtained using non-compartmental analysis. Comparative assessments for Cmax and AUC were performed between the solution and tablet under fed and fasting conditions and between fed and fasting states for both formulations. Bioequivalent exposure was defined as the geometric mean ratio and its 90% confidence interval falling within 80.0-125.0% for Cmax and AUC. Adverse events (AEs) were monitored throughout the trial. Sixty-one percent of the 36 randomized subjects were male, 91.7% were Caucasian, and the mean (standard deviation [SD]) age was 31.9 (7.6) years. Thirty-three (91.7%) subjects completed all 4 treatments. When taken under fed conditions, the oral solution resulted in an approximately 80% faster median tmax (0.17 vs 1.25 hours, P = .00015) and a 21% lower Cmax (mean ± SD, ng/mL: 506 ± 305 vs 835 ± 449, P = .00061) compared with the tablet. AUC values were similar between the 2 formulations. When taken under fasting conditions, the oral solution exhibited a 50% faster median tmax (0.25 vs 0.50 hours, P = .00035) to achieve a 77% higher Cmax (mean ± SD, ng/mL: 1620 ± 538 vs 1160 ± 452, P = .00032) compared with the tablet. AUCt and AUC∞ were similar between the 2 formulations. When taken under fed conditions, the oral solution resulted in a similar median tmax (0.17 vs 0.25 hours, P = .185) and 64% lower Cmax (mean ± SD, ng/mL: 506 ± 305 vs 1620 ± 538, P Diclofenac potassium oral solution and tablet formulations produced statistically significantly different Cmax and tmax but similar AUC under fed and fasting conditions. Fed conditions produced significantly lower Cmax for both formulations and profoundly delayed tmax for the

  2. conditions

    Directory of Open Access Journals (Sweden)

    M. Venkatesulu

    1996-01-01

    Full Text Available Solutions of initial value problems associated with a pair of ordinary differential systems (L1,L2 defined on two adjacent intervals I1 and I2 and satisfying certain interface-spatial conditions at the common end (interface point are studied.

  3. Assessment of infection control practices for interventional techniques: a best evidence synthesis of safe injection practices and use of single-dose medication vials.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Falco, Frank J E; Benyamin, Ramsin M; Caraway, David L; Helm Ii, Standiford; Wargo, Bradley W; Hansen, Hans; Parr, Allan T; Singh, Vijay; Hirsch, Joshua A

    2012-01-01

    It is universally accepted that transmission of bloodborne pathogens during health care procedures continues to occur because of the use of unsafe and improper injection, infusion, and medication administration practices by health care professionals in various clinical settings. This resulted in development of multiple guidelines based on case reports; however, these case reports are confounded by multiple factors without causal relationship to a single factor. Even then, single-dose vials used for multiple patients have been singled out and became the focus of infection control policies resulting in inordinate expenses for practices without improving patient safety. The cost of implementation of single dose vial policy in interventional pain management for drugs alone may cost $750 million, whereas with single use radional gloves may exceed $1 billion per year. Best evidence synthesis. To critically appraise and synthesize the literature on infection control practices for interventional techniques, including safe injection and medication vial utilization. The available literature on infection control practices was reviewed. Due to the nature of the studies involved, with the majority being case reports, and a few prospective evaluations, quality assessment and clinical relevance criteria were not applied. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 through June 2012, literature from the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and manual searches of the bibliographies of known primary and review articles. The primary outcome measure was correlating infection to a breach of standards in infection control practices. The secondary objective was to assess the contribution of single-dose vials independently for infection. A total of 60 reports met inclusion criteria, with 16 reports related to pain management and other procedures, of which 9 reports were

  4. Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

    2017-06-01

    In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

  5. Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Brønden, Andreas; Albér, Anders; Rohde, Ulrich

    2017-01-01

    -controlled, and double-blinded crossover study. Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark. Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study. Interventions: Four experimental study days in randomized order...... with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline. Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve. Results: Single-dose metformin further enhanced bile acid...

  6. Efficacy of single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lyimo Fadhili M

    2012-06-01

    Full Text Available Abstract Background Caesarean section is a commonly performed operation worldwide. It has been found to increase rates of maternal infectious morbidities more than five times when compared to vaginal delivery. Provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to caesarean section has been found to reduce post-caesarean infection tremendously. Many centers recommend provision of a single dose of antibiotics, as repeated doses offer no benefit over a single dose. At Bugando Medical Centre post caesarean infection is among the top five causes of admission at the post-natal ward. Unfortunately, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are designated for caesarean section. Common practice and generally the clinician’s preference are to provide repeated dosages of antibiotic prophylaxis after caesarean section to most of the patients. This study aims to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post caesarean infection. Methods/Design The study is an interventional, open-label, two-armed, randomized, single-center study conducted at Bugando Medical Centre Mwanza, Tanzania. It is an ongoing trial for the period of seven months; 490 eligible candidates will be enrolled in the study. Study subjects will be randomly allocated into two study arms; “A” and “B”. Candidates in “A” will receive a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation and candidates in “B” will receive the same drugs prior to the operation and continue with gentamicin and metronidazole for 24 hours. The two groups will be followed up for a period of one month and assessed for signs and symptoms of surgical site infection. Data will be extracted from a case record form and entered into Epi data3.1 software before being transferred to SPSS

  7. Longitudinal effects of single-dose simulation education with structured debriefing and verbal feedback on endotracheal suctioning knowledge and skills: A randomized controlled trial.

    Science.gov (United States)

    Jansson, Miia M; Syrjälä, Hannu P; Ohtonen, Pasi P; Meriläinen, Merja H; Kyngäs, Helvi A; Ala-Kokko, Tero I

    2017-01-01

    We evaluated the longitudinal effects of single-dose simulation education with structured debriefing and verbal feedback on critical care nurses' endotracheal suctioning knowledge and skills. To do this we used an experimental design without other competing intervention. Twenty-four months after simulation education, no significant time and group differences or time × group interactions were identified between the study groups. The need for regularly repeated educational interventions with audiovisual or individualized performance feedback and repeated bedside demonstrations is evident. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  8. FastStats: Sinus Conditions

    Science.gov (United States)

    ... Childbearing Deaths Deaths and Mortality Leading Causes of Death Life Expectancy Race and Ethnicity Health of American Indian or Alaska Native Population Health of Asian or Pacific Islander Population Health of Black or African American non-Hispanic Population Health of ...

  9. Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

    International Nuclear Information System (INIS)

    Kempen-Harteveld, M. Loes van; Belkacemi, Yazid; Kal, Henk B.; Labopin, Myriam; Frassoni, Francesco

    2002-01-01

    Purpose: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, α/β, and the rate of repair of sublethal damage, μ value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. Methods and Materials: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for α/β and μ were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, α/β and μ values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of α/β and μ values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. Results: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was

  10. Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study.

    Science.gov (United States)

    Marriage, Barbara J; Williams, Jennifer A; Choe, Yong S; Maki, Kevin C; Vurma, Mustafa; DeMichele, Stephen J

    2017-11-01

    With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (Plutein at 48 and 336 h (Plutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

  11. Single-dose pharmacokinetic properties of esomeprazole in children aged 1 - 11 years with endoscopically proven GERD: a randomized, open-label study.

    Science.gov (United States)

    Youssef, Nader N; Tron, Eduardo; Tolia, Vasundhara; Hamer-Maansson, Jennifer E; Lundborg, Per; Illueca, Marta

    2014-11-01

    To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD). Oral esomeprazole administered as an intact capsule with 30 - 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 - 180 mL of water. In this randomized, open-label study of children aged 1 - 11 years with endoscopically proven GERD, patients weighing 8 - esomeprazole, and patients weighing >= 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC(0-∞)), AUC from zero to last measurable concentration (AUC(0-t)), maximum plasma concentration (C(max)), time to C(max) (t(max)), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined. 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 - = 20 kg). The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing >= 20 kg but not in children weighing 8 to < 20 kg.

  12. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects.

    Science.gov (United States)

    Min, Bokyung; Cios, Deborah; Kluger, Jeffrey; White, C Michael

    2005-12-01

    To evaluate the hemodynamic and electrocardiographic effects of a single dose of commercially available bitter-orange dried-fruit extract, which is increasingly being used in dietary supplements. Randomized, double-blind, placebo-controlled, crossover study. University of Connecticut, Storrs Campus. Eighteen healthy volunteers aged 18 years or older. Subjects were given either placebo or bitter-orange dried-fruit extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The opposite treatment was given during phase 2 after a washout period of at least 7 days. The rate-corrected QT (QTc) interval and blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after dosing. Mean+/-SD values of the maximum postdose values were compared between groups. Subjects receiving bitter-orange extract versus those receiving placebo had similar postdose QTc intervals (402+/-29 vs 403+/-24 msec, p=0.653), systolic blood pressure (114+/-10 vs 115+/-8 mm Hg, p=0.686) and diastolic blood pressure (68+/-9 vs 68+/-8, p=0.879). Bitter-orange dried-fruit extract standardized to m- or p-synephrine 27 mg did not significantly alter the QTc interval or blood pressure after a single dose was administered. Future studies are necessary to ensure the safety of this herbal product with multiple doses.

  13. Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

    Science.gov (United States)

    Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

    2015-01-01

    Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; pbupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; pbupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

  14. A Single Dose of Beetroot Gel Rich in Nitrate Does Not Improve Performance but Lowers Blood Glucose in Physically Active Individuals

    Directory of Open Access Journals (Sweden)

    Julia Vasconcellos

    2017-01-01

    Full Text Available Background. Beetroot consumption has been proposed to improve exercise performance, since the nitrate content of this food is able to stimulate the synthesis of nitric oxide. Objective. The acute effect of 100 g of a beetroot gel containing ~10 mmol of nitrate was tested on the nitric oxide synthesis, on metabolic and biochemical parameters, and on performance in physically active individuals. Methods. Through a double blind, crossover, placebo-controlled study, 25 healthy runners ingested a single dose of beetroot and placebo gels. Participants performed an aerobic exercise protocol on a treadmill (3 min warm-up of 40% peak oxygen consumption, 4 min at 90% of gas exchange threshold I and 70% (Δ maximal end speed until volitional fatigue. Results. Urinary levels of nitrite and nitrate increased after 90 min of beetroot gel ingestion. Plasma glucose concentrations lowered after the exercise and the decrease was maintained for 20 min. Systolic and diastolic blood pressures, serum cortisol, and blood lactate were not altered after the beetroot gel ingestion compared to a placebo gel. Conclusion. The single dose of beetroot gel provoked an increase of nitric oxide synthesis although no improvement on the physical performance of athletes during aerobic submaximal exercise was observed.

  15. Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model.

    Science.gov (United States)

    Cekanova, Maria; Uddin, Md Jashim; Legendre, Alfred M; Galyon, Gina; Bartges, Joseph W; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J

    2012-11-01

    We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1  mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1  mg/kg showed a peak of fluorocoxib A (92±28  ng/ml) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

  16. Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.

    Science.gov (United States)

    Kim, Yunjeong; Jeon, Ji-Young; Kim, Eun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul

    2017-09-01

    DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C max ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC last ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M. © 2017, The American College of Clinical Pharmacology.

  17. Comparison between Single-Dose Esomeprazole- and Pantoprazole-Based Triple Therapy on the Effectiveness for Helicobacter pylori Eradication in Taiwanese Population

    Directory of Open Access Journals (Sweden)

    Hsiang-Yao Shih

    2012-01-01

    Full Text Available Background and Study Aims. To compare the effectiveness of two regimens, single-dose esomeprazole- and pantoprazole-based triple therapy, for Helicobacter pylori (H. pylori eradication. Patients and Methods. A total of 453 patients were enrolled for H. pylori eradication. They were randomly assigned to either EAC group (Esomeprazole 40 mg once daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days or PAC group (Pantoprazole 40 mg twice daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days. Follow-up endoscopy or urea breath test was scheduled 12–16 weeks after the eradication to evaluate the therapeutic response. Results. Higher eradication rate in EAC group than PAC group was shown by intention-to-treat analysis (EAC 72% versus PAC 55%, P<0.05 and per-protocol analysis (EAC 91% versus PAC 72%, P<0.05. The incidence of adverse effects (EAC 19% versus PAC 17%, P=0.712 and the compliance (EAC 87% versus PAC 91%, P=0.083 were comparable between these 2 groups. Conclusions. Single-dose esomeprazole-based triple therapy is effective for H. pylori eradication.

  18. Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

    International Nuclear Information System (INIS)

    Chang Mengya; Chen Yuhung; Chang Chihjui; Chen Helen H-W; Wu Chaoliang; Shiau Aili

    2008-01-01

    High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P=0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P<0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P<0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (author)

  19. Immunogenicity and protection from a single dose of internationally available killed oral cholera vaccine: a systematic review and meta-analysis.

    Science.gov (United States)

    Lopez, Anna Lena; Deen, Jacqueline; Azman, Andrew S; Luquero, Francisco J; Kanungo, Suman; Dutta, Shanta; von Seidlein, Lorenz; Sack, David A

    2017-11-21

    In addition to improved water supply and sanitation, the two-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The meta-analysis showed an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggests otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  20. Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide.

    Science.gov (United States)

    Speich, Benjamin; Marti, Hanspeter; Ame, Shaali M; Ali, Said M; Bogoch, Isaac I; Utzinger, Jürg; Albonico, Marco; Keiser, Jennifer

    2013-01-04

    Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg-400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects.

  1. Efficacy of single dose albendazole on the prevalence and intensity of infection of soil-transmitted helminths in Orang Asli children in Malaysia.

    Science.gov (United States)

    Norhayati, M; Oothuman, P; Azizi, O; Fatmah, M S

    1997-09-01

    The efficacy of a single-dose 400 mg albendazole to treat Ascaris, Trichuris and hookworm infection was studied in Orang Asli community. Kato-Katz examination was performed on fecal samples which were collected before treatment, 1 and 4 months after treatment. A total of 123 children were involved in all three surveys. The cure rate of Ascaris infection was 97.4% and the egg reduction after treatment was 99.9%. The cure rate for hookworm infection was 93.1% with 96.6% egg reduction. Although the cure rate was low in Trichuris infection (5.5%), egg reduction was more evident (49.1%). The reinfection rate at 4 months after treatment was 54.5%, 3.6% and 10.3% for Ascaris, Trichuris and hookworm infection, respectively. Within 4 months after treatment almost one-fifth children with Ascaris and hookworm infection reached pre-treatment intensity infection. In Trichuris infection, however more than half of the children reached their pre-treatment intensity infection at 4 months after treatment. Findings suggest that 4-monthly targeted periodic treatment with 400 mg single-dose albendazole in highly endemic areas can have a significant impact on intensity infection of Ascaris and hookworm, but not on Trichuris infection.

  2. Prevention of perinatal HIV I transmission by protease inhibitor based triple drug antiretroviral therapy versus nevirapine as single dose at the time of delivery.

    Science.gov (United States)

    Bendle, Meenakshi; Bajpai, Smrati; Choudhary, Ashwini; Pazare, Amar

    2012-12-01

    In India, parent to child transmission is the most important source of HIV infection in children below fifteen years of age. Transmission of HIV from mother to child can occur even at low or undetectable HIV virus levels. CD4 count or HIV RNA levels should not be the determining factor when deciding whether to use antiretroviral drugs for prevention of perinatal transmission of HIV. Use of single dose nevirapine during labour, in prevention of parent to child transmission (PPTCT) programme for pregnant females with CD4 count > 250 cells/cumm has less efficacy in reducing perinatal transmission. And there are high chances of development of nevirapine resistance to both mother and baby after single dose nevirapine exposure. Short course Protease inhibitor(PI) based triple drug combination ART from 28 weeks till delivery for perinatal prophylaxis is effective in reducing perinatal HIV transmission. PI's are safe in pregnancy and also have less chances of development of resistance when used for perinatal prophylaxis and stopped post delivery.Hence, it is opined that PI based combination ART should be offered to pregnant females in PPTCT programme, thereby preventing occurrence of paediatric HIV infection in India. This can have significant impact on the society at large.

  3. Single-dose compared with multiple day antibiotic prophylaxis for cesarean section in low-resource settings, a randomized controlled, noninferiority trial.

    Science.gov (United States)

    Westen, Esther H M N; Kolk, Pascal R; van Velzen, Christine L; Unkels, Regine; Mmuni, Nicholaus S; Hamisi, Alex D; Nakua, Ritha E; Vlek, Anne L M; van Beekhuizen, Heleen J

    2015-01-01

    To investigate the efficacy of a single prophylactic dose of ampicillin combined with metronidazole to prevent postcesarean section infections compared with a multiple day regimen in low-resource settings. An evaluator-blinded randomized, controlled, noninferiority trial. Two rural hospitals in Tanzania. Of 181 enrolled eligible women with an indication for cesarean section, information on 176 was analyzed by intention-to-treat. The women were randomly assigned to either the intervention group who received a single dose of ampicillin and metronidazole, or to the control group who received a multiple-day regimen of ampicillin/amoxicillin and metronidazole. The primary outcome was maternal postcesarean infection. Secondary outcomes were severity of these infections, other maternal complications, and the duration of hospital stay. In the intervention group (n = 89), six women (6.7%) developed a wound infection compared with nine (10.3%) in the control group (n = 87) (difference 3.60; 95% CI -4.65 to 11.85) (p = 0.40). A single dose of prophylactic ampicillin and metronidazole is equally effective as a multiple-day regimen in preventing postcesarean wound infections in low-resource settings, therefore it can be considered as a good strategy in low-resource settings. The reduced quantity of prophylactic antibiotics will reduce costs without increasing the risk of maternal infection. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg.

    Science.gov (United States)

    Wesnes, Keith A; Edgar, Chris; Tretter, Reiner N; Bolodeoku, John

    2009-11-01

    To assess the cognitive effects of single doses of solifenacin 10 mg compared with placebo (primary objective) and oxybutynin immediate release (IR) 10 mg (secondary objective) in elderly subjects. Single-centre, randomised, double-blind, placebo-controlled study in 12 healthy elderly volunteers, with three crossover periods separated by two 14-day washout periods. Each sequence consisted of a single dose of solifenacin 10 mg in one period, oxybutynin IR 10 mg in another and placebo in another. Aspects of attention, information processing, working memory, episodic memory and self-rated mood and alertness were tested using the validated Cognitive Drug Research computerised assessment system. There was no evidence from absolute mean values or changes from baseline to suggest that solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no statistically significant cognitive deterioration with solifenacin versus placebo, when measured at a time point closest to the probable C(max) of solifenacin. Oxybutynin was associated with statistically significant impairments in several measures of cognitive function at a time point corresponding with its probable C(max). In this pilot study, single 10 mg doses of solifenacin did not show any clear propensity to impair cognitive function in a healthy elderly population.

  5. A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission.

    Science.gov (United States)

    Samuel, Reshmi; Paredes, Roger; Parboosing, Raveen; Moodley, Pravi; Singh, Lavanya; Naidoo, Anneta; Gordon, Michelle

    2015-10-01

    Although the rates of vertical transmission of HIV in the developing world have improved to around 3% in countries like South Africa, resistance to antiretrovirals (ARV) used in Prevention of Mother-to-Child transmission (pMTCT) strategies may thwart such outcomes and affect the efficacy of future ARV regimens in mothers and children. This study conducted in Durban, South Africa, between 2010 and 2013 found a high rate of nevirapine (NVP) resistance among women receiving Zidovudine (AZT) from 14 weeks gestation, single dose nevirapine (sd NVP) at the onset of labor and a single dose of coformulated Tenofovir/Emtricitabine (TDF/FTC) postpartum. Using Sanger sequencing, high and intermediate levels of nevirapine (NVP) resistance were detected in 15/44 (34%) and in 1/44 (2%) of women tested, respectively. Most subjects selected the K103N mutation (22% (10/45) of all patients and 66% (10/15) of those with high-level NVP resistance). Such rate of NVP resistance is comparable to studies where only sd NVP was used. In conclusion, a post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum sd NVP to prevent mother-to-child HIV-1 transmission. © 2015 Wiley Periodicals, Inc.

  6. Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation.

    Science.gov (United States)

    Hampel, Daniela; Shahab-Ferdows, Setareh; Islam, M Munirul; Peerson, Janet M; Allen, Lindsay H

    2017-04-01

    Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake

  7. Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions.

    Science.gov (United States)

    Hénin, Emilie; Bergstrand, Martin; Weitschies, Werner; Karlsson, Mats O

    2016-03-01

    To develop a model predicting movement of non-disintegrating single unit dosage forms (or "tablet") through the gastrointestinal tract and characterizing the effect of food intake, based on Magnetic Marker Monitoring data, allowing real-time location of a magnetically labeled formulation. Five studies including 30 individuals in 94 occasions under 3 food status were considered. The mean residence time (MRT) of the tablet and the effect of food intake in proximal (PS) and distal stomach (DS), small intestine (SI), ascending (AC), transverse (TC) and descending colon (DC) were estimated using a Markov model for probabilities of movement. Under fasting conditions, tablet MRTs were 9.4 min in PS, 10.4 in DS, 246 in SI, 545 in AC, 135 in TC, and 286 in DC. A meal taken simultaneous to tablet intake prolonged tablet MRT to 99 min in PS and to 232 in DS; probability of gastric emptying increased of 89% each hour from 2.25 h after meal. The effect of a gastroileac reflex, caused by a secondary meal, accelerated the transit from terminal SI to AC. This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation.

  8. Relative bioavailability of two formulations of nevirapine 200-mg tablets in healthy Chinese male volunteers: a single-dose, randomized-sequence, open-label, two-way crossover study.

    Science.gov (United States)

    Zhu, Yubing; Zhang, Qian; Yu, Cuixia; Zou, Jianjun; Yang, Xiaohong; Hu, Yunfang

    2010-12-01

    Nevirapine was the first member of the nonnucleoside reverse transcriptase inhibitor class to be approved for the treatment of HIV infection. It binds directly to the allosteric site on the reverse transcriptase and inhibits the activity of both RNA- and DNA-dependent DNA polymerases. This study compared the pharmacokinetics and relative bioavailability of a test and reference formulation of nevirapine 200-mg tablets after single oral doses in healthy Chinese men to meet regulatory criteria for marketing of the new generic formulation. This single-dose, randomized-sequence, open-label, 2-way crossover study was conducted at the Nanjing First Hospital of Nanjing Medical University, Nanjing, China. Healthy male Chinese volunteers were randomized in a 1∶1 ratio to receive a single 200-mg (3.2-mg/kg) tablet of the test or reference formulation, followed by a 2-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Concentrations of nevirapine were assayed using an HPLC-UV method. For analysis of nevirapine pharmacokinetic parameters, blood samples were obtained before dosing and at regularly scheduled intervals over 168 hours after administration. The 2 formulations would be assumed to be bioequivalent for regulatory purposes if the 90% CIs for the log-transformed ratios of nevirapine AUC and C(max) were within the range established by the US Food and Drug Administration (0.80-1.25). Tolerability was evaluated throughout the study based on vital signs, physical examinations, 12-lead ECGs, and subject interviews concerning adverse events (AEs). Twenty Chinese male subjects were enrolled in and completed the study. Their mean age was 23 years (range, 21-25 years), mean weight was 63 kg (range, 56-70 kg), and mean height was 171 cm (range, 166-176 cm). No period or sequence effect was observed. The mean (SD) t(½) was 38.12 (2.23) hours for the test tablet and 36.79 (5.06) hours for the

  9. Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers.

    Science.gov (United States)

    Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner Farid

    2010-11-01

    Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m

  10. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  11. A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT.

    Science.gov (United States)

    Sciammarella, Maria; Shrestha, Uttam M; Seo, Youngho; Gullberg, Grant T; Botvinick, Elias H

    2017-08-03

    SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99m Tc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image

  12. Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

    2015-10-01

    As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

  13. A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.

    Science.gov (United States)

    Kwakye-Maclean, Cynthia; Agana, Nsiire; Gyapong, John; Nortey, Priscilia; Adu-Sarkodie, Yaw; Aryee, Esther; Asiedu, Kingsley; Ballard, Roland; Binka, Fred

    2017-01-01

    Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular

  14. Safety, efficacy, and patient acceptability of single-dose fosaprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Celio L

    2013-05-01

    Full Text Available Luigi Celio, Francesca Ricchini, Filippo De BraudMedical Oncology Unit 1, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Control of chemotherapy-induced nausea and vomiting (CINV is a crucial factor in ensuring that patients undergoing cancer chemotherapy can get the full benefit of therapy. Current antiemetic guidelines recommend that the neurokinin-1 receptor (NK-1R antagonist aprepitant should be used as part of a combination regimen with dexamethasone and a serotonin receptor antagonist for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC. Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant that, when infused, is rapidly metabolized back to an active aprepitant. The existing literature in PubMed about fosaprepitant was screened and selected in order to address the emerging data from two randomized clinical trials evaluating the efficacy and safety of a single-dose fosaprepitant regimen. These phase III trials demonstrated that fosaprepitant given as a single intravenous dose of 150 mg was either noninferior to the conventional 3-day aprepitant or significantly superior to placebo for the prevention of acute and delayed CINV in patients receiving high-dose cisplatin. In both trials, fosaprepitant was well tolerated although more frequent infusion-site adverse events were observed with fosaprepitant. The new dosage regimen of fosaprepitant, therefore, would be an option for CINV control in patients receiving cisplatin-based chemotherapy. The clinical efficacy is consistent with the findings from a time-on-target, positron-emission tomography study evaluating the NK-1R occupancy in the central nervous system (CNS over 5 days after a single-dose infusion of 150 mg fosaprepitant in healthy participants. The single-dose regimen is capable of blocking more than 90% of the NK-1Rs in the CNS for at least 48 hours after infusion, which is sufficient

  15. Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, X.J. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China); Liu, X.L. [Qilu Hospital, Shandong University, Department of Cardiology, Jinan, China, Department of Cardiology, Qilu Hospital, Shandong University, Jinan (China); He, G.X. [Third Military Medical University, Southwest Hospital, Department of Cardiology, Chongqing, China, Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing (China); Xu, H.P. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China)

    2014-03-03

    The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in

  16. The stimulatory effect of single-dose pre-irradiation administration of indomethacin and diclofenac on haemopoietic recovery in the spleen of gamma-irradiated mice

    International Nuclear Information System (INIS)

    Kozubik, A.; Pospisil, M.; Netikova, J.

    1989-01-01

    The aim of the work was to examine the effect of the single-dose pre-irradiation administration of non-steroid anti-inflammatory drugs, i.e. indomethacin (0.15 mg/mouse) and diclofenac (0.6 mg/mouse) on the recovery of haemopoiesis in the spleen of whole-body irradiated male mice (CBA x C57BL/10)F 1 . It was shown that the administation of these substances 1-24 h prior to sublethal irradiation stimulates the recovery of the proliferation activity of the spleen and the formation of endogenous spleen colonies. These results can be explained as the inhibitory effect of the substances administered on biosynthesis of prostaglandins. (author)

  17. Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

    Science.gov (United States)

    Morita, Tatsushi; Momota, Yutaka; Mori, Akihiro; Oda, Hitomi; Ike, Kazunori; Sako, Toshinori

    2018-03-08

    A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.

  18. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    Science.gov (United States)

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  19. Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.

    Science.gov (United States)

    Qadri, Firdausi; Ali, Mohammad; Lynch, Julia; Chowdhury, Fahima; Khan, Ashraful Islam; Wierzba, Thomas F; Excler, Jean-Louis; Saha, Amit; Islam, Md Taufiqul; Begum, Yasmin A; Bhuiyan, Taufiqur R; Khanam, Farhana; Chowdhury, Mohiul I; Khan, Iqbal Ansary; Kabir, Alamgir; Riaz, Baizid Khoorshid; Akter, Afroza; Khan, Arifuzzaman; Asaduzzaman, Muhammad; Kim, Deok Ryun; Siddik, Ashraf U; Saha, Nirod C; Cravioto, Alejandro; Singh, Ajit P; Clemens, John D

    2018-03-14

    A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up. In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207. Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0

  20. Radioprotective effects in mice by a single dose of subcutaneous administration of cobaltous chloride post γ-rays irradiation with a sublethal dose

    International Nuclear Information System (INIS)

    Izumo, Yoshiro; Ogata, Hiromitsu

    1993-01-01

    Radioprotective effects were investigated in mice which received subcutaneously a single dose of each inorganic metal: Co, Cu, Rb, Sr, Mo and W 24 hours post irradiation of 60 Co γ-rays with a sublethal dose. The effects were observed in mice injected with Co at an optimum dosage of 20 mg/kg·body weight. Then to elucidate mechanisms of the effects, mice were injected with Co containing the radioactive tracer ( 60 Co) following the radiation exposure, measured elimination of the radioactivity for 7 days, then sacrificed and divided to some tissues and organs. The radioactivity in whole body during this period resulted in a markedly higher retention than that for mice injected with [ 60 Co] alone, as well as liver in the organs. These higher retentions appeared to be related to the radioprotective effects. (author)

  1. Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis

    DEFF Research Database (Denmark)

    Kjeldsen, J; Laursen, L S; Hillingsø, Jens

    1995-01-01

    5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations...... containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5......-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema...

  2. Comparison of 2 commercial single-dose Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines on pigs dually infected with M. hyopneumoniae and PRRSV.

    Science.gov (United States)

    Park, Changhoon; Kang, Ikjae; Seo, Hwi Won; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee

    2016-04-01

    The objective of this study was to compare the efficacy of 2 different commercial Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines in regard to growth performance, microbiological and immunological analyses, and pathological observation from wean to finish (175 d of age). Pigs were administered M. hyopneumoniae and PRRSV vaccines at 7 and 21 d of age, respectively, or both at 21 d old and then challenged with both M. hyopneumoniae and PRRSV at 49 d old. Significant (P hyopneumoniae, M. hyopneumoniae-specific interferon-γ secreting cells, and macroscopic and microscopic lung lesions. Induction of interleukin-10 following PRRSV vaccination does not interfere with the immune responses induced by M. hyopneumoniae vaccine. The present study demonstrated that the single-dose vaccination regimen for M. hyopneumoniae and PRRSV vaccine is efficacious for controlling coinfection with M. hyopneumoniae and PRRSV based on clinical, microbiological, immunological, and pathological evaluation.

  3. Using a decline in serum hCG between days 0–4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Skubisz Monika

    2013-02-01

    Full Text Available Abstract Background The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4–7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0–4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications. Methods We conducted a retrospective study of women (n=206 treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L at Scottish hospitals between 2006–2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0–4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4–7 of treatment and an alternate early measure ( Results In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94% (121/136. A falling serum hCG between days 0–4 predicted treatment success in 85% (95% CI 79-92% of cases (94/110 and a Conclusions We have verified that a decline in serum hCG between days 0–4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.

  4. Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients.

    Science.gov (United States)

    Tamasawa, Atsuko; Mochizuki, Kazuki; Hariya, Natsuyo; Saito, Miyoko; Ishida, Hidenori; Doguchi, Satako; Yanagiya, Syoko; Osonoi, Takeshi

    2015-09-05

    Acarbose, an α-glucosidase inhibitor, leads to the production of hydrogen gas, which reduces oxidative stress. In this study, we examined the effects of a single dose of acarbose immediately before a test meal on postprandial hydrogen gas in breath and peripheral blood interleukin (IL)-1β mRNA expression in Japanese type 2 diabetic patients. Sixteen Japanese patients (14 men, 2 women) participated in this study. The mean±standard deviation age, hemoglobin A1c and body mass index were 52.1±15.4 years, 10.2±2.0%, and 27.7±8.0kg/m(2), respectively. The patients were admitted into our hospital for 2 days and underwent test meals at breakfast without (day 1) or with acarbose (day 2). We performed continuous glucose monitoring and measured hydrogen gas levels in breath, and peripheral blood IL-1β mRNA levels before (0min) and after the test meal (hydrogen gas: 60, 120, 180, and 300min; IL-1β: 180min). The induction of hydrogen gas production and the reduction in peripheral blood IL-1β mRNA after the test meal were not significant between days 1 (without acarbose) and 2 (with acarbose). However, the changes in total hydrogen gas production from day 1 to day 2 were closely and inversely associated with the changes in peripheral blood IL-1β mRNA levels. Our results suggest that an increase in hydrogen gas production is inversely associated with a reduction of the peripheral blood IL-1β mRNA level after a single dose of acarbose in Japanese type 2 diabetic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

    Science.gov (United States)

    Balkus, Jennifer E; Richardson, Barbra A; Mochache, Vernon; Chohan, Vrasha; Chan, Jeannie D; Masese, Linnet; Shafi, Juma; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R Scott

    2013-06-01

    This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16-3.09). The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

  6. Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.

    Science.gov (United States)

    Chi, Benjamin H; Sinkala, Moses; Stringer, Elizabeth M; Cantrell, Ronald A; Mtonga, Velepi; Bulterys, Marc; Zulu, Isaac; Kankasa, Chipepo; Wilfert, Catherine; Weidle, Paul J; Vermund, Sten H; Stringer, Jeffrey S A

    2007-05-11

    To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.

  7. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

    2015-01-01

    This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

  8. Wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medicine: a single-dose, dose-escalation safety and pharmacokinetic study.

    Science.gov (United States)

    Kuge, Tomoo; Shibata, Takashi; Willett, Michael S

    2003-11-01

    To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent. Randomized, double-blind, placebo-controlled study. Clinical research center. Forty (32 men, 8 women) healthy volunteers aged 19-42 years. By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo). Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated. Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.

  9. Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging

    International Nuclear Information System (INIS)

    Kinner, Sonja; Steinweg, Verena; Maderwald, Stefan; Radtke, Arnold; Sotiropoulos, Georgios; Forsting, Michael; Schroeder, Tobias

    2014-01-01

    Introduction: Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). Materials and methods: 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w ± IR) were acquired 20–30 min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann–Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. Results: All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. Conclusions: Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR

  10. Fast and sensitive in vivo studies under controlled environmental conditions to substitute long-term field trials with genetically modified plants.

    Science.gov (United States)

    Horn, Patricia; Schlichting, André; Baum, Christel; Hammesfahr, Ute; Thiele-Bruhn, Sören; Leinweber, Peter; Broer, Inge

    2017-02-10

    We introduce an easy, fast and effective method to analyze the influence of genetically modified (GM) plants on soil and model organisms in the laboratory to substitute laborious and time consuming field trials. For the studies described here we focused on two GM plants of the so-called 3rd generation: GM plants producing pharmaceuticals (PMP) and plant made industrials (PMI). Cyanophycin synthetase (cphA) was chosen as model for PMI and Choleratoxin B (CTB) as model for PMP. The model genes are expressed in transgenic roots of composite Vicia hirsuta plants grown in petri dishes for semi-sterile growth or small containers filled with non-sterile soil. No significant influence of the model gene expression on root induction, growth, biomass, interaction with symbionts such as rhizobia (number, size and functionality of nodules, selection of nodulating strains) or arbuscular mycorrhizal fungi could be detected. In vitro, but not in situ under field conditions, structural diversity of the bulk soil microbial community between transgenic and non-transgenic cultivars was determined by PLFA pattern-derived ratios of bacteria: fungi and of gram + : gram - bacteria. Significant differences in PLFA ratios were associated with dissimilarities in the quantity and molecular composition of rhizodeposits as revealed by Py-FIMS analyses. Contrary to field trials, where small effects based on the transgene expression might be hidden by the immense influence of various environmental factors, our in vitro system can detect even minor effects and correlates them to transgene expression with less space, time and labour. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Radio-contaminant behaviour in the cover-gas space and the containment building of a sodium-cooled fast reactor in accident conditions

    International Nuclear Information System (INIS)

    Mathe, Emmanuel

    2014-01-01

    In the context of the Generation IV initiative, the consequences of a severe-accident (SA) in a sodium-cooled fast reactor must be studied. A SFR (Sodium cooled Fast Reactor) severe accident involves the disruption of the core by super-criticality involving the destruction of a certain number of fuel assemblies. Subsequently the interaction between hot fuel and liquid sodium can lead to a vapor explosion which could create a breach in the primary system. Some contaminated liquid sodium would thus be ejected into the containment building. In this situation, the evaluation of potential releases to the environment (the source term) must forecast the quantity and the chemical speciation of the radio-contaminants likely to be released from the containment building. One critical risk of a SA is the production of contaminated aerosols in the containment building by spray ejection of primary-system sodium. Being pyrophoric, the sodium droplets react with oxygen first oxidizing then burning, with significant heat of combustion. As well as evaluating the consequences of a pressure rise inside the containment, the evolution of the sodium must be assessed since not only is it activated and contaminated but, in oxide form, very toxic. Ultimately, the aerosols are the main radiological risk acting as the vector for radionuclide transport to the environment in the event of a problem with the confinement. These aerosols could evolve and interact with the FP (Fissile Products) and these interactions could modify the physical and chemical nature of the PF. We model a large part of the events that occur during a SA inside a SFR from the sodium spray fire to the reaction between sodium aerosols and PF (iodine). At first, we develop a numerical model (NATRAC) that simulates the sodium spray fire, calculates the temperature and the pressure inside the containment as well as the mass of aerosols produced during this kind of fire. The simulation has been validated with different

  12. Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences.

    Science.gov (United States)

    Wong, Alexander; Keats, Kirily; Rooney, Kieron; Hicks, Callum; Allsop, David J; Arnold, Jonathon C; McGregor, Iain S

    2014-10-01

    Δ(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods. Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase. However, it is unclear whether this has behavioural consequences. Here, we examined whether rats pre-treated with multiple or single doses of THC followed by a washout would show elevated plasma cannabinoids and altered behaviour following fasting or exercise manipulations designed to increase fat utilisation. Behavioural impairment was measured as an inhibition of spontaneous locomotor activity or a failure to successfully complete a treadmill exercise session. Fat utilisation was indexed by plasma free fatty acid (FFA) levels with plasma concentrations of THC and its terminal metabolite (-)-11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THC-COOH) also measured. Rats given daily THC (10 mg/kg) for 5 days followed by a 4-day washout showed elevated plasma THC-COOH when fasted for 24 h relative to non-fasted controls. Fasted rats showed lower locomotor activity than controls suggesting a behavioural effect of fat-released THC. However, rats fasted for 20 h after a single 5-mg/kg THC injection did not show locomotor suppression, despite modestly elevated plasma THC-COOH. Rats pre-treated with THC (5 mg/kg) and exercised 20 h later also showed elevated plasma THC-COOH but did not differ from controls in their likelihood of completing 30 min of treadmill exercise. These results confirm that fasting and exercise can increase plasma cannabinoid levels. Behavioural consequences are more clearly observed with pre-treatment regimes involving repeated rather than single THC dosing.

  13. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

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    Sun CL

    2015-05-01

    Full Text Available Changling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 2National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 3Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China*These authors have contributed equally to this workAbstract: This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA stealth nanoparticles loaded with dexamethasone (DEX. DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4, 5 days in artificial perilymph (pH 7.4, and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8

  14. Using a decline in serum hCG between days 0-4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study.

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    Skubisz, Monika; Dutton, Philip; Duncan, William Colin; Horne, Andrew W; Tong, Stephen

    2013-02-01

    The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4-7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0-4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications. We conducted a retrospective study of women (n=206) treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L) at Scottish hospitals between 2006-2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0-4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4-7 of treatment) and an alternate early measure (treatment), and all three measures were compared for their ability to predict medical treatment success. In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94%) (121/136). A falling serum hCG between days 0-4 predicted treatment success in 85% (95% CI 79-92%) of cases (94/110) and a treatment success in 94% (95% CI 88-100%) of cases (59/63). There was no significant difference in the ability of these tests to predict medical treatment success. We have verified that a decline in serum hCG between days 0-4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.

  15. Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study.

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    Kaplan, Volkan; Eroğlu, Cennet Neslihan

    2016-10-01

    The aim of the present study was to compare the effects of daily single-dose use of flurbiprofen, diclofenac sodium, and tenoxicam on pain, swelling, and trismus that occur after surgical extraction of impacted wisdom teeth using local anesthesia. The present study included 3 groups with 30 patients in each group. Those volunteering to participate in this double-blind randomized study (n = 90) were selected from a patient population with an indication for extraction of impacted wisdom teeth. Group 1 patients received 200 mg flurbiprofen, group 2 patients received 100 mg diclofenac sodium, and group 3 patients received 20 mg tenoxicam. All doses were once a day, starting preoperatively. Pain was evaluated postoperatively at 1, 2, 3, 6, 8, and 24 hours and at 2 and 7 days using a visual analog scale (VAS). For comparison with the preoperative measurements, the patients were invited to postoperative follow-up visits 2 and 7 days after extraction to evaluate for swelling and trismus. The statistical analysis was performed using descriptive statistics in SAS, version 9.4 (SAS Institute, Cary, NC), software. Statistical analysis of the pain, swelling, and trismus data was performed using the Kruskal-Wallis, Dunn, and Wilcoxon-Mann-Whitney U tests. The statistical level of significance was accepted at P = .05 and power of 0.80. Clinically, tenoxicam showed better analgesic and anti-inflammatory efficacy compared with diclofenac sodium and, in particular, flurbiprofen. Although the VAS scores in the evaluation of pain showed statistically significant differences at 2 days, no statistically significant difference was found for swelling and trismus. Our study evaluated the analgesic and anti-inflammatory effects with a daily single dose of flurbiprofen, diclofenac sodium, and tenoxicam. Daily 20 mg tenoxicam can be accepted as an adequate and safe option for patients after a surgical procedure. Copyright © 2016 American Association of Oral and Maxillofacial

  16. A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

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    Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

    2015-01-01

    Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

  17. Single-Dose Universal Hepatitis A Immunization in Argentina: Low Viral Circulation and High Persistence of Protective Antibodies Up to 4 Years.

    Science.gov (United States)

    Vizzotti, C; González, J; Rearte, A; Urueña, A; Pérez Carrega, M; Calli, R; Gentile, A; Uboldi, A; Ramonet, M; Cañero-Velasco, M; Diosque, M

    2015-12-01

    Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children aged 12 months in 2005. Between 2005 and 2011, a dramatic decline was observed in HAV infection rates, fulminant hepatitis, and liver transplantation. This study assessed current viral circulation and estimated protective antibody persistence 4 years after vaccination. Prevalence of prevaccination anti-HAV antibodies in 12-month-old children was evaluated as an indirect estimation of viral circulation (Group A). Seroprevalence was also measured in 5-year-old children who received 1 dose of HAV vaccine at 1 year of age (Group B). Blood samples were tested for immunoglobulin (Ig)G anti-HAV antibodies (seroprotection = ≥10 mIU/mL). All Group A-positive samples were tested for IgM anti-HAV antibodies to identify recent infections. Logistic regression analysis was done to evaluate associations between demographic and socioeconomic variables and seroprotection. Of 433 children from Group A, 29.5% (95% confidence interval [CI], 25.2-33.8) were positive for IgG anti-HAV antibodies with a geometric mean concentration (GMC) of 6.17 mIU/mL (95% CI, 5.33-7.15 mIU/mL); all IgM anti-HAV were negative. From 1139 in Group B, 93% (95% CI, 91.7-94.6) maintained seroprotection with a GMC of 97.96 mIU/mL (95% CI, 89.21-107.57 mIU/mL). Kindergarten attendance was associated with seroprotection in Group B (odds ratio [OR], 2.0; 95% CI, 1.26-3.3). In contrast, high maternal educational level was associated with a lack of seroprotection in this group (OR, .26; 95% CI, .09-.8). Single-dose, universal hepatitis A immunization in infants resulted in low HAV circulation and persistent immunologic protection up to 4 years in Argentina. Variables associated with presence or absence of seroprotection in vaccinated children could be related to differences in hygiene habits in settings with residual viral circulation. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric

  18. Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

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    Sunju Park

    2015-09-01

    Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

  19. Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge.

    Science.gov (United States)

    Erasmus, Jesse H; Seymour, Robert L; Kaelber, Jason T; Kim, Dal Y; Leal, Grace; Sherman, Michael B; Frolov, Ilya; Chiu, Wah; Weaver, Scott C; Nasar, Farooq

    2018-02-15

    Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines. IMPORTANCE Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored the use of the mosquito-specific alphavirus EILV as an alphavirus vaccine

  20. Comparison of clinical applications of single-dose intravenous injection of mivacurium and cisatracurium in adults’ vocalcordpolyps resection under self-retaining laryngoscope

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    Han Fanglei

    2017-01-01

    Full Text Available Objective: Through comparing the clinical observation of mivacurium and cisatracurium in vocal polyp extraction, to study the advantage of mivacurium in vocal polyp extraction. Methods: Forty American Society of Anesthesiologists(ASA physical status I~II patients for vocal polyp extraction, aged 18~60 years old, were randomly divided into two groups as Mivacurium injection group(Group M and Cis-atracurium injection group(Group C, each group includes 20 subjects. None of the patients are allergic, has serious diseases of cardiovascular system, liver or kidney.None of them has asthma, airway high response, difficult airway or neuromuscular diseases.Those patients who use beta-blockers or calcium channel blockers for a long time were excluded .All the subjects had the same premedication, fasting and fluid fobidden time. All the subjects who get into the operating room get the routine monitoring of electrocardiogram(EEG, blood pressure(BP, heart rate(HR, pulse oxygen saturation(SpO2 and the TOF WATCH SX. Each group gives the same medicine other than the muscle relaxant during induction of general anesthesia to do the vocal polyp extraction by the same experienced operator. Two groups were recorded in each index of anesthesia induction and tracheal intubation conditions, operation conditions, anesthesia, muscle relaxation monitoring. Results: There are no statistically significant in Cormack-Lehane grading system,Cooper’s grading system and operation satifaction(p>0.05. 2. Group A have shorter intubation time than Group B(p0.05. Conclusion: 1. A single intubating dose of mivacurium can provide similar intubation and surgeon satisfaction for the vocal polyp extraction. 2. Compared with cis-atracurium, mivacurium can shorten the intubation time and the recovery time of anesthesia. The adverse reactions of mivacurium is mild, and it has less Residual muscle relaxation. Therefore mivacurium is more suitable for the vocal polyp extraction than cis-atracurium.

  1. Comparison of postoperative analgesic efficacy of intraoperative single-dose intravenous administration of dexketoprofen trometamol and diclofenac sodium in laparoscopic cholecystectomy.

    Science.gov (United States)

    Anıl, Ali; Kaya, Fatma Nur; Yavaşcaoğlu, Belgin; Mercanoğlu Efe, Esra; Türker, Gürkan; Demirci, Abdurrahman

    2016-08-01

    The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. A randomized fashion. Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery. Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded. Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Reduced lung lesions in pigs challenged 25 weeks after the administration of a single dose of Mycoplasma hyopneumoniae vaccine at approximately 1 week of age.

    Science.gov (United States)

    Reynolds, S C; St Aubin, L B; Sabbadini, L G; Kula, J; Vogelaar, J; Runnels, P; Peters, A R

    2009-09-01

    Two independent studies assessed the duration of immunity of an inactivated adjuvanted Mycoplasma hyopneumoniae vaccine against mycoplasmal pneumonia in seronegative (study A, n=52) and seropositive (study B, n=52) pigs. The pigs were allocated randomly to treatment and were then injected with a single dose of either the vaccine or a placebo at approximately 1 week of age. Twenty-five weeks after treatment administration, the pigs were challenged with a virulent strain (LI 36, Strain 232) of M. hyopneumoniae and the extent of lung lesions consistent with mycoplasmal pneumonia was assessed 4 weeks later. In study A, the geometric mean lung lesion score (expressed as least squares mean percentages of lung lesions) was significantly (P=0.0001) lower in vaccinated (0.3%, n=20) than in control pigs (5.9%, n=24) seronegative to M. hyopneumoniae at enrolment; similarly, in study B, the extent of lung lesions was significantly reduced (P=0.0385) in seropositive vaccinated pigs (2.0%, n=22) compared to controls (4.5%, n=26). At the end of the investigation period, 4 weeks after challenge, mean antibody sample-to-positive (S/P) ratios were significantly higher both in seronegative (P=0.0012) and seropositive (P=0.0001) vaccinated pigs (mean values=0.77 and 0.81, respectively) than in controls (mean values=0.51 and 0.38, respectively).

  3. Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD™ vaccine?

    Science.gov (United States)

    Whitehead, Stephen S

    2016-01-01

    Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYD™, a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYD™.

  4. Introducing Single Dose Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis in Rural Bangladesh: Feasibility and Acceptance to Patients and Health Staff

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    Eva-Maria Maintz

    2014-01-01

    Full Text Available Background. For the treatment of visceral leishmaniasis in Bangladesh, single dose liposomal amphotericin B (ambisome is supposed to be the safest and most effective treatment. Specific needs for application and storage raise questions about feasibility of its implementation and acceptance by patients and health staff. Methods. The study was carried out in the most endemic district of Bangladesh. Study population includes patients treated with ambisome or miltefosine, hospital staff, and a director of the national visceral leishmaniasis program. Study methods include direct observation (subdistrict hospitals, open interviews (heath staff and program personnel, structured questionnaires, and focus group discussions (patients. Results. Politicalcommitment for ambisome is strong; the general hospital infrastructure favours implementation but further strengthening is required, particularly for drug storage below 25°C (refrigerators, back-up energy (fuel for generators, and supplies for ambisome administration (like 5% dextrose solution. Ambisome created high satisfaction in patients and hospital staff, less adverse events, and less income loss for patients compared to miltefosine. Conclusions. High political commitment, general capacities of subdistrict hospitals, and high acceptability favour the implementation of ambisome treatment in Bangladesh. However, strengthening of the infrastructure and uninterrupted supplies of essential accessories is mandatory before introducing sLAB in Bangladesh.

  5. Two-step irradiance schedule versus single-dose cold compress for pain control during 5-aminolevulinic acid-based photodynamic therapy of condyloma acuminatum.

    Science.gov (United States)

    Shao, Xiaonan; Wang, Fang; Xu, Bin

    2017-12-01

    The purpose of this study was to investigate the effect of two-step irradiance schedule in relieving pain during PDT of CA. The study was a prospective, controlled trial of 141 CA patients who were randomly divided into Group A (two-step irradiance schedule) and Group B (single-dose cold compress). The numeric rating scales (NRS) of patients' pain were recorded at 5, 10, 15, and 20 minutes during each PDT. The efficacy of PDT and NRS scores of patients in the two groups were compared. There was no significant difference in gender, age, lesion site, and disease course between the two groups (P > 0.05). In addition, the cure rate of patients in the two groups was not significantly different (97.1% vs. 95.8%, χ 2  = 0.000, P = 1.000). However, the NRS scores at different time points and number of PDT sessions were significantly different (F = 198.233 and 165.224, respectively, P two-step irradiance schedule could more significantly reduce the patients' pain degree during treatment, especially for vulva and crissum. Lasers Surg. Med. 49:908-912, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Efficacy of a single dose of low-level laser therapy in reducing pain, swelling, and trismus following third molar extraction surgery.

    Science.gov (United States)

    Landucci, A; Wosny, A C; Uetanabaro, L C; Moro, A; Araujo, M R

    2016-03-01

    The clinical efficacy of low-level laser therapy (LLLT) for the reduction of pain, swelling, and trismus following the surgical extraction of third molars was evaluated. Mandibular third molars, with similar radiographic positions on two distinct sections, were extracted from 22 patients. Immediately after extraction from the randomly selected right or left side, LLLT was applied (study group). The same extraction procedure was performed 21 days later on the other third molar, without the application of LLLT (control group). LLLT was applied at 10 points: four intraoral in close proximity to the socket and six extraoral along the masseter muscle. Pain intensity was assessed using a visual analogue scale, swelling was measured as the distance from the tragus to the median base of the mentum, and trismus was assessed by the extent of mouth opening. Data were collected at four time points: before surgery, immediately after surgery, 48h postoperatively, and 7 days postoperatively. Compared with the control group, the study group showed significant reductions in pain, swelling, and trismus at 48h and 7 days postoperatively. In conclusion, a single dose of LLLT was effective at reducing the postoperative discomforts (pain, swelling, and trismus) associated with third molar extraction surgery. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: A cohort study

    Directory of Open Access Journals (Sweden)

    Sinkala Moses

    2008-12-01

    Full Text Available Abstract Background Single-dose nevirapine (SDNVP for the prevention of mother-to-child HIV transmission (PMTCT results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood. Methods We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed and those that had not (unexposed and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders. Results Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0. Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19% at both the first (unexposed and second (exposed delivery. The results were unchanged, if infant death was included as an outcome. Conclusion These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.

  8. Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: A phase-1, single-dose, randomized, open-label study.

    Science.gov (United States)

    Ravenstijn, Paulien; Remmerie, Bart; Savitz, Adam; Samtani, Mahesh N; Nuamah, Isaac; Chang, Cheng-Tao; De Meulder, Marc; Hough, David; Gopal, Srihari

    2016-03-01

    This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18-65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single-dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75-525 mg eq) separated by a washout of 7-21 days. Overall, 245 of 308 (79.5%) PP3M-dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half-life was ∼2-4 months. Mean plasma AUC∞ and Cmax of paliperidone appeared to be dose-proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment-emergent adverse events. Overall, safety and tolerability were similar to those of the 1-month formulation. Results support a once-every-3-months dosing interval in patients with schizophrenia or schizoaffective disorder. © 2015, The American College of Clinical Pharmacology.

  9. [Comparison of the efficacy and safety of praziquantel administered in single dose of 40 versus 60 mg/kg for treating urinary schistosomiasis in Mauritania].

    Science.gov (United States)

    Ouldabdallahi, M; Ousmane, B; Ouldbezeid, M; Mamadou, D; Konaté, L; Chitsulo, L

    2013-08-01

    During the last twenty years, praziquantel (PZQ) was the drug of choice for the treatment of schistosomiasis in the majority of national programs. However, a lower rate of cure had been significantly noted on the left bank of the Senegal River. To explain this unusual rate of cure, the assumption of a possible resistance to the drug as well as under-dosing was considered. With an aim of testing this hypothesis of underdosing, we compared the amount of a single dose of 60 mg/kg of PZQ versus the standardized dose of 40 mg/kg used in curing urinary schistosomiasis in Mauritania. One hundred and fifty-one children aged from 10 to 19 years, including 77 in the group of 60 mg/kg and 74 in the group of 40 mg/ kg, were included in the study. The rates of cure were respectively 64.8% for 60 mg/kg and 67.5% for 40 mg/kg three weeks after the administration of the treatment without statistically significant difference. For the majority of the patients, the drug was well tolerated and no serious adverse events were noted; however, clinical signs in the form of abdominal pain associated or not with diarrhea and vomiting were noted. Praziquantel remains an effective and well-tolerated drug: the amount of 40 mg/kg of body weight can still be maintained for the treatment of schistosomiasis in Mauritania.

  10. Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan.

    Science.gov (United States)

    Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Ciglenecki, Iza; Luquero, Francisco J; Azman, Andrew S; Cabrol, Jean-Clement

    2017-04-01

    Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The occurrence of apoptosis, abnormal mitoses, cells dying in mitosis and micronuclei in a human melanoma xenograft exposed to single dose irradiation

    International Nuclear Information System (INIS)

    Falkvoll, K.H.; Norske Radiumhospital, Oslo)

    1990-01-01

    The mechanisms of cell loss, the cell proliferation and the immediate growth response were investigated in a human melanoma xenograft given single dose irradiation with 7.5 Gy and 15.0 Gy, respectively. The frequencies of apoptotic cells, mitoses, abnormal mitoses, cells dying in mitosis and micronuclei, were scored in histological sections. In the untreated xenograft, the occurrence of micronuclei and abnormal mitoses indicated the presence of reproductively dead cells. Cell loss manifested itself through the appearance of apoptosis, cells dying in mitosis and necrosis. After irradiation, the cell proliferation was temporarily inhibited due to a radiation induced division delay. When proliferation resumed, there was a dose-dependent increase in the frequencies of abnormal mitoses and micronuclei and thus in the fraction of reproductively dead cells. The incidence of cell loss through apoptosis and cells dying in mitosis also increased. This cell loss probably reduced transiently the fraction of reproductively dead cells, and accounted for the reduced amount of tumour cells the first days after 15.0 Gy irradiation. The incidence of apoptotic cell loss and micronuclei decreased, and the incidence of normal mitoses increased when tumour growth resumed. (orig.) [de

  12. Flavanols from green tea and phenolic acids from coffee: critical quantitative evaluation of the pharmacokinetic data in humans after consumption of single doses of beverages.

    Science.gov (United States)

    Williamson, Gary; Dionisi, Fabiola; Renouf, Mathieu

    2011-06-01

    Coffee contains a complex mixture of chlorogenic acids, which are mainly ferulic and caffeic acids ester-linked to quinic acid. Green tea contains flavanols, mainly (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC). For healthy humans, we identified seven studies on green tea in liquid form and five on coffee beverage reporting single-dose plasma pharmacokinetics. Weighted averages, based on the number of subjects, and elimination of outliers, allowed estimation of some pharmacokinetic parameters. After consumption of an "average" cup of green tea containing 112 mg of (-)-epigallocatechin gallate, 51 mg of EGC and 15 mg of EC in 200 mL, the predicted C(max) values (total free and sulfate/glucuronide conjugates) in plasma are 125, 181 and 76 nM, respectively, together with 94 nM methyl-EGC and 51 nM methyl-EC (standard deviation <20%). After consumption of an "average" cup of coffee (160 mg total chlorogenic acids (0.46 mmol)/200 mL), predicted C(max) values of caffeic, ferulic, isoferulic, dihydrocaffeic and dihydroferulic acids are 114, 96, 50, 384 and 594 nM, respectively (too few studies to calculate standard deviation). Most studies report a very low amount of intact chlorogenic acids in plasma, with one exception. More studies on absorption of chlorogenic acids from coffee are required, including dose-response studies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: a cohort study.

    Science.gov (United States)

    Walter, Jan; Kuhn, Louise; Kankasa, Chipepo; Semrau, Katherine; Sinkala, Moses; Thea, Donald M; Aldrovandi, Grace M

    2008-12-30

    Single-dose nevirapine (SDNVP) for the prevention of mother-to-child HIV transmission (PMTCT) results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood. We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed) and those that had not (unexposed) and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders. Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0). Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19%) at both the first (unexposed) and second (exposed) delivery. The results were unchanged, if infant death was included as an outcome. These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.

  14. Mortality and virologic outcomes after access to antiretroviral therapy among a cohort of HIV-infected women who received single-dose nevirapine in Lusaka, Zambia.

    Science.gov (United States)

    Kuhn, Louise; Semrau, Katherine; Ramachandran, Shobana; Sinkala, Moses; Scott, Nancy; Kasonde, Prisca; Mwiya, Mwiya; Kankasa, Chipepo; Decker, Don; Thea, Donald M; Aldrovandi, Grace M

    2009-09-01

    Single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission selects mutations conferring resistance to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. We investigated mortality and virologic and clinical outcomes after introduction of antiretroviral treatment (ART) among a cohort of women given SDNVP. When ART programs were introduced in 2004 in Lusaka, Zambia, we were completing a trial of infant feeding, which involved following HIV-infected women who received SDNVP between 2001 and 2005. Women still in follow-up or who could be contacted were evaluated for eligibility for ART (CD4 count or=3) and started on NNRTI-based therapy if eligible. We compared mortality in the cohort of women before and after ART access, and examined, among women initiating ART, whether virologic response was better allowing a longer time to elapse between SDNVP and treatment initiation. In the cohort of 872 women, mortality more than halved after ART became available (relative hazard = 0.46, 95% confidence interval: 0.23 to 0.91, P = 0.03). Of 161 SDNVP-exposed women followed on NNRTI-based ART, 70.8% suppressed (viral load 24 months after exposure (chi2 trend P = 0.01). Most SDNVP-exposed women respond well to NNRTI-based therapy, but there was an attenuation of therapy efficacy that persisted to 12 months after exposure. Women should be screened for ART eligibility during pregnancy and started on effective regimens before delivery.

  15. Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial.

    Science.gov (United States)

    Wolz, Martin; Schleiffer, Christine; Klingelhöfer, Lisa; Schneider, Christine; Proft, Florian; Schwanebeck, Uta; Reichmann, Heinz; Riederer, Peter; Storch, Alexander

    2012-11-01

    A previous questionnaire study suggests an increased chocolate consumption in Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and biogenic amines, such as β-phenylethylamine, with assumed antiparkinsonian effects. We thus tested the effects of 200 g of chocolate containing 80 % of cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non-fluctuating PD in a mono-center, single-dose, investigator-blinded crossover study using cacao-free white chocolate as placebo comparator. At 1 h after chocolate intake, mean UPDRS motor scores were mildly decreased compared to baseline in both treatments with significant results only for dark chocolate [-1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013¸ Bonferroni p = 0.021 for 1 h values)]. A 2 × 2-cross-over analysis revealed no significant differences between both treatments [-0.54 ± 0.47 (95 % CI -1.50 to 0.42), p = 0.258]. Similar results were obtained at 3 h after intake. β-phenylethylamine blood levels were unaltered. Together, chocolate did not show significant improvement over white cacao-free chocolate in PD motor function.

  16. A new approach to characterise pharmaceutical aerosols: measurement of aerosol from a single dose aqueous inhaler with an optical particle counter.

    Science.gov (United States)

    Kuhli, Maren; Weiss, Maximilian; Steckel, Hartwig

    2010-01-31

    An in-line sampling system with dilution units for aqueous droplet aerosols from single dose inhalers (Berodual Respimat, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany) for an optical particle counter is described. The device has been designed to interface with a white light aerosol spectrometer (welas digital 2100, Palas GmbH, Germany) that allows the time-resolved measurement of highly concentrated aerosols. Performance of the sampling system with regard to the measured particle size distribution (PSD) is compared to Next Generation Impactor (NGI) and to laser diffraction measurements (Sympatec Inhaler and open bench). Optimal settings of the sampling system lead to PSDs that correspond well to those measured by the evaporation minimising NGI approach (15 L/min, cooled) and laser diffraction. The better accuracy of the new dilution unit in presence of an additional aerosol sampling filter in comparison to a previously described aerosol sampling system is shown for different settings of the sampling system. This allows a more precise quantification of the delivered drug amount which is also well correlated to the aerosol volume measured by the welas system. In addition, using time-resolved welas measurements provides insight into droplet size, evaporation and size changes of aerosol clouds delivered by liquid inhalers. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Development of a new Xe-133 single dose multi-step method (SDMM) for muscle blood flow measurement using gamma camera

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Seto, Mikito; Taki, Junichi

    1985-01-01

    In order to measure the muscle blood flow (MBF) during exercise (Ex), a new Xe-133 single dose multi-step method (SDMM) for leg MBF measurement before, during and after Ex using gamma camera was developped. Theoretically, if the activity of Xe-133 in the muscle immediately before and after Ex are known, then the mean MBF during Ex can be calculated. In SDMM, these activities are corrected through correction formula using time delays between end of data aquisition (DA) at rest (R1) and begining of the Ex (TAB), and between end of Ex and begining of the DA after Ex (R2) (TDA). Validity of the SDMM and MBF response on mild and heavy Ex were evaluated in 11 normal volunteers. Ex MBF calculated from 5 and 2.5 min DA (5 sec/frame) both at R1 and R2 were highly correlated (r=.996). Ex MBF by SDMM and direct(measurement by fixed leg exercise were also highly correlated (r=.999). Reproducibility of the R1 and Ex MBF were excellent (r=.999). The highest MBF was seen in GCM on miled walking Ex and in VLM on heavy squatting Ex. After miled Ex, MBF rapidly returned to normal. After heavy Ex, MBF remaind high in VLM In conclusion, SDMM is simple and accurate method for evaluation of dynamic MBF response according to exercise. SDMM is also applicable to the field of sports medicine. (author)

  18. The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial.

    Science.gov (United States)

    Cramer, Steven C; Fitzpatrick, Camille; Warren, Michael; Hill, Michael D; Brown, David; Whitaker, Laura; Ryckborst, Karla J; Plon, Lawrence

    2010-05-01

    Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial. Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points. A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures. Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset.

  19. The effects of A single dose of gamma-rays applied on the head on behavior of rats in Morris's water maze and in the open field test

    International Nuclear Information System (INIS)

    Smajda, B.; Kiskova, J.; Lievajova, K.; Capicikova, M.

    2006-01-01

    The effects of a sublethal dose of gamma-rays applied on the head on selected behavioral parameters were investigated in this study. Adult male Sprague-Dowley rats (n=9) were irradiated with a single dose of 20 Gy of gamma-rays from a 60 Co radiation source. The irradiated animals as well as sham-irradiated controls were tested daily in Morris water maze (MWM) (2 sessions per day) and in the open field test. The ability of spatial learning given by latency time to find the hidden platform was followed in MWM. The horizontal and vertical locomotion, the number of crossings of the center of the field and the washing behavior were recorded during an 8-minute test in the open field. The results obtained show, that radiation didn't altered significantly the dynamic of learning in MWM during the experiment. The level of horizontal and vertical locomotory activity in open field was lower in irradiated group in comparison with controls. The number of the crossings of the field's center, related to the level of anxiozity of animals was non-significantly lower in irradiated animals, whereas no differences in number of washing between both groups were detected. The results point to differences in radiosensitivity in various behavioral parameters in rats, maybe due to different level of their control and coordination in CNS. (authors)

  20. Study on a Single-Dose Toxicity Test of D-Amino Acid Oxidase (DAAO Extracts Injected into the Tail Vein of Rats

    Directory of Open Access Journals (Sweden)

    Kang Jungue

    2013-06-01

    Full Text Available Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the LD50 of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

  1. Single-dose pharmacokinetics of methylphenidate extended-release multiple layer beads administered as intact capsule or sprinkles versus methylphenidate immediate-release tablets (Ritalin(®)) in healthy adult volunteers.

    Science.gov (United States)

    Adjei, Akwete; Teuscher, Nathan S; Kupper, Robert J; Chang, Wei-Wei; Greenhill, Laurence; Newcorn, Jeffrey H; Connor, Daniel F; Wigal, Sharon

    2014-12-01

    The purpose of this study was to evaluate the relative bioavailability and safety of a multilayer extended-release bead methylphenidate (MPH) hydrochloride 80 mg (MPH-MLR) capsule or sprinkles (37% immediate-release [IR]) versus MPH hydrochloride IR(Ritalin(®)) tablets, and to develop a pharmacokinetic (PK) model simulating MPH concentration-time data for different MPH-MLR dosage strengths. This was a single-center, randomized, open-label, three-period crossover study conducted in 26 fasted healthy adults (mean weight±standard deviation, 70.4±11.7 kg) assigned to single-dose oral MPH-MLR 80 mg capsule or sprinkles with applesauce, or Ritalin IR 25 mg (1×5 mg and 1×20 mg tablet) administered at 0, 4, and 8 hours. MPH-MLR 80 mg capsule and sprinkles were bioequivalent; ratios for maximum concentration (Cmax), area under plasma drug concentration versus time curve (AUC)0-t, and AUC0-inf were 1.04 (95% confidence interval [CI], 96.3-112.4), 0.99 (95% CI, 95.3-102.8), and 0.99 (95% CI, 95.4-103.0), respectively. MPH-MLR capsule/sprinkles produced highly comparable, biphasic profiles of plasma MPH concentrations characterized by rapid initial peak, followed by moderate decline until 5 hours postdose, and gradual increase until 7 hours postdose, culminating in an attenuated second peak. Based on 90% CIs, total systemic exposure to MPH-MLR 80 mg capsule/sprinkles was similar to that for Ritalin IR 25 mg three times daily, but marked differences in Cmax values indicated that MPH-MLR regimens were not bioequivalent to Ritalin. MPH Cmax and total systemic exposure over the first 4 hours postdose with MPH-MLR capsule/sprinkles was markedly higher than that associated with the first dose of Ritalin. All study drugs were safe and well tolerated. The PK modeling in adults suggested that differences in MPH pharmacokinetics between MPH-MLR and Ritalin are the result of dosage form design attributes and the associated absorption profiles of MPH. MPH-MLR 80

  2. Single-Dose Pharmacokinetics of Methylphenidate Extended-Release Multiple Layer Beads Administered as Intact Capsule or Sprinkles Versus Methylphenidate Immediate-Release Tablets (Ritalin®) in Healthy Adult Volunteers

    Science.gov (United States)

    Teuscher, Nathan S.; Kupper, Robert J.; Chang, Wei-Wei; Greenhill, Laurence; Newcorn, Jeffrey H.; Connor, Daniel F.; Wigal, Sharon

    2014-01-01

    Abstract Objectives: The purpose of this study was to evaluate the relative bioavailability and safety of a multilayer extended-release bead methylphenidate (MPH) hydrochloride 80 mg (MPH-MLR) capsule or sprinkles (37% immediate-release [IR]) versus MPH hydrochloride IR(Ritalin®) tablets, and to develop a pharmacokinetic (PK) model simulating MPH concentration-time data for different MPH-MLR dosage strengths. Methods: This was a single-center, randomized, open-label, three-period crossover study conducted in 26 fasted healthy adults (mean weight±standard deviation, 70.4±11.7 kg) assigned to single-dose oral MPH-MLR 80 mg capsule or sprinkles with applesauce, or Ritalin IR 25 mg (1×5 mg and 1×20 mg tablet) administered at 0, 4, and 8 hours. Results: MPH-MLR 80 mg capsule and sprinkles were bioequivalent; ratios for maximum concentration (Cmax), area under plasma drug concentration versus time curve (AUC)0-t, and AUC0-inf were 1.04 (95% confidence interval [CI], 96.3–112.4), 0.99 (95% CI, 95.3–102.8), and 0.99 (95% CI, 95.4–103.0), respectively. MPH-MLR capsule/sprinkles produced highly comparable, biphasic profiles of plasma MPH concentrations characterized by rapid initial peak, followed by moderate decline until 5 hours postdose, and gradual increase until 7 hours postdose, culminating in an attenuated second peak. Based on 90% CIs, total systemic exposure to MPH-MLR 80 mg capsule/sprinkles was similar to that for Ritalin IR 25 mg three times daily, but marked differences in Cmax values indicated that MPH-MLR regimens were not bioequivalent to Ritalin. MPH Cmax and total systemic exposure over the first 4 hours postdose with MPH-MLR capsule/sprinkles was markedly higher than that associated with the first dose of Ritalin. All study drugs were safe and well tolerated. The PK modeling in adults suggested that differences in MPH pharmacokinetics between MPH-MLR and Ritalin are the result of dosage form design attributes and the associated

  3. One single dose of 200 mu g of antenatal RhIG halves the risk of anti-D immunization and hemolytic disease of the fetus and newborn in the next pregnancy

    NARCIS (Netherlands)

    Koelewijn, Joke M.; de Haas, Masja; Vrijkotte, Tanja G. M.; Bonsel, Gouke J.; van der Schoot, C. Ellen

    2008-01-01

    BACKGROUND: The objective was the evaluation of the effect of the Dutch national routine antenatal RhIG (anti-D) immunization prevention (RAADP) program comprising one single dose of 200 mu g (1000 IU) of RhIG in the 30th week of pregnancy, restricted to women without a living child. STUDY DESIGN

  4. Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

    Science.gov (United States)

    Liem-Moolenaar, Marieke; Rad, Mandana; Zamuner, Stefano; Cohen, Adam F; Lemme, Francesca; Franson, Kari L; van Gerven, Joop M A; Pich, Emilio Merlo

    2011-01-01

    AIM Several lines of evidence suggest a possible role of 5-HT6receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established. PMID:21223356

  5. Effects of single dose GnRH agonist as luteal support on pregnancy outcome in frozen-thawed embryo transfer cycles: an RCT

    Directory of Open Access Journals (Sweden)

    Robab Davar

    2015-08-01

    Full Text Available Background: There is no doubt that luteal phase support is essential to enhance the reproductive outcome in IVF cycles. In addition to progesterone and human chorionic gonadotropin, several studies have described GnRH agonists as luteal phase support to improve implantation rate, pregnancy rate and live birth rate, whereas other studies showed dissimilar conclusions. All of these studies have been done in fresh IVF cycles. Objective: To determine whether an additional GnRH agonist administered at the time of implantation for luteal phase support in frozen-thawed embryo transfer (FET improves the embryo developmental potential. Materials and Methods: This is a prospective controlled trial study in 200 FET cycles, patients were randomized on the day of embryo transfer into group 1 (n=100 to whom a single dose of GnRH agonist (0.1 mg triptorelin was administered three days after transfer and group 2 (n=100, who did not receive agonist. Both groups received daily vaginal progesterone suppositories plus estradiol valerate 6 mg daily. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were implantation rate, chemical, ongoing pregnancy rate and abortion rate. Results: A total of 200 FET cycles were analyzed. Demographic data and embryo quality were comparable between two groups. No statistically significant difference in clinical and ongoing pregnancy rates was observed between the two groups (26% versus 21%, p=0.40 and 21% versus 17%, p=0.37, respectively. Conclusion: Administration of a subcutaneous GnRH agonist at the time of implantation does not increase clinical or ongoing pregnancy.

  6. Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).

    Science.gov (United States)

    Mayer, Tzur Alexander; Matar, Michael Alex; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

    2014-07-01

    The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The effect of a single dose of multivitamin and mineral combinations with and without guaraná on functional brain activity during a continuous performance task.

    Science.gov (United States)

    White, David J; Camfield, David A; Maggini, Silvia; Pipingas, Andrew; Silberstein, Richard; Stough, Con; Scholey, Andrew

    2017-01-01

    Relatively few studies have explored the possibility of acute cognitive effects of multivitamin ingestion. This report explores the acute brain electrophysiological changes associated with multivitamin and mineral supplementation, with and without guaraná, using the steady-state visually evoked potential (SSVEP). Based on the known SSVEP correlates of A-X continuous performance task (CPT) performance, and sensitivity to acute psychopharmacological manipulations, the A-X CPT was adopted as a task paradigm to explore treatment-related neurophysiological changes in attentional processing. Twenty healthy non-smoking adults aged 21-39 years (mean age = 28.35 years, SD = 5.52) took part in this double-blind, placebo-controlled, randomized, balanced crossover design study. The study demonstrated both transient and tonic changes in the SSVEP response during completion of the A-X CPT following multivitamin and mineral treatment both with and without guaraná. Transient changes in SSVEP response in prefrontal regions were observed after a single dose of a multivitamin and mineral preparation indicative of enhanced activity within brain regions engaged by the attentional demands of the task. This pattern of change in frontal regions was correlated with improved behavioural performance after treatment with the multivitamin and mineral combination. Where tonic shifts in SSVEP response were investigated, multivitamin and mineral treatment was associated with a pattern of increased inhibition across posterior regions, with enhanced excitatory processing in prefrontal regions. In contrast, multivitamin and mineral treatment with additional guaraná showed a tonic shift towards greater excitatory processes after a single treatment, consistent with the caffeine content of this treatment. While preliminary in nature, these findings suggest a single multivitamin/mineral dose is sufficient to impact on functional brain activity in task-related brain regions.

  8. Semi-quantification of endolymphatic size on MR imaging after intravenous injection of single-dose gadodiamide: comparison between two types of processing strategies.

    Science.gov (United States)

    Naganawa, Shinji; Suzuki, Kojiro; Nakamichi, Rei; Bokura, Kiminori; Yoshida, Tadao; Sone, Michihiko; Homann, Georg; Nakashima, Tsutomu; Ikeda, Mitsuru

    2013-12-25

    Many inner ear disorders, including Ménière's disease, are believed to be based on endolymphatic hydrops. We evaluated a newly proposed method for semi-quantification of endolymphatic size in patients with suspected endolymphatic hydrops that uses 2 kinds of processed magnetic resonance (MR) images. Twenty-four consecutive patients underwent heavily T2-weighted (hT2W) MR cisternography (MRC), hT2W 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) with inversion time of 2250 ms (positive perilymph image, PPI), and hT2W-3D-IR with inversion time of 2050 ms (positive endolymph image, PEI) 4 hours after intravenous administration of single-dose gadolinium-based contrast material (IV-SD-GBCM). Two images were generated using 2 new methods to process PPI, PEI, and MRC. Three radiologists contoured the cochlea and vestibule on MRC, copied regions of interest (ROIs) onto the 2 kinds of generated images, and semi-quantitatively measured the size of the endolymph for the cochlea and vestibule by setting a threshold pixel value. Each observer noted a strong linear correlation between endolymphatic size of both the cochlea and vestibule of the 2 kinds of generated images. The Pearson correlation coefficients (r) were 0.783, 0.734, and 0.800 in the cochlea and 0.924, 0.930, and 0.933 in the vestibule (P<0.001, for all). In both the cochlea and vestibule, repeated-measures analysis of variance showed no statistically significant difference between observers. Use of the 2 kinds of generated images generated from MR images obtained 4 hours after IV-SD-GBCM might enable semi-quantification of endolymphatic size with little observer dependency.

  9. Bacillus thuringiensis Cry5B protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    2010-03-01

    Full Text Available Intestinal parasitic nematode diseases are one of the great diseases of our time. Intestinal roundworm parasites, including hookworms, whipworms, and Ascaris, infect well over 1 billion people and cause significant morbidity, especially in children and pregnant women. To date, there is only one drug, albendazole, with adequate efficacy against these parasites to be used in mass drug administration, although tribendimidine may emerge as a second. Given the hundreds of millions of people to be treated, the threat of parasite resistance, and the inadequacy of current treatments, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt crystal (Cry proteins are the most common used biologically produced insecticides in the world and are considered non-toxic to vertebrates.Here we study the ability of a nematicidal Cry protein, Cry5B, to effect a cure in mice of a chronic roundworm infection caused by the natural intestinal parasite, Heligmosomoides bakeri (formerly polygyrus. We show that Cry5B produced from either of two Bt strains can act as an anthelmintic in vivo when administered as a single dose, achieving a approximately 98% reduction in parasite egg production and approximately 70% reduction in worm burdens when delivered per os at approximately 700 nmoles/kg (90-100 mg/kg. Furthermore, our data, combined with the findings of others, suggest that the relative efficacy of Cry5B is either comparable or superior to current anthelmintics. We also demonstrate that Cry5B is likely to be degraded quite rapidly in the stomach, suggesting that the actual dose reaching the parasites is very small.This study indicates that Bt Cry proteins such as Cry5B have excellent anthelmintic properties in vivo and that proper formulation of the protein is likely to reveal a superior anthelmintic.

  10. A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea.

    Science.gov (United States)

    Hook, Edward W; Golden, Matthew; Jamieson, Brian D; Dixon, Paula B; Harbison, Hanne S; Lowens, Sylvan; Fernandes, Prabhavathi

    2015-10-01

    Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. NCT01591447. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Pharmacokinetics of solithromycin (CEM-101) after single or multiple oral doses and effects of food on single-dose bioavailability in healthy adult subjects.

    Science.gov (United States)

    Still, J Gordon; Schranz, Jennifer; Degenhardt, Thorsten P; Scott, Drusilla; Fernandes, Prabhavathi; Gutierrez, Maria J; Clark, Kay

    2011-05-01

    The pharmacokinetics of orally administered solithromycin (CEM-101), a novel fluoroketolide, were evaluated in healthy subjects in three phase 1 studies. In two randomized, double-blinded, placebo-controlled studies, escalating single oral doses of solithromycin (50 to 1,600 mg) or seven oral daily doses (200 to 600 mg) of solithromycin were administered. A third study evaluated the effects of food on the bioavailability of single oral doses (400 mg) of solithromycin. Following single doses, the median time to peak concentration (Tmax) ranged from 1.5 h to 6 h. The mean maximum measured plasma concentration (Cmax) ranged from 0.0223 μg/ml to 19.647 μg/ml, and the area under the concentration-versus-time curve from time zero to time t (AUC0-t) ranged from 0.0402 μg·h/ml to 28.599 μg·h/ml. There was no effect of high-fat food on the oral bioavailability of solithromycin. In the multiple-dose study, after 7 days, the mean maximum measured plasma solithromycin concentration at steady-state (Cmax,ss) ranged from 0.248 to 1.50 μg/ml, and the area under the concentration-versus-time curve over the final dosing interval (AUCτ) ranged from 2.310 to 18.41 μg·h/ml. These values indicate a greater than proportional increase in exposure at 200 and 400 mg but a proportional exposure at 600 mg. Median Tmax values remained constant between day 1 and day 7. Moderate accumulation ratios of solithromycin were observed after 7 days of dosing. All dose regimens of solithromycin were well tolerated, and no discontinuations due to an adverse event occurred. The human pharmacokinetic profile and tolerability of solithromycin, combined with its in vitro potency and efficacy in animal models against a broad spectrum of pathogens, support further development of solithromycin.

  12. Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45.

    Science.gov (United States)

    McCarty, James M; Lock, Michael D; Hunt, Kristin M; Simon, Jakub K; Gurwith, Marc

    2018-02-01

    The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18-45 years of age were randomized 8:1 to receive a single dose of 1 × 10 9 CFU of PXVX0200 from three production lots or saline placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events through day 29 and serious adverse events through day 181. A total of 3146 participants were enrolled, including 2795 vaccine and 351 placebo recipients. The SVA seroconversion rates at day 11 were 94% and 4% in the PXVX0200 and placebo recipients, respectively (P < .0001). Cumulative SVA seroconversion occurred among 96% of vaccine recipients. PXVX0200 SVA GMTs peaked on day 11 and remained significantly higher than placebo through day 181 while the fold-rise over baseline in PXVX0200 anti-CT antibody was significantly greater than placebo at every post-vaccination time point. Most reactogenicity was mild and resolved within 1-3 days with headache and diarrhea more frequently reported in PXVX0200 recipients. There were no differences in unsolicited adverse events and no study-related serious adverse events. Immunogenicity and safety endpoints were equivalent between the three production lots. PXVX0200 is immunogenic and well tolerated across multiple production lots. Clinicaltrials.gov NCT02094586. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Value of Single-Dose Contrast-Enhanced Magnetic Resonance Angiography Versus Intraarterial Digital Subtraction Angiography in Therapy Indications in Abdominal and Iliac Arteries

    International Nuclear Information System (INIS)

    Schaefer, Philipp J.; Schaefer, Fritz K. W.; Mueller-Huelsbeck, Stefan; Both, Markus; Heller, Martin; Jahnke, Thomas

    2007-01-01

    The objective of the study was to prove the value of single-dose contrast-enhanced magnetic resonance angiography [three-dimensional (3D) ceMRA] in abdominal and iliac arteries versus the reference standard intra-arterial digital subtraction angiography (i.a.DSA) when indicating a therapy. Patients suspected of having abdominal or iliac artery stenosis were included in this study. A positive vote of the local Ethics Committee was given. After written informed consent was obtained, 37 patients were enrolled, of which 34 were available for image evaluation. Both 3D ceMRA and i.a. DSA were performed for each patient. The dosage for 3D ceMRA was 0.1 mmol/kg body weight in a 1.5-T scanner with a phased-array coil. The parameters of the 3D-FLASH sequence were as follows: TR/TE 4.6/1.8 ms, effective thickness 3.5 mm, matrix 512 x 200, flip angle 30 o , field of view 420 mm, TA 23 s, coronal scan orientation. Totally, 476 vessel segments were evaluated for stenosis degree by two radiologists in a consensus fashion in a blinded read. For each patient, a therapy was proposed, if clinically indicated. Sensitivity, specificity, positive and negative predictive values, and accuracy for stenoses ≥50% were 68%, 92%, 44%, 97%, and 90%, respectively. In 13/34 patients, a discrepancy was found concerning therapy decisions based on MRA findings versus therapy decisions based on the reference standard DSA. The results showed that the used MRA imaging technique of abdominal and iliac arteries is not competitive to i.a. DSA, with a high rate of misinterpretation of the MRAs resulting in incorrect therapies

  14. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis.

    Science.gov (United States)

    Wilkinson, Samuel T; Ballard, Elizabeth D; Bloch, Michael H; Mathew, Sanjay J; Murrough, James W; Feder, Adriana; Sos, Peter; Wang, Gang; Zarate, Carlos A; Sanacora, Gerard

    2018-02-01

    Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine's effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine's long-term safety and its efficacy in reducing suicide

  15. A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

    Science.gov (United States)

    Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

    2017-10-01

    This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

  16. Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B).

    Science.gov (United States)

    Hattenbach, Lars-Olof; Feltgen, Nicolas; Bertelmann, Thomas; Schmitz-Valckenberg, Steffen; Berk, Hüsnü; Eter, Nicole; Lang, Gabriele E; Rehak, Matus; Taylor, Simon R; Wolf, Armin; Weiss, Claudia; Paulus, Eva-Maria; Pielen, Amelie; Hoerauf, Hans

    2018-02-01

    To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Patients received either monthly ranibizumab for 3 months followed by Pro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followed by PRN sham injections (n = 118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. jConsequences of two different doses to the lungs during a single dose of total body irradiation: Results of a radomized study on 85 patients

    International Nuclear Information System (INIS)

    Girinsky, T.; Socie, G.; Ammarguellat, H.

    1994-01-01

    To evaluate the incidence of lung complications and leukemia recurrences after two different doses to the lungs during total body irradiation. Seventy-nine patients with acute leukemia (AML or ALL) in first complete remission or chronic myeloid leukemia in the chronic phase, five patients with high grade lymphoma, and one with chronic lymphocytic leukemia were entered in the study. They were given a single dose of total body irradiation (10 Gy over 4 h) with two different doses to the lungs (6 Gy or 8 Gy) prior to bone marrow transplantation. The median dose rate was 0.04 Gy/min. The median follow-up for both groups of patients was 24 months. The actuarial 5-year overall survival rate was similar in both groups, 59% and 43% for patients given 8 Gy and 6 Gy to the lungs, respectively. The lung complication rate was similar in the two groups (28% vs. 22% for the 8 Gy and 6 Gy group, respectively). The actuarial leukemia recurrence rate was significantly higher in the group of patients given 6 Gy to the lungs (25%) vs. 0% in the 8 Gy group. Interestingly, fall recurrences occurred in the group of patients who were given 6 Gy to the lungs, who had acute leukemia, and no chromic graft vs. host disease (GVHD). Although the number of patients was not very large and the follow-up relatively short, these findings suggest that a lower dose to the lungs could lead to an increased incidence of leukemia recurrences due to a lower dose to the thoracic wall or to a lower incidence of chronic GVHD. 9 refs., 4 figs., 1 tab

  18. Influence of activated charcoal on the pharmacokinetics of moxifloxacin following intravenous and oral administration of a 400 mg single dose to healthy males

    Science.gov (United States)

    Stass, H; Kubitza, D; Möller, J-G; Delesen, H

    2005-01-01

    Aims To evaluate the extent to which enterohepatic recycling circulation contributes to moxifloxacin bioavailability in healthy, males by administration of activated charcoal and to evaluate the efficacy of activated charcoal administration in decreasing systemic concentrations of moxifloxacin in the event of overdose. Methods Nine healthy males, mean age 34 years (range 23–45 years) participated in a single centre, randomized, nonplacebo-controlled, three way crossover study. The pharmacokinetics of moxifloxacin in plasma and urine were determined for up to 96 h following a 400 mg single dose randomly administered on three separate occasions with a minimum washout phase of 1 week. Treatment A was 400 mg moxifloxacin IV as a 1 h infusion, treatment B was 400 mg moxifloxacin IV as a 1 h infusion with oral activated charcoal (5 g directly before the start of the infusion, 5 g immediately after the end of the infusion, and 10 g at 2, 4 and 8 h after the start of the infusion), treatment C was 400 mg oral moxifloxacin with activated charcoal (10 g 15 min before and at 2, 4 and 8 h after drug administration). The subjects underwent a series of clinical and laboratory tests. Results Single 400 mg doses of moxifloxacin (PO and/or IV) were safe and well tolerated. The bioavailability of moxifloxacin was significantly decreased when given with charcoal (AUC = 35.5 (IV reference) vs 5.40 (PO) vs 28.5 (IV) mg l−1 h). Concurrently peak concentrations were lowered Cmax = 3.38 (IV reference) vs 0.62(PO) vs 2.97 (IV) mg l−1) by approximately 85% (P activated charcoal may be useful in treating moxifloxacin overdose by preventing its absorption. PMID:15842551

  19. Differences in Clinical Results After LINAC-Based Single-Dose Radiosurgery Versus Fractionated Stereotactic Radiotherapy for Patients With Vestibular Schwannomas

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Welzel, Thomas; Schulz-Ertner, Daniela; Huber, Peter E.; Debus, Juergen

    2010-01-01

    Purpose: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). Methods and Materials: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. Results: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of ≤13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (≤13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of ≤13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. Conclusions: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of ≤13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.

  20. A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

    Science.gov (United States)

    Ofotokun, Ighovwerha; Titanji, Kehmia; Lahiri, Cecile D.; Vunnava, Aswani; Foster, Antonina; Sanford, Sara E.; Sheth, Anandi N.; Lennox, Jeffrey L.; Knezevic, Andrea; Ward, Laura; Easley, Kirk A.; Powers, Philip; Weitzmann, M. Neale

    2016-01-01

    Background. Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. Methods. In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. Results. The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. Conclusions. A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. Clinical Trials Registration. NCT01228318. PMID:27193748

  1. Single-dose rosuvastatin ameliorates lung ischemia-reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension.

    Science.gov (United States)

    Matsuo, Satoshi; Saiki, Yuriko; Adachi, Osamu; Kawamoto, Shunsuke; Fukushige, Shinichi; Horii, Akira; Saiki, Yoshikatsu

    2015-03-01

    Lung ischemia-reperfusion (IR) injury during cardiopulmonary surgery is associated with postoperative morbidity and mortality, particularly in patients with pulmonary hypertension (PH). Using a rat model for monocrotaline-induced PH, we investigated the protective effect of rosuvastatin against IR injury in lungs affected by PH and attempted to elucidate its mechanism of action. Male Sprague-Dawley monocrotaline-treated rats were divided into 4 groups (n = 8-9): sham, control + IR, statin + IR, and statin + mevalonolactone + IR. Lung ischemia was induced by left pulmonary artery occlusion (1 hour), followed by reperfusion (4 hours). Rosuvastatin (2 mg/kg) was injected 18 hours before reperfusion and mevalonolactone (1 mg/kg) was injected immediately before reperfusion. The arterial oxygen tension/inspired oxygen fraction ratio was used as a measure of lung oxygenation. Left lung tissue was analyzed for the wet-to-dry lung weight ratio and protein expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS. Macrophage recruitment was assessed by CD68 immunostaining. Our results showed that rosuvastatin decreased IR lung injury (control + IR vs statin + IR) in terms of the arterial oxygen tension/inspired oxygen fraction ratio (272 ± 43 vs 442 ± 13), wet-to-dry ratio (5.7 ± 0.7 vs 4.8 ± 0.6), and macrophage infiltration (8.0 ± 0.6/field vs 4.0 ± 0.5/field) (P < .05 for all). eNOS and phospho-eNOS were downregulated by IR, which was blocked by rosuvastatin. Effects of rosuvastatin were blunted by mevalonolactone. Single-dose rosuvastatin decreased IR injury in lungs affected by PH via 2 anti-inflammatory mechanisms: preserving eNOS function and inhibiting macrophage infiltration. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. Visualization of endolymphatic hydrops in meniere's disease after single-dose intravenous gadolinium-based contrast medium. Timing of optimal enhancement

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Bokura, Kiminori; Sone, Michihiko; Nakashima, Tsutomu

    2012-01-01

    Visualization of endolymphatic hydrops (EH) in patients with Meniere's disease (MD) is now possible by heavily T 2 -weighted 3-dimensional fluid-attenuated inversion recovery (h T 2 W-3D-FLAIR) obtained 4 hours after intravenous (IV) administration of single dose gadolinium-based contrast medium (GBCM). Although maximum enhancement has been reported 4 hours after contrast administration in healthy volunteers, the timing of optimal enhancement in patients with MD is not reported. We investigated if that optimal timing is earlier or later than 4 hours. We evaluated 10 consecutive patients with suspected MD whom we randomly divided into 2 groups. We obtained h T 2 W-3D-FLAIR before GBCM administration and 10 min, 3.5 hours, and 4 hours after GBCM administration in Group A and before and 10 min, 4 hours, and 4.5 hours after GBCM administration in Group B. We compared signal intensity ratio (SIR) values of the perilymph and pons between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B and evaluated grades of EH at 3.5 and 4 hours in Group A and at 4 and 4.5 hours in Group B. SIR values did not differ significantly between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. However, SIR values at 4 hours were significantly higher in Group A than Group B. Grades of EH agreed between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. The optimal timing of contrast enhancement in patients with suspected MD remains unclear, but evaluation of EH may be possible from 3.5 to 4.5 hours after contrast administration. (author)

  3. The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food.

    Science.gov (United States)

    Ericsson, Hans; Sjöberg, Folke; Heijer, Maria; Dorani, Hassan; Johansson, Peter; Wollbratt, Maria; Norjavaara, Ensio

    2012-12-01

    To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n=8). In Part B, patients (n=8) received placebo and a total dose of AZD6370 180 mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. AZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (pfasted versus fed state (0-4 h). Dosing AZD6370 twice or four-times over 1 day gave a smoother 24-h glucose profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well tolerated. AZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Singl