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Sample records for adult healthy volunteers

  1. Cryptosporidium meleagridis: Infectivity in Healthy Adult Volunteers

    PubMed Central

    Chappell, Cynthia L.; Okhuysen, Pablo C.; Langer-Curry, Rebecca C.; Akiyoshi, Donna E.; Widmer, Giovanni; Tzipori, Saul

    2011-01-01

    Most Cryptosporidium infections in humans are caused by C. parvum or C. hominis. However, genotyping techniques have identified infections caused by unusual Cryptosporidium species. Cryptosporidium meleagridis has been identified in ≤ 1% of persons with diarrhea, although prevalence is higher in developing nations. We examined the infectivity of C. meleagridis in healthy adults. Five volunteers were challenged with 105 C. meleagridis oocysts and monitored six weeks for fecal oocysts and clinical manifestations. Four volunteers had diarrhea; three had detectable fecal oocysts; and one infected volunteer remained asymptomatic. Fecal DNA from two volunteers was amplified by using a polymerase chain reaction specific for the Cryptosporidium small subunit ribosomal RNA gene. Nucleotide sequence of these amplicons was diagnostic for C. meleagridis. All infections were self-limited; oocysts were cleared within ≤ 12 days of challenge. These studies establish that healthy adults can be infected and become ill from ingestion of C. meleagridis oocysts. PMID:21813841

  2. Cryptosporidium muris: Infectivity and Illness in Healthy Adult Volunteers

    PubMed Central

    Chappell, Cynthia L.; Okhuysen, Pablo C.; Langer-Curry, Rebecca C.; Lupo, Philip J.; Widmer, Giovanni; Tzipori, Saul

    2015-01-01

    Although Cryptosporidium parvum and C. hominis cause the majority of human cryptosporidiosis cases, other Cryptosporidium species are also capable of infecting humans, particularly when individuals are immunocompromised. Ten C. muris cases have been reported, primarily in human immunodeficiency virus (HIV) -positive patients with diarrhea. However, asymptomatic cases were reported in two HIV-negative children, and in another case, age and immune status were not described. This study examines the infectivity of C. muris in six healthy adults. Volunteers were challenged with 105 C. muris oocysts and monitored for 6 weeks for infection and/or illness. All six patients became infected. Two patients experienced a self-limited diarrheal illness. Total oocysts shed during the study ranged from 6.7 × 106 to 4.1 × 108, and the number was slightly higher in volunteers with diarrhea (2.8 × 108) than asymptomatic shedders (4.4 × 107). C. muris-infected subjects shed oocysts longer than occurred with other species studied in healthy volunteers. Three volunteers shed oocysts for 7 months. Physical examinations were normal, with no reported recurrence of diarrhea or other gastrointestinal complaints. Two persistent shedders were treated with nitazoxanide, and the infection was resolved. Thus, healthy adults are susceptible to C. muris, which can cause mild diarrhea and result in persistent, asymptomatic infection. PMID:25311695

  3. Reassessment of stiripentol pharmacokinetics in healthy adult volunteers.

    PubMed

    Peigné, Sophie; Rey, Elisabeth; Le Guern, Marie-Emmanuelle; Dulac, Olivier; Chiron, Catherine; Pons, Gerard; Jullien, Vincent

    2014-07-01

    Because children who have been receiving stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7 and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of stiripentol for the treatment of Dravet patients in adulthood. PMID:24725808

  4. Diurnal variation in the quantitative EEG in healthy adult volunteers

    PubMed Central

    Cummings, L; Dane, A; Rhodes, J; Lynch, P; Hughes, A M

    2000-01-01

    Aims To define the change in power in standard waveband frequencies of quantitative cortical electroencephalogram (EEG) data over a 24 h period, in a drug free representative healthy volunteer population. Methods This was an open, non randomised study in which 18 volunteers (9 male and 9 female) were studied on 1 study day, over a 24 h period. Volunteers had a cortical EEG recording taken at 0, 2, 4, 6, 8, 10, 12, 16 and 24 h. Each recording lasted for 6 min (3 min eyes open, 3 min eyes closed). All EEG recordings were taken in a quietened ward environment with the curtains drawn round the bed and the volunteer supine. During the 3 min eyes open, volunteers were asked to look at a red circle on a screen at the foot of the bed, and refrain from talking. Results Plots produced of geometric mean power by time of the standard wave band frequencies gave some indication of a circadian rhythm over the 24 h period for θ (4.75–6.75 Hz), α1 (7.0–9.5 Hz) and β1 (12.75–18.50 Hz) wavebands. Mixed models were fitted to both the eyes open and eyes closed data which confirmed a change in mean waveband power with time with statistical significance at the conventional 5% level (P < 0.05). Conclusions These data indicate the presence of a diurnal variation in the cortical quantitative EEG. They support the use of a placebo control group when designing clinical trials which utilize quantitative EEG to screen for central nervous system (CNS) activity of pharmaceutical agents, to control for the confounding variable of time of day at which the EEG recordings were made. PMID:10886113

  5. Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers

    PubMed Central

    Williams, Gemma; Lee, Amy; Meek, Judith; Slater, Rebeccah; Olhede, Sofia; Fitzgerald, Maria

    2013-01-01

    Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21–40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100–300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1–5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain. PMID:23427303

  6. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    PubMed

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. PMID:21112749

  7. Subacromial space in adult patients with thoracic hyperkyphosis and in healthy volunteers.

    PubMed

    Gumina, Stefano; Di Giorgio, Giantony; Postacchini, Franco; Postacchini, Roberto

    2008-02-01

    The assumption that subacromial space decreases in patients with thoracic hyperkyphosis arises from sporadic and personal observations. The purpose of this study was to compare width of subacromial space calculated on radiographs and CT scans of a high number of patients with thoracic hyperkyphosis that registered on exams of healthy volunteers. We measured the subacromial space, using Petersson's method, on radiographs of 47 patients with idiopathic or acquired thoracic hyperkyphosis and of 175 healthy shoulder volunteers. Both groups were further distinguished considering gender and age. Females with hyperkyphosis were also divided in two subgroups: those with a kyphotic curve of less (24 patients) or more (19 patients) than 50 degrees , respectively. Subacromial space of all patients and of 21 volunteers was also evaluated using CT. Acromio-humeral space was less wide in patients with hyperkyphosis with respect to coeval volunteers of the same gender; in females and in subjects older than 60. Subacromial width of females with hyperkyphosis whose curve was more than 50 degrees was significantly narrower (p<0.05) than that measured on radiograms or CT scans of females with a less severe spinal deformity. Decrease of subacromial space may be attributed to less posterior tilting of the scapula and to dyskinesis of the scapular movement. Scapular malposition causes an anomalous orientation of the acromion that may contribute to subacromial impingement. Patients with thoracic hyperkyphosis greater than 50 degrees had a subacromial space narrower than that measured in patients with a less severe kyphosis. This suggests that subacromial width is directly related to severity of thoracic kyphosis. Because hyperkyphosis of patients with osteoporotic vertebral fractures may worsen over the time, subacromial decompression could give only temporary shoulder pain relief. PMID:18320381

  8. The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

    PubMed

    Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

    2016-05-01

    Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. PMID:26919658

  9. Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh

    SciTech Connect

    Sarker, Shafiqul Alam; McCallin, Shawna; Barretto, Caroline; Berger, Bernard; Pittet, Anne-Cecile; Sultana, Shamima; Krause, Lutz; Huq, Sayeda; Bibiloni, Rodrigo; Bruttin, Anne; Reuteler, Gloria; Bruessow, Harald

    2012-12-20

    The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3 Multiplication-Sign 10{sup 9} and 3 Multiplication-Sign 10{sup 7} plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.

  10. Cooking Healthy, Eating Smart (CHES): Evaluating the feasibility of using volunteers to deliver nutrition and food safety education to rural older adults

    NASA Astrophysics Data System (ADS)

    Getty, Morgan

    Due to their limited resources, rural, older adults in the United States are at risk for poor diet-related health outcomes. Nutrition education is a key component in improving health outcomes in older adults. Cooking Healthy, Eating Smart (CHES) is a nine-lesson curriculum designed to teach rural, older adults culturally appropriate nutrition and food safety information. Funding to hire health professionals to deliver such a curriculum is limited, presenting the need to explore a less expensive mode of dissemination. In this community-based, participatory research study, a formative evaluation and feasibility study were conducted to examine the use of volunteers to deliver a nutrition and food safety curriculum to rural, older adults in South Carolina. Seven focus groups were conducted with members of the South Carolina Family and Community Leaders (SCFCL) and members of the American Association of Retired Persons (AARP) in the four regions of South Carolina to explore barriers and facilitators of volunteers delivering CHES (N=65 participants). The focus group findings informed the development of the volunteer training manual. A comparative case study method was used to examine the feasibility of a volunteer-based approach by observing and describing the delivery of CHES by two groups of volunteers in SC. The case study findings, including volunteer knowledge change, self-efficacy change, curriculum experience, program experience, and project team observations of volunteers indicated that using volunteers to deliver CHES is a plausible approach with the assistance of paid staff or project team members.

  11. Cobalt whole blood concentrations in healthy adult male volunteers following two-weeks of ingesting a cobalt supplement.

    PubMed

    Tvermoes, Brooke E; Finley, Brent L; Unice, Kenneth M; Otani, Joanne M; Paustenbach, Dennis J; Galbraith, David A

    2013-03-01

    Recently, there has been an increase in the marketing and sales of dietary supplements, energy drinks, and other consumer products that may contain relatively high concentrations of essential elements. Cobalt-containing supplements are readily available in the U.S. and have been marketed to consumers as energy enhancers. However, little information is available regarding cobalt (Co) body burden and steady-state blood concentrations following the intake of Co dietary supplements. We assessed Co whole blood concentrations in four healthy adult male volunteers who ingested a commercially available Co supplement (0.4 mg Co/day) for 15 or 16 days. Pre-supplementation blood Co concentrations were less than the reporting limit of 0.5 μg/L, consistent with background concentrations reported to range between 0.1 and 0.4 μg/L. The mean whole blood Co concentration in the volunteers after 15 or 16 days of dosing was 3.6 μg Co/L and ranged from 1.8 to 5.1 μg Co/L. The mean observed concentration in the study group was approximately 9-36 times greater than background concentrations. Further studies of Co whole blood concentrations following supplementation over longer time periods with additional monitoring of physiological parameters may provide useful information for evaluating the health of persons who take various doses of Co. PMID:23207477

  12. Comparative fasting bioavailability and pharmacokinetic properties of 2 formulations of glucosamine hydrochloride in healthy Chinese adult male volunteers.

    PubMed

    Wu, H; Liu, M; Wang, S; Zhao, H; Yao, W; Feng, W; Yan, M; Tang, Y; Wei, M

    2012-08-01

    Glucosamine (CAS 66-84-2) hydrochloride is an amino monosaccharide indicated for the treatment of arthrosis, especially osteoarthritis of the knee joint. This study was conducted to assess and compare the pharmacokinetic (PK) properties, bioavailability of a newly developed dispersible tablet formulation (test) of glucosamine hydrochloride with those of an established branded capsule formulation (reference) in healthy Chinese adult male volunteers.This single-dose, randomized, open-label, 2-period crossover study was conducted in 18 healthy Chinese adult male volunteers under fasting condition. Plasma samples were collected at pre-specified times over a 12-h period following administration in each period and analyzed the plasma glucosamine concentrations by Liquid Chromatography coupled with Tandem Mass Spectrometry (LC/MS/MS) method. The mean (SD) PK parameters of Cmax, Tmax, AUC0-12, and AUC0-∞ after administration of the test and reference formulations were, respectively, as follows: Cmax, 907.01 (444.22) vs. 944.40 (429.89) ng/mL, Tmax, 3.03 (0.95) vs. 3.30 (0.99) hours, AUC0-12, 2891.41 (1352.30) vs. 2889.69 (925.48) ng/mL/h, and AUC0-∞, 3029.90 (1321.36) vs. 3091.87 (870.36) ng/mL/h. The mean (SD) t1/2 was 1.10 (0.52) hours for the test formulation and 1.50 (1.17) hours for the reference formulation. On ANOVA, neither period nor sequence effects were observed for any PK properties. The relative bioavailability of the test formulation was 98.3% assessed by AUC0-12. The 90% CIs of glucosamine for the log-transformed ratios of Cmax, AUC0-12, and AUC0-∞ were 78.4-113.9%, 80.8-108.5% and 80.8-105.8%, respectively, meeting the predetermined criteria for bioequivalence of SFDA. PMID:22791244

  13. Institutional Facilitation in Sustained Volunteering among Older Adult Volunteers

    ERIC Educational Resources Information Center

    Tang, Fengyan; Morrow-Howell, Nancy; Hong, Songiee

    2009-01-01

    As more nonprofit organizations rely on older adult volunteers to provide services, it is important to retain volunteers for an extended period of time to ensure service quality and the beneficial outcomes of volunteering. Nonprofit organizations are positioned to facilitate older adult volunteers' role performance. Based on an institutional…

  14. Understanding paratyphoid infection: study protocol for the development of a human model of Salmonella enterica serovar Paratyphi A challenge in healthy adult volunteers

    PubMed Central

    McCullagh, David; Dobinson, Hazel C; Darton, Thomas; Campbell, Danielle; Jones, Claire; Snape, Matthew; Stevens, Zoe; Plested, Emma; Voysey, Merryn; Kerridge, Simon; Martin, Laura B; Angus, Brian; Pollard, Andrew J

    2015-01-01

    Introduction This study will develop the first human challenge model of paratyphoid infection which may then be taken forward to evaluate paratyphoid vaccine candidates. Salmonella Paratyphi A is believed to cause a quarter of the estimated 20 million cases of enteric fever annually. Epidemiological evidence also suggests that an increasing proportion of the enteric fever burden is attributable to S. Paratyphi infection meriting further attention and interest in vaccine development. Assessment of paratyphoid vaccine efficacy in preclinical studies is complicated by the lack of a small animal model and the human-restricted nature of the infection. The use of experimental human infection in healthy volunteers provides an opportunity to address these problems in a cost-effective manner. Methods and analysis Volunteers will ingest virulent S. Paratyphi A bacteria (NVGH308 strain) with a bicarbonate buffer solution to establish the infectious dose resulting in an ‘attack rate’ of 60–75%. Using an a priori decision-making algorithm, the challenge dose will be escalated or de-escalated to achieve the target attack rate, with the aim of reaching the study end point while exposing as few individuals as possible to infection. The attack rate will be determined by the proportion of paratyphoid infection in groups of 20 healthy adult volunteers, with infection being defined by one or more positive blood cultures (microbiological end point) and/or fever, defined as an oral temperature exceeding 38°C sustained for at least 12 h (clinical end point); 20–80 participants will be required. Challenge participants will start a 2-week course of an oral antibiotic on diagnosis of infection, or after 14 days follow-up. Ethics and dissemination The strict eligibility criterion aims to minimise risk to participants and their close contacts. Ethical approval has been obtained. The results will be disseminated in a peer-reviewed journal and presented at international congresses

  15. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

    PubMed Central

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

    2013-01-01

    Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

  16. Healthy Volunteer 2020: Comparing Peace Corps Volunteers' health metrics with Healthy People 2020 national objectives.

    PubMed

    Henderson, Susan J; Newman, Jeannette; Ferguson, Rennie W; Jung, Paul

    2016-12-01

    Healthy People 2020 (HP2020) provides a set of quantifiable objectives for improving the health and well-being of Americans. This study examines Peace Corps Volunteers' health metrics in comparison with the Leading Health Indicators (LHIs) in order to set baseline measures for Volunteers' health care and align our measurements with Healthy People 2020 standards. Health data from multiple internal Peace Corps datasets were compared with relevant LHIs and analyzed using descriptive statistics. Seventeen (65%) of the 26 LHIs were relevant to Peace Corps Volunteers. Of these, Volunteers' health measures met or were more favorable than the goals of 13 (76%) of the LHIs. There were no data available for 4 (24%) of the LHIs. The entire Volunteer population has full access to primary care, oral health, and reproductive health services. No suicides or homicides were reported among Volunteers during the analyzed time period. Utilizing the LHIs, we have identified high-priority public health issues relevant for the Peace Corps Volunteer population. We discuss the need for quality data to measure and monitor Volunteers' health progress and outcomes over time, and also to standardize our measurements with Healthy People 2020 benchmarks. This framework may foster greater collaboration to engage in health promotion and disease prevention activities driven by evidence-based information, which may, in turn, encourage healthy behavior among Volunteers. PMID:27413680

  17. Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study

    PubMed Central

    Ullah, Ashik; Azad, Mohammad Abul Kalam; Sultana, Rebeka; Akbor, Maruf Mohammad; Hasan, Ahasanul; Latif, Mahbub; Hasnat, Abul

    2008-01-01

    Background: Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population. Objective: The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox®; reference, Amoxil-Bencard®) using serum data. Methods: This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement. Results: Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23–34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m2) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: Cmax, 9.85 (2.73) and 10.63 (2.12) μg/mL; Tmax, 1.29 (0.58) and 1.33 (0.49) hours; and AUC0–12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h−1. No period, sequence, or formulation effects

  18. Handbook for Volunteers: Adult Education Program.

    ERIC Educational Resources Information Center

    Koehler, C. Russell

    Designed for volunteers in Olympic College's Adult Education Volunteer Classroom Assistant Project, this handbook discusses volunteer tutors' roles, characteristics of Adult Basic Education (ABE) and English as a Second Language (ESL) students, suggested teaching techniques, tips for working with instructors, and college policies and regulations.…

  19. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers.

    PubMed

    Hirawat, Samit; Welch, Ellen M; Elfring, Gary L; Northcutt, Valerie J; Paushkin, Sergey; Hwang, Seongwoo; Leonard, Eileen M; Almstead, Neil G; Ju, William; Peltz, Stuart W; Miller, Langdon L

    2007-04-01

    Nonsense (premature stop codon) mutations are causative in 5% to 15% of patients with monogenetic inherited disorders. PTC124, a 284-Dalton 1,2,4-oxadiazole, promotes ribosomal readthrough of premature stop codons in mRNA and offers therapeutic potential for multiple genetic diseases. The authors conducted 2 phase I studies of PTC124 in 62 healthy adult volunteers. The initial, single-dose study evaluated doses of 3 to 200 mg/kg and assessed fed-fasting status on pharmacokinetics following a dose of 50 mg/kg. The subsequent multiple-dose study evaluated doses from 10 to 50 mg/kg/dose twice per day (bid) for up to 14 days. PTC124 administered orally as a liquid suspension was palatable and well tolerated through single doses of 100 mg/kg. At 150 and 200 mg/kg, PTC124 induced mild headache, dizziness, and gastrointestinal events. With repeated doses through 50 mg/kg/dose bid, reversible transaminase elevations <2 times the upper limit of normal were sometimes observed. Immunoblot analyses of peripheral blood mononuclear cell extracts revealed no protein elongation due to nonspecific ribosomal readthrough of normal stop codons. PTC124 plasma concentrations exceeding the 2- to 10-microg/mL values associated with activity in preclinical genetic disease models were safely achieved. No sex-related differences in pharmacokinetics were seen. No drug accumulation with repeated dosing was apparent. Diurnal variation was observed, with greater PTC124 exposures after evening doses. PTC124 excretion in the urine was <2%. PTC124 pharmacokinetics were described by a 1-compartment model. Collectively, the data support initiation of phase II studies of PTC124 in patients with nonsense mutation-mediated cystic fibrosis and Duchenne muscular dystrophy. PMID:17389552

  20. Pharmacogenetics of healthy volunteers in Puerto Rico

    PubMed Central

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y.; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L.; Duconge, Jorge

    2016-01-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer’s disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  1. Pharmacogenetics of healthy volunteers in Puerto Rico.

    PubMed

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L; Duconge, Jorge

    2015-12-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  2. Prediction of Psilocybin Response in Healthy Volunteers

    PubMed Central

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X.

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin. PMID:22363492

  3. Pharmacokinetics of cefoperazone in healthy volunteers.

    PubMed

    Saudek, F; Morávek, J; Modr, Z

    1986-01-01

    Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two-compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller. PMID:3095076

  4. Relative bioavailability of two 5-mg montelukast sodium chewable tablets: a single dose, randomized, open-label, 2-period crossover comparison in healthy korean adult male volunteers.

    PubMed

    Kim, H T; Song, Y-K; Lee, S D; Park, Y; Kim, C-K

    2012-03-01

    Montelukast sodium, cysteinyl leukotriene receptor 1 specific antagonist, has been marketed in Korea for the treatment of bronchial asthma and allergic rhinitis. The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of montelukast 5-mg chewable tablets in healthy Korean male volunteers to meet KFDA regulatory criteria for marketing of the new generic formulation. This study was designed as a single-dose, 2-treatment, and 2-period crossover trial with 32 healthy volunteers. Each subject was randomly assigned to receive the test (Dong-Kook Montelukast Sodium Chewable Tablet 5 mg®) or reference (Singulair Chewable Tablet 5 mg®) formulation. The tablet was chewed 20 times, and then swallowed with 240 mL of water. Plasma concentrations of montelukast up to 24 h after the dose were determined using a validated UPLC-MS/MS method, and the bioequivalence between the 2 formulations was assessed by statistical analysis of mean ratios of log-transformed AUC0-24 h and Cmax. No period or sequence effects were detected. The AUC0-24 h was 1 835 ng·h/mL for the test formulation, and 1 930 ng·h/mL for the reference formulation. The respective values of AUC0-∞ were 1 917 and 2 015 ng·h/mL. The Cmax of the test and reference products (247 and 283 ng/mL, respectively) reached at 2.25 and 2.72 h, respectively. Then, they gradually decreased with the mean terminal t1/2 of 5.25 and 5.30 h for the test and reference products, respectively. The 90% CIs for the ratio of log-transformed AUC0-24 h and Cmax for the test and reference formulations were 0.92-0.99 and 0.83-0.91, respectively. No adverse events were reported in this study. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these fasting healthy Korean male volunteers. PMID:22407900

  5. Pharmacokinetics of ambroxol and clenbuterol tablets in healthy Chinese volunteers

    PubMed Central

    Yang, Yong-Ge; Song, Li-Xue; Jiang, Nan; Xu, Xue-Ting; Di, Xiao-Hui; Zhang, Mei

    2015-01-01

    Objective: To investigate the pharmacokinetics of Ambroxol and Clenbuterol Tablets in Chinese healthy volunteers after a single or multiple dosages oral administration. Methods: A total of 9 healthy adult subjects were given Ambroxol and Clenbuterol Tablets in a single dosage or multiple dosages respectively. LC/MS/MS were used for the determination of Ambroxol and Clenbuterol of in plasma. The important pharmacokinetic parameters were calculated by DAS 2.0 software (compartment model). Results: Single and multiple dosage groups of Ambroxol and Clenbuterol were all fitted two-compartment model. The pharmacokinetics fitted first order kinetics process. No difference in pharmacokinetics of Ambroxol in single and multiple dosage groups volunteers was observed, Which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Moreover, parameters of Clenbuterol had significant difference between the single and multiple dosage groups (P<0.05), showing there was accumulation in the body. 9 subjects had completed single or multiple dosages oral administration test, with no adverse drug reactions appeared during the test. Conclusion: There was no obvious accumulation of Ambroxol after repeated dosing. But obvious accumulation of Clenbuterol was noted in multiple-dose administration. The established method is sensitive, accurate, reliable and specific, and it can meet the requirement of clinical pharmacokinetic trial. PMID:26770490

  6. Organizational Support and Volunteering Benefits for Older Adults

    ERIC Educational Resources Information Center

    Tang, Fengyan; Choi, Eunhee; Morrow-Howell, Nancy

    2010-01-01

    Purpose: This study tested a theoretical model of volunteering benefits and examined the mechanism through which volunteering benefits older adults. Design and Methods: This is a 2-wave study of 253 older adult volunteers serving in 10 volunteer programs. Older volunteers completed the mailed surveys in 2005 and 2006. Structural equation modeling…

  7. Healthy Family 2009: Practicing Healthy Adult Living

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Healthy Family 2009 Practicing Healthy Adult Living Past Issues / Winter ... diabetes, or if heart disease runs in your family, begin checking cholesterol at age 20. Colorectal Cancer : ...

  8. [Drug evaluation in healthy volunteers. Legislative and ethical aspects].

    PubMed

    Warot, D

    1991-01-01

    Studies in healthy volunteers have been legalized since December 20th 1988 in France. The healthy volunteer is employed for a variety of studies in phases I and IV of drug development. This type of research can equally be called nontherapeutic in nature. Every experiment involving healthy volunteers should be approved by the Ethics Committee. Using volunteers within the department, company or other organisation, while offering advantages for the investigator should be prohibited as freedom of concept might not be safeguarded. As well, financial incentives may over-persuade individuals, including students, who have low incomes and promote the "professional volunteer". To avoid this problem, French law planned a national register. The potential benefits of such a disposition are still unknown. Having been given appropriate information concerning the drug trial, his obligations and rights, the healthy volunteer gives his written consent. Specific recommendations for nontherapeutic assessments of drug effects are given concerning prisoners, the mentally handicapped, women with a risk of frequency, children. Ethical considerations concerning research on a healthy population must go beyond the law recently promulgated in France. PMID:2050001

  9. Dose Proportionality of Fentanyl Buccal Tablet in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Thompson, Jeffrey; Simonson, Philip G

    2008-01-01

    Objective This study was conducted to assess the dose proportionality, safety, and tolerability of fentanyl buccal tablet (FBT) in Japanese volunteers. Methods Healthy, opioid-naive Japanese adults received single-dose FBT 100, 200, 400, and 800 µg in a randomized, open-label, crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Peak serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum fentanyl concentration-time curve (AUC) from time 0 to infinity (AUC0–∞), and AUC from 0 to the last quantifiable concentration (AUC0–last) were summarized using descriptive statistics. Dose proportionality was claimed if the ln-ln plots of Cmax, AUC0–∞, and AUC0–last vs. dose were linear and the 90% confidence intervals (CI) of the slopes were within 0.8927 and 1.1073. The safety population comprised volunteers who received ≥1 FBT. Results Twenty-five volunteers were enrolled, 23 were included in the safety population (mean age 35.3 years), and 19 completed the study. The assessment of dose proportionality did not meet the statistical criteria (slope [90% CI]: 0.9118 [0.8601, 0.9635] for Cmax, 1.0756 [1.0377, 1.1136] for AUC0–∞, and 1.0992 [1.0677, 1.1307] for AUC0–last). However, the increase in systemic exposure with dose appeared linear, and a post hoc analysis of partial AUCs from time 0 to 8, 12, 18, and 24 hours supported dose proportionality. Median tmax of 90 minutes (range 30–180 minutes) was independent of dose. Adverse events (AEs) were mild or moderate. The most frequent AEs were nausea (N = 9), dizziness (N = 8), headache (N = 6), somnolence (N = 6), dyspepsia (N = 5), and vomiting (N = 3). No application-site or serious AEs were reported. Conclusions Systemic exposure to FBT was approximately dose proportional across the range 100 µg to 800 µg in healthy Japanese adults. Adverse events were mild or moderate. PMID:19915713

  10. Reactivity of allergy skin test in healthy volunteers

    PubMed Central

    Supakthanasiri, Phisit; Klaewsongkram, Jettanong; Chantaphakul, Hiroshi

    2014-01-01

    INTRODUCTION Healthy individuals may be exposed and sensitised to allergens, and have a positive response to a skin prick test despite being asymptomatic. The objectives of this study were to evaluate the prevalence of atopic sensitisation and identify the reactivity of healthy volunteers to common aeroallergens. METHODS Healthy volunteers with no known allergic symptoms were recruited in this study. All volunteers were scheduled to undergo a skin prick test with 16 common aeroallergens that were previously identified among atopic patients. RESULTS A total of 100 volunteers (mean age 28 years) were enrolled in this study. 42 volunteers had positive skin prick tests for at least one allergen. The median number of sensitised allergen was 2 (range 1–7). Volunteers with positive skin tests (n = 42) were younger than those with negative skin tests (n = 58) (mean age 25.5 vs. 29.2 years; p < 0.05). The group with positive skin tests also had a higher proportion of males (57.1% vs. 31.0%; p < 0.01) and first-degree relatives with a history of atopic diseases (31.0% vs. 10.3%; p < 0.05). The most common sensitised allergens in these healthy asymptomatic volunteers were mite (n = 33), house dust (n = 23) and American cockroach (n = 20). CONCLUSION In this study, up to 42% of healthy volunteers, particularly those with a family history of atopy, were sensitised to allergens. Reactivity of the skin test without allergic symptoms, however, does not indicate allergic disease. Therefore, the skin test should only be indicated in atopic symptomatic individuals. PMID:24452975

  11. Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers.

    PubMed

    Vandepapelière, Pierre; Horsmans, Yves; Moris, Philippe; Van Mechelen, Marcelle; Janssens, Michel; Koutsoukos, Marguerite; Van Belle, Pascale; Clement, Frédéric; Hanon, Emmanuel; Wettendorff, Martine; Garçon, Nathalie; Leroux-Roels, Geert

    2008-03-01

    A randomised, double-blind study assessing the potential of four adjuvants in combination with recombinant hepatitis B surface antigen has been conducted to evaluate humoral and cell-mediated immune responses in healthy adults after three vaccine doses at months 0, 1 and 10. Three Adjuvant Systems (AS) contained 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21, formulated either with an oil-in-water emulsion (AS02B and AS02V) or with liposomes (AS01B). The fourth adjuvant was CpG oligonucleotide. High levels of antibodies were induced by all adjuvants, whereas cell-mediated immune responses, including cytolytic T cells and strong and persistent CD4(+) T cell response were mainly observed with the three MPL/QS21-containing Adjuvant Systems. The CD4(+) T cell response was characterised in vitro by vigorous lymphoproliferation, high IFN-gamma and moderate IL-5 production. Antigen-specific T cell immune response was further confirmed ex vivo by detection of IL-2- and IFN-gamma-producing CD4(+) T cells, and in vivo by measuring increased levels of IFN-gamma in the serum and delayed-type hypersensitivity (DTH) responses. The CpG adjuvanted vaccine induced consistently lower immune responses for all parameters. All vaccine adjuvants were shown to be safe with acceptable reactogenicity profiles. The majority of subjects reported local reactions at the injection site after vaccination while general reactions were recorded less frequently. No vaccine-related serious adverse event was reported. Importantly, no increase in markers of auto-immunity and allergy was detected over the whole study course. In conclusion, the Adjuvant Systems containing MPL/QS21, in combination with hepatitis B surface antigen, induced very strong humoral and cellular immune responses in healthy adults. The AS01B-adjuvanted vaccine induced the strongest and most durable specific cellular immune responses after two doses. These Adjuvant Systems, when added to recombinant protein antigens, can be

  12. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers.

    PubMed

    Tildesley, N T J; Kennedy, D O; Perry, E K; Ballard, C G; Savelev, S; Wesnes, K A; Scholey, A B

    2003-06-01

    Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults. PMID:12895685

  13. Effects of a wheat bran extract containing arabinoxylan oligosaccharides on gastrointestinal health parameters in healthy adult human volunteers: a double-blind, randomised, placebo-controlled, cross-over trial.

    PubMed

    François, Isabelle E J A; Lescroart, Olivier; Veraverbeke, Wim S; Marzorati, Massimo; Possemiers, Sam; Evenepoel, Pieter; Hamer, Henrike; Houben, Els; Windey, Karen; Welling, Gjalt W; Delcour, Jan A; Courtin, Christophe M; Verbeke, Kristin; Broekaert, Willem F

    2012-12-28

    Wheat bran extract (WBE) is a food-grade soluble fibre preparation that is highly enriched in arabinoxylan oligosaccharides. In this placebo-controlled cross-over human intervention trial, tolerance and effects on colonic protein and carbohydrate fermentation were studied. After a 1-week run-in period, sixty-three healthy adult volunteers consumed 3, 10 and 0 g WBE/d for 3 weeks in a random order, with 2 weeks' washout between each treatment period. Fasting blood samples were collected at the end of the run-in period and at the end of each treatment period for analysis of haematological and clinical chemistry parameters. Additionally, subjects collected a stool sample for analysis of microbiota, SCFA and pH. A urine sample, collected over 48 h, was used for analysis of p-cresol and phenol content. Finally, the subjects completed questionnaires scoring occurrence frequency and distress severity of eighteen gastrointestinal symptoms. Urinary p-cresol excretion was significantly decreased after WBE consumption at 10 g/d. Faecal bifidobacteria levels were significantly increased after daily intake of 10 g WBE. Additionally, WBE intake at 10 g/d increased faecal SCFA concentrations and lowered faecal pH, indicating increased colonic fermentation of WBE into desired metabolites. At 10 g/d, WBE caused a mild increase in flatulence occurrence frequency and distress severity and a tendency for a mild decrease in constipation occurrence frequency. In conclusion, WBE is well tolerated at doses up to 10 g/d in healthy adults volunteers. Intake of 10 g WBE/d exerts beneficial effects on gut health parameters. PMID:22370444

  14. A randomized, crossover pharmacodynamic study of immediate-release omeprazole/sodium bicarbonate and delayed-release lansoprazole in healthy adult volunteers.

    PubMed

    Pratha, Vijayalakshmi S; McGraw, Thomas; Tobin, William

    2016-06-01

    Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single-center, open-label, three-way crossover study, onset of action of immediate-release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR-OME) and delayed-release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR-OME, or DR-lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR-OME and DR-lansoprazole in median intragastric pH scores for three consecutive 5-min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR-OME was observed on day 7 starting at the 10- to 15-min interval postdosing (P = 0.024) and sustaining through the 115- to 120-min interval (P = 0.017). On day 1, IR-OME achieved sustained inhibition of intragastric acidity significantly faster than DR-lansoprazole. IR-OME maintained pH >4 significantly longer than DR-lansoprazole over a 24-h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR-OME is safe and well tolerated and that treatment with IR-OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR-lansoprazole. PMID:27433347

  15. Limits on Risks for Healthy Volunteers in Biomedical Research

    PubMed Central

    Resnik, David B.

    2012-01-01

    Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism, because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. PMID:22198413

  16. Self-selection for personality variables among healthy volunteers.

    PubMed

    Pieters, M S; Jennekens-Schinkel, A; Schoemaker, H C; Cohen, A F

    1992-01-01

    1. Healthy student volunteers (n = 103) participating in ongoing clinical pharmacological research completed the Dutch Personality Inventory (DPI), the Dutch version of the Spielberger State-Trait Anxiety Inventory (STAI-DY) and the Dutch version of the Sensation Seeking Scale (SSS). 2. The volunteers were more extrovert (P less than 0.001), more flexible (P less than 0.001), more tolerant or less impulsive (P less than 0.001), had more self-confidence and initiative (P less than 0.001), and were more satisfied and optimistic (P less than 0.01) when compared with the general norm. When compared with a student norm, volunteers had lower levels of state (P less than 0.001) and trait (P less than 0.05) anxiety. The general sensation seeking tendency of volunteers was higher than in the student norm group (P less than 0.001). The volunteers had a greater tendency to thrill-and-adventure-seeking (P less than 0.001) and to disinhibition (P less than 0.01). 3. Hence, volunteers were a selected sample of the total population of students. This may influence the interpretation of pharmacokinetic and pharmacodynamic parameters. 4. Personality screening should be added to the screening procedures for volunteers. PMID:1540478

  17. Randomized, Double-Blind, Placebo-Controlled, Safety and Immunogenicity Study of 4 Formulations of Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909) in Healthy Adult Volunteers

    PubMed Central

    Hopkins, Robert J.; Daczkowski, Nancy F.; Kaptur, Paulina E.; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L.; Bernton, Edward

    2013-01-01

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax® (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18 to 50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA + 0.25 mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA + 0.25 mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909. PMID:23701746

  18. Adult Literacy Volunteers. Overview. ERIC Digest No. 48.

    ERIC Educational Resources Information Center

    Imel, Susan

    Although volunteer tutors traditionally have formed the basis of the programs of Laubach Literacy Action and Literacy Volunteers of America, volunteers have begun to play a greater role in adult literacy instruction provided through community-based organizations, correctional institutions, churches, and federally funded adult basic education.…

  19. Pharmacokinetic Interaction Study of Ranitidine and Daijokito in Healthy Volunteers

    PubMed Central

    Endo, Yusuke; Ishihara, Yoshitaka; Tsuno, Satoshi; Matsuda, Akiko; Qian, Weibin; Miura, Norimasa; Hasegawa, Junichi

    2016-01-01

    Background Ranitidine is a histamine 2 receptor antagonist, and daijokito is a Kampo (Chinese herbal medicine as practiced in Japan) formula, which is traditionally used for treating constipation and digestive trouble. Previous study demonstrated that daijokito significantly affected the pharmacokinetics of ranitidine in rats; however, the doses of ranitidine and daijokito in that study were higher than in clinical practice. Therefore, we examined the pharmacokinetic interaction between ranitidine and daijokito in clinical practice doses in healthy volunteers. Methods This was a randomized, open label, two-period crossover study in healthy volunteers (n = 7). Volunteers received administrations of either a single dose of ranitidine 300 mg, or ranitidine 300 mg in combination with daijokito extract granules 2.5 g. Plasma concentrations of ranitidine were measured over 12 h by LC/MS/MS method. Results Plasma concentrations of ranitidine were lower with co-administration of daijokito compared with ranitidine alone. Co-administration of daijokito significantly decreased ranitidine area under the plasma concentration-time curve from 0 to 12 h (AUC0–12) and maximum plasma concentration (Cmax) with geometric mean (GM) ratio [90% confidence interval (CI)] for AUC0–12 of 0.609 (0.449, 0.826) and Cmax of 0.515 (0.345, 0.771). Conclusion Co-administration of ranitidine with daijokito resulted in a significant decrease in plasma level of ranitidine in healthy volunteers. PMID:27493481

  20. Repeat participation among normal healthy research volunteers: professional guinea pigs in clinical trials?

    PubMed

    Tishler, Carl L; Bartholomae, Suzanne

    2003-01-01

    The recent death of a normal healthy volunteer, as well as the increased use of normal volunteers as research subjects, has heightened the attention given to the participation of normal volunteers in clinical research. An overlooked sub-population of normal healthy volunteers are repeat, veteran volunteers. This essay discusses ethical and methodological issues associated with the use of repeat volunteers in research, along with existing guidelines regarding the use of repeat healthy volunteers, and concludes with recommendations for safeguarding repeat volunteers and ideas supporting centralized recruiting. PMID:14593220

  1. Nebivolol decreases systemic oxidative stress in healthy volunteers

    PubMed Central

    Troost, R; Schwedhelm, E; Rojczyk, S; Tsikas, D; Frölich, J C

    2000-01-01

    Aims Nebivolol is a selective, vasodilatory β1-adrenergic receptor antagonist which has been suggested to possess additional antioxidative properties. The aim of the present study was to assess the actions of nebivolol in antihypertensive doses on systemic oxidative stress in healthy volunteers, reflected by 24h urinary excretion of 8-iso-PGF2α. Methods In a double-blind, cross-over study, 12 healthy volunteers received 5 mg nebivolol once daily or placebo for a total of 7 days, separated by a wash out period of 2 weeks. After each treatment period 24h urinary excretion of 8-iso-PGF2α was determined by gas chromatography-tandem mass spectrometry. Results After the 7 day treatment period nebivolol decreased significantly urinary excretion of 8-iso-PGF2α by 24% from 55.3 ± 5.1 pmol mmol−1 creatinine during the placebo period to 42.3 ± 4.7 pmol mmol−1 creatinine (mean ± s.e. mean, P = 0.01), a mean decrease of 13 pmol mmol−1 creatinine (95% CI: −22.8; −3.1). Conclusions Our data show for the first time that nebivolol decreases systemic oxidative stress in young healthy volunteers. PMID:11012562

  2. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    PubMed Central

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  3. Pharmacokinetic-Pharmacodynamic Modeling of Intravenous and Oral Topiramate and Its Effect on the Symbol-Digit Modalities Test in Adult Healthy Volunteers.

    PubMed

    Lim, Chay Ngee; Birnbaum, Angela K; Brundage, Richard C; Leppik, Ilo E; Cloyd, James C; Clark, Annie; Marino, Susan E

    2016-06-01

    A sequential pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to quantify the effects of a single dose of topiramate (100 or 200 mg) on working memory, attention, and psychomotor speed as measured by the Symbol-Digit Modalities Test (SDMT). Established on data pooled from 3 randomized, crossover studies in healthy subjects (19-55 years of age), using both oral and a novel stable-labeled intravenous (IV) formulation of topiramate, an inhibitory Emax model was found to characterize the topiramate concentration-SDMT score relationship well. At the EC50 of 2.85 μg/mL, this topiramate plasma concentration value was estimated to be associated with a 25.5% reduction of SDMT score relative to baseline. Age was an important determinant of the baseline SDMT score, with an estimated decrease of 1.13% in baseline SDMT score with every year of age. Moreover, this approach enabled the quantification of the practice effect observed with repeated administration of the neuropsychological test over shorter testing intervals than have previously been reported in the literature. The finding of a significant effect following a single dose of topiramate in the range widely used to treat migraine and epilepsy needs to be evaluated in a broader patient population undergoing chronic treatment, as the narrow range of resultant concentrations limits the generalizability of the findings. PMID:26395889

  4. Safety assessment of inhaled xylitol in mice and healthy volunteers

    PubMed Central

    Durairaj, Lakshmi; Launspach, Janice; Watt, Janet L; Businga, Thomas R; Kline, Joel N; Thorne, Peter S; Zabner, Joseph

    2004-01-01

    Background Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. Methods This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. Results In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were

  5. Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

    PubMed Central

    Stauffer, Emilie; Kalicki, Robert; Hildebrandt, Tatjana; Frey, Brigitte M.; Frey, Felix J.; Uehlinger, Dominik E.; Pasch, Andreas

    2011-01-01

    Summary Background and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet. Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. Results In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). Conclusions Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS. PMID:21566113

  6. Safety Evaluation of Crocin (a constituent of saffron) Tablets in Healthy Volunteers

    PubMed Central

    Mohamadpour, Amir Houshang; Ayati, Zahara; Parizadeh, Mohammad–Reza; Rajbai, Omid; Hosseinzadeh, Hossein

    2013-01-01

    Objective(s): Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects such as antioxidant, anticancer and memory improving activities. Crocin tablets were evaluated for short-term safety and tolerability in healthy adult volunteers. Materials and Methods: The study was a randomized, double-blind, placebo-controlled design consisting of one month treatment of crocin tablets. Volunteers who fulfilled inclusion and exclusion criteria were randomized into 2 groups of 22 each (males and females) and received 20 mg crocin tablets or placebo. General measures of health were recorded during the study such as hematological, biochemical, hormonal and urinary parameters in pre and post-treatment periods. Results: No major adverse events were reported during the trial. Crocin tablets did not change the above parameters except that it decreased amylase, mixed white blood cells and PTT in healthy volunteers after one month. Conclusion: This clinical safety evaluation showed a relatively safe and normal profile for crocin in healthy volunteers at the given doses within the trial period. PMID:23638291

  7. Immediate effects of two relaxation techniques on healthy volunteers.

    PubMed

    Khemka, Sushilkumar S; Rao, Nagendra H Rama; Nagarathna, Raghuram

    2009-01-01

    This controlled study compared immediate effects of two relaxation techniques on state anxiety and sustained attention in healthy subjects. 86 volunteers (56 men and 30 women) were divided into two groups: the first 43 volunteers (age range 18 to 64) practiced 20 minutes of yoga-based Deep Relaxation Technique (DRT), while the second group of 43 volunteers (same age range), practiced 20 minutes Supine Rest (SR). State anxiety was assessed using the State Trait Anxiety Inventory (STAI A-State), and sustained attention was assessed using the Six Letter Cancellation (SLC) and Digit Letter Substitution (DLS) tests. All tests were administered immediately before, and immediately after, practice. A significant reduction in State Anxiety score (P < 0.001) was observed for the group practicing DRT, but not for the group practicing SR. For the sustained attention tests, however, there were significant increases in scores by both DRT and SR groups (P < 0.001). The results suggest that both interventions improve attention, but that only DRT reduces State Anxiety. PMID:19810579

  8. Evaluation of a one week intradermal regimen for rabies post-exposure prophylaxis: results of a randomized, open label, active-controlled trial in healthy adult volunteers in India.

    PubMed

    Sudarshan, Mysore Kalappa; Narayana, Doddabele Hanumanthaiah Ashwath; Madhusudana, Shampur Narayan; Holla, Ramesh; Ashwin, Belludi Yajaman; Gangaboraiah, Bilagumba; Ravish, Haradanahalli S

    2012-08-01

    The currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. There is a need to introduce and evaluate short course regimens to overcome this problem. This study was conducted to evaluate the immunogenicity and safety of a "new one week intradermal regimen" for rabies post-exposure prophylaxis. A total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick embryo cell (PCECV) rabies vaccine or purified verocell rabies vaccine (PVRV), 40 in each group. Each subject received intradermally one of the vaccines , using the one week regimen (4-4-4). Blood samples were collected on Days 0, 7, 14, 28,180 and 365 for estimation of rabies virus neutralizing antibody (RVNA) concentration. The sera samples were analyzed by rapid fluorescent focus inhibition test (RFFIT). All subjects in both the groups had adequate RVNA concentration of  0.5 IU/mL from day 14 to till day 180 and the difference of geometric mean concentrations between the two groups was not significant (P > 0.606). Further to assess the immunological memory produced by this new regimen, a "single visit four site" intradermal booster vaccination was given to those who did not have adequate RVNA concentration on day 365. This resulted in a quick and enhanced RVNA concentration in these subjects thus denoting a successful anamnestic response. The incidence of adverse events was 8.3% in PCECV group and 1.6% in PVRV group (P=0.001) and the regimen was well tolerated without any dropouts. In conclusion, the new "one week intradermal regimen" is immunogenic and safe for rabies post-exposure prophylaxis and needs to be further evaluated in persons exposed to rabies. PMID:22699446

  9. Indomethacin and cognitive function in healthy elderly volunteers.

    PubMed

    Bruce-Jones, P N; Crome, P; Kalra, L

    1994-07-01

    1. Cognitive function was studied after single and multiple doses of indomethacin (I) and matched placebo (P) in 20 healthy elderly volunteers using a double-blind crossover design. 2. Arousal, attention, integration, coordination, memory and mood were investigated using a battery of psychomotor tests and the Hospital Anxiety and Depression Scale. Assessments were performed before and after the first and last doses of a 7 day course of medication. 3. Critical flicker fusion threshold fell by a mean of 1.96% on indomethacin compared with a 1.13% rise on placebo 5 h after the first dose (P = 0.029). A beneficial effect on choice reaction time latency (P = 0.012) was seen both after acute and continuing administration of indomethacin. Performance at the most discriminating level (level 3) of the paired word association test was significantly better following 8 days of treatment with indomethacin in the younger (55-65 year-old) age group (P = 0.001). 4. There was no significant difference in performance on the symbol-digit substitution test and the continuous attention task. No change was seen in hospital anxiety and depression scale scores. 5. These results suggest that performance on tests of sensorimotor coordination and short term memory may improve in healthy volunteers following indomethacin administration, whereas tests of attention and psychomotor speed remain unaffected. However, further controlled studies in rheumatic patients are needed to evaluate fully the psychomotor effects of indomethacin and other NSAIDs in clinical practice. PMID:7946936

  10. A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers.

    PubMed

    Leong, F Joel; Zhao, Rong; Zeng, Shuqi; Magnusson, Baldur; Diagana, Thierry T; Pertel, Peter

    2014-11-01

    KAF156 belongs to a new class of antimalarial, the imidazolopiperazines, and is currently in clinical development for the treatment of uncomplicated malaria. This first-in-human, single- and multiple-ascending-dose study in 70 healthy male volunteers determined the maximum oral dose of KAF156 tolerated by healthy adults and derived pharmacokinetic data (including preliminary food effect) to enable dose calculations for malaria patients. KAF156 was studied in single-dose cohorts (10 to 1,200 mg, including one 400-mg food effect cohort (4 to 10 subjects/cohort), and in multiple-dose cohorts (60 to 600 mg once daily for 3 days; 8 subjects/cohort). The follow-up period was 6 to 14 days after the last dose. KAF156 was tolerated, with self-limited mild to moderate gastrointestinal and neurological adverse events. In treated subjects after single doses, headache (n = 4; 11.1%), diarrhea (n = 3; 8.3%), dizziness (n = 3; 8.3%), and abdominal pain (n = 2; 5.6%) were the most common adverse events. Headache (n = 4; 16.7%), nausea (n = 3; 12.5%), upper respiratory tract infection (n = 3; 12.5%), and dizziness (n = 2; 8.3%) were the most common adverse events following multiple doses. KAF156 time to maximum concentration (Tmax) was between 1.0 and 6.0 h. Both the area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased more than dose-proportionally in both single- and multiple-ascending-dose cohorts (terminal half-life, 42.5 to 70.7 h). There was no significant accumulation over 3-day repeated administration. The extent of absorption was not significantly affected by food at a single dose of 400 mg, while mean Cmax decreased from 778 ng/ml to 627 ng/ml and Tmax was delayed from a median of 3.0 h under fasting conditions to 6.0 h under fed conditions. Renal elimination is a minor route. PMID:25136017

  11. Volunteer drivers: their contributions to older adults and to themselves.

    PubMed

    Kerschner, Helen; Rousseau, Marie-Hélène

    2008-01-01

    In 2004 and 2005 the Beverly Foundation surveyed volunteer drivers in an effort to better understand how and why they support older adults. The sample comprised 714 volunteer drivers from 367 communities, representing 40 states, who responded to the survey. Their responses provided qualitative and quantitative information about who they are, why they volunteer, the challenges they face, and the satisfaction they receive from volunteering to drive. They also addressed current topics including mobility and transportation for older adults, volunteerism and civic engagement, and an innovative method of joining the two sides of aging--the "wellderly" and the elderly. The involvement of volunteer drivers and the organizations that enable them to provide transportation services may be one solution for today and a hope of the future for meeting the transportation needs of older adults. PMID:19064473

  12. Volunteer Drivers: Their Contributions to Older Adults and to Themselves

    ERIC Educational Resources Information Center

    Kerschner, Helen; Rousseau, Marie-Helene

    2008-01-01

    In 2004 and 2005 the Beverly Foundation surveyed volunteer drivers in an effort to better understand how and why they support older adults. The sample comprised 714 volunteer drivers from 367 communities, representing 40 states, who responded to the survey. Their responses provided qualitative and quantitative information about who they are, why…

  13. MDMA Impairs Response to Water Intake in Healthy Volunteers.

    PubMed

    Baggott, Matthew J; Garrison, Kathleen J; Coyle, Jeremy R; Galloway, Gantt P; Barnes, Allan J; Huestis, Marilyn A; Mendelson, John E

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  14. MDMA Impairs Response to Water Intake in Healthy Volunteers

    PubMed Central

    Garrison, Kathleen J.; Coyle, Jeremy R.; Galloway, Gantt P.; Huestis, Marilyn A.; Mendelson, John E.

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  15. CNS effects of sumatriptan and rizatriptan in healthy female volunteers.

    PubMed

    van der Post, J; Schram, M T; Schoemaker, R C; Pieters, M S M; Fuseau, E; Pereira, A; Baggen, S; Cohen, A F; van Gerven, J M A

    2002-05-01

    This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation. PMID:12100089

  16. Apomorphine-induced blinking and yawning in healthy volunteers.

    PubMed Central

    Blin, O; Masson, G; Azulay, J P; Fondarai, J; Serratrice, G

    1990-01-01

    Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine-dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg-1 s.c.), was compared with a placebo in a double-blind latin-square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose-related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10-30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine-induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man. PMID:2271377

  17. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers.

    PubMed

    Curran, H V; Java, R

    1993-01-01

    Cognitive and psychomotor impairments can be unwanted adverse effects of antiepileptic drugs. The present double-blind, cross-over study with healthy volunteers was designed to assess the effects of two doses of oxcarbazepine (OXCZ) (150 mg b.i.d.; 300 mg b.i.d.) and a placebo, each given over a two week period. Twelve subjects completed a battery of tests before and 4 h after morning doses on days 1, 8 and 15. Results of objective tests indicated that OXCZ improved performance on a focussed attention task and increased manual writing speed. Subjective ratings showed OXCZ increased feelings of altertness, clear-headedness and quickwittedness. OXCZ had no effect on the range of long-term memory processes assessed in this study. It is concluded that at the doses employed, OXCZ has a slightly stimulant effect on some aspects of psychomotor functioning. PMID:8405007

  18. Comparison of aspirin and indobufen in healthy volunteers.

    PubMed

    Lee, Jong-Young; Sung, Ki-Chul; Choi, Hyo-In

    2016-01-01

    The aim of this study is to quantify the extent and recovery of platelet inhibition after administration of indobufen and aspirin in healthy volunteers. Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme, thereby suppressing thromboxane synthesis. Twenty healthy volunteers completed the study and received aspirin (200 mg/day for 2 weeks) followed by a 4-week washout period and then indobufen (200 mg twice a day for 2 weeks). The percent (%) inhibition of platelet aggregation (IPA) was assessed using arachidonic acid (0.5 mg/ml) and adenosine diphosphate (5 µM) at 4, 12, 24 and 48 hours after last dose of each drug. IPA assessed using arachidonic acid as the agonist was similar at 4 hours after the last dose of indobufen (81.07 ± 9.36%) and aspirin (96.99 ± 0.29%, p = 0.10), but significantly lower at 12 hours (74.04 ± 9.55% vs. 97.94 ± 0.28%, p = 0.02), 24 hours (33.39 ± 11.13% vs. 97.48 ± 0.32%, p < 0.001) and 48 hours (14.12 ± 9.74% vs. 98.22 ± 0.31%, p < 0.001) after indobufen, compared to the relative values for aspirin. IPA assessed using adenosine diphosphate as the agonist was similar in the two groups at 4, 12 and 24 hours after the last dose, but significantly lower 48 hours after the last dose of indobufen, compared to the relative value for aspirin (1.98 ± 3.57% vs. 12.61 ± 2.71%, p = 0.002). Indobufen (200 mg twice a day) caused equivalent initial inhibition of platelet aggregation to aspirin (200 mg daily), and the anti-aggregation effect diminished faster than after aspirin. PMID:26083594

  19. Shirodhara: A psycho-physiological profile in healthy volunteers

    PubMed Central

    Dhuri, Kalpana D.; Bodhe, Prashant V.; Vaidya, Ashok B.

    2013-01-01

    Background: Shirodhara is a classical and a well-established ayurvedic procedure of slowly and steadily dripping medicated oil or other liquids on the forehead. This procedure induces a relaxed state of awareness that results in a dynamic psycho-somatic balance. Objectives: The objective of the study is to evaluate the psychological and physiological effects of Shirodhara in healthy volunteers by monitoring the rating of mood and levels of stress, electrocardiogram (ECG), electroencephalogram (EEG), and selected biochemical markers of stress. Materials and Methods: The study was conducted in the human pharmacology laboratory. The study design was open labeled, comparing the baseline variables with values after Shirodhara. The subjects (n = 16) chosen were healthy human volunteers who gave an informed consent. Shirodhara was preceded by Abhyanga – whole body massage. The Shirodhara method was standardized for rate of dripping with peristaltic pump and temperature was controlled with a thermostat. Mood and stress levels were assessed by validated rating scales. The pre- and post-Shirodhara ECG and EEG records were evaluated. Results: Student's paired “t” test was applied to the means + SE of the variables to calculate statistical significance at P <0.05. There was a significant improvement in mood scores and the level of stress (P <0.001). These changes were accompanied by significant decrease in rate of breathing and reduction in diastolic blood pressure along with reduction in heart rate. The relaxed alert state, after Shirodhara, was co-related with an increase in alfa rhythm in EEG. Conclusion: A standardized Shirodhara leads to a state of alert calmness similar to the relaxation response observed in meditation. The clinical benefits observed with Shirodhara in anxiety neurosis, hypertension, and stress aggravation due to chronic degenerative diseases could be mediated through these adaptive physiological effects. PMID:23741161

  20. Factors associated with resilience in healthy adults.

    PubMed

    Simeon, Daphne; Yehuda, Rachel; Cunill, Ruth; Knutelska, Margaret; Putnam, Frank W; Smith, Lisa M

    2007-01-01

    Mature defenses comprise one well-validated indicator of resilience. We investigated the relationships of resilience to trauma, attachment, temperament, cortisol, and cognitive performance in adult healthy volunteers. Participants were administered the Defense Style Questionnaire; the Relationship Questionnaire; the Childhood Trauma Questionnaire, and the Tridimensional Personality Questionnaire. Cortisol determinations included 24-h urinary, mean hourly plasma, response to low-dose dexamethasone suppression, and reactivity to the Trier social stress test (TSST). Mathematical performance during the TSST was quantified. Twenty-five women and 29 men participated. Resilience was significantly negatively correlated with childhood interpersonal trauma and with harm avoidance. Resilience was significantly positively correlated with urinary cortisol, secure attachment, reward dependence, and superior performance. In a linear regression analysis, the strongest predictor of resilience was childhood trauma, followed by math performance under stress and harm avoidance. We conclude that in young adults without manifest psychiatric disorder, resilience was associated with developmental, biological, and cognitive measures which merit further investigation. PMID:17913377

  1. Effect of transdermic acetylsalicylic acid on hemostasis in healthy volunteers.

    PubMed

    Martínez, Adriana B; Funosas, Esteban; Maestri, Lorella; Lucena, Perla Hermida

    2007-01-01

    Acetylsalicylic acid (ASA) exerts an antiaggregatory effect on platelets by irreversible inhibition of the enzyme thrombocyte cyclooxigenase when it is administered orally at doses above 80 mg/day. For several years ASA has been available as a solution that can be topically applied on the skin. It is widely used by athletes and individuals with chronic rheumatic disorders. However, it has not been established to date whether the plasma levels that result from these doses of ASA affect hemostasis during odontological procedures that involve bleeding, causing platelet dysfunction. The aim of the present study was to evaluate whether topical application is capable of affecting hemostasis. Three studies were conducted: A, B y C. Each of the 3 groups included 12 healthy volunteers of both sexes. The aim of study A was to evaluate if the formulation for topical application resulted in plasma levels of ASA that resembled those observed for the oral formulation and affect hemostasis. In experiment A, plasma levels of salicylic acid (SA) were assessed for each volunteer at 30 minutes, 60 minutes, 6 hours, 12 hours and 24 hours after oral administration of a dose of 500 mg ASA. Experiment B was identical to experiment A except for the fact that ASA was topically applied employing a commercial preparation Aspirub in a predetermined area at a rate of 2 ml/day over a period of 15 days. Experiment C was designed in the same way as experiment B, for a higher dose and a longer period of time (4 ml/day over a period of 30 days). One of the volunteers exhibited detectable salicylemia that could affect hemostasis as occurs with the oral formulation. The following two studies (C1 and C2) employed doses of Aspirub of 8 and 16 ml/day respectively, over a period of 30 days. We measured biochemical parameters associated to platelet function. The dose of 8 ml/day induced moderate alterations in all the parameters related to platelet function and the daily dose of 16 ml inhibited platelet

  2. Exercise increases endostatin in circulation of healthy volunteers

    PubMed Central

    Gu, Jian-Wei; Gadonski, Giovani; Wang, Julie; Makey, Ian; Adair, Thomas H

    2004-01-01

    Background Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis. Results We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2) was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined using ELISA. The total peak VO2 (L) in 7 male subjects was 29.5 ± 17.8 over a 4–10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise) were 20.3 ± 3.2 pg/ml, the plasma levels increased to 29.3 ± 4.2, 35.2 ± 1.8, and 27.1 ± 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (%) and the total peak VO2 (L) related to exercise (R2 = 0.9388; P < 0.01). Concurrently, VEGF levels decreased to 28.3 ± 6.4, 17.6 ± 2.4, and 26.5 ± 12.5 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There were no significant changes in plasma bFGF levels in those subjects before and after exercise. Conclusions The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as

  3. Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics

    PubMed Central

    Li, Junfeng; Zhang, Zhaoyun; Liu, Xiaoxia; Wang, Yi; Mao, Fei; Mao, Junjun; Lu, Xiaolan; Jiang, Dongdong; Wan, Yun; Lv, Jia-Ying; Cao, Guoying; Zhang, Jing; Zhao, Naiqing; Atkinson, Mark; Greiner, Dale L.; Prud'homme, Gerald J.; Jiao, Zheng; Li, Yiming; Wang, Qinghua

    2015-01-01

    Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes. PMID:26617516

  4. Tryptophan supplementation and the response to unfairness in healthy volunteers

    PubMed Central

    Cerit, Hilâl; Schuur, Rachel J.; de Bruijn, Ellen R. A.; Van der Does, Willem

    2015-01-01

    Experimental manipulation of serotonin (5-HT) availability has been shown to modulate social behavior. For instance, serotonin depletion increased the rejection rates of unfair offers in the ultimatum game (UG), whereas a single dose of the serotonin reuptake inhibitor (citalopram) decreased rejection rates. These effects were observed immediately after the manipulation. The aim of this study was to investigate the effect of prolonged tryptophan (TRP) supplementation on UG performance in healthy individuals. A randomized double-blind placebo (PLC)-controlled design was used. Healthy volunteers (N = 47) completed the UG before and after a 6-day intervention of TRP (2.8 g/day) or PLC. Impulsivity was measured with a Go-Stop task. The overall analyses showed that TRP supplementation had no significant effect on UG scores, but the direction of the effect was opposite from expectations. Because repeated performance of the UG may lead to unwanted learning effects or strategical changes, additional analyses were conducted in which participants (N = 7) who accepted all offers on the second measurement were excluded. These analyses revealed that the TRP-group rejected very unfair offers more often than the PLC group. The groups did not differ on impulsivity. Increasing serotonin through TRP supplements increased the rejection of very unfair offers. The direction of our findings is inconsistent with earlier studies that showed that increasing 5-HT availability results in less rejection of unfair offers. The current findings thus importantly suggest that effects of acute vs. prolonged enhancement of 5-HT availability may differ. Also, the outcomes show that the UG is a complex task and participants’ decisions may depend on context, e.g., prior experience with the task. PMID:26236273

  5. Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers.

    PubMed

    Joseph, David; Rose, Peter; Strelkowa, Natalja; Schultz, Armin; Garcia, Jeanette; Elgadi, Mabrouk; Huang, Fenglei

    2015-04-01

    Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label, 2-period, fixed-sequence study, 24 healthy volunteers (12 males) received faldaprevir 240 mg and raltegravir 400 mg in 2 treatment schedules (A and B) separated by a washout phase of ≥7 days: (A) twice-daily raltegravir (Days 1-3), once-daily raltegravir (Day 4); (B) twice-daily raltegravir and twice-daily faldaprevir (loading dose, Day 1), twice-daily raltegravir and once-daily faldaprevir (Days 2-5), once-daily raltegravir and once-daily faldaprevir (Day 6). Pharmacokinetics and safety were assessed over 132 hours post-dosing. Compared with raltegravir alone, co-administration with faldaprevir led to 2.7-fold and 2.5-fold increases in raltegravir geometric mean AUC(τ,ss) and C(max,ss), respectively, and a similar increase in raltegravir glucuronide metabolite exposure. No serious adverse events (AEs) were reported and no subject discontinued due to AEs. Faldaprevir and raltegravir co-administration was well tolerated and resulted in a moderate increase in raltegravir exposure. PMID:25352040

  6. Pomelo enhances cyclosporine bioavailability in healthy male Thai volunteers.

    PubMed

    Anlamlert, Wirin; Sermsappasuk, Pakawadee; Yokubol, Dhirayudh; Jones, Sirada

    2015-04-01

    The aim of this study was to investigate the effect of pomelo pulp on the pharmacokinetics of cyclosporine in healthy male Thai volunteers. The study design was an open-label, randomized, single dose, crossover study with a 2-week washout period. A single oral dose of 2 × 100 mg cyclosporine was administered with 200 mL of water. Each subject received 250 g of pomelo pulp or 250 mL of water 1 hour before drug administration and once again 10 minutes following drug administration. Blood samples were collected over a 24 hour period. The point estimates (90% confidence intervals) of the test/control ratio using logarithmic transformed data for the area under the curve (AUC) for blood concentration from time 0 to infinity (AUC(0- ∞)) and the observed maximum concentration (C(max)) were 128.8% (120.6-137.6) and 136.1% (126.0-146.8), respectively. These 90% confidence intervals were higher than the accepted bioequivalence range defined by the European Medicines Agency guidelines for narrow therapeutic index drugs (90%-111% for AUC and 80%-125% for C(max)). However, the apparent terminal half-life (t(1/2)) was not significantly different. In conclusion, co-administration of cyclosporine and pomelo pulp increased the relative bioavailability of cyclosporine. PMID:25408261

  7. [Meteoadaptogenic properties of peptide drugs in healthy volunteers].

    PubMed

    Shabanov, P D; Ganapol'skiĭ, V P; Aleksandrov, P V

    2007-01-01

    The meteoadaptogenic properties of a series of drugs with peptide (cortexin, noopept, dilept) and nonpeptide (vinpotropil) structure were investigated in a climate thermobarocomplex (Tabay, Japan) on a group of healthy volunteers aged 20-24. All the studied drugs produced a meteoadaptogenic action, the extent of which depended on the environmental test conditions (overcooling, overheating, hypobaric hypoxia). Vinpotropil, optimizing a physiological component of the functional state, can be recommended as a meteoadaptogen for both cold and hot climate as well as for hypobaric hypoxia, where it improved the psychological component of the functional state. Cortexin is qualified as an adaptogen and actoprotector only for hypobaric hypoxia conditions (uplands). Noopept, affecting positively a psychological component of the functional state, can be used for rapid adaptation to both cold and hot climate. In the hot climate, noopept also enhanced the physical work capacity. Dilept mostly elevated the psychological component of the functional state and can be considered as a psychomotor enhancer and adaptogen. Therefore, all the drugs studied (vinpotropil, cortexin, noopept and dilept) can be recommended as the agents producing activation, support and recovery of the physical and psychological efficiency under rapidly changing environment conditions. PMID:18318195

  8. Hemodynamic characteristics of midazolam, propofol, and dexmedetomidine in healthy volunteers

    PubMed Central

    Frölich, Michael A.; Arabshahi, Ali; Katholi, Charles; Prasain, Jeevan; Barnes, Stephen

    2013-01-01

    Study Objective To study the effect of intravenous (IV) sedation on blood pressure (BP), heart rate (HR), and respiratory rates (RR) to determine if IV sedatives differ with respect to their effect on BP, HR, and RR. Design Prospective, randomized, single-blinded, placebo-controlled study. Setting Monitored patient care room at a clinical research center. Subjects 60 healthy ASA physical status 1 volunteers. Interventions Subjects were randomized to receive, in increasing doses, one of three IV sedatives: propofol, midazolam, or dexmedetomidine; or saline control. Measurements Blood pressure (systolic, diastolic), HR, and RR were recorded. Main Results A significant dose-dependent BP reduction occurred with dexmedetomidine and, to a lesser degree, with propofol; and there was good agreement of predicted versus measured drug concentrations for all sedatives. Blood pressure and HR of participants who received midazolam did not change. Conclusions When administered in sedative doses, dexmedetomidine and, to a lesser extent, midazolam, reduces BP in a dose-dependent fashion. Dexmedetomidine also reduces HR. Midazolam does not affect BP or HR. PMID:21570617

  9. Pharmacokinetics of cefroxadine after infusion to healthy volunteers.

    PubMed

    Cadórniga, R; Molina, I T; Pastoriza, P; Negro, S; Evora, C M; Gutierrez, J A

    1990-10-01

    The pharmacokinetics of cefroxadine in healthy human volunteers was studied in plasma and urine, after an infusion administration of 1 g of this drug for 0.5 h. Blood and urine samples were microbiologically quantified by diffusion on solid gelose using Bacillus Subtilis ATCC 6633 as the test organism. Plasma and urine profiles were fitted to a reduced two-compartment model not having inactivating biotransformation as a route of elimination. The parameters of distribution for this model show a rapid disposition (t1/2 alpha = 0.28 h) and an average volume of the central compartment of 0.15 +/- 0.04 l/kg (range 0.20-0.09). The dominant terminal half-life (beta-phase) was 1.17 +/- 0.26 h (range 0.90-1.67). The total body volume 0.41 +/- 0.09 l/kg (range 0.30-0.52) indicates that there is no diffusion of the antibiotic into intracellular fluids of poorly perfused tissues due to its high elimination rate. PMID:2258253

  10. Bioequivalence Study of Donepezil Hydrochloride Tablets in Healthy Male Volunteers

    PubMed Central

    Rojanasthien, Noppamas; Aunmuang, Siriluk; Hanprasertpong, Nutthiya; Roongapinun, Sukit; Teekachunhatean, Supanimit

    2012-01-01

    The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0–∞ and Cmax were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0–∞ and Cmax values of the test product over those of the reference product were 1.08 (1.02–1.14) and 1.08 (0.99–1.17), respectively (within the bioequivalence range of 0.8–1.25). The median Tmax for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the Tmax difference between the two preparations was –0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the Tmax of the reference formulation. Our study demonstrated the bioequivalence of the two preparations. PMID:23209934

  11. Interaction between ketoconazole and almotriptan in healthy volunteers.

    PubMed

    Fleishaker, Joseph C; Herman, Beth D; Carel, Barbara J; Azie, Nkechi E

    2003-04-01

    The interaction between almotriptan, a 5-HT1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3-day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4-mediated metabolism and a slight effect on the active tubular secretion of almotriptan. PMID:12723463

  12. Pharmacokinetics and safety of oral almotriptan in healthy male volunteers.

    PubMed

    McEwen, J; Salva, M; Jansat, J M; Cabarrocas, X

    2004-10-01

    Almotriptan (LAS 31416) is a new, oral, specific 5-hydroxytryptamine(1B/1D) receptor agonist for the treatment of migraine. The pharmacokinetics and safety of a range of oral doses were assessed in 23 healthy male volunteers. Peak plasma concentrations were reached between 1.5 and 4 h after dosing. The maximum plasma concentration and area under the curve showed dose proportionality over the dose range 5-200 mg. The elimination half-life was constant at approximately 3 h across all dose levels. A substantial proportion of the initial dose was excreted in urine (27%-39%) during 12 h post-dose and the main excretory product was unchanged drug. Three major urinary metabolites were detected, all of which were pharmacologically inactive. The most common events following almotriptan administration were headache, tiredness and mild nausea. Nine events (18%) were classed as probably related to almotriptan and these were all at the highest dose level of 200 mg. The maximum tolerated dose of almotriptan was, therefore, determined as 150 mg. In conclusion, almotriptan is well tolerated following single, oral doses up to 150 mg and has predictable pharmacokinetics. PMID:15386481

  13. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    PubMed

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg. PMID:25283522

  14. Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

    PubMed

    Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

    2016-09-01

    The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. PMID:27109453

  15. Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

    PubMed

    Chaplin, M F; Chaudhury, S; Dettmar, P W; Sykes, J; Shaw, A D; Davies, G J

    2000-04-01

    Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation. PMID:10822018

  16. Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers

    PubMed Central

    Komatsu, Ryu; Sengupta, Papiya; Cherynak, Grigory; Wadhwa, Anupama; Sessler, Daniel I.; Liu, Jin; Hurst, Harrell E.; Lenhardt, Rainer

    2005-01-01

    We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on two days: Control and Doxapram (intravenous infusion to a plasma concentration of 2.4 ±0.8 μg/mL, 2.5 ±0.9 μg/mL, and 2.6 ±1.1 μg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t tests and presented as means ± SDs; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (Control: 37.5±0.4°C, Doxapram: 37.3±0.4°C, P=0.290) or the vasoconstriction threshold (36.8±0.7 vs. 36.4±0.5°C; P=0.110). However, it significantly reduced the shivering threshold from 36.2±0.5 to 35.7±0.7°C (P=0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole agent. PMID:16243996

  17. Sensorimotor function of the cervical spine in healthy volunteers

    PubMed Central

    Artz, Neil J.; Adams, Michael A.; Dolan, Patricia

    2015-01-01

    Background Sensorimotor mechanisms are important for controlling head motion. However, relatively little is known about sensorimotor function in the cervical spine. This study investigated how age, gender and variations in the test conditions affect measures of position sense, movement sense and reflex activation in cervical muscles. Methods Forty healthy volunteers (19M/21F, aged 19–59 years) participated. Position sense was assessed by determining repositioning errors in upright and flexed neck postures during tests performed in 25%, 50% and 75% cervical flexion. Movement sense was assessed by detecting thresholds to passive flexion and extension at velocities between 1 and 25°s− 1. Reflexes were assessed by determining the latency and amplitude of reflex activation in trapezius and sternocleidomastoid muscles. Reliability was evaluated from intraclass correlation coefficients. Findings Mean repositioning errors ranged from 1.5° to 2.6°, were greater in flexed than upright postures (P = 0.006) and in people aged over 25 years (P = 0.05). Time to detect head motion decreased with increasing velocity (P < 0.001) and was lower during flexion than extension movements (P = 0.002). Reflexes demonstrated shorter latency (P < 0.001) and greater amplitude (P = 0.009) in trapezius compared to sternocleidomastoid, and became slower and weaker with age. None of the measures were influenced by gender. Reliability was good for movement sense measures, but was influenced by the test conditions when assessing position sense. Interpretation Increased repositioning errors and slower reflexes in older subjects suggest that sensorimotor function in the cervical spine becomes impaired with age. In position sense tests, reliability was influenced by the test conditions with mid-range flexion movements, performed in standing, providing the most reliable measurements. PMID:25686675

  18. Cardiopulmonary interactions of salbutamol and hypoxaemia in healthy young volunteers.

    PubMed Central

    Kiely, D G; Cargill, R I; Lipworth, B J

    1995-01-01

    1. Nebulised salbutamol is frequently used in the treatment of asthma and chronic obstructive pulmonary disease. Its effects on the cardiovascular system have been extensively investigated although as yet little is known concerning its effects on the pulmonary circulation, particularly during hypoxaemia. We have therefore examined the effects of nebulised salbutamol on pulmonary haemodynamics to see if it modifies hypoxic pulmonary vasoconstriction. 2. Eight healthy normal volunteers were studied on two separate occasions. After resting to achieve baseline haemodynamics patients were randomised to receive 5 mg salbutamol or placebo via a nebuliser. They were restudied after 30 min and then rendered hypoxaemic by breathing an N2/O2 mixture to achieve an SaO2 of 75-80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output (CO) and hence pulmonary vascular resistance (PVR). 3. Treatment with salbutamol significantly increased MPAP during normoxaemia and hypoxaemia compared with placebo at 12.0 +/- 1.2 vs 8.0 +/- 0.7 mm Hg and 28.6 +/- 0.9 vs 25.2 +/- 1.0 mm Hg, respectively (P < 0.05). Salbutamol caused a significant increase in heart rate compared with placebo and effects were additive to those of hypoxia at 74 +/- 2 vs 67 +/- 3 beats min-1 during normoxaemia and 84 +/- 3 vs 77 +/- 4 beats min-1 during hypoxaemia, respectively (P < 0.05). Whilst systemic vascular resistance fell in response to salbutamol, PVR was unchanged by salbutamol during either normoxaemia or hypoxaemia. Cardiac output was increased by salbutamol and by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8554932

  19. Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers.

    PubMed

    Mosci, Camila; Kumar, Meena; Smolarz, Kamilla; Koglin, Norman; Stephens, Andrew W; Schwaiger, Markus; Gambhir, Sanjiv S; Mittra, Erik S

    2016-06-01

    Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was

  20. Prograf five milligrams versus Tacrolimus medis in healthy volunteers: a bioequivalence study.

    PubMed

    Masri, M; Rizk, S; Boujbel, L; Bellahirich, W; Baassoumi, D; Attia, M; Matha, V

    2013-01-01

    For FDA approval, bioequivalence of a generic version of Tacrolimus must be demonstrated in a randomized, two-treatments, two-periods, two-sequences, single-dose crossover study in healthy adult volunteers. Currently there are at least 3 differents generic equivalent for Tacrolimus, that are approved by the EMA and the FDA, with a USA market share of nearly 50%. However, the market share of generic immunosuppressive drugs in the Middle East region is still very low due to the reluctance of the physician to accept Tacrolimus generics, considered to be a narrow therapeutic window drug, that are approved using the standard bioequivalence criteria of 80% to 125%. Herein we present a bioequivalence study of a new Tacrolimus generic, Tacrolimus Medis 5 mg developed by Medis Tunisia batch number 12G3003 compared with Prograf® 5 mg batch number 7202 manufactured by Astellas Toyama Co., Ltd. Japan and HIKMA Pharmaceuticals, Amman-Jordan in healthy adult volunteers using the 90%-111% criteria recommended for drugs with narrow therapeutic window. The study was, balanced, randomized, two-treatments, two-periods, two-sequences, single dose, crossover, comparative oral bioavailability study in healthy adult human volunteers. The study was carried out in accordance with the Basic Principles defined in the U.S. 21 CFR Part 312.20, the principles enunciated in the Declaration of Helsinki (World Medical Association Declaration of Helsinki). Thirty six non-smoking healthy, as determined by medical history, volunteers, 18 years and older, were included. Following randomization using a computer software (pharma solution) the volunteers were given a single oral dose of 5 milligrams following a 12 hour fast with a wash out period of 7 days. Pharmacokinetics profile with blood levels at: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours were performed following each dose. Tacrolimus plasma level was determined using an HPLC validated method (Transmedical For Life S.A.R.L. Beirut

  1. More than the money: A review of the literature examining healthy volunteer motivations

    PubMed Central

    Stunkel, Leanne; Grady, Christine

    2016-01-01

    Background and Objective Few existing data report the motivations of healthy volunteers in clinical research trials. Some worry that volunteers consider only financial motivations. This study summarized and analyzed existing empirical research on self-reported motivations of healthy volunteers participating in studies not intended to offer benefit from participation. Study Selection A systematic PubMed search was conducted. Inclusion criteria captured English-language empirical studies on the self-reported motivations, reasons, or factors influencing the decision of healthy volunteers to enroll in clinical research. Twelve studies involving more than 2000 healthy volunteers met the criteria and were included in this review. Data Extraction Independent review by the authors and extraction of information about the sample, methodology and objective of the motivations study, description of the clinical trial and whether participation was actual or hypothetical, reported primary and secondary motivations of the healthy volunteers, risk evaluation, and reported differences in motivations related to sociodemographic variables. Results This review showed that although financial reward is the primary motivation for healthy volunteers to participate in clinical trials, financial motivations are one among many other reported motivations, including contributing to science or the health of others, accessing ancillary healthcare benefits, scientific interest or interest in the goals of the study, as well as meeting people and curiosity. Volunteers consider risk when making a decision about participation. Conclusions Although financial incentives are important in recruiting healthy volunteers, their motivations are not limited to financial motivations. Further research is needed to examine motivations in different contexts and countries, the decision making of healthy volunteers, and the dynamics of repeat participation. PMID:21146635

  2. Biomechanical Correlates of Surface Electromyography Signals Obtained during Swallowing by Healthy Adults

    ERIC Educational Resources Information Center

    Crary, Michael A.; Carnaby (Mann), Giselle D.; Groher, Michael E.

    2006-01-01

    Purpose: The purpose of this study was to describe biomechanical correlates of the surface electromyographic signal obtained during swallowing by healthy adult volunteers. Method: Seventeen healthy adults were evaluated with simultaneous videofluoroscopy and surface electromyography (sEMG) while swallowing 5 mL of liquid barium sulfate. Three…

  3. Adults Who Learn Differently: Help through a Volunteer Literacy Program.

    ERIC Educational Resources Information Center

    Skinner, Louise; Gillespie, Phyllis; Balkam, Lynda

    1997-01-01

    Presents an overview of preservice volunteer training at READ/San Diego, an adult literacy program. It discusses the program's informal assessment procedures that help identify possible language/learning disabilities and provide valuable information for instructional planning. Also described are selected multisensory teaching techniques designed…

  4. Less May Be More: Rethinking Adult Literacy Volunteer Tutor Training

    ERIC Educational Resources Information Center

    Belzer, Alisa

    2006-01-01

    This study analyzed the relation between volunteer tutor training and reading instruction in 4 adult literacy programs. The data focus on tutors' choices of reading materials and strategies for assisting in the development of comprehension and word identification skills. Tutor training did not always transfer to practice, and it did not always…

  5. Comparative bioavailability study of two brands of prazosin-containing tablets in healthy volunteers.

    PubMed

    Guelen, P J; Janssen, T J; Lam, M H; Vree, T B; Exler, P S

    1990-10-19

    The bioavailability of two prazosin formulations was studied in 12 healthy volunteers. 1 Subject left the study. Based on the statistical tests of the pharmacokinetic parameters of prazosin in 11 volunteers, such as t 1/2, Cmax, tmax and AUC, it could be concluded that both preparations had comparable bioavailabilities. PMID:2255586

  6. CONCENTRATED AMBIENT AIR PARTICLES INDUCE PULMONARY INFLAMMATION IN HEALTHY HUMAN VOLUNTEERS

    EPA Science Inventory


    We tested the hypothesis that exposure of healthy volunteers to concentrated ambient particles (CAPS) is associated with an influx of inflammatory cells into the lower respiratory tract. Thirty-eight volunteers were exposed to either filtered air or particles concentrated fro...

  7. Exposure to wood smoke particles produces an inflammation in healthy volunteers

    EPA Science Inventory

    Background. Human exposure to wood smoke particles (WSP) is of consequence in indoor air quality, exposures from wild fires, burning ofbiomass, and air pollution. This investigation tested the postulate that healthy volunteers exposed to WSP would demonstrate pulmonary and cardio...

  8. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles.

    PubMed

    Gong, Henry; Linn, William S; Terrell, Sheryl L; Clark, Kenneth W; Geller, Michael D; Anderson, Karen R; Cascio, Wayne E; Sioutas, Constantinos

    2004-06-01

    Twelve mildly asthmatic and four healthy adults were exposed to filtered air (FA) and concentrated ambient coarse particles (CCP) supplied to a whole-body exposure chamber via a coarse particle concentrator with 15 parallel virtual impactors. Exposures were conducted in a Los Angeles suburb with high levels of motor-vehicle pollution and lasted 2 h with intermittent exercise. Mean CCP concentration was 157 microg/m(3) (range: 56-218 microg/m(3)) measured by continuous monitoring with a tapered-element oscillating microbalance (TEOM). On average, 80% of mass was coarse (2.5-10 microm aerodynamic diameter) and the rest <2.5 microm. Relative to FA, CCP exposure did not significantly alter respiratory symptoms, spirometry, arterial oxygen saturation, or airway inflammation according to exhaled nitric oxide and total and differential cell counts of induced sputum. After CCP exposure, Holter electrocardiograms showed small (p <.05) increases in heart rate and decreases in heart-rate variability, which were larger in healthy than in asthmatic subjects. Cardiac ectopy did not increase. In conclusion, acute exposure to elevated concentrations of ambient coarse particles elicited no obvious pulmonary effects but appeared to alter the autonomic nervous system of the heart in adult volunteers. PMID:15204749

  9. Payment to healthy volunteers in clinical research: the research subject's perspective.

    PubMed

    Czarny, M J; Kass, N E; Flexner, C; Carson, K A; Myers, R K; Fuchs, E J

    2010-03-01

    Although there is much discussion regarding the ethics of making payments to healthy volunteers for participating in clinical research, little data are available from the point of view of the volunteers as to what they would consider to be fair payment. The objectives of this study were to determine healthy volunteers' estimates of appropriate payments for participation in hypothetical clinical trials in order to explore the reasoning behind these estimates and to examine the association between volunteer demographics and payment expectations. Sixty participants with previous experience as healthy volunteers in research studies were presented with four hypothetical studies and interviewed about their impressions of burden and risks involved in the studies. They were also asked to estimate an appropriate payment to the volunteers for each of the studies. For each of the studies, the payment estimates made by the participants varied over a wide range. However, each individual tended to be consistent in estimate placement within this range. No demographic factor was significantly associated with the estimated study payment. Subjects frequently mentioned risk and logistical burden as factors that should determine payment levels. Healthy volunteer subjects appear to have individualized yet consistent methods of arriving at estimates of payments for participating in clinical studies. These estimates are based on each subject's perception of study burden and associated risk. PMID:20090675

  10. Adult 4-H Volunteer Empowerment in 4-H Youth Development Settings

    ERIC Educational Resources Information Center

    Olsen, Pamela

    2009-01-01

    The primary purpose of this study was to determine which factors related to adult 4-H volunteer empowerment in 4-H youth development settings. This study examined the relationship of adult 4-H volunteers' perceived leadership styles of Oregon 4-H Youth Development Educators (YDE) to the adult 4-H volunteer sense of empowerment. In addition,…

  11. Relative Bioavailability of Fentanyl Following Various Dosing Regimens of Fentanyl Buccal Tablet in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Simonson, Philip G

    2008-01-01

    Background Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc., Frazer, PA, USA) is indicated in the US for breakthrough pain in patients with cancer who are already receiving and are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. For each individual patient, FBT should be titrated to the effective dose. Objective The primary objective was to characterize the pharmacokinetic parameters of FBT 400 µg administered as a single 400 µg tablet (regimen A) or as two 200 µg tablets given simultaneously (regimen B) and determine whether these are bioequivalent in healthy Japanese volunteers. Regimen C (two 200 µg tablets 30 minutes apart) was also compared as a secondary objective. Methods Healthy Japanese adults received regimens A, B, and C in a crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Serum fentanyl concentrations were determined in venous blood collected through 36 hours post dose. Regimens were declared bioequivalent with respect to bioavailability (as reflected by AUC0–∞, AUC0–last, and Cmax) if the 90% confidence interval (CI) of the regimens' ratio fell within 0.80–1.25 (80%–125%). Results Twenty-nine volunteers (13 men, 16 women) were enrolled; 24 completed the study. Regimens A and B had bioequivalent systemic exposure parameters (B/A [90% CI]: AUC0–∞108.4 [103.4, 113.7], AUC0–last 106.1 [100.7, 111.7], and Cmax 92.3 [83.2, 102.4]). Regimen C was bioequivalent to both A and B for AUCs, but only to B for Cmax. Median time to Cmax was 45 minutes for regimen A and 60 minutes for regimens B and C. The most frequent AEs were dizziness, application-site erythema, headache, somnolence, nausea, and vomiting. All AEs were mild or moderate. Conclusions Bioavailability of fentanyl after FBT 400 µg administered as a single tablet was bioequivalent to that after 2 simultaneously administered 200 µg tablets in healthy Japanese volunteers. AEs were mild or moderate. PMID

  12. Giving monoclonal antibodies to healthy volunteers in phase 1 trials: is it safe?

    PubMed Central

    Tranter, Elizabeth; Peters, Gary; Boyce, Malcolm; Warrington, Steve

    2013-01-01

    Many monoclonal antibodies (MAbs) have been studied in healthy volunteers in phase 1, but few data have been published on the safety of that practice. We aimed to review the available data, and thereby to estimate the risks of participation in phase 1 trials of MAbs. We searched PubMed, the ClinicalTrials.gov database and Google, using the search terms ‘monoclonal antibody’, ‘phase 1’ and ‘healthy volunteers’. We identified 70 completed trials of MAbs in healthy volunteers, but the published data were too sparse to allow confident assessment of the risks of MAbs in healthy volunteers. Our best estimate of risk of a life-threatening adverse event was between 1 : 425 and 1 : 1700 volunteer-trials, but all such events occurred in a single trial (of TGN1412). In a phase 1 trial of a small molecule, the risk of death or a life-threatening adverse event appears to be 1 : 100 000–1 000 000 volunteer-trials, which is similar to the risk of many ordinary daily activities. Most people would consider that level of risk to be ‘minimal’ or ‘negligible’ and, therefore, acceptable. On that basis, the safety record of MAbs in healthy volunteers has been ruined by the TGN1412 disaster. However, that experience is unlikely to be repeated, because of improvements in governance and practice of phase 1 trials. If the experience of TGN1412 is disregarded, it seems reasonable to continue using healthy volunteers in phase 1 trials of MAbs, provided that there are scientific and medical reasons to conclude that the risk is truly minimal. PMID:23438102

  13. Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine

    PubMed Central

    2010-01-01

    Background Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers. Methods Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis. Results Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin. Conclusions The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations. PMID:20932349

  14. Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

    PubMed Central

    Matar, Kamal M.; Awad, Abdelmoneim I.; Elamin, Sakina B.

    2014-01-01

    Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, Tmax values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons. PMID:24615137

  15. Experimental manipulations of pain catastrophizing influence pain levels in patients with chronic pain and healthy volunteers.

    PubMed

    Kjøgx, Heidi; Kasch, Helge; Zachariae, Robert; Svensson, Peter; Jensen, Troels S; Vase, Lene

    2016-06-01

    Pain catastrophizing (PC) has been related to pain levels in both patients experiencing acute or chronic pain and in healthy volunteers exposed to experimental pain. Still, it is unclear whether high levels of pain catastrophizing lead to high levels of pain or vice versa. We therefore tested whether levels of pain catastrophizing could be increased and decreased in the same participant through hypnotic suggestions and whether the altered level of situation-specific pain catastrophizing was related to increased and decreased pain levels, respectively. Using the spontaneous pain of 22 patients with chronic tension-type headache and experimentally induced pain in 22 healthy volunteers, participants were tested in 3 randomized sessions where they received 3 types of hypnotic suggestions: Negative (based on the 13 items in the Pain Catastrophizing Scale), Positive (coping-oriented reversion of the Pain Catastrophizing Scale), and Neutral (neutral sentence) hypnotic suggestions. The hypnotic suggestions significantly increased and decreased situation-specific PC in both patients and healthy volunteers (P < 0.001). Also, the levels of pain intensity and pain unpleasantness were significantly altered in both patients and healthy volunteers (P < 0.001). Furthermore, regression analyses showed that changes in pain catastrophizing predicted changes in pain in patients (R = 0.204-0.304; P < 0.045) and in healthy volunteers (R = 0.328-0.252; P < 0.018). This is the first study to successfully manipulate PC in positive and negative directions in both patients with chronic pain and healthy volunteers and to show that these manipulations significantly influence pain levels. These findings may have important theoretical and clinical implications. PMID:26871534

  16. 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

    PubMed Central

    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

  17. Pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.

    PubMed

    Jackson, Douglass L; Milgrom, Peter; Heacox, Gail A; Kharasch, Evan D

    2006-02-01

    Triazolam is increasing in popularity as a premedication prescribed by dentists to help their fearful and anxious patients tolerate the potentially aversive nature of some dental procedures. Recent anecdotal reports suggest that incremental sublingual dosing of triazolam may be an effective technique for producing conscious sedation in the dental setting. Although promising, no laboratory or clinical data have been available to evaluate the efficacy or safety of this approach. This study was designed to determine the pharmacokinetics and sedative effects of incremental sublingual dosing of triazolam (total, 1.0 mg) in healthy adults. Ten healthy adult volunteers received sublingual triazolam (0.25 mg) followed by additional doses after 60 (0.50 mg) and 90 (0.25 mg) minutes. Plasma triazolam concentrations, clinical effects (Observer's Assessment of Alertness/Sedation score), and processed electroencephalogram (bispectral index score) were measured intermittently for 3 hours. Plasma triazolam concentrations (mean +/- SD, 5.1 +/- 1.1 ng/mL) and drug effects (Observer's Assessment of Alertness/Sedation score, 2 +/- 1; and the bispectral index score, 62 +/- 16) were greatest in all subjects at the end of the 3-hour evaluation period. Eight of the subjects had Observer's Assessment of Alertness/Sedation scores consistent with the definition of deep sedation or general anesthesia (Observer's Assessment of Alertness/Sedation score, <3) at some of the later time points in the 180 minutes of data collection. In comparison, 4 of the subjects had bispectral index scores less than 60 during these later time points of data collection. Given the considerable intersubject variability in triazolam concentrations and effects, additional research is needed to assess this multidosing strategy before it can be endorsed as a useful and safe sedation technique for managing fearful and anxious patients in dental practice. PMID:16415697

  18. Recruiting Healthy Volunteers for Research Participation via Internet Advertising

    PubMed Central

    Bramstedt, Katrina A.

    2007-01-01

    Objective: The Internet is frequently used as a tool to recruit research subjects, and the US Food and Drug Administration (FDA) provides general guidance regarding such advertising. The goal of this study was to explore the incidence and nature of ethically inappropriate recruiting advertisements on the Internet and to provide descriptive guidance to researchers for responsible Internet recruiting. Methods: In this study, 119 advertisements recruiting health volunteers and listed on the CenterWatch Clinical Trials Listing Service website were reviewed for content as well as text style and visual effects. Results: The majority of advertisements satisfied FDA guidance. However, 21 (18%) were ethically troubling with regard to font size, font style, and/or verbiage. In many advertisements, it was unclear if “medication” meant “investigational drug,” “over-the-counter medication” or US FDA approved “prescription medication.” Nearly 30% of the 119 advertisements used the terms “free,” “no charge” or “no cost” as lures. Conclusion: Ethically problematic recruiting advertisements can be coercive and misleading. Descriptive guidance provided in this paper can help clinical researchers create ethically appropriate recruiting advertisements. PMID:17607043

  19. Percentage of Adults with a Healthy Weight

    MedlinePlus

    ... small sample sizes for NHANES data, 95% confidence intervals are provided, which are important for interpreting the ... Percentage of Adults with a Healthy Weight by Education Level euvy-mq8a Download these data » Click on ...

  20. Increased Set Shifting Costs in Fasted Healthy Volunteers

    PubMed Central

    Bolton, Heather M.; Burgess, Paul W.; Gilbert, Sam J.; Serpell, Lucy

    2014-01-01

    We investigated the impact of temporary food restriction on a set shifting task requiring participants to judge clusters of pictures against a frequently changing rule. 60 healthy female participants underwent two testing sessions: once after fasting for 16 hours and once in a satiated state. Participants also completed a battery of questionnaires (Hospital Anxiety and Depression Scale [HADS]; Persistence, Perseveration and Perfectionism Questionnaire [PPPQ-22]; and Eating Disorders Examination Questionnaire [EDE-Q6]). Set shifting costs were significantly increased after fasting; this effect was independent of self-reported mood and perseveration. Furthermore, higher levels of weight concern predicted a general performance decrement under conditions of fasting. We conclude that relatively short periods of fasting can lead to set shifting impairments. This finding may have relevance to studies of development, individual differences, and the interpretation of psychometric tests. It also could have implications for understanding the etiology and maintenance of eating disorders, in which impaired set shifting has been implicated. PMID:25025179

  1. Increased set shifting costs in fasted healthy volunteers.

    PubMed

    Bolton, Heather M; Burgess, Paul W; Gilbert, Sam J; Serpell, Lucy

    2014-01-01

    We investigated the impact of temporary food restriction on a set shifting task requiring participants to judge clusters of pictures against a frequently changing rule. 60 healthy female participants underwent two testing sessions: once after fasting for 16 hours and once in a satiated state. Participants also completed a battery of questionnaires (Hospital Anxiety and Depression Scale [HADS]; Persistence, Perseveration and Perfectionism Questionnaire [PPPQ-22]; and Eating Disorders Examination Questionnaire [EDE-Q6]). Set shifting costs were significantly increased after fasting; this effect was independent of self-reported mood and perseveration. Furthermore, higher levels of weight concern predicted a general performance decrement under conditions of fasting. We conclude that relatively short periods of fasting can lead to set shifting impairments. This finding may have relevance to studies of development, individual differences, and the interpretation of psychometric tests. It also could have implications for understanding the etiology and maintenance of eating disorders, in which impaired set shifting has been implicated. PMID:25025179

  2. Platelet activation during angiotensin II infusion in healthy volunteers.

    PubMed

    Larsson, P T; Schwieler, J H; Wallén, N H

    2000-01-01

    The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified. PMID:10691100

  3. Absolute bioavailability and regional absorption of ticagrelor in healthy volunteers

    PubMed Central

    Teng, Renli; Maya, Juan

    2014-01-01

    Objective Ticagrelor is a direct-acting, reversibly-binding, oral P2Y12 receptor antagonist. It demonstrates predictable, linear pharmacokinetics. Two studies were undertaken to further elucidate the absolute bioavailability of ticagrelor and its regional absorption in the gastrointestinal (GI) tract. Design and methods In two open-label, randomized, cross-over studies, 12 volunteers received a single dose of ticagrelor: oral 90 mg and 15 mg IV (Study 1); or 100 mg oral suspension vs 100 mg immediate release (IR) tablet (Study 2). After the initial cross-over period in Study 2, patients received 100 mg suspension delivered to specific sites in the GI tract using an Enterion capsule. In both studies, plasma concentrations of ticagrelor and AR-C124910XX were measured following administration of each formulation. Results The mean absolute bioavailability of ticagrelor was 36% (95% confidence interval = 30–42%). Metabolite:parent ratios were higher after oral administration, compared with IV administration (maximum plasma concentration [Cmax] = 0.356 and 0.037; area under the plasma concentration-time curves [AUC] = 0.530 and 0.173, respectively). Following oral administration of the 100 mg IR tablet, the AUC and Cmax of ticagrelor were 78% and 58%, respectively, of those following oral administration of the 100 mg suspension. Exposure to ticagrelor decreased the further down the GI tract it was released: mean Cmax for ticagrelor was 91%, 68%, and 13% that for the oral suspension when released in the proximal small bowel, distal small bowel and ascending colon, respectively; mean AUCs were 89%, 73%, and 32%, respectively. Conclusion The mean absolute bioavailability of ticagrelor was 36% and the proportion of ticagrelor absorbed decreased the further down the GI tract it was released: the mean AUC for ticagrelor was 89% (proximal small bowel), 73% (distal small bowel), and 32% (ascending colon) that of the mean AUC for the orally

  4. Early effects of duloxetine on emotion recognition in healthy volunteers

    PubMed Central

    Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

    2015-01-01

    The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants’ ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects. PMID:25759400

  5. Early effects of duloxetine on emotion recognition in healthy volunteers.

    PubMed

    Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

    2015-05-01

    The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants' ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects. PMID:25759400

  6. Diesel Exhaust Modulates Ozone-induced Lung Function Decrements in Healthy Human Volunteers

    EPA Science Inventory

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (03), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min...

  7. Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

    PubMed Central

    HAYASHI, Naokazu; MATSUMAE, Mitsunori; YATSUSHIRO, Satoshi; HIRAYAMA, Akihiro; ABDULLAH, Afnizanfaizal; KURODA, Kagayaki

    2015-01-01

    Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image. PMID:26226976

  8. Diclofenac does not interact with codeine metabolism in vivo: A study in healthy volunteers

    PubMed Central

    Ammon, Susanne; Marx, Claudia; Behrens, Christoph; Hofmann, Ute; Mürdter, Thomas; Griese, Ernst-Ulrich; Mikus, Gerd

    2002-01-01

    Background Previously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers. Methods In a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codeine phosphate plus 50 mg diclofenac sodium or codeine phosphate plus placebo. Over a 36 hour period serum concentrations of codeine and its metabolites as well as urinary excretion were analysed using LC-mass spectrometry. Side effects were recorded and analgesic efficacy was determined using the cold pressor test (0–6 h). Results A single dose of diclofenac did not alter the formation of codeine-6-glucuronide in healthy volunteers. Metabolic clearance of codeine to morphine was not affected by diclofenac. In terms of side effects, both treatments were well tolerated. Diclofenac did not significantly influence the analgesic effects of codeine in the cold pressor test. Conclusions In contrast to recent in vitro data, a single oral dose of diclofenac did not alter the glucuronidation of codeine in healthy volunteers. PMID:11943073

  9. Speaking-Related Dyspnea in Healthy Adults

    ERIC Educational Resources Information Center

    Hoit, Jeannette D.; Lansing, Robert W.; Perona, Kristen E.

    2007-01-01

    Purpose: To reveal the qualities and intensity of speaking-related dyspnea in healthy adults under conditions of high ventilatory drive, in which the behavioral and metabolic control of breathing must compete. Method: Eleven adults read aloud while breathing different levels of inspired carbon dioxide (CO[subscript 2]). After the highest level,…

  10. Validation of G6PD Point-of-Care Tests among Healthy Volunteers in Yangon, Myanmar

    PubMed Central

    Maw, Lwin Zar; Chowwiwat, Nongnud; Bansil, Pooja; Domingo, Gonzalo J.; Htun, Moh Moh; Thant, Kyaw Zin; Htut, Ye; Nosten, Francois

    2016-01-01

    Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct diagnosis of G6PD status in patients is crucial for safe treatment of both relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium falciparum. Lack of suitable point-of-care tests has hampered a much needed wide use of primaquine for malaria elimination. In this study we have assessed the performances of two qualitative tests, the fluorescent spot test (FST) and the G6PD CareStart test (CST), against the gold standard quantitative spectrophotometric assay in a population of 1000 random adult healthy volunteers living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and 6.8% (11.1% in males) respectively. The FST and CST showed comparable performances with sensitivity over 95% and specificity over 90%, however for cases with severe G6PD activity the FTS had improved performance. If used with a conservative interpretation of the signal, the CareStart test has the potential to be used in the field and, by allowing a wider use of primaquine, to help malaria elimination. PMID:27035821

  11. Validation of G6PD Point-of-Care Tests among Healthy Volunteers in Yangon, Myanmar.

    PubMed

    Oo, Nwe Nwe; Bancone, Germana; Maw, Lwin Zar; Chowwiwat, Nongnud; Bansil, Pooja; Domingo, Gonzalo J; Htun, Moh Moh; Thant, Kyaw Zin; Htut, Ye; Nosten, Francois

    2016-01-01

    Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct diagnosis of G6PD status in patients is crucial for safe treatment of both relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium falciparum. Lack of suitable point-of-care tests has hampered a much needed wide use of primaquine for malaria elimination. In this study we have assessed the performances of two qualitative tests, the fluorescent spot test (FST) and the G6PD CareStart test (CST), against the gold standard quantitative spectrophotometric assay in a population of 1000 random adult healthy volunteers living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and 6.8% (11.1% in males) respectively. The FST and CST showed comparable performances with sensitivity over 95% and specificity over 90%, however for cases with severe G6PD activity the FTS had improved performance. If used with a conservative interpretation of the signal, the CareStart test has the potential to be used in the field and, by allowing a wider use of primaquine, to help malaria elimination. PMID:27035821

  12. Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers

    PubMed Central

    Tawbi, Hussein; Christner, Susan M.; Lin, Yan; Johnson, Matthew; Mowrey, Emily T.; Cherrin, Craig; Chu, Edward; Lee, James J.; Puhalla, Shannon; Stoller, Ronald; Appleman, Leonard R.; Miller, Brian M.; Beumer, Jan H.

    2013-01-01

    Purpose Imatinib mesylate (Gleevec®/Glivec®), has revolutionized the treatment of chronic myeloid leukemias (CML) and gastrointestinal stromal tumors (GIST), and there is evidence for an exposure response relationship. Calcium carbonate is increasingly used as a calcium supplement and in the setting of gastric upset associated with imatinib therapy. Calcium carbonate could conceivably elevate gastric pH and complex imatinib, thereby influencing imatinib absorption and exposure. We aimed to evaluate whether use of calcium carbonate has a significant effect on imatinib pharmacokinetics. Methods Eleven healthy subjects were enrolled in a 2-period, open-label, single-institution, randomized cross-over, fixed-schedule study. In one period, each subject received 400 mg of imatinib p.o.. In the other period, 4000 mg calcium carbonate (Tums Ultra®) was administered p.o. 15 min before 400 mg of imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC-MS; data were analyzed non-compartmentally, and compared after log transformation. Results Calcium carbonate administration did not significantly affect the imatinib area under the plasma concentration versus time curve (AUC) (41.2 μg/mL•h alone versus 40.8 μg/mL•h with calcium carbonate, P=0.99), maximum plasma concentration (Cmax) (2.35 μg/mL alone versus 2.39 μg/mL with calcium carbonate, P=0.89). Conclusions Our results indicate that the use of calcium carbonate does not significantly affect imatinib pharmacokinetics. PMID:24170263

  13. The OxyMask™ development and performance in healthy volunteers

    PubMed Central

    Paul, James E; Hangan, Horia; Hajgato, Julius

    2009-01-01

    Background The OxyMask™ is a unique, open-style, oxygen mask that was originally developed in 2005. The original mask was modified, using computational fluid dynamics numerical simulations, with the goal of allowing it to produce a wider range of FiO2. This analysis was used to guide the modification of the mask shell and the location for the oxygen diffuser. Methods The new OxyMask was attached to 10 healthy subjects and used to deliver escalating levels of oxygen (1.5, 2, 2.5, 3, 5, 10, 15, 20, 25 and 30 LPM) for 90 seconds at each level and the resulting FiO2 was recorded (at the lips) from 5 consecutive measurements at each oxygen flow rate. Results Mean FiO2 was 25.4% at 1.5 LPM of oxygen, 30.1% at 2 LPM, 36.5% at 2.5 LPM, 41.8% at 3 LPM, 57.6% at 5 LPM, 74.4% at 10 LPM, and 80.1% at 15 LPM. Each FiO2 achieved at these escalating oxygen levels was significantly greater than all the previous levels. The mean FiO2 was 82.8 at 20 LPM, 84.2% at 25 LPM and 84.3% at 30 LPM. All of these values on average were not significantly greater than the FiO2 achieved with 15 LPM. In a few subjects a maximum FiO2 of 90% was reached. Conclusion The original OxyMask was successfully modified so that the second generation of the mask can provide a wide range of FiO2, from 25% to 90%, while keeping its unique open design. PMID:22915909

  14. Clinical pharmacology of DP-b99 in healthy volunteers: First administration to humans

    PubMed Central

    Rosenberg, Gilad; Angel, Itzchak; Kozak, Alex

    2005-01-01

    Aims To investigate the safety, tolerability and pharmacokinetics of DP-b99 in healthy volunteers. DP-b99 is a newly developed lipophilic, cell permeable derivative of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid), which selectively modulates the distribution of metal ions in hydrophobic milieu, and is in clinical development as a neuroprotectant for cerebral ischaemic stroke. To our knowledge no BAPTA derivative has ever been administered to man. Here we report the first human administration of DP-b99 in a phase I, two-part, double-blind, randomized placebo controlled study, with single IV doses of 0.003–1.0 mg kg−1 day−1 DP-b99 (part 1) or multiple ascending doses of 0.03–1.0 mg kg−1 day−1 DP-b99 over 4 days (part 2). Methods A double-blind, dose escalating tolerability study of DP-b99 in normal (young – aged between 18 and 40 years and elderly – aged between 65 and 85 years) healthy adult male volunteers was conducted. Part 1 of the study investigated single administration of ascending intravenous doses, and part 2 examined the effects of ascending doses given repeatedly over 4 days. Twenty-four young volunteers in part 1 received single dose administrations and 26 young volunteers in part 2 received repeated ascending dose administrations of either intravenous DP-b99 or placebo. Subsequently, 10 elderly volunteers received repeated intravenous DP-b99 (1 mg kg−1) or placebo in part 2 over 4 days. Adverse events were identified by either subject self reporting or based upon laboratory parameters (blood chemistry, complete blood cell count, prothrombin time (PT), activated partial thromboplastin (PTT), physical examination, vital signs (blood pressure, pulse rate, respiratory rate, body temperature) and urinalysis. A comprehensive set of cardiovascular parameters was assessed as well (blood pressure, 12 lead-ECG recordings and continuous bedside cardiac monitoring for 6 h on day 1). Results The administration of DP-b99 up

  15. Comparative Pharmacokinetics of Levofloxacin in Healthy Volunteers and in Patients Suffering from Typhoid Fever

    PubMed Central

    Usman, Muhammad; Ashraf, Muhammad; Khokhar, Muhammad Imran; Ashiq, Bilal; Masood, Muhammad Irfan; Afzal, Shehryar; Omer, Ovais; Ali, Mohsin; Qadir, M. Imran

    2013-01-01

    The aim of this study was to characterize the effect of typhoid fever on pharmacokinetic parameters of levofloxacin (LF) and compare the pharmacokinetic parameters of the said antibiotic in healthy human volunteers and patients with typhoid fever. Total of 12 subjects were divided into two groups “A” (healthy volunteers) and “B” (typhoid patients). Single oral dose of LF 500 mg was given and 5 mL of blood was collected from each subject at 0, 0.25, 0.5, 1, 2, 3, 6, 12, 24, 36 and 72 h. Plasma concentrations of LF were measured by HPLC. Pharmacokinetic parameters were calculated from plasma concentration-time data by using MW/PHARM pharmacological analysis. In healthy volunteers, the average pharmacokinetic parameters were as Cmax (6.79 μg/mL), Tmax (1.84 h), T½ (10.03 h), Ka (2.23 h-1), AUC (110.09 μgh/mL), Vd (85.84 L), Cl (4.57 L/h) and in typhoid patients were Cmax (6.90 μg/mL), Tmax (1.82 h), T½ (9.42 h), Ka (2.21 h-1), AUC (105.55 μgh/mL), Vd (64.31 L), Cl (4.75 L/h). The difference between pharmacokinetic parameters of LF in healthy human volunteers and typhoid patients was calculated by using unpaired t-test. As the p-value in case of all pharmacokinetic parameters was more than 0.05, the difference between pharmacokinetic parameters in both healthy human volunteers and typhoid patients was insignificant. It is concluded that there is no need to adjust the dose of LF in typhoid patients. PMID:24250583

  16. Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

    PubMed Central

    Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

    2016-01-01

    Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults. PMID:26507875

  17. Volunteering and Psychological Well-Being among Young-Old Adults: How Much Is Too Much?

    ERIC Educational Resources Information Center

    Windsor, Timothy D.; Anstey, Kaarin J.; Rodgers, Bryan

    2008-01-01

    Purpose: Research concerned with the relationship between volunteer activity and psychological well-being has typically reported higher levels of well-being among older adult volunteers relative to nonvolunteers. However, few studies have examined nonlinear associations between frequency of volunteer activity and well-being. We examined nonlinear…

  18. Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers.

    PubMed

    Guo, Song; Goetze, Jens P; Jeppesen, Jørgen L; Burnett, John C; Olesen, Jes; Jansen-Olesen, Inger; Ashina, Messoud

    2015-12-01

    The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive functions that concern humans and most animals, but their specific effects on cerebral circulation are poorly understood. We therefore examined the responsiveness of cerebral arteries to different doses of the natriuretic peptides in animals and humans. We conducted a dose-response experiment in guinea pigs (in vitro) and a double-blind, three-way cross-over study in healthy volunteers (in vivo). In the animal experiment, we administered cumulative doses of NPs to pre-contracted segments of cerebral arteries. In the main study, six healthy volunteers were randomly allocated to receive two intravenous doses of ANP, BNP or CNP, respectively, over 20 min on three separate study days. We recorded blood flow velocity in the middle cerebral artery (VMCA) by transcranial Doppler. In addition, we measured temporal and radial artery diameters, headache response and plasma concentrations of the NPs. In guinea pigs, ANP and BNP but not CNP showed significant dose-dependent relaxation of cerebral arteries. In healthy humans, NP infusion had no effect on mean VMCA, and we found no difference in hemodynamic responses between the NPs. Furthermore, natriuretic peptides did not affect temporal and radial artery diameters or induce headache. In conclusion, natriuretic peptides in physiological and pharmacological doses do not affect blood flow velocity in the middle cerebral artery or dilate extracerebral arteries in healthy volunteers. PMID:26417835

  19. Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.

    PubMed

    Caminero, Alberto; Nistal, Esther; Herrán, Alexandra R; Pérez-Andrés, Jénifer; Ferrero, Miguel A; Vaquero Ayala, Luis; Vivas, Santiago; Ruiz de Morales, José M G; Albillos, Silvia M; Casqueiro, Francisco Javier

    2015-10-28

    Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients. PMID:26428276

  20. Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers.

    PubMed

    Myre, S A; McCann, J; First, M R; Cluxton, R J

    1987-06-01

    The effect of trimethoprim (TMP) on serum creatinine concentration (SCr) was studied in 10 healthy (H) subjects and nine subjects with chronic renal failure (CRF). Each volunteer was given TMP 100 mg perorally every 12 h for 10 days followed by a 7-day washout period. SCr was measured colorimetrically immediately before the study (baseline), on day 10 of TMP, and 7 days after TMP had been discontinued. SCr increased an average of 14.8% from baseline during TMP administration in the H volunteers, but this increase was not statistically significant. During TMP administration to the CRF volunteers, a pronounced elevation (34.6%) of mean SCr from baseline was observed (p less than 0.05). SCr returned to baseline values in both groups following the 7-day washout period. These results are consistent with the hypothesis that TMP competitively inhibits the renal tubular secretion of creatinine. PMID:3617154

  1. Effect of banana on cold stress test & peak expiratory flow rate in healthy volunteers.

    PubMed

    Sarkar, C; Bairy, K L; Rao, N M; Udupa, E G

    1999-07-01

    The effect of banana on cold stress induced hypertension, peak expiratory flow rate and plasma ACE activity in healthy human volunteers was tested. Systolic blood pressure (P < 0.005), diastolic blood pressure (P < 0.025) and mean arterial blood pressure (P < 0.005) were significantly decreased during cold stress after banana treatment compared to controls subjected to cold stress. There was no significant changes in heart rate and peak expiratory flow rate but only significant decrease in plasma ACE activity after banana treatment. Banana decreased the rise of systolic blood pressure and diastolic blood pressure in healthy volunteers subjected to cold stress test without much effect on heart rate and peak expiratory flow rate. PMID:10709336

  2. Urinary excretion of diazepam metabolites in healthy volunteers and drug users.

    PubMed

    Smith-Kielland, A; Skuterud, B; Olsen, K M; Mørland, J

    2001-05-01

    Urinary excretion profiles of diazepam metabolites were investigated. The subjects were healthy volunteers receiving one single 10-mg dose of diazepam or drug abusers starting a prison sentence. Urinary excretion of metabolites was analysed by immunological screening, liquid chromatography and gas chromatography-mass spectrometry. Relating the metabolite concentration to creatinine concentration in the specimens decreased sample-to-sample variations. In some cases such correction could protect a subject from erroneous accusations of a new intake. PMID:11386610

  3. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

    PubMed

    Persson, M L; Wasserman, D; Geijer, T; Frisch, A; Rockah, R; Michaelovsky, E; Apter, A; Weizman, A; Jönsson, E G; Bergman, H

    2000-01-01

    An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism. PMID:11009073

  4. Concomitant efavirenz reduces pharmacokinetic exposure to the antimalarial drug artemether-lumefantrine in healthy volunteers

    PubMed Central

    Huang, Liusheng; Parikh, Sunil; Rosenthal, Philip J.; Lizak, Patricia; Marzan, Florence; Dorsey, Grant; Havlir, Diane; Aweeka, Francesca T.

    2012-01-01

    Background The antiretroviral drug efavirenz (EFV) and the antimalarial artemisinin-based combination therapy (ACT) artemether-lumefantrine (AL) are commonly co-administered to treat HIV and malaria. EFV is a known inducer of cytochrome P450 3A4, which converts artemether to dihydroartemisinin (DHA) that is also active and metabolizes longer acting lumefantrine (LR). A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics (PK). Methods Adults received AL (80/480 mg BID) for 3-days prior to and during EFV co-administration (600 mg daily for 26-days) with intensive PK for artemether, DHA, and LR conducted after the last AL dose for each period. EFV PK was evaluated with and without AL. PK parameters were estimated using non-compartmental methods. Results Twelve subjects completed the two-period study. PK exposure for artemether, DHA, and LR [as estimated by the area under the concentration time curve (AUClast)] decreased or trended toward decrease with EFV, compared to when administered alone [−51% (p=0.084), −46% (p=0.005), and −21% (p=0.102), respectively]. Day 7 LR levels, previously deemed predictive of treatment success, were 46% lower (p=0.002) with EFV, but the LR half-life was unchanged. EFV PK exposure was minimally altered following AL co-administration [AUC0–24h decreased by 17% (p=0.034)]. Conclusions Exposure to DHA, but not LR, was significantly lower during EFV-AL co-administration compared to that during administration of AL alone. These findings may have implications for the treatment efficacy of AL, particularly in children. However, the observed modest changes probably do not warrant dosage adjustment during co-administration of AL with EFV. PMID:22918158

  5. Benign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine

    PubMed Central

    2014-01-01

    Background There are currently no serum biomarkers capable of distinguishing elevations in serum alanine aminotransferase (ALT) that portend serious liver injury potential from benign elevations such as those occurring during cholestyramine treatment. The aim of the research was to test the hypothesis that newly proposed biomarkers of hepatotoxicity would not significantly rise in serum during elevations in serum ALT associated with cholestyramine treatment, which has never been associated with clinically relevant liver injury. Methods In a double-blind placebo-controlled trial, cholestyramine (8g) was administered for 11 days to healthy adult volunteers. Serum from subjects with elevations in alanine aminotransferase (ALT) exceeding three-fold the upper limit of normal (ULN) were utilized for biomarker quantification. Results In 11 of 67 subjects, cholestyramine treatment resulted in ALT elevation by >3x ULN (mean 6.9 fold; range 3–28 fold). In these 11 subjects, there was a 22.4-fold mean increase in serum levels of miR-122 relative to baseline, supporting a liver origin of the serum ALT. Significant elevations were noted in mean levels of necrosis biomarkers sorbitol dehydrogenase (8.1 fold), cytokeratin 18 (2.1 fold) and HMGB1 (1.7 fold). Caspase-cleaved cytokeratin 18, a biomarker of apoptosis was also significantly elevated (1.7 fold). A rise in glutamate dehydrogenase (7.3 fold) may support mitochondrial dysfunction. Conclusion All toxicity biomarkers measured in this study were elevated along with ALT, confirming the liver origin and reflecting both hepatocyte necrosis and apoptosis. Since cholestyramine treatment has no clinical liver safety concerns, we conclude that interpretation of the biomarkers studied may not be straightforward in the context of assessing liver safety of new drugs. PMID:25086653

  6. Effect of tamsulosin on the pharmacokinetics of dutasteride in Chinese male healthy volunteers.

    PubMed

    Li, Huafang; Yang, Jiansong; Zhao, Hongxin; Fossler, Michael J; Wang, Chunrong

    2015-11-01

    The purpose of this study was to evaluate the effect of tamsulosin (0.2 mg) on the pharmacokinetics of dutasteride (0.5 mg) in a group of healthy Chinese male volunteers. This was an open-label, single-sequence, 3-period, drug-drug interaction phase 1 study. Twenty-four healthy Chinese male volunteers were enrolled and administered a single dose of 0.5 mg dutasteride and, following a 28- to 30-day washout period, 0.2 mg tamsulosin once daily for 7 days. On day 5, subjects received 0.2 mg tamsulosin coadministered with 0.5 mg dutasteride. Serum dutasteride and tamsulosin concentrations were monitored. In the presence or absence of tamsulosin, there were no apparent changes in dutasteride AUC and Cmax . Adverse events reported were mild to moderate in intensity and resolved by the end of the study. In healthy Chinese male volunteers, tamsulosin 0.2 mg at steady state had no apparent effect on dutasteride pharmacokinetics. Dutasteride and tamsulosin when administered alone or in combination were well tolerated. PMID:27137714

  7. Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers.

    PubMed

    Vesali, Rokhsareh F; Klaude, Maria; Rooyackers, Olav; Wernerman, Jan

    2005-02-01

    Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the postabsorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 h before and 4 h after an intravenous endotoxin injection (4 ng/kg body wt). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (P = 0.001) and of glutamine by 25% (P = 0.004) the 3rd h after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (P = 0.05) and 9% (P = 0.09), respectively. In parallel, the efflux from the leg increased by 35% (P = 0.004) for the total sum of amino acids and by 43% (P = 0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased. PMID:15367399

  8. Sensitive and specific radioimmunoassay for fialuridine: initial assessment of pharmacokinetics after single oral doses to healthy volunteers.

    PubMed Central

    Bowsher, R R; Compton, J A; Kirkwood, J A; Place, G D; Jones, C D; Mabry, T E; Hyslop, D L; Hatcher, B L; DeSante, K A

    1994-01-01

    Fialuridine (FIAU) is a halogen-substituted analog of thymidine that was undergoing clinical investigation as a drug for the treatment of chronic hepatitis B viral infection. However, clinical trials of FIAU were terminated after adverse events occurred following chronic oral administration. Prior to the termination of clinical trials, a sensitive assay was needed for the measurement of FIAU because of the anticipated low dose administered to patients. We therefore undertook the development of a radioimmunoassay (RIA). A specific antiserum was raised in rabbits following immunization with a 5'-O-hemisuccinate analog of FIAU coupled to keyhole limpet hemocyanin. Radiolabeled FIAU was synthesized by a destannylation procedure by using sodium [125I]iodide. We developed a competitive-binding procedure and used precipitation with polyethylene glycol as the method for separating the bound and free forms of FIAU. The RIA is sensitive (0.2 ng/ml), specific (negligible interference from known metabolites and endogenous nucleosides), and reproducible (interassay coefficients of variation range from 5 to 19.7% for serum controls). We used the RIA to assess the pharmacokinetics of FIAU in healthy adult volunteers following administration of a single 5-mg oral dose. The sensitivity of the RIA permitted the detection of a prolonged elimination phase for FIAU in healthy volunteers and dogs, with mean elimination half-lives of 29.3 and 35.3 h, respectively. We conclude the RIA is a valid method for the quantification of FIAU in biological fluids. PMID:7811032

  9. Pharmacokinetic profile of two different pharmaceutical forms of theophylline (a slow release tablet and a syrup) after multiple dose administration to healthy human volunteers.

    PubMed

    Muscará, M N; Hofstätter, E A; de Nucci, G

    1993-01-01

    Due to the narrow therapeutic range of theophylline, plasma concentrations of this drug are monitored in patients undergoing chronic therapy. Slow-release preparations avoid the fluctuations in plasma levels and improve patient compliance. In this study, we have compared the pharmacokinetic profiles of a theophylline slow-release tablet and a syrup form, when administered in multiple doses to healthy adult volunteers. The classification based upon releasing patterns is confirmed. PMID:8246751

  10. Diagnosing Bladder Outlet Obstruction Using Non-invasive Decorrelation-Based Ultrasound Imaging: A Feasibility Study in Healthy Male Volunteers.

    PubMed

    Arif, Muhammad; Idzenga, Tim; van Mastrigt, Ron; de Korte, Chris L

    2015-12-01

    A feasibility study on the applicability of an ultrasound decorrelation method to urinary flow imaging was carried out in 20 healthy male volunteers, to provide a basis for a non-invasive approach to diagnose bladder outlet obstruction. Each volunteer voided five times in a flow meter in standing position. During each voiding, ultrasound radiofrequency frames were acquired transperineally at different flow rates. The results indicated that the decrease in correlation (decorrelation) of ultrasound radiofrequency signals had no unique relation with flow rate, but decreased distinctively with urinary flow velocity. In most of the healthy volunteers, the decorrelation was small because of the low flow velocity. However, because of the different flow velocities in volunteers, the variation in slope between volunteers was statistically significant. Therefore, it is probably possible to use the decorrelation method to differentiate between healthy persons and patients with obstruction. PMID:26403699

  11. Sufentanil does not increase cerebral blood flow in healthy human volunteers

    SciTech Connect

    Mayer, N.; Weinstabl, C.; Podreka, I.; Spiss, C.K. )

    1990-08-01

    The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers.

  12. Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

    PubMed Central

    Carter, Lawrence P.; Griffiths, Roland R.; Mintzer, Miriam Z.

    2009-01-01

    Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers. PMID:19543883

  13. Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials

    PubMed Central

    Fisher, Jill A.

    2015-01-01

    Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. PMID:25914430

  14. New Combined Parameter of Liver and Splenic Stiffness as Determined by Elastography in Healthy Volunteers

    PubMed Central

    Kassym, Laura; Nounou, Mohammed A.; Zhumadilova, Zauresh; Dajani, Asad I.; Barkibayeva, Nurgul; Myssayev, Ayan; Rakhypbekov, Tolebay; Abuhammour, Adnan M.

    2016-01-01

    Background: The diagnosis of chronic liver disease (CLD) leading to fibrosis, cirrhosis, and portal hypertension had witnessed dramatic changes after the introduction of noninvasive figure accessible tools over the past few years. Imaging techniques that are based on evaluation of the liver stiffness was particularly useful in this respect. Acoustic radiation force impulse (ARFI) emerged as an interesting figure tool with reliable repute and high precision. Aims: To evaluate liver stiffness measurement (LSM) and splenic stiffness measurement (SSM) in healthy volunteers as concluded by the ARFI technique and to out a numeric calculated ratio that may reflect their correlation in the otherwise healthy liver. Patients and Methods: A ratio (splenic stiffness/liver stiffness in kPa) was determined in 207 consenting healthy subjects and was investigated with respect to age, gender, ethnic origin, body mass index (BMI), liver and spleen sizes healthy volunteers, alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelet count (PLT), APRI, and FIB-4 scores. Results: Data from this work led to computing an index of 4.72 (3.42–7.33) in healthy persons on an average. Females had a higher index than males 6.37 vs 4.92, P=0.002. There was not any significant difference of the ratio in different age groups; ethnic origins; any correlation between SSM/LSM ratio and BMI; liver and spleen sizes; or ALT, AST, PLT, APRI, and FIB-4 scores. Conclusions: A quantifiable numeric relationship between splenic and liver stiffness in the healthy subjects could be computed to a parameter expressed as SSM/LSM ratio. We believe that this ratio can be a useful reference tool for further researches in CLD. PMID:27488328

  15. Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

    PubMed Central

    John, D N; Fort, S; Lewis, M J; Luscombe, D K

    1992-01-01

    1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers. PMID:1389935

  16. Effects of acute CDP-choline treatment on resting state brain oscillations in healthy volunteers.

    PubMed

    Knott, Verner; de la Salle, Sara; Smith, Dylan; Choueiry, Joelle; Impey, Danielle; Smith, Meaghan; Beaudry, Elise; Saghir, Salman; Ilivitsky, Vadim; Labelle, Alain

    2015-03-30

    CDP-choline (cytidine-5'-diphosphocholine) is a phospholipid used to treat cognitive disorders, presumably repairing and maintaining brain cell membranes. Additional mechanisms may include enhanced cholinergic neurotransmission as the α7 nicotinic receptor actions of choline and increased acetylcholine synthesis accompanying CDP-choline administration may modulate brain oscillations underlying cognitive processes. This study utilizes electroencephalographic (EEG) recordings in healthy volunteers to evaluate CDP-choline induction of an oscillatory response profile associated with nicotinic stimulation. Resting state EEG was acquired in 24 male volunteers administered low (500mg) and moderate (1000mg) doses of CDP-choline in a randomized placebo-controlled, crossover trial. Consistent with nicotinic agonist treatment, spectral analysis showed dose-dependent reductions in delta and increases in alpha oscillations, which were also accompanied by decreases in beta and gamma oscillatory activity. These findings support the posit that CDP-choline cognitive enhancement involves multiple mechanisms including facilitated nicotinic cholinergic action. PMID:25700947

  17. A Single Consumption of High Amounts of the Brazil Nuts Improves Lipid Profile of Healthy Volunteers

    PubMed Central

    Colpo, Elisângela; Vilanova, Carlos Dalton de Avila; Medeiros Frescura Duarte, Marta Maria; Farias, Iria Luiza Gomes; Irineu Muller, Edson; Muller, Aline Lima Hermes; Moraes Flores, Erico Marlon; da Rocha, João Batista Teixeira

    2013-01-01

    Background. This study investigates the effects of Brazil nut ingestion on serum lipid profile in healthy volunteers. Methods. Ten healthy subjects were enrolled in the study. Each subject was tested 4 times in a randomized crossover in relation to the ingestion of different serving sizes of the Brazil nut: 0, 5, 20, or 50 g. At each treatment point, peripheral blood was drawn before and at 1, 3, 6, 9, 24, and 48 hours and 5 and 30 days. Blood samples were tested for total cholesterol, high- and low-density lipoprotein cholesterol (HDL-c and LDL-c, resp.), triglycerides, selenium, aspartate and alanine aminotransferases, albumin, total protein, alkaline phosphatase, gamma GT, urea, creatinine, and C-reactive protein. Results. A significant increase of the plasma selenium levels was observed at 6 hours within the groups receiving the nuts. Serum LDL-c was significantly lower, whereas HDL-c was significantly higher 9 hours after the ingestion of 20 or 50 g of nuts. The biochemical parameters of liver and kidney function were not modified by ingestion of nuts. Conclusions. This study shows that the ingestion of a single serving of Brazil nut can acutely improve the serum lipid profile of healthy volunteers. PMID:23840948

  18. Rectal Visceral Sensitivity in Women with Irritable Bowel Syndrome without Psychiatric Comorbidity Compared with Healthy Volunteers

    PubMed Central

    Spetalen, Signe; Sandvik, Leiv; Blomhoff, Svein; Jacobsen, Morten B.

    2009-01-01

    Background. Psychiatric comorbidity and visceral hypersensitivity are common in patients with irritable bowel syndrome (IBS), but little is known about visceral sensitivity in IBS patients without psychiatric disorders. Aim. We wanted to examine rectal visceral sensitivity in IBS patients without comorbid psychiatric disorders, IBS patients with phobic anxiety and healthy volunteers. Methods. A total of thirty-eight female, non-constipated IBS patients without psychiatric disorders and eleven female IBS patients with phobic anxiety were compared to nine healthy women using a barostat double random staircase method. The non-psychiatric patients were divided into those with diarrhoea predominant symptoms and those with alternating stool habits. Results. The IBS patients without psychiatric disorders had normal visceral pressure thresholds. However, in the diarrhoea predominant subgroup, the volume discomfort threshold was reduced while it was unchanged in those with alternating stool habits. The phobic IBS patients had similar thresholds to the healthy volunteers. The rectal tone was increased in the non-psychiatric IBS patients with diarrhoea predominant symptoms and in the IBS patients with phobic anxiety. Conclusions. Non-constipated IBS patients without psychiatric disorders had increased visceral sensitivity regarding volume thresholds but normal pressure thresholds. Our study suggests that the lowered volume threshold was due to increased rectal tone. PMID:19789637

  19. Brain structural correlates of schizotypy and psychosis proneness in a non-clinical healthy volunteer sample.

    PubMed

    Nenadic, Igor; Lorenz, Carsten; Langbein, Kerstin; Dietzek, Maren; Smesny, Stefan; Schönfeld, Nils; Fañanás, Lourdes; Sauer, Heinrich; Gaser, Christian

    2015-10-01

    Schizotypal traits are phenotypic risk factors for schizophrenia, associated with biological changes across a putative schizophrenia spectrum. In this study, we tested the hypothesis that brain structural changes in key brain areas relevant to this spectrum (esp. medial and lateral prefrontal cortex) would vary across different degrees of schizotypal trait expression and/or phenotypic markers of psychosis proneness in healthy non-clinical volunteers. We analysed high-resolution 3Tesla magnetic resonance images (MRI) of 59 healthy volunteers using voxel-based morphometry (VBM), correlating grey matter values to the positive and negative symptom factors of the schizotypal personality questionnaire (SPQ, German version) and a measure of psychosis proneness (community assessment of psychic experiences, CAPE). We found positive correlations between positive SPQ dimension and bilateral inferior and right superior frontal cortices, and positive CAPE dimension and left inferior frontal cortex, as well as CAPE negative dimension and right supplementary motor area (SMA) and left inferior parietal cortex. However, only the positive correlation of the right precuneus with negative schizotypy scores was significant after FWE correction for multiple comparisons. Our findings confirm an effect of schizotypal traits and psychosis proneness on brain structure in healthy subjects, providing further support to a biological continuum model. PMID:26164819

  20. Factors Affecting Volunteering among Older Rural and City Dwelling Adults in Australia

    ERIC Educational Resources Information Center

    Warburton, Jeni; Stirling, Christine

    2007-01-01

    In the absence of large scale Australian studies of volunteering among older adults, this study compared the relevance of two theoretical approaches--social capital theory and sociostructural resources theory--to predict voluntary activity in relation to a large national database. The paper explores volunteering by older people (aged 55+) in order…

  1. Goals and Personal Resources that Contribute to the Development and Agency Attachment of Older Adult Volunteers

    ERIC Educational Resources Information Center

    Gillespie, Alayna A.; Gottlieb, Benjamin H.; Maitland, Scott B.

    2011-01-01

    We examined the volunteer service contribution of older adults (N = 100) to volunteer role development and agency attachment. Informed by a developmental regulation framework and socio-emotional selectivity theory, we tested a twofold hypothesis for the premise that greater role development and agency attachment would be experienced by (1) older…

  2. Effect of ABCB1 polymorphisms and atorvastatin on sitagliptin pharmacokinetics in healthy volunteers

    PubMed Central

    Aquilante, Christina L.; Wempe, Michael F.; Sidhom, Maha S.; Kosmiski, Lisa A.; Predhomme, Julie A.

    2013-01-01

    Objectives The objectives of this study were to determine if ABCB1 polymorphisms are associated with interindividual variability in sitagliptin pharmacokinetics, and if atorvastatin alters the pharmacokinetic disposition of sitagliptin in healthy volunteers. Methods In this open-label, randomized, two-phase crossover study, healthy volunteers were prospectively stratified according to ABCB1 1236/2677/3435 diplotype (n=9, CGC/CGC; n=10, CGC/TTT; and n=10, TTT/TTT). In one phase, participants received a single 100 mg dose of sitagliptin. In the other phase, participants received 40 mg of atorvastatin for five days, with a single 100 mg dose of sitagliptin administered on day 5. A 24 hour pharmacokinetic study followed each sitagliptin dose, and the study phases were separated by a 14-day washout period. Results Sitagliptin pharmacokinetic parameters did not differ significantly between ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotype groups during the monotherapy phase. Atorvastatin administration did not significantly affect sitagliptin pharmacokinetics, with GMRs (90% CIs) for sitagliptin Cmax, AUC0-∞, CLR, and fe of 0.93 (0.86, 1.01), 0.96 (0.91, 1.01), 1.02 (0.93, 1.12), and 0.98 (0.90, 1.06), respectively. Conclusions ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes did not influence sitagliptin pharmacokinetics in healthy volunteers. Furthermore, atorvastatin had no effect on the pharmacokinetics of sitagliptin in the setting of ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes. PMID:23407853

  3. Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

    PubMed

    Pandit, S; Biswas, S; Jana, U; De, R K; Mukhopadhyay, S C; Biswas, T K

    2016-06-01

    Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. PMID:26395129

  4. Single-dose oral guanidinoacetic acid exhibits dose-dependent pharmacokinetics in healthy volunteers.

    PubMed

    Ostojic, Sergej M; Vojvodic-Ostojic, Aleksandra

    2015-03-01

    Guanidinoacetic acid (GAA), the natural precursor of creatine, has potential as a dietary supplement for human nutrition, yet no data are available regarding its dose-dependent pharmacokinetic (PK) behavior. We hypothesized that a single dose of orally administered GAA exhibited dose-dependent PK behavior in healthy volunteers. Forty-eight young adults were enrolled in a randomized, placebo-controlled, double-blind, parallel-group trial to receive single oral doses of GAA (1.2, 2.4, and 4.8 g) or a placebo. Pharmacokinetic metrics for plasma GAA and creatine were assessed immediately before (0 hours) and at 1, 2, 4, 6, 8, 12, and 24 hours after GAA ingestion. The lag time appeared to be similar after the bolus ingestion of GAA (0.14 ± 0.17 hours for low-dose GAA, 0.31 ± 0.18 hours for medium-dose GAA, and 0.38 ± 0.32 hours for high-dose GAA; P = .05). An increase in the area under the concentration-time curve for plasma GAA was found for the dose range tested, with 2.4- and 9.3-fold increases in the area under the concentration-time curve for every 2-fold increase in the GAA dose (P < .0001). No differences were found for elimination half-time between the low-dose and medium-dose groups (<1.75 hours), whereas the elimination half-time was significantly longer (>2.1 hours) for the high-dose GAA regimen (P = .001). The volume of distribution was affected by the dosage of GAA applied (102.6 ± 17.3 L for low-dose GAA, 97.5 ± 15.7 L for medium-dose GAA, and 61.1 ± 12.7 L for high-dose GAA; P < .0001). Ingestion of GAA elevated plasma creatine by 80%, 116%, and 293% compared with the placebo for the 1.2, 2.4, and 4.8 g doses, respectively (P < .0001). Guanidinoacetic acid single-dose PK metrics were nonlinear with respect to dose size. Across the dose range of 1.2 to 4.8 g, systemic exposure to GAA increased in a greater than dose-proportional manner. PMID:25622538

  5. Comparative bioavailability and pharmacokinetic study of Cefadroxil capsules in male healthy volunteers of Pakistan.

    PubMed

    Rahim, Najia; Naqvi, Syed Baqir Shyum; Alam, Mehtab; Rasheed, Abdur; Khalique, Urooj Abdul

    2016-03-01

    The current study was aimed to judge bioequivalence between two formulations of cefadroxil capsules as guided by FDA guidelines. Another objective was to conduct pharmacokinetic evaluation in Pakistani population. A single-dose, randomized, cross-over pharmacokinetic study was conducted during the month of May'2013 to August'2013. Washout period was one week. Fourteen healthy male adult volunteers were enrolled in the study, however twelve completed the study. Cefadroxil plasma concentration was analyzed by using validated HPLC method. Protein precipitation was achieved by the addition of 6% tri chloro acetic acid in 1:1 ratio and detection was done at 260 nm. Retention time was 7.792 min and correlation coefficient (R2) was 0.9953 showing linearity of the method. Blood sampling was carried out at different time intervals after administration of either test (TEST 500 mg) or reference (REF® 500 mg) formulation. Pharmacokinetic parameters (AUC0→ ∞, AUC0→ t, Cmax, Tmax, t1/2 and kel) were calculated using Kinetica® PK/PD software. The geometric mean ratios and 90% confidence interval (CI) of these pharmacokinetic parameters for cefadroxil (test and reference) formulations were 0.986 (90.83-106.98%) for AUC0→ t; 0.967 (89.13-104.92%) for AUC0→ ∞ and 0.999 (91.06-109.69%) for Cmax. The differences between Tmax of both formulations were not found to be statistically significant (p-value was more than 0.05). The 90% CI of the test/reference AUC and Cmax ratio of cefadroxil were within the FDA recommended range for bioequivalence. Maximum plasma concentration Cmax was 12.5 μg/ml for test and 12.47 μg/ml for reference formulations. Average time to reach Cmax for test and reference formulation was 1.54 and 1.5 hrs. The two formulations of cefadroxil studied during the above study were verified bioequivalent. Maximum plasma concentration of cefadroxil was lower than those mentioned in some previous studies, while Tmax and half-life were near to values reported

  6. A Case Study of a Volunteer-Based Literacy Class with Adults with Developmental Disabilities

    ERIC Educational Resources Information Center

    Lynch, Jacqueline

    2013-01-01

    The purpose of this study was to examine participants' perspectives on how a volunteer-based adult literacy class supports the learning of adults with developmental/intellectual disabilities. Interviews were conducted with four tutors, three adult learners, and two coordinators and observations of the class occurred over a 6-month period…

  7. Marketing Public Health Through Older Adult Volunteering: Experience Corps as a Social Marketing Intervention

    PubMed Central

    Tanner, Elizabeth K.; Seeman, Teresa E.; Xue, Qian-Li; Rebok, George W.; Frick, Kevin D.; Carlson, Michelle C.; Wang, Tao; Piferi, Rachel L.; McGill, Sylvia; Whitfield, Keith E.; Fried, Linda P.

    2010-01-01

    Objectives. We present a social marketing conceptual framework for Experience Corps Baltimore City (EC) in which the desired health outcome is not the promoted product or behavior. We also demonstrate the feasibility of a social marketing–based recruitment campaign for the first year of the Baltimore Experience Corps Trial (BECT), a randomized, controlled trial of the health benefits of EC participation for older adults. Methods. We recruited older adults from the Baltimore, MD, area. Participants randomized to the intervention were placed in public schools in volunteer roles designed to increase healthy behaviors. We examined the effectiveness of a recruitment message that appealed to generativity (i.e., to make a difference for the next generation), rather than potential health benefits. Results. Among the 155 participants recruited in the first year of the BECT, the average age was 69 years; 87% were women and 85% were African American. Participants reported primarily generative motives as their reason for interest in the BECT. Conclusions. Public health interventions embedded in civic engagement have the potential to engage older adults who might not respond to a direct appeal to improve their health. PMID:20167888

  8. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers.

    PubMed

    Ayatollahi, Hossein; Javan, Atefeh Ordoei; Khajedaluee, Mohammad; Shahroodian, Masood; Hosseinzadeh, Hossein

    2014-04-01

    Saffron showed some effects on blood coagulation and platelet aggregation in in vitro and in vivo studies. In a clinical trial with a limited number volunteers, saffron tablets influenced on bleeding time. In this study, the effect of saffron on plasma level of fibrinogen, factor VII (as coagulant agent), C and S protein (as anti-coagulant agent), PT and PTT in a larger sample size was evaluated. The study was a double-blind, placebo-controlled study consisting of 1 week treatment with 200 mg and 400 mg saffron tablets. Sixty healthy volunteers (age range 20-50 years) were selected for the study. The volunteers were divided into three groups of 20 each. Group 1 received placebo; Groups 2 and 3 received 200 mg and 400 mg saffron tablets, respectively, for 7 days (1 tablet per day). Before and after 7 days treatment and also 1 month after that, blood samples were taken. The plasma levels of fibrinogen, factor VII, C and S protein, PT and PTT were evaluated. Statistical analysis showed no difference between groups for any of evaluated factors. This study rejected any effect of saffron with dose of 200 and 400 mg for 1 week on coagulant and anticoagulant system. PMID:23733488

  9. Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers

    PubMed Central

    Zhang, Yi-fan; Dai, Xiao-jian; Yang, Yong; Chen, Xiao-yan; Wang, Ting; Tang, Yun-biao; Tsai, Cheng-yuan; Chang, Li-wen; Chang, Yu-ting; Zhong, Da-fang

    2016-01-01

    Purpose To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans. Methods Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography–tandem mass spectrometry methods. Results Coadministration of nemonoxacin with probenecid reduced the renal clearance (CLr) of nemonoxacin by 22.6%, and increased the area under the plasma concentration–time curve from time 0 to infinity (AUC0−∞) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC0−∞ by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine. Conclusion Although probenecid reduced the CLr and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin. PMID:26855561

  10. Impact of injectable cephalosporins on the gastrointestinal microflora: observations in healthy volunteers and hospitalized patients.

    PubMed

    Knothe, H; Dette, G A; Shah, P M

    1985-01-01

    A disturbed microbiological ecosystem of the gut flora is frequently seen as a consequence of antibiotic therapy. Because this impact on the physiological balance is known to be causative for severe nosocomial infections and is mainly seen with antibiotics that are massively excreted via the bile (e.g. broadspectrum penicillins, ceftriaxone and cefoperazone), we investigated cefotaxime (CTX), cefotiam (CTM), cefmenoxime (CMX), ceftazidime (CAZ), ceftizoxime (CZX) and cefazolin + netilmicin (CEZ + NTL) in healthy volunteers. The respective daily i.v. doses, days of medication and numbers of volunteers were: CTX 3 g, 1 d, n = 8; CTM 6 g, 3 d, n = 15; CMX 4 g, 3 d, n = 15; CAZ 4 g, 1 d, n = 8; CZX 4 g, 1 d, n = 8; CEZ + NTL 2 X 3 g + 1 X 3 mg/kg/day, 4 d, n = 15. CTX was also investigated in 11 selected hospitalized patients. One or two stool specimens were taken before, during and several days after medication. The microorganisms were also tested for ampicillin and CEZ resistance on selective media. Ampicillin and CEZ resistance was much higher in hospitalized patients than in volunteers (mainly Proteus and Serratia sp.): 90% vs. 42% and 63.6% vs. 43%, respectively. CTX did not affect the anaerobes (Bacteroides sp. and lactobacilli) that are antagonistic to clostridia and Candida. No selection of strains resistant to ampicillin or CEZ occurred. In hospitalized patients, the level of resistance to these drugs was lower after treatment than before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4055042

  11. Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers

    PubMed Central

    Tasnim, Sara; Haque, Parsa Sanjana; Bari, Md. Sazzadul; Hossain, Md. Monir; Islam, Sardar Mohd. Ashraful; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Bin Sayeed, Muhammad Shahdaat

    2015-01-01

    Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide-induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS. PMID:26351508

  12. Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers.

    PubMed

    Tasnim, Sara; Haque, Parsa Sanjana; Bari, Md Sazzadul; Hossain, Md Monir; Islam, Sardar Mohd Ashraful; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Bin Sayeed, Muhammad Shahdaat

    2015-01-01

    Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide-induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS. PMID:26351508

  13. Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa.

    PubMed

    Barthelmebs, M; Mbou, P; Stephan, D; Grima, M; Imbs, J L

    1993-01-01

    L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion. PMID:8458598

  14. Effects of Danshen Ethanol Extract on the Pharmacokinetics of Fexofenadine in Healthy Volunteers

    PubMed Central

    Qiu, Furong; Zeng, Jin; Liu, Songcan; He, Min; Zhu, Leilei; Ye, Yujie; Miao, Ping; Shen, Shujiao; Jiang, Jian

    2014-01-01

    This study investigated the effect of multidose administration of danshen ethanol extract on fexofenadine pharmacokinetics in healthy volunteers. A sequential, open-label, two-period pharmacokinetic interaction design was used. 12 healthy male volunteers received a single oral dose of fexofenadine (60 mg) followed by danshen ethanol extract (1 g orally, three times a day) for 10 days, after which they received 1 g of the danshen extract with fexofenadine (60 mg) on the last day. The plasma concentrations of fexofenadine was measured by LC-MS/MS. After 10 days of the danshen extract administration, the mean AUC and Cmax⁡ of the fexofenadine was decreased by 37.2% and 27.4% compared with the control, respectively. The mean clearance of fexofenadine was increased by 104.9%. The in vitro study showed that tanshinone IIA and cryptotanshinone could induce MDR1 mRNA. This study showed that multidose administration of danshen ethanol extract could increase oral clearance of fexofenadine. The increased oral clearance of fexofenadine is attributable to induction of intestinal P-glycoprotein. PMID:25538791

  15. Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects.

    PubMed

    Cabaleiro, Teresa; López-Rodríguez, Rosario; Román, Manuel; Ochoa, Dolores; Novalbos, Jesús; Borobia, Alberto; Carcas, Antonio; Abad-Santos, Francisco

    2015-03-01

    Quetiapine is an atypical antipsychotic used for treatment of schizophrenia. Variability in response to this drug may be associated with pharmacogenetics. The aim of this study was to identify genetic markers related to the pharmacokinetics, pharmacodynamics, and adverse effects of quetiapine. The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes, receptors, and transporters. Quetiapine plasma levels were quantified using high-performance liquid chromatography/mass spectrometry. Prolactin plasma levels were detected by indirect chemiluminescence. Possible adverse effects were recorded throughout the study. Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis (logistic regression for adverse reactions). The area under the curve and clearance of quetiapine were affected by polymorphisms in CYP1A2 and DRD3, respectively. Men had a lower quetiapine area under the curve compared with women. Prolactin iC(max) was higher in volunteers harboring polymorphisms in CYP2C19 and AGT. An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence. Several polymorphisms are responsible for differences in the pharmacokinetics, pharmacodynamics, and safety of quetiapine in healthy individuals. PMID:25025989

  16. Acute effects of exposure to air contaminants in a sawmill on healthy volunteers.

    PubMed Central

    Dahlqvist, M; Palmberg, L; Malmberg, P; Sundblad, B M; Ulfvarson, U; Zhiping, W

    1996-01-01

    OBJECTIVES: To study whether air contaminants in sawmills can induce acute changes in the upper and lower airways of previously non-exposed subjects. METHODS: Nineteen healthy volunteers were examined to find the concentration of interleukin 6 (IL-6) in nasal lavage fluid and lung function before and after five hour exposure to dusts and fumes generated in a sawmill where timber from Scots pine was sawed. When exposed, the subjects had respirators with and without a particle filter. RESULTS: The median for daily time weighted average concentration of total dust for subjects with respirators without a filter was 0.13 mg/m3, which was significantly higher than the median of 0.04 mg/m3 for subjects who had respirators with a filter. The median for the concentration of IL-6 in the nasal lavage fluid increased after exposure from 0.5 to 5.9 pg/ml in subjects with respirators without a particle filter (P < 0.05). The increase of the concentration of IL-6 was significantly correlated with the dust concentration. A decrease in transfer factor of the lung was significantly correlated with daily time weighted average concentrations of terpenes. CONCLUSION: The findings suggest that healthy volunteers, exposed to air contaminants in a sawmill, show a slight inflammatory reaction. Also, the results of the study indicate the importance of decreasing the concentrations of wood dust in the work environment. PMID:8882114

  17. Distribution and Respiratory Activity of Mycobacteria in Household Water System of Healthy Volunteers in Japan

    PubMed Central

    Ichijo, Tomoaki; Izumi, Yoko; Nakamoto, Sayuri; Yamaguchi, Nobuyasu; Nasu, Masao

    2014-01-01

    The primary infectious source of nontuberculous mycobacteria (NTM), which are known as opportunistic pathogens, appears to be environmental exposure, and it is important to reduce the frequency of exposure from environmental sources for preventing NTM infections. In order to achieve this, the distribution and respiratory activity of NTM in the environments must be clarified. In this study, we determined the abundance of mycobacteria and respiratory active mycobacteria in the household water system of healthy volunteers using quantitative PCR and a fluorescent staining method, because household water has been considered as one of the possible infectious sources. We chose healthy volunteer households in order to lessen the effect of possible residential contamination from an infected patient. We evaluated whether each sampling site (bathroom drain, kitchen drain, bath heater pipe and showerhead) have the potential to be the sources of NTM infections. Our results indicated that drains in the bathroom and kitchen sink are the niche for Mycobacterium spp. and M. avium cells were only detected in the bathtub inlet. Both physicochemical and biologic selective pressures may affect the preferred habitat of Mycobacterium spp. Regional differences also appear to exist as demonstrated by the presence (US) or absence (Japan) of Mycobacterium spp. on showerheads. Understanding of the country specific human activities and water usage will help to elucidate the infectious source and route of nontuberculous mycobacterial disease. PMID:25350137

  18. Neurobehavioral and Cognitive Changes Induced by Sleep Deprivation in Healthy Volunteers.

    PubMed

    Cassé-Perrot, Catherine; Lanteaume, Laura; Deguil, Julie; Bordet, Régis; Auffret, Alexandra; Otten, Lisa; Blin, Olivier; Bartrés-Faz, David; Micallef, Joëlle

    2016-01-01

    To this day, the pharmacological treatment of Alzheimer's disease remains limited to the temporary stabilisation of cognitive decline and the reduction of neuropsychiatric symptoms. It is moreover with great difficulty to predict and select promising drug candidates in the early stages of the discovery and developmental process. In this context, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.e. the Cognitive Challenge Models. In the last decade, a great amount of literature on Sleep Deprivation was published which mainly focused on the consequences of sleep loss for public health. However, sleep deprivation paradigm may also be regarded as a cognitive challenge model. It is commonly accepted that sleep deprivation induces cognitive impairments related to a global decrease in vigilance, while in fact, there is a controversial approach related to the selective effects on cognitive functions. The identification and validation of cognitive challenge models in healthy volunteers are suitable in early clinical development of drugs to determine the 'hint of efficacy' of drug candidates. The present review aims at exploring in detail the methods, designs and cognitive paradigms used in non pharmacological sleep deprivation studies. Sleep deprivation can be induced by different methods. Probing the four main cognitive functions will allow identifying the extent to which different sleep deprivation designs selectively compromise executive function, working memory, episodic memory and attention. Findings will be discussed in line with cognitive processing levels that are required according to the tasks. PMID:27189463

  19. The effect of cryotherapy on oral mucosa: a study in healthy volunteers.

    PubMed

    Svanberg, Anncarin; Ohrn, Kerstin; Broström, Hans; Birgegård, Gunnar

    2012-12-01

    Oral cryotherapy causes local vasoconstriction, which reduces blood flow and reduces the cytotoxic damage to the oral mucosa, has been shown to reduce oral mucositis after intense cytostatic treatment. The main object of this study was to investigate the effect of oral cryotherapy on the temperature in the oral mucosa, the level of proinflammatory cytokine interleukin-6 (IL-6) in saliva and the effect on blood pressure in healthy volunteers, before and after 1 h of cooling the oral cavity with crushed ice. Twelve healthy volunteers [mean age 32.4 (SD 13.2) (20-56) years] were treated with oral cryotherapy in the form of crushed ice. Temperature measurements were performed in the oral mucosa using infrared thermograph following a flowchart protocol. Blood pressure (BP) was measured with a sphygmomanometer. Saliva was analysed for inflammatory cytokine IL-6, using an enzyme-linked immunosorbent assay (ELISA). All participants fulfilled the cooling session. The temperature in the oral cavity decreased significantly (mean 12.9 °C, p < .002). The systolic BP was marginally but significantly higher after cooling (~5 mmHg, p = .019). We could not detect any differences in cytokine IL-6 levels before and after oral cooling. We conclude that cryotherapy during 1 h lowers the mucosal temperature as much as ~12.9 °C, which explains the significant protective effect against mucosal damage by cytostatic drugs. The cooling caused no increase in IL-6 levels. Systemic blood pressure was marginally increased. PMID:22476810

  20. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

    PubMed

    Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence

    2015-02-01

    Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. PMID:25279818

  1. Objective and subjective assessment of digestion after ingestion of an iced dessert in healthy volunteers.

    PubMed

    Garzaro, Massimiliano; Pecorari, G; Nadalin, J; Raimondo, L; Palmo, A; Baccega, M; Giordano, C

    2010-01-01

    The aim of our study is to assess, with objective measures, the impact on digestion of a coffee-flavoured iced dessert ingested at the end of a standardized meal; moreover, a subjective assessment, using a specific questionnaire, was carried out in order to compare objective and subjective data. Ten healthy male volunteers, after ENT and psychological assessment, underwent two scintigraphic evaluations (standardized meal without and with coffee-flavoured iced dessert) and, after the meal, filled in a specific questionnaire named dynamic digestibility questionnaire. In our sample the ingestion of the coffee-flavoured iced dessert seemed to improve the digestibility of a standardized meal: the difference between the curves of gastric emptying without and with iced dessert is statistically significant. These data are strongly confirmed by subjective assessment: the dynamic digestibility questionnaire (DDQ) showed a higher digestibility of a standardized meal with the coffee-flavoured iced dessert in comparison to a normal meal. The current study represents a preliminary report on this topic with a small sample of healthy volunteers: further studies on larger population are requested in order to confirm all the encouraging results herein discussed. PMID:20487635

  2. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers:

    PubMed Central

    Leary, Andrew C.; Dowling, Muiris; Cussen, Kathleen; O'Brien, Jackie; Stote, Robert M.

    2008-01-01

    Background The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers. Methods Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). Results The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. Conclusions This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle. PMID:19885293

  3. Extent of Fentanyl Accumulation Following Multiple Doses of Fentanyl Buccal Tablet 400 µg in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Simonson, Philip G

    2008-01-01

    Objective This study was conducted to characterize the pharmacokinetics, including extent of accumulation, and safety and tolerability of fentanyl following multiple doses of fentanyl buccal tablet (FBT) in healthy Japanese volunteers. Methods Healthy Japanese adults received 10 successive doses of open-label FBT 400 µg at 6-hour intervals. Naltrexone was given to minimize the opioid effects of fentanyl. FBT was placed above a molar tooth between the gum and cheek. Peak serum fentanyl concentration (Cmax), time to Cmax (tmax), and area under the serum fentanyl concentration-time curve from 0 to 6 hours (AUC0–6) were summarized using descriptive statistics. Accumulation ratio was calculated as Cmax for dose 10/Cmax for dose 1, and was calculated similarly for AUC0–6. Results Fourteen volunteers (mean age 33 years) were enrolled, and 13 completed the study. After doses 1 and 10, respectively, mean (SD) Cmax was 1.70 (0.49) ng/mL and 1.97 (0.42) ng/mL, AUC0–6 was 4.46 (1.14) ng·h/mL and 6.81 (0.90) ng·h/mL, and median (range) tmax was 50 (30–110) minutes and 30 (15–120) minutes. Following 10 successive doses, systemic exposure (AUC0–6) was 55% higher than after dose 1, and Cmax was 23% higher. Steady state was achieved within 3 days of dosing at 6-hour intervals, i.e., prior to dose 10. The most frequent adverse events (AEs) were somnolence (N = 9), decreased oxygen saturation (N = 4), headache (N = 3), application-site pain (N = 8), application-site erythema (N = 6), and application-site reaction (N = 5). All AEs were mild or moderate. Conclusions Following administration of FBT at 6-hour intervals to healthy Japanese volunteers, at steady state, fentanyl exposure was higher by 55% (AUC0–6) and 23% (Cmax) than after a single dose of FBT. Adverse events were mild or moderate. PMID:19915714

  4. Body image distortions in healthy adults.

    PubMed

    Fuentes, Christina T; Longo, Matthew R; Haggard, Patrick

    2013-10-01

    Distortions of body image have often been investigated in clinical disorders. Much of this literature implicitly assumes healthy adults maintain an accurate body image. We recently developed a novel, implicit, and quantitative measure of body image - the Body Image Task (BIT). Here, we report a large-scale analysis of performance on this task by healthy adults. In both an in-person and an online version of the BIT, participants were presented with an image of a head as an anchoring stimulus on a computer screen, and told to imagine that the head was part of a mirror image of themselves in a standing position. They were then instructed to judge where, relative to the head, each of several parts of their body would be located. The relative positions of each landmark can be used to construct an implicit perceptual map of bodily structure. We could thus measure the internally-stored body image, although we cannot exclude contributions from other representations. Our results show several distortions of body image. First, we found a large and systematic over-estimation of width relative to height. These distortions were similar for both males and females, and did not closely track the idiosyncrasies of individual participant's own bodies. Comparisons of individual body parts showed that participants overestimated the width of their shoulders and the length of their upper arms, relative to their height, while underestimating the lengths of their lower arms and legs. Principal components analysis showed a clear spatial structure to the distortions, suggesting spatial organisation and segmentation of the body image into upper and lower limb components that are bilaterally integrated. These results provide new insight into the body image of healthy adults, and have implications for the study and rehabilitation of clinical populations. PMID:23933684

  5. Noninvasive estimation of tissue edema in healthy volunteers and in patients suffering from heart failure

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yuri I.; Mikhailov, Valery M.; Kudutkina, Marina I.

    2004-06-01

    Capillaries play a critical role in cardiovascular function as the point of exchange of nutrients and waste products between tissues and circulation. A common problem for healthy volunteers examined during isolation, and for the patients suffering from heart failure is a quantitative estimation tissue oedema. Until now, objective assessment body fluids retention in tissues did not exist. Optical imaging of living capillaries is a challenging and medically important scientific problem. Goal of the investigation was to study dynamic of microcriculation parameters including tissue oedema in healthy volunteers during extended isolation and relative hypokinesia as a model of mission to the International Space Station. The other aim was to study dynamic of microcirculation parameters including tissue oedema in patients suffering from heart failure under treatment. Healthy volunteers and patients. We studied four healthy male subjects at the age of 41, 37, 40, and 48 before the experiment (June 1999), and during the 240-d isolation period starting from July3, 1999. Unique hermetic chambers with artidicial environmental parameters allowed performing this study with maximum similarity to real conditions in the International Space Station (ISS). With the regularity of 3 times a week at the same time, each subject recorded three video episodes with the total length of one-minute using the optical computerized capillaroscope for noninvasive measurement of the capillary diameters sizes, capillary blood velocity as well as the size of the perivascular zone. All this parameters of microcirculation determined during three weeks in 15 patients (10 male, 5 female, aged 62,2+/-8,8) suffering from heart failure under Furosemid 40 mg 2 times a week, as diuretic. Results. About 1500 episodes recorded on laser disks and analyzed during this experiment. Every subject had wave-like variations of capillary blood velocity within the minute, week, and month ranges. It was found that the

  6. Changing Geomagnetic Field and Heart Rates Variability in Healthy Volunteers: A Pilot Study

    NASA Astrophysics Data System (ADS)

    Jordanova, Malina; Zenchenko, Tatiana; Poskotinova, Lilia; Medvedeva, Anna; Uzunov, Todor; Alenikova, Alexandra

    Space Climate is an interdisciplinary science that deals with the long-term change in the Sun, and its effects in the near-Earth environment, including possible effects on human health. This paper will present the first results from simultaneous experiments performed at 3 different locations - Sofia, Bulgaria 42° 40' N 23° 20' E; Moscow, Russia 55° 45' N 37° 36‘ E and Arkhangelsk, Russia 64° 34' N / 40° 32' E. Subjects are 5 healthy volunteers, women, mean age 39,4 years. The experiments are part of the project “Heliobiology” (2011 - 2015) that reflects the intense interest towards the influence of solar activity and meteorology on the human health. The aim of the experiments is to study the degree of conjugation of the heart rate variability and the variations of the geomagnetic field. To minimize the experimental bias one and the same hard- and software were applied during the testing. ECG signals were recorder via "KARDI-2", the software package is "Ecosan-2007", both developed by "Medical Computer Systems", Zelenograd, Russia. The duration of the observations ranged from 60 to 120 minutes. A comparison of the dynamics of the minute variations of the heart rate with the horizontal components of the geomagnetic field vector revealed a synchronization of some of the research parameters as well as specific individual differences. Despite of the small sample size (5 subjects per 8 measures), in over 70% of the experimental data a similar patterns of variation of geophysical and heart rate variability were recorded. The experiments discussed involved healthy volunteers, i.e. people that have good adaptation reserves, and the response to variation of geomagnetic field will not push them beyond the physiological norms. The observed effect of synchronization of heart rate fluctuations of healthy subjects with fluctuations of geomagnetic field may give an effective tool to address further one especially interesting problems - the mechanism of geomagnetic

  7. Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

    PubMed Central

    Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

    2009-01-01

    Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally

  8. Report: pharmacokinetic and drug interaction studies of pefloxacin with paracetamol (NNAID) in healthy volunteers in Pakistan.

    PubMed

    Gauhar, Shahnaz; Ali, Syed Ayub; Naqvi, Syed Baqir; Shoaib, Muhammad Harris

    2014-03-01

    In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years (means), with a mean weight of 76.45±12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18±1 min and paracetamol were approximately 6±1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0mg/ml with r(2)=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC0-∞ in control was 67.355±3.174μg.h/ml, in treatment 61.242±3.868μg.h/ml along with relative bioavailability =91.395±4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679±0.248 μg/ml and 4.6595±0.266 μg/ml respectively. The average T(max) for plasma concentrations was 1.819±0.1743hr and 1.605 ±0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953±0.33hr in control and 7.7257±0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter

  9. The nasal cavity microbiota of healthy adults

    PubMed Central

    2014-01-01

    Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. Conclusions There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities. PMID:25143824

  10. UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers

    PubMed Central

    Limenta, Lie Michael George; Jirasomprasert, Totsapol; Tankanitlert, Jeeranut; Svasti, Saovaros; Wilairat, Prapin; Chantharaksri, Udom; Fucharoen, Suthat; Morales, Noppawan Phumala

    2008-01-01

    AIMS To examine the effects of UGT1A6 polymorphisms on the pharmacokinetics of deferiprone in healthy volunteers. METHODS Twenty-two healthy volunteers were enrolled and grouped according to UGT1A6 genotype. After an overnight fast, the subjects received a single oral dose of 25 mg kg−1 deferiprone. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min after dosing. Urine output was collected at 0, 0–2, 2–4, 4–8, 8–12 and 12–24 h. Deferiprone (L1) and deferiprone-glucuronide (L1G) concentrations in serum and urine were determined using a validated high-performance liquid chromatography method. UGT1A6 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS No statistically significant differences in any pharmacokinetic parameters of either deferiprone or deferiprone-glucuronide among the genotype groups were noted. Likewise, there were no statistically significant differences in 24-h urinary deferiprone and deferiprone-glucuronide excretion among the genotype groups. Significant differences between men and women were found in AUC0–∞, Vd/F, and CL/F of deferiprone. Gender differences in 24-h urinary deferiprone and its metabolite excretion, however, failed to reach statistical significance. The Vd/F of deferiprone was found to correlate significantly with serum ferritin (rs = 0.665; P = 0.001). CONCLUSION The studied single nucleotide polymorphisms in UGT1A6 do not appear to exert statistically significant effects on the single-dose pharmacokinetics of deferiprone. Gender appears to influence the serum pharmacokinetics of deferiprone, but not urinary excretion of deferiprone and its metabolite. Body iron stores may have an influence on the extent of extravascular deferiprone distribution. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT UGT1A6 has been proposed as the predominant isoform responsible for the glucuronidation of deferiprone. UGT1A6*2 allele has been

  11. Gastric Re-acidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria

    PubMed Central

    Yago, Marc Anthony R.; Frymoyer, Adam R.; Smelick, Gillian S.; Frassetto, Lynda A.; Budha, Nageshwar R.; Dresser, Mark J.; Ware, Joseph A.; Benet, Leslie Z.

    2013-01-01

    Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H2-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric re-acidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically-induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 minutes, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 hours. Betaine HCl significantly lowered gastric pH by 4.5 (±0.5) units from 5.2 (±0.5) to 0.6 (±0.2) (P <0.001) during the 30 minute interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (±4.3) minutes. The re-acidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (±33) and 77 (±30) minutes, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically-induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions. PMID:23980906

  12. Quantification of serotonin O-sulphate by LC-MS method in plasma of healthy volunteers

    PubMed Central

    Lozda, Raimonds; Purviņš, Indulis

    2014-01-01

    The objective of this study was to test the hypothesis that serotonin O-sulphate (5-HT-SO4) could be quantified in human plasma using modern liquid chromatography–mass spectrometry (LC-MS) method as well as develop and validate that method. First, a suitable LC-MS method for detection of 5-HT-SO4 in human plasma samples was developed and validated. Second, a Pilot phase involving four healthy volunteers was executed, where a basal plasma level of 5-HT-SO4 was measured for all subjects and for one after the intake of 100 mg of a 5-hydroxytryptophan (5-HTP) -containing food supplement used to promote serotonergic stimulation of the central nervous system. The basal level of 0.9–2.8 ng/mL of 5-HT-SO4 was observed. The changes of plasma 5HT-O-SO4 showed 1.2 ng/mL before and 22.6 ng/mL 1 h after stimulation. Finally, nine healthy volunteers were selected for the Study phase, where a basal plasma level of 5-HT-SO4 was measured before and after the intake of 5-HTP. One hour after stimulation, six study subjects showed a decrease in 5-HT-SO4 levels while three subjects showed an increase. The changes of plasma 5HT-O-SO4 from the Study phase showed an average 5-HT-SO4 level of 19.2 ng/mL before and 15.7 ng/mL 1 h after stimulation indicating ability of method to emphasize quantitative changes. This was the first study in which naturally occurring 5-HT-SO4 was detected in the samples of human plasma obtained from healthy volunteers. The method developed herein is specific to the measurement of 5-HT-SO4, sensitive enough to quantify intra-individual changes in the samples of plasma and opens up new possibilities to evaluate pathways of serotonin metabolism by minimally invasive methods. The discovery of novel biomarkers using such approaches is increasingly required to expedite development of mechanism-based therapeutics and patient stratification. PMID:24782770

  13. Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.

    PubMed

    Ritz, E; Benck, U; Franek, E; Keller, C; Seyfarth, M; Clorius, J

    1998-10-01

    Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of

  14. An evaluation of diphtheria--tetanus (adult) vaccine in unselected human volunteers.

    PubMed

    Harcus, A W; Ward, A E; Roberts, J S; Bryett, K A

    1989-01-01

    One hundred unselected adult volunteers received an adult diphtheria (less than 2 Lf)-tetanus (greater than or equal to 40 IU) adsorbed vaccine without prior Schick testing. No volunteer had a moderate or severe reaction although 39% complained of a transient sore arm. Only 10% reported local erythema. Of the study group, 37/43 (86%) patients who were initially seronegative for diphtheria attained levels normally considered as seropositive. The results confirm the safety and efficacy of adult diphtheria-tetanus vaccine and allow its recommendation for use in 'at risk' individuals without the need for prior Schick testing. PMID:2767328

  15. Impact of Surotomycin on the Gut Microbiota of Healthy Volunteers in a Phase 1 Clinical Trial.

    PubMed

    Citron, Diane M; Tyrrell, Kerin L; Dale, Suzanne E; Chesnel, Laurent; Goldstein, Ellie J C

    2016-04-01

    Clostridium difficile-associated diarrhea has been associated with disruption of the normal intestinal microbiota, particularly theBacteroides fragilisgroup andPrevotellaspecies. Surotomycin is a bactericidal cyclic lipopeptide in development for treatment ofClostridium difficile-associated diarrhea that has selective and potent activity againstC. difficileand other Gram-positive bacteria and a minimal impact on intestinal Gram-negative organisms. The impacts of ascending doses of surotomycin on major organism groups in the gut microbiota of healthy volunteers were evaluated during a randomized, double-blind, placebo-controlled, multiple-dose phase 1 study. Thirty volunteers were randomized into 3 cohorts, using a 4:1 ratio, to receive 250 mg, 500 mg, or 1,000 mg of surotomycin, or placebo, twice daily for 14 days. Stool samples collected at baseline (days 0 and 1) and at the end of treatment (days 13 to 15) were cultured quantitatively. TheB. fragilisgroup, theBacteroides/Prevotellagroup, andEnterobacteriaceaewere also quantified by quantitative real-time PCR. Baseline and end-of-treatment stool samples showed 1- to 2-log10CFU/g reductions in total bacterial counts for most volunteers. Various decreases in clostridial,Lactobacillus-Bifidobacteriumgroup, and enterococcus-streptococcus group counts occurred while patients were receiving surotomycin, whereas the enterobacteria and theB. fragilisgroup persisted at the end of treatment. There was no change in enterococcus MICs of surotomycin, nor was vancomycin-resistantEnterococcusdetected after exposure. Surotomycin at doses of up to 1,000 mg twice daily had only modest disruptive effects on the gut microbiota. The potential sparing of the gut microbiota by surotomycin may decrease the risk of disease recurrence. PMID:26787687

  16. Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers

    PubMed Central

    Teng, Renli; Butler, Kathleen

    2013-01-01

    Objectives Two open-label, two-period, crossover studies in healthy volunteers were designed to determine the pharmacokinetic interactions between ticagrelor, a P2Y12 receptor antagonist, and a moderate (diltiazem) and a strong (ketoconazole) cytochrome P450 (CYP) 3A inhibitor. Methods Seventeen volunteers received diltiazem (240 mg once daily) for 14 days. In the second study, ketoconazole (n = 14) 200 mg twice daily was given for 10 days. A single oral 90-mg ticagrelor dose was administered on day 8 (diltiazem) or day 4 (ketoconazole). In each study, volunteers received a single 90-mg oral dose of ticagrelor before or after washout (≥14 days). Pharmacokinetic parameters for ticagrelor, AR-C124910XX (primary metabolite), diltiazem, and ketoconazole were assessed. Results Compared with ticagrelor alone, diltiazem co-administration significantly increased the mean maximum concentration (Cmax) and mean area under the plasma concentration–time curve (AUC) for ticagrelor by 69% and 174%, respectively. Diltiazem co-administration reduced Cmax by 38% but had no significant effect on AUC for AR-C124910XX. Cmax and AUC for ticagrelor were increased by 135% and 632%, respectively, by ketoconazole co-administration, whereas these parameters were reduced by 89% and 56%, respectively, for AR-C124910XX. Diltiazem and ketoconazole pharmacokinetic parameters were not significantly affected by the presence of ticagrelor. Conclusions These results suggest that ticagrelor can be co-administered with moderate CYP3A inhibitors. However, co-administration of strong CYP3A inhibitors with ticagrelor is not recommended.

  17. Cognitive effects of intramuscular ketamine and oral triazolam in healthy volunteers

    PubMed Central

    Carter, Lawrence P.; Kleykamp, Bethea A.; Griffiths, Roland R.

    2012-01-01

    Rationale Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs. Objectives The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers. Methods Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance. Conclusions Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam. PMID:23096769

  18. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2013-01-01

    Background There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Methods Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5 mg alprazolam, 10mg oxycodone, and 0.5 mg alprazolam combined with 10mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Results Oxycodone by itself increased drug liking and “take again” ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. Conclusions In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. PMID:22365897

  19. The interplay of frequency of volunteering and prosocial motivation on purpose in life in emerging adults.

    PubMed

    Okun, Morris A; Kim, Ga Young

    2016-01-01

    One developmental task in emerging adulthood is finding meaning and purpose in life. Volunteering has been touted as one role that fosters purpose in life. We examined whether the association between frequency of volunteering and purpose in life varies with pleasure-based prosocial motivation and pressure-based prosocial motivation in a sample of 576 undergraduates, ages 18-22 years old. In a regression analysis predicting purpose in life, the frequency of volunteering by pleasure-based prosocial motivation by pressure-based prosocial motivation interaction effect was significant (p = .042). Simple slopes analyses revealed that frequency of volunteering was not significantly (p = .478) related to purpose in life among college students who were low in both pleasure-based and pressure-based prosocial motivation. The findings of the present study highlight the importance of prosocial motivation for understanding whether emerging adults' purpose in life will be enhanced by volunteering. PMID:27064183

  20. [Pharmacokinetics of cefixime in healthy volunteers after a single oral administration of 200 mg].

    PubMed

    Montay, G; Le Liboux, A; Thebault, J J; Roche, G; Frydman, A; Gaillot, J

    1989-10-11

    The antibacterial activity of cefixime is identical with that of parenteral third generation cephalosporins. Its kinetics were studied in 24 healthy male volunteers who received one single 200 mg tablet. Cmax was 3.25 mg/l and Tmax was 4 h. After 12 hours, serum concentrations were still as high as 0.70 mg/l. Half-life was 3.3 h and urinary excretion was not predominant. Thus, cefixime was characterized by its relatively long serum half-life as compared with other cephalosporins. Despite some degree of individual variations, serum and urine concentrations of the antibiotic remained for 12 hours above the MIC of susceptible pathogens. PMID:2530537

  1. Bioequivalence study of 2 orodispersible formulations of ondansetron 8 mg in healthy volunteers.

    PubMed

    Cánovas, M; Rios, J; Domenech, G; Cebrecos, J; Pelagio, P; Canals, M; Polonio, F; Cabré, F

    2012-02-01

    This study was designed to compare the rate and extent of absorption of 2 oral formulations of ondansetron (CAS 99614-02-5) 8 mg orodispersible tablets in healthy volunteers. 22 subjects were administered ondansetron orodispersible tablets of test and reference formulation in a single-dose, 2-period, 2-sequence, fasting, open-label, crossover and randomised study. Plasma concentrations were determined by LC/MS/MS. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline [1] it may be therefore concluded that test formulation of ondansetron 8 mg orodispersible tablet is bioequivalent to the reference formulation. PMID:22344549

  2. Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers.

    PubMed Central

    Flor, S C; Rogge, M C; Chow, A T

    1993-01-01

    The bioequivalence of oral and intravenous ofloxacin was investigated after the administration of multiple doses of 400 mg every 12 h to 20 healthy male volunteers in a randomized, crossover, open-label study. Ofloxacin concentrations in plasma were evaluated after 4 days of oral or intravenous (1-h infusion) dosing with a 3-day wash-out period between regimens. As expected, delivery to the systemic circulation took slightly longer after the oral dosing (time to maximum concentration of drug in serum of 1.7 h) relative to the 1-h intravenous infusion, but the systemic availabilities of ofloxacin by the two routes of administration were equivalent (area under the concentration-time curve from 0 to 12 h ratio of 95%). Since previous studies have not demonstrated any change in the bioavailability of ofloxacin in infectious disease patients, this study supports the interchangeability of these dosing regimens. PMID:8363378

  3. Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla.

    PubMed

    Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N; Smith, Seth A; Gore, John C

    2016-06-01

    We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity. PMID:26924285

  4. Nostrils of healthy volunteers are independent with regard to Staphylococcus aureus carriage.

    PubMed

    Kildow, Beau J; Conradie, Johan P; Robson, Rachel L

    2012-11-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  5. Nostrils of Healthy Volunteers Are Independent with Regard to Staphylococcus aureus Carriage

    PubMed Central

    Kildow, Beau J.; Conradie, Johan P.

    2012-01-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  6. Virtual Reality-Guided Motor Imagery Increases Corticomotor Excitability in Healthy Volunteers and Stroke Patients

    PubMed Central

    2016-01-01

    Objective To investigate the effects of using motor imagery (MI) in combination with a virtual reality (VR) program on healthy volunteers and stroke patients. In addition, this study investigated whether task variability within the VR-guided MI programs would influence corticomotor excitability. Methods The present study included 15 stroke patients and 15 healthy right-handed volunteers who were presented with four different conditions in a random order: rest, MI alone, VR-guided MI, and VR-guided MI with task variability. The corticomotor excitability of each participant was assessed before, during, and after each condition by measuring changes in the various parameters of motor-evoked potentials (MEPs) of the extensor carpi radials (ECR). Changes in intracortical inhibition (ICI) and intracortical facilitation (ICF) were calculated after each condition as percentages of inhibition (%INH) and facilitation (%FAC) at rest. Results In both groups, the increases in MEP amplitudes were greater during the two VR-guided MI conditions than during MI alone. Additionally, the reductions in ECR %INH in both groups were greater under the condition involving VR-guided MI with task variability than under that involving VR-guided MI with regular interval. Conclusion The corticomotor excitability elicited by MI using a VR avatar representation was greater than that elicited by MI with real body observations. Furthermore, the use of task variability in a VR program may enhance neural regeneration after stroke by reducing ICI. The present findings support the use of various VR programs as well as the concept of combining MI with VR programs for neurorehabilitation. PMID:27446778

  7. Characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers

    PubMed Central

    Brott, David A; Adler, Scott H; Arani, Ramin; Lovick, Susan C; Pinches, Mark; Furlong, Stephen T

    2014-01-01

    Background Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency) for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals), intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons. Methods Spot urine samples from 20 male and 19 female healthy volunteers collected on multiple days were analyzed using single analyte and multiplex assays. The following analytes were measured: α-1-microglobulin, β-2-microglobulin, calbindin, clusterin, connective tissue growth factor, creatinine, cystatin C, glutathione S-transferase-α, kidney injury marker-1, microalbumin, N-acetyl-β-(D) glucosaminidase, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein, tissue inhibitor of metalloproteinase 1, trefoil factor 3, and vascular endothelial growth factor. Results Confidence intervals were determined from the single analyte and multiplex assays. Intersubject and intrasubject variability ranged from 38% to 299% and from 29% to 82% for biomarker concentration, and from 24% to 331% and from 10% to 67% for biomarker concentration normalized to creatinine, respectively. There was no major effect of food intake or sex. Single analyte and multiplex assays correlated with r2≥0.700 for five of six biomarkers when evaluating biomarker concentration, but for only two biomarkers when evaluating concentration normalized to creatinine. Conclusion Confidence intervals as well as

  8. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

    PubMed

    Wezenberg, Elke; Verkes, Robert Jan; Ruigt, Ge S F; Hulstijn, Wouter; Sabbe, Bernard G C

    2007-06-01

    Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia. PMID:17119538

  9. Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers

    PubMed Central

    Pickering, Gisèle; Macian, Nicolas; Libert, Frédéric; Cardot, J Michel; Coissard, Séverine; Perovitch, Philippe; Maury, Marc; Dubray, Claude

    2014-01-01

    Background Acetaminophen (APAP) by oral or intravenous (iv) routes is used for mild to moderate pain but may take time to be effective. When fast relief is required and/or oral or iv routes are not available because of the patient’s condition, the transmucosal route may be an alternative. Methodology A new transmucosal/buccal (b) pharmaceutical form of APAP dissolved in 50% wt alcohol is compared with other routes of administration. Two consecutive randomized, crossover, double-blind clinical trials (CT1: NCT00982215 and CT2: NCT01206985) included 16 healthy volunteers. CT1 compared the pharmacology of 250 mg bAPAP with 1 g iv APAP. CT2 compared the pharmacodynamics of 125 mg bAPAP with 1 g iv and 125 mg sublingual (s) APAP. Mechanical pain thresholds are recorded in response to mechanical stimuli applied on the forearm several times during 120 minutes. The objective is to compare the time of onset of antinociception and the antinociception (area under the curve) between the routes of administration with analysis of variance (significance P<0.05). Results bAPAP has a faster time of antinociception onset (15 minutes, P<0.01) and greater antinociception at 50 minutes (P<0.01, CT1) and 30 minutes (P<0.01, CT2) than ivAPAP and sAPAP. All routes are similar after 50 minutes. Conclusion bAPAP has a faster antinociceptive action in healthy volunteers. This attractive alternative to other routes would be useful in situations where oral or iv routes are not available. This finding must now be confirmed in patients suffering from acute pain of mild and moderate intensity. PMID:25302017

  10. Keep Your Mouth Healthy: Oral Care for Older Adults

    MedlinePlus

    ... please review our exit disclaimer . Subscribe Keep Your Mouth Healthy Oral Care for Older Adults Oral health ... decay. You can take steps to keep your mouth healthy throughout your lifetime. And if you’re ...

  11. Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers

    PubMed Central

    Fromonot, Julien; Chaumet, Guillaume; Gavarry, Olivier; Rostain, Jean-Claude; Lucciano, Michel; Joulia, Fabrice; Brignole, Michele; Deharo, Jean-Claude; Guieu, Regis; Boussuges, Alain

    2016-01-01

    Abstract Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing. Seventeen healthy male volunteers (mean age 35 ± 11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels. No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ± 0.08 μM) and during head-up tilt test (0.33 ± 0.09 μM) when compared with baseline (0.6 ± 0.1 μM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ± 0.1 μM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air. These results suggest that hyperoxia was able to increase blood pressure during head

  12. Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers.

    PubMed

    Nagalla, S; Thomson, L; Oppong, Y; Bachman, B; Chervoneva, I; Kraft, W K

    2016-06-01

    It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points. PMID:27170068

  13. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers.

    PubMed

    Sacher, Julia; Mossaheb, Nilufar; Spindelegger, Christoph; Klein, Nikolas; Geiss-Granadia, Thomas; Sauermann, Robert; Lackner, Edith; Joukhadar, Christian; Müller, Markus; Kasper, Siegfried

    2008-06-01

    Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic. PMID:17712347

  14. Abdominal wall muscle elasticity and abdomen local stiffness on healthy volunteers during various physiological activities.

    PubMed

    Tran, D; Podwojewski, F; Beillas, P; Ottenio, M; Voirin, D; Turquier, F; Mitton, D

    2016-07-01

    The performance of hernia treatment could benefit from more extensive knowledge of the mechanical behavior of the abdominal wall in a healthy state. To supply this knowledge, the antero-lateral abdominal wall was characterized in vivo on 11 healthy volunteers during 4 activities: rest, pullback loading, abdominal breathing and the "Valsalva maneuver". The elasticity of the abdominal muscles (rectus abdominis, obliquus externus, obliquus internus and transversus abdominis) was assessed using ultrasound shear wave elastography. In addition, the abdomen was subjected to a low external load at three locations: on the midline (linea alba), on the rectus abdominis region and on lateral muscles region in order to evaluate the local stiffness of the abdomen, at rest and during "Valsalva maneuver". The results showed that the "Valsalva maneuver" leads to a statistically significant increase of the muscle shear modulus compared to the other activities. This study also showed that the local stiffness of the abdomen was related to the activity. At rest, a significant difference has been observed between the anterior (0.5N/mm) and the lateral abdomen locations (1N/mm). Then, during the Valsalva maneuver, the local stiffness values were similar for all locations (ranging from 1.6 to 2.2N/mm). This work focuses on the in vivo characterization of the mechanical response of the human abdominal wall and abdomen during several activities. In the future, this protocol could be helpful for investigation on herniated patients. PMID:26994992

  15. First clinical experience with TRV027: pharmacokinetics and pharmacodynamics in healthy volunteers.

    PubMed

    Soergel, David G; Subach, Ruth Ann; Cowan, Conrad L; Violin, Jonathan D; Lark, Michael W

    2013-09-01

    TRV027 is a novel β-arrestin biased peptide ligand of the angiotensin II type 1 receptor (AT1R). The compound antagonizes G protein coupling while simultaneously stimulating β-arrestin-mediated signaling. In preclinical studies, TRV027 reversibly reduced blood pressure while preserving renal function in a dog tachypaced heart failure model and stimulating cardiomyocyte contractility in vitro. This profile suggests that TRV027 may have unique benefits in acute heart failure, a condition associated with renin-angiotensin system activation. A first-time-in-human study was conducted with ascending doses of TRV027 to explore its tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. Subjects' salt intake was restricted to stimulate RAS activation. In this study TRV027 was safe and well tolerated with a short-half-life (ranging between 2.4 and 13.2 minutes) and dose-proportional increases in systemic exposure. Consistent with the pre-clinical findings, TRV027 reduced blood pressure to a greater degree in subjects with RAS activation, measured as elevated plasma renin activity, than in those with normal PRA levels. This study in sodium-restricted healthy subjects suggests that TRV027 will successfully target a core mechanism of acute heart failure pathophysiology. Further clinical studies with TRV027 in patients with heart failure are underway. PMID:23813302

  16. Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

    PubMed

    Suzuki, Yosuke; Itoh, Hiroki; Abe, Tomohide; Nishimura, Fumihiro; Sato, Yuhki; Takeyama, Masaharu

    2011-01-01

    Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels. PMID:21963510

  17. Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers.

    PubMed

    Salinsky, M C; Spencer, D C; Oken, B S; Storzbach, D

    2004-12-01

    We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs. PMID:15582838

  18. Altruism, personal benefit, and anxieties: a phenomenological study of healthy volunteers' experiences in a placebo‐controlled trial of duloxetine

    PubMed Central

    Kwakye, Isaac N.; Garner, Matthew; Baldwin, David S.; Bamford, Susan; Pinkney, Verity

    2016-01-01

    Objective The objective of this study was to develop an in‐depth understanding of healthy volunteers' experiences of mental health trials. Methods A qualitative study was nested within a healthy volunteer placebo‐controlled trial of duloxetine, a psychotropic drug used for treating patients with major depression and generalized anxiety disorder. Eight participants were interviewed, and data were analyzed using interpretative phenomenological analysis. Results Interviewees described volunteering for the trial because they were interested in research, wanted the monetary incentive, wanted to help researchers, and wanted to be part of something. On entering the trial, participants considered the possible risks and described feeling anxious, excited, and determined; they had some clear expectations and some loosely held hopes about what would happen. During the trial, participants were curious about whether they were taking duloxetine or placebo, self‐monitored their bodies' reactions, and guessed which treatment they received. On being un‐blinded to treatment allocation after completing the trial, some participants' guesses were confirmed, but others were surprised, and a few were disappointed. Conclusions Small changes to advertising/consent materials to reflect volunteers' motivations could improve recruitment rates to similar trials; “active” placebos might be particularly useful for maintaining blinding in healthy volunteer trials; and sensitive procedures are needed for un‐blinding participants to treatment allocation. © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd. PMID:27378326

  19. Short- and midterm repeatability of magnetic resonance elastography in healthy volunteers at 3.0 T.

    PubMed

    Shi, Yu; Guo, Qiyong; Xia, Fei; Sun, Jiaxing; Gao, Yuying

    2014-07-01

    The purpose of this study was to evaluate the short- and midterm repeatability of liver stiffness measurements with magnetic resonance elastography (MRE) in healthy subjects at 3.0T. Twenty-two healthy volunteers were enrolled in this prospective study. The stiffness measurements were obtained from three slices with three repeated acquisitions for each slice (session 1) by two independent raters. After a mean period of 7±2days (session 2) and 195±15days (session 3), each subject was scanned again using the same protocol and MR system. The liver stiffness differences were calculated between sessions or raters. The intraclass correlation coefficient (ICC) was calculated to assess interrater agreement and intersession agreement. The stiffness differences over the short- and midterm intervals was (-0.004±0.086) kPa for sessions 1-2, lower than (-0.055±0.150) kPa for sessions 1-3 and (-0.051±0.173) kPa for sessions 2-3. The liver stiffness was more repeatable for the short-term interval with the mean overall ICC of 0.96 (sessions 1-2) (95% confidence interval [CI]: 0.90-0.98) compared with 0.91 (sessions 1-3) (95% CI: 0.78-0.96) and 0.87 (sessions 2-3) (95% CI: 0.69-0.95) for the midterm intervals. The overall ICC of interrater agreement was excellent at 0.987 (95% CI: 0.983 to 0.990). These results confirm that MRE is a reproducible technique for liver stiffness quantification over short- and midterm intervals up to 6months in a healthy population at 3.0T. PMID:24650683

  20. Volunteer Client Adult Attachment, Memory for In-Session Emotion, and Mood Awareness: An Affect Regulation Perspective

    ERIC Educational Resources Information Center

    Woodhouse, Susan S.; Gelso, Charles J.

    2008-01-01

    In this study, the authors examined relations between volunteer client adult attachment and both (a) memory for negative affect occurring within the first session of therapy and (b) mood awareness (mood labeling and mood monitoring). Participants were 80 volunteer clients (students with a personal issue who volunteered to participate in the…

  1. Amphetamine sensitisation and memory in healthy human volunteers: a functional magnetic resonance imaging study.

    PubMed

    O'Daly, Owen G; Joyce, Daniel; Tracy, Derek K; Stephan, Klaas E; Murray, Robin M; Shergill, Sukhwinder

    2014-09-01

    Amphetamine sensitisation (AS) is an established animal model of the hypersensitivity to psychostimulants seen in patients with schizophrenia. AS also models the dysregulation of mesolimbic dopamine signalling which has been implicated in the development of psychotic symptoms. Recent data suggest that the enhanced excitability of mesolimbic dopamine neurons in AS is driven by a hyperactivity of hippocampal (subiculum) neurons, consistent with a strong association between hippocampal dysfunction and schizophrenia. While AS can be modelled in human volunteers, its functional consequences on dopaminoceptive brain regions (i.e. striatum and hippocampus) remains unclear. Here we describe the effects of a sensitising dosage pattern of dextroamphetamine on the neural correlates of motor sequence learning in healthy volunteers, within a randomised, double-blind, parallel-groups design. Behaviourally, sensitisation was characterised by enhanced subjective responses to amphetamine but did not change performance (i.e. learning rate) during an explicit sequence learning task. In contrast, functional magnetic resonance imaging (fMRI) measurements showed that repeated intermittent amphetamine exposure was associated with increased blood-oxygen-level dependent (BOLD) signal within the medial temporal lobe (MTL) (subiculum/entorhinal cortex) and midbrain, in the vicinity of the substantia nigra/ventral tegmental area (SN/VTA) during sequence encoding. Importantly, MTL hyperactivity correlated with the sensitisation of amphetamine-induced attentiveness. The MTL-midbrain hyperactivity reported here mirrors observations in sensitised rodents and is consistent with contemporary models of schizophrenia and behavioural sensitisation. These findings of meso-hippocampal hyperactivity during AS thus link pathophysiological concepts of dopamine dysregulation to cognitive models of psychosis. PMID:24671338

  2. A Natural Electromagnetic Fields Effect on Healthy Volunteers During Long-Term Experiment with Isolation

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yury I.; Mikhailov, Valery M.; Ushakov, Boris B.

    2008-06-01

    There were investigated four healthy volunteers at the age of 37, 40, 41 and 48 during the baseline 240-d isolation period starting from July 3, 1999 in the frame of SFINCSS-99 - "SIMULATION OF FLIGHT OF INTERNATIONAL CREW ON SPACE STATION". Before a starting of experiment with long-term isolation were carried out measurements of magnetic properties of module and sleeping places. With the regularity of 3 times a week each subject made records of no less then 3 video episodes with the total length of one minute minimum at the same time between 1 and 2 p.m. Applying vital non-invasive computer capillaroscopy of nailbed has allowed quantitatively estimating a capillary blood velocity (CBV). The microcirculation parameters obtained during experiment were compared to local indexes of geomagnetic activity. About 1500 episodes were recorded on laser disks and analyzed. Parameters of microcirculation were compared with other physiological parameters monitored in the experiment. CBV investigation during the most intensive magnetic storm for the period of isolation (A-index- 44) show, that CBV at all volunteers was considerably slowed down. The greatest delay of blood flow velocity revealed at the subject which the factor of shielding of a constant magnetic field at the level of the sleeping berth has made 2,0. CBV at the subject has made 498 ± 46 μm/s with (- 65,8 % from base line). Least delay of a CBV is revealed at the subject which the factor of shielding of a constant magnetic field at the level of the sleeping berth has made 3, 15 (-12 % from base line).

  3. Closed and open breathing circuit function in healthy volunteers during exercise at Mount Everest base camp (5300 m).

    PubMed

    McMorrow, R C N; Windsor, J S; Hart, N D; Richards, P; Rodway, G W; Ahuja, V Y; O'Dwyer, M J; Mythen, M G; Grocott, M P W

    2012-08-01

    We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen saturations were improved at rest with both circuits. There was no difference in the magnitude of this improvement as both circuits restored median (IQR [range]) saturation from 75%, (69.5-78.9 [68-80]%) to > 99.8% (p = 0.028). During exercise, the CXE closed circuit improved median (IQR [range]) saturation from a baseline of 70.8% (63.8-74.5 [57-76]%) to 98.8% (96.5-100 [95-100]%) vs the open circuit improvement to 87.5%, (84.1-88.6 [82-89]%; p = 0.028). These data demonstrate the inverse relationship between supply and demand with open circuits and suggest that ambulatory closed circuits may offer twin advantages of supplying higher inspired oxygen concentrations and/or economy of gas use for exercising hypoxic adults. PMID:22519895

  4. Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.

    PubMed

    Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph

    2015-11-01

    Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors. PMID:26075963

  5. Absolute and Trend Accuracy of a New Regional Oximeter in Healthy Volunteers During Controlled Hypoxia

    PubMed Central

    Paidy, Samata; Kashif, Faisal

    2014-01-01

    BACKGROUND: Traditional patient monitoring may not detect cerebral tissue hypoxia, and typical interventions may not improve tissue oxygenation. Therefore, monitoring cerebral tissue oxygen status with regional oximetry is being increasingly used by anesthesiologists and perfusionists during surgery. In this study, we evaluated absolute and trend accuracy of a new regional oximetry technology in healthy volunteers. METHODS: A near-infrared spectroscopy sensor connected to a regional oximetry system (O3TM, Masimo, Irvine, CA) was placed on the subject’s forehead, to provide continuous measurement of regional oxygen saturation (rSo2). Reference blood samples were taken from the radial artery and internal jugular bulb vein, at baseline and after a series of increasingly hypoxic states induced by altering the inspired oxygen concentration while maintaining normocapnic arterial carbon dioxide pressure (Paco2). Absolute and trend accuracy of the regional oximetry system was determined by comparing rSo2 against reference cerebral oxygen saturation (Savo2), that is calculated by combining arterial and venous saturations of oxygen in the blood samples. RESULTS: Twenty-seven subjects were enrolled. Bias (test method mean error), standard deviation of error, standard error of the mean, and root mean square accuracy (ARMS) of rSo2 compared to Savo2 were 0.4%, 4.0%, 0.3%, and 4.0%, respectively. The limits of agreement were 8.4% (95% confidence interval, 7.6%–9.3%) to −7.6% (95% confidence interval, −8.4% to −6.7%). Trend accuracy analysis yielded a relative mean error of 0%, with a standard deviation of 2.1%, a standard error of 0.1%, and an ARMS of 2.1%. Multiple regression analysis showed that age and skin color did not affect the bias (all P > 0.1). CONCLUSIONS: Masimo O3 regional oximetry provided absolute root-mean-squared error of 4% and relative root-mean-squared error of 2.1% in healthy volunteers undergoing controlled hypoxia. PMID:25405692

  6. Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

    PubMed Central

    Soyinka, Julius O; Onyeji, Cyprian O; Omoruyi, Sharon I; Owolabi, Adegbenga R; Sarma, Pullela V; Cook, James M

    2010-01-01

    AIMS To evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers. METHODS Ten healthy volunteers were each given 600-mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three-period pharmacokinetic nonrandomized sequential design study. Quinine was co-administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3-hydroxyquinine, using a validated high-performance liquid chromatography method. RESULTS Concurrent ritonavir administration resulted in about fourfold increases in both the Cmax and AUCT[Cmax 2.79 ± 0.22 vs. 10.72 ± 0.32 mg l−1, 95% confidence interval (CI) 7.81, 8.04; AUC 50.06 ± 2.52 vs. 220.47 ± 6.68 mg h−1 l−1, 95% CI 166.3, 175.3], a significant increase (P < 0.01) in the elimination half-life (11.15 ± 0.80 vs. 13.37 ± 0.33 h, 95% CI 1.64, 2.77) and about a 4.5-fold decrease in CL/F (12.01 ± 0.61 vs. 2.71 ± 0.09 l h−1) of quinine. Also, with ritonavir, there was a pronounced reduction of AUC(metabolite)/AUC(unchanged drug) ratio of quinine (1.35 ± 0.10 vs. 0.13 ± 0.02) along with a marked decrease in Cmax (1.80 ± 0.12 vs. 0.96 ± 0.09 mg l−1) and AUC0–48h (62.80 ± 6.30 vs. 25.61 ± 2.44 mg h−1 l−1) of the metabolite. Similarly, quinine caused modest but significant increases (P < 0.01) in the Cmax, AUC and elimination T½ of ritonavir. CONCLUSIONS Downward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir. PMID:20233197

  7. Integrating Volunteering into the Adult Immigrant Second Language Experience

    ERIC Educational Resources Information Center

    Dudley, Lesley

    2007-01-01

    For immigrants, the acquisition of language, specifically the ability to communicate effectively, is one prerequisite of full integration into the host society. For an adult immigrant second language (L2) learner in Canada, access to opportunities that may enhance communicative ability are often limited to the ESL classroom. However, while…

  8. Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

    PubMed Central

    Mzayek, Fawaz; Deng, Haiyan; Mather, Frances J; Wasilevich, Elizabeth C; Liu, Huayin; Hadi, Christiane M; Chansolme, David H; Murphy, Holly A; Melek, Bekir H; Tenaglia, Alan N; Mushatt, David M; Dreisbach, Albert W; Lertora, Juan J. L; Krogstad, Donald J

    2007-01-01

    Objectives: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. Design: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. Setting: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. Participants: 126 healthy adults 21–45 years of age. Interventions: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. Outcome Measures: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. Results: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. Conclusions: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics. PMID:17213921

  9. Upper Gastrointestinal Symptoms Are More Frequent in Female than Male Young Healthy Japanese Volunteers as Evaluated by Questionnaire

    PubMed Central

    Kawakubo, Hiroharu; Tanaka, Yuichiro; Tsuruoka, Nanae; Hara, Megumi; Yamamoto, Koji; Hidaka, Hidenori; Sakata, Yasuhisa; Shimoda, Ryo; Iwakiri, Ryuichi; Kusano, Motoyasu; Fujimoto, Kazuma

    2016-01-01

    Background/Aims Upper gastrointestinal symptoms are more frequent and severe in female than in male outpatients in Japan. This study compared the upper gastrointestinal symptoms between healthy male and female young adult volunteers using a questionnaire. Methods In total, 581 third-grade medical students at Saga Medical School aged 22 to 30 years underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease) from 2007 to 2013. Of these 581 students, 298 who were negative for Helicobacter pylori infection and had no particular lesions on endoscopic examination were enrolled in the present evaluation. A symptom was defined as positive when the subject evaluated the frequency of the symptom as sometimes, often, or always. Results The subjects comprised of 163 males (average age, 23.7 years) and 135 females (average age, 23.1 years). Upper gastrointestinal symptoms were more frequent in the females (75 of 135, 55.6%) than males (69 of 163, 42.3%; P < 0.05), with a high score for 4 symptoms (bloated stomach, heavy feeling in the stomach after meals, subconscious rubbing of the chest with the hand, and feeling of fullness while eating meals). Of the 144 subjects (69 males and 75 females) who complained of these symptoms, the females complained of dysmotility symptoms more often than did the males, but this was not true for reflux symptoms. Conclusions This study suggests that females develop upper gastrointestinal symptoms more frequently than do males among the young healthy Japanese population. PMID:26755685

  10. Connecting Socially Isolated Older Rural Adults with Older Volunteers through Expressive Arts.

    PubMed

    MacLeod, Ann; Skinner, Mark W; Wilkinson, Fay; Reid, Heather

    2016-03-01

    Employing a participatory arts-based research approach, we examined an innovative program from rural Ontario, Canada, designed to address social isolation among older people. Older socially isolated adults were matched to trained volunteers, where in dyads, the eight pairs created expressive art in their home setting over the course of 10 home visits. With thematic and narrative inquiry, we analysed the experiences and perceptions of the program leader, older participants, and older volunteers via their artistic creations, weekly logs, evaluations, and field notes. The findings reveal a successful intervention that positively influenced the well-being of older adult participants and older volunteers, especially in regards to relationships, personal development, and creating meaning as well as extending the intervention's impact beyond the program's duration. We also discuss opportunities for similar programs to inform policy and enable positive community-based health and social service responses to rural social isolation. PMID:26934547

  11. The effects of ketamine and risperidone on eye movement control in healthy volunteers

    PubMed Central

    Schmechtig, A; Lees, J; Perkins, A; Altavilla, A; Craig, K J; Dawson, G R; William Deakin, J F; Dourish, C T; Evans, L H; Koychev, I; Weaver, K; Smallman, R; Walters, J; Wilkinson, L S; Morris, R; Williams, S C R; Ettinger, U

    2013-01-01

    The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone. In this randomized double-blind, placebo-controlled study, 72 healthy participants performed smooth pursuit eye movements (SPEM), prosaccades (PS) and antisaccades (AS) while being randomly assigned to one of four drug groups (intravenous 100 ng ml−1 ketamine, 2 mg oral risperidone, 100 ng ml−1 ketamine plus 2 mg oral risperidone, placebo). Drug administration did not lead to harmful adverse events. Ketamine increased saccadic frequency and decreased velocity gain of SPEM (all P<0.01) but had no significant effects on PS or AS (all P⩾0.07). An effect of risperidone was observed for amplitude gain and peak velocity of PS and AS, indicating hypometric gain and slower velocities compared with placebo (both P⩽0.04). No ketamine by risperidone interactions were found (all P⩾0.26). The results confirm that the administration of ketamine produces oculomotor performance deficits similar in part to those seen in schizophrenia. The atypical antipsychotic risperidone did not reverse ketamine-induced deteriorations. These findings do not support the cognitive enhancing potential of risperidone on oculomotor biomarkers in this model system of schizophrenia and point towards the importance of developing alternative performance-enhancing compounds to optimise pharmacological treatment of schizophrenia. PMID:24326395

  12. Assessment of Tandem Measurements of pH and Total Gut Transit Time in Healthy Volunteers

    PubMed Central

    Mikolajczyk, Adam E; Watson, Sydeaka; Surma, Bonnie L; Rubin, David T

    2015-01-01

    Objectives: The variation of luminal pH and transit time in an individual is unknown, yet is necessary to interpret single measurements. This study aimed to assess the intrasubject variability of gut pH and transit time in healthy volunteers using SmartPill devices (Covidien, Minneapolis, MN). Methods: Each subject (n=10) ingested two SmartPill devices separated by 24 h. Mean pH values were calculated for 30 min after gastric emptying (AGE), before the ileocecal (BIC) valve, after the ileocecal (AIC) valve, and before body exit (BBE). Intrasubject variability was determined by comparing mean values from both ingestions for an individual subject using standard deviations, 95% limits of agreement, and Bland-Altman plots. Results: Tandem device ingestion occurred without complication. The median (full range) intrasubject standard deviations for pH were 0.02 (0.0002–0.2048) for AGE, 0.06 (0.0002–0.3445) for BIC, 0.14 (0.0018–0.3042) for AIC, and 0.08 (0.0098–0.5202) for BBE. There was a significant change in pH for AIC (mean difference: −0.45±0.31, P=0.0015) observed across all subjects. The mean coefficients of variation for transit time were 12.0±7.4% and 25.8±15.8% for small and large bowels, respectively (P=0.01). Conclusions: This study demonstrates the safety and feasibility of tandem gut transit and pH assessments using the SmartPill device. In healthy individuals and over 24 h, the gut pH profile does not markedly fluctuate in a given region with more variation seen in the colon compared with the small bowel, which has important implications for future physiology and drug delivery studies. PMID:26158610

  13. Central nervous system effects of haloperidol on THC in healthy male volunteers.

    PubMed

    Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

    2010-11-01

    In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers. PMID:20142302

  14. Pharmacokinetic and Pharmacodynamic Modeling Analysis of Intravenous Esomeprazole in Healthy Volunteers.

    PubMed

    Liu, Dongyang; Yang, Hong; Jiang, Ji; Nagy, Péter; Shen, Kai; Qian, Jiaming; Hu, Pei

    2016-07-01

    Esomeprazole is one of the most commonly used drugs to treat gastroesophageal reflux disease and peptic ulcers, but the quantitative relationships among the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenomics (PG) of the drug are not fully understood in special patient populations. A clinical PK/PD/PG study of intravenous (IV) esomeprazole in 5 dosing regimens was conducted in 20 healthy Chinese volunteers, who were categorized into Helicobacter pylori (HP)-negative and HP-positive subgroups. Plasma esomeprazole concentration and intragastric H(+) concentration were monitored for 24 hours postdosing. Population PK (PopPK) models were tested based on elimination characteristics and other data. For a single-dose IV esomeprazole regimen, a 2-compartment model with nonlinear elimination characteristics fitted the PK data well. The elimination of esomeprazole was found to be significantly linked to CYP2C19 genotype by 11% to 29%. A mechanism-based PD model was first tested to mimic the irreversible inhibition of H(+) /K(+) -ATPase by esomeprazole using a cell-killing mechanism and models of gastric H(+) secretion that included the effects of an asymmetric circadian rhythm and food effects. Results from this PD model showed that the turnover rate of H(+) /K(+) -ATPase was significantly different between HP-negative and HP-positive subgroups. In conclusion, the PopPK model quantitatively identified the effects of the CYP2C19 genotype on esomeprazole elimination in healthy subjects for the first time. In addition, the effects of HP status on drug effect, H(+) /K(+) -ATPase turnover, and circadian rhythm amplitude were preliminarily explored using a mechanism-based PD model. PMID:26970404

  15. Rifampin enhances cytochrome P450 (CYP) 2B6-mediated efavirenz 8-hydroxylation in healthy volunteers

    PubMed Central

    Cho, Doo-Yeoun; Shen, Joan H.Q.; Lemler, Suzanne M.; Skaar, Todd C; Li, Lang; Blievernicht, Julia; Zanger, Ulrich M.; Kim, Kwon-Bok; Shin, Jae-Gook; Flockhart, David A.; Desta, Zeruesenay

    2016-01-01

    The effect of rifampin on the in vivo metabolism of the antiretroviral drug efavirenz was evaluated in healthy volunteers. In a cross-over placebo control trial, healthy subjects (n = 20) were administered a single 600 mg oral dose of efavirenz after pretreatment with placebo or rifampin (600 mg/day for 10 days). Plasma and urine concentrations of efavirenz, 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz were measured by LC–MS/MS. Compared to placebo treatment, rifampin increased the oral clearance (by ~2.5-fold) and decreased maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–∞) of efavirenz (by ~1.6- and ~2.5-fold respectively) (p < 0.001). Rifampin treatment substantially increased the Cmax and AUC0–12h of 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz, metabolic ratio (AUC0–72h of metabolites to AUC0–72h efavirenz) and the amount of metabolites excreted in urine (Ae0–12hr) (all, p < 0.01). Female subjects had longer elimination half-life (1.6–2.2-fold) and larger weight-adjusted distribution volume (1.6– 1.9-fold) of efavirenz than male subjects (p < 0.05) in placebo and rifampin treated groups respectively. In conclusion, rifampin enhances CYP2B6-mediated efavirenz 8-hydroxylation in vivo. The metabolism of a single oral dose of efavirenz may be a suitable in vivo marker of CYP2B6 activity to evaluate induction drug interactions involving this enzyme. PMID:27053325

  16. Motives and Determinants of Volunteering in Older Adults: An Integrated Model

    ERIC Educational Resources Information Center

    Grano, Caterina; Lucidi, Fabio; Zelli, Arnaldo; Violani, Cristiano

    2008-01-01

    The present study focused on changes in volunteering over time among Italian adults and examined a model in which motives from self-determination theory (SDT) were hypothesized to influence a series of social-cognitive processes including self-efficacy judgments and constructs from the theory of planned behavior (TPB). The study was conducted with…

  17. A One-to-One Programme for At-Risk Readers Delivered by Older Adult Volunteers

    ERIC Educational Resources Information Center

    Fives, Allyn; Kearns, Noreen; Devaney, Carmel; Canavan, John; Russell, Dan; Lyons, Rena; Eaton, Patricia; O'Brien, Aoife

    2013-01-01

    This paper is based on a randomized controlled trial (RCT) evaluation of a reading programme delivered by older adult volunteers for at-risk early readers. Wizards of Words (WoW) was targeted at socially disadvantaged children in first and second grade experiencing delays in reading but who were not eligible for formal literacy supports. The…

  18. Everyday Memory Function of Older Adults: The Impact of Intergenerational School Volunteer Programs.

    ERIC Educational Resources Information Center

    Newman, Sally; And Others

    1995-01-01

    Participants in an intergenerational school volunteer program (26 adults over 60) completed memory instruments at 3 time periods. The effect of program participating on actual and perceived memory function varied with age and educational level. Dramatic positive mood changes were noted for those over 70 and those who were college educated. (SK)

  19. Time perception and its neuropsychological correlates in patients with schizophrenia and in healthy volunteers.

    PubMed

    Lee, Kwang-Hyuk; Bhaker, Rajinder S; Mysore, Ashok; Parks, Randolph W; Birkett, Paul B L; Woodruff, Peter W R

    2009-04-30

    Disordered time perception has been reported in schizophrenia. We investigated time perception dysfunction and its neuropsychological correlates in patients with schizophrenia. Participants comprised 38 patients and 38 age- and sex-matched healthy volunteers who were compared in an auditory temporal bisection paradigm using two interval ranges (a 400/800 ms condition and a 1000/2000 ms condition). In the temporal bisection, subjects were required to categorise a probe duration as short or long, based upon the similarity with two reference durations. All subjects also completed a battery of neuropsychological tests measuring sustained attention, short- and long-term memory and executive function. In the 400/800 ms condition, patients judged durations significantly shorter than did control subjects. Patients also exhibited decreased temporal sensitivity in both conditions. We found in both groups a negative association between temporal sensitivity and sustained attention for the 400/800 ms condition, and between temporal sensitivity and long-term memory for the 1000/200 ms condition. In patients, short-term memory performance was negatively associated with duration judgement in both conditions, while executive dysfunction was correlated to a general performance deficit in the 400/800 ms condition. These findings suggest the possibility that time perception abnormalities in schizophrenia are part of neuropsychological dysfunction and are likely to adversely impact upon activity of daily living. PMID:19278734

  20. Emission rates of selected volatile organic compounds from skin of healthy volunteers

    PubMed Central

    Mochalski, Paweł; King, Julian; Unterkofler, Karl; Hinterhuber, Hartmann; Amann, Anton

    2014-01-01

    Gas chromatography with mass spectrometric detection (GC–MS) coupled with solid phase micro-extraction as pre-concentration method (SPME) was applied to identify and quantify volatile organic compounds (VOCs) emitted by human skin. A total of 64 C4-C10 compounds were quantified in skin emanation of 31 healthy volunteers. Amongst them aldehydes and hydrocarbons were the predominant chemical families with eighteen and seventeen species, respectively. Apart from these, there were eight ketones, six heterocyclic compounds, six terpenes, four esters, two alcohols, two volatile sulphur compounds, and one nitrile. The observed median emission rates ranged from 0.55 to 4790 fmol cm−2 min−1. Within this set of analytes three volatiles; acetone, 6-methyl-5-hepten-2-one, and acetaldehyde exhibited especially high emission rates exceeding 100 fmol cm−2 min−1. Thirty-three volatiles were highly present in skin emanation with incidence rates over 80%. These species can be considered as potential markers of human presence, which could be used for early location of entrapped victims during Urban Search and Rescue Operations (USaR). PMID:24768920

  1. Brain-Modulated Effects of Auricular Acupressure on the Regulation of Autonomic Function in Healthy Volunteers

    PubMed Central

    Gao, Xin-Yan; Wang, Lu; Gaischek, Ingrid; Michenthaler, Yvonne; Zhu, Bing; Litscher, Gerhard

    2012-01-01

    Auricular acupuncture has been described in ancient China as well as Egypt, Greece, and Rome. At the end of the 1950s, ear acupuncture was further developed by the French physician Dr. Paul Nogier. The goal of this study was to develop a new system for ear acupressure (vibration stimulation) and to perform pilot investigations on the possible acute effects of vibration and manual ear acupressure on heart rate (HR), heart rate variability (HRV), pulse wave velocity (PWV), and the augmentation index (AIx) using new noninvasive recording methods. Investigations were performed in 14 healthy volunteers (mean age ± SD: 26.3 ± 4.3 years; 9 females, 5 males) before, during, and after acupressure vibration and manual acupressure stimulation at the “heart” auricular acupuncture point. The results showed a significant decrease in HR (P ≤ 0.001) and a significant increase in HRV total (P = 0.008) after manual ear acupressure. The PWV decreased markedly (yet insignificantly) whereas the AIx increased immediately after both methods of stimulation. The increase in the low-frequency band of HRV was mainly based on the intensification of the related mechanism of blood pressure regulation (10-s-rhythm). Further studies in Beijing using animal models and investigations in Graz using human subjects are already in progress. PMID:21904563

  2. Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

    PubMed

    Hodges, L A; Connolly, S M; Band, J; O'Mahony, B; Ugurlu, T; Turkoglu, M; Wilson, C G; Stevens, H N E

    2009-03-31

    The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion. PMID:19114096

  3. Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers.

    PubMed

    Sanga, Madhu; Banach, John; Ledvina, Aaron; Modi, Nishit B; Mittur, Aravind

    2016-11-01

    1. The disposition of nefopam, a serotonin-norepinephrine reuptake inhibitor, was characterized in eight healthy male volunteers following a single oral dose of 75 mg [(14)C]-nefopam (100 μCi). Blood, urine, and feces were sampled for 168 h post-dose. 2. Mean (± SD) maximum blood and plasma radioactivity concentrations were 359 ± 34.2 and 638 ± 64.7 ngEq free base/g, respectively, at 2 h post-dose. Recovery of radioactive dose was complete (mean 92.6%); a mean of 79.3% and 13.4% of the dose was recovered in urine and feces, respectively. 3. Three main radioactive peaks were observed in plasma (metabolites M2 A-D, M61, and M63). Intact [(14)C]-nefopam was less than 5% of the total radioactivity in plasma. In urine, the major metabolites were M63, M2 A-D, and M51 which accounted for 22.9%, 9.8%, and 8.1% of the dose, respectively. An unknown entity, M55, was the major metabolite in feces (4.6% of dose). Excretion of unchanged [(14)C]-nefopam was minimal. PMID:26796604

  4. A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers.

    PubMed

    McConville, Jason T; Hodges, Lee-Ann; Jones, Tamara; Band, Janet P; O'Mahony, Bridget; Lindsay, Blythe; Ross, Alistair C; Florence, Alastair J; Stanley, Adrian J; Humphrey, Michael J; Wilson, Clive G; Stevens, Howard N E

    2009-11-01

    Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release characteristics of the TDC relied on the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug release scintigraphically (theophylline was a marker compound). Three formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were shown to compare favourably with mean in vivo scintigraphic release times of 2.7, 3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC concentrations respectively. An increase in HPMC concentration was associated with a delayed technetium release time, and followed the same rank order as the in vitro dissolution study. Observed radiolabel dispersion always occurred in the small intestine. In conclusion, the study established that the TDC performs and demonstrates an in vitro-in vivo correlation. Additionally, time and site of release were accurately visualized by gamma scintigraphy, and confirmed with determination of theophylline absorption. PMID:19387976

  5. Bioequivalence study of two oral formulations of irbesartan 300 mg in healthy volunteers.

    PubMed

    Cánovas, M; Cabré, F; Polonio, F

    2014-01-01

    A bioequivalence study of 2 irbesartan (CAS 138402-11-6) film-coated tablet formulations was carried out in 40 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 96 h following drug administration. Plasma concentrations of irbesartan were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference). tmax was analysed nonparametrically. The 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t (98.06-109.48%, point estimator 103.61%) and Cmax (88.93-100.87%, point estimator 94.72%) were within the bioequivalence acceptance range of 80-125%. According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that test formulation of irbesartan 300 mg film-coated tablet is bioequivalent to the reference formulation. Overall, it was judged that the study was conducted with a good tolerance of the subjects to both study drugs. PMID:24048950

  6. Pharmacokinetics and bioequivalence of two trimebutine formulations in healthy volunteers using desmethyl-trimebutine levels.

    PubMed

    Saivin, S; Lavit, M; Michel, F; Labaune, J P; Martin, A; Cahiez, G; Donazzolo, C; Chomard, J M; Houin, G

    2000-08-01

    Trimebutine tablets (dimethylamino-2-phenyl-2-n-butyl-3,4,5- trimethoxybenzoate maleate, CAS 34140-59-5, reference) and a new tablet formulation (Eurogalena, test) were administered in 24 healthy volunteers of both sexes according to a cross-over design, in a single dose of one 100 mg tablet of each formulation. Blood samples were drawn off over a 24-h period, before (time 0) and after each administration at specific intervals. Trimebutine and its main active metabolite, desmethyl-trimebutine, were measured in plasma using a validated HPLC method with UV detection. For both compounds, the sensitivity was 20 ng.ml-1 and the analytical method was proved to be linear for concentrations between 20 ng.ml-1 and 5000 ng.ml-1, with a variability less than 11%. The non-compartmental method was used for pharmacokinetic analysis. The confidence interval approach was used for comparison of the formulations according to the EU guidance note on bioavailability and bioequivalence on Cmax, AUC0-t and AUC0-infinity, log transformed. Tmax values were statistically compared using the Friedman non-parametric test. No trimebutine concentration was measured in the plasma samples. The obtained data with desmethyl-trimebutine proved the bioequivalence of the two tested formulations. PMID:10994155

  7. Acute loading with proteins from different sources in healthy volunteers and diabetic patients.

    PubMed

    Nakamura, H; Yamazaki, M; Chiba, Y; Tani, N; Momotsu, T; Kamoi, K; Ito, S; Yamaji, T; Shibata, A

    1991-01-01

    To evaluate the effects of protein loading on glomerular filtration rate (GFR), urinary excretion rate of albumin (AER), and plasma concentration of amino acids, 10 healthy volunteers and six diabetics were studied before and after eating tuna fish, egg white, cheese, or tofu. Furthermore, to study the possible role of glucagon, growth hormone (GH), atrial natriuretic peptide (ANP), or kallikrein in the responses of GFR, these substances were measured before and after protein loading. GFR increased significantly (p less than .001) after ingestion of tuna fish. No significant differences were seen between the GFR before and that after ingestion of the other foods. AER was unchanged following protein loading. Plasma concentrations of alanine, glycine, and arginine increased to a greater degree after ingestion of tuna fish than after digestion of the other foods. This result suggests that the response of GFR after protein loading may differ from one protein to another, and that these responses may not be directly mediated by glucagon, GH, ANP, or kallikrein. PMID:1770024

  8. Pharmacokinetic and pharmacodynamic interaction of nadolol with itraconazole, rifampicin and grapefruit juice in healthy volunteers.

    PubMed

    Misaka, Shingen; Miyazaki, Nozomu; Yatabe, Midori S; Ono, Tomoyuki; Shikama, Yayoi; Fukushima, Tetsuhito; Kimura, Junko

    2013-07-01

    To evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non-selective β-adrenoceptor blocker nadolol, we conducted an open-label, four-way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6-day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration-time curve (AUC0-∞ ) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0-∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half-life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P-glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics. PMID:23677858

  9. Incidence of associated events during the performance of invasive procedures in healthy human volunteers.

    PubMed

    Highstead, R Grant; Tipton, Kevin D; Creson, Daniel L; Wolfe, Robert R; Ferrando, Arny A

    2005-04-01

    Metabolic investigations often utilize arteriovenous sampling and muscle biopsy. These investigations represent some risk to the subject. We examined 369 studies performed in the General Clinical Research Center between January 1994 and May 2003 for events related to femoral catheterization and muscle biopsies. Incidents were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr, n=28). There were no clinically defined major complications associated with either procedure. The incidence of femoral catheter repositioning or reinsertion was higher in the older group (25.5 vs. 9.7%). There was no difference in the incidence of premature removal of catheters, ecchymosis or hematoma, or the persistence of pain after discharge. The occurrence of all incidents did not increase with multiple catheterizations. Muscle biopsy was associated with infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and older groups, respectively). Both procedures entail a small likelihood of a vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a loss of consciousness. These results indicate that, in skilled hands and a defined clinical setting, the incidents associated with femoral catheterization and muscle biopsy in healthy volunteers are reasonable and largely controllable. PMID:15563628

  10. Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers.

    PubMed

    Ruiz-Garcia, Ana; Masters, Joanna C; Mendes da Costa, Laure; LaBadie, Robert R; Liang, Yali; Ni, Grace; Ellery, Craig A; Boutros, Tanya; Goldberg, Zelanna; Bello, Carlo L

    2016-02-01

    This phase 1, open-label crossover study evaluated the relative bioavailability of dacomitinib in healthy volunteers under fed and fasted conditions and following coadministration with rabeprazole, a potent acid-reducing proton pump inhibitor (PPI). Twenty-four male subjects received a single dacomitinib 45-mg dose under 3 different conditions separated by washout periods of ≥ 16 days: coadministered with rabeprazole 40 mg under fasting conditions; alone under fasting conditions; and alone after a high-fat, high-calorie meal. Increased peak exposure of 23.7% (90% confidence interval [CI], 5.3%-45.2%) was detected with dacomitinib taken after food versus fasting. The adjusted geometric mean ratio (fed/fasted) for area under the plasma concentration-time curve from time zero to infinity (AUCinf ) was 114.2% (90%CI, 104.7%-124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUCinf was observed following rabeprazole versus dacomitinib alone (PPI+fasted/fasted alone): 71.1% (90%CI, 61.7%-81.8%). Dacomitinib was generally well tolerated. Dacomitinib may be taken with or without food. Use of long-acting acid-reducing agents, such as PPIs with dacomitinib should be avoided if possible. Shorter-acting agents such as antacids and H2-receptor antagonists may have lesser impact on dacomitinib exposure and may be preferable to PPIs if acid reduction is clinically required. PMID:26179237

  11. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  12. Uric acid quantification in fingernail of gout patients and healthy volunteers using HPLC-UV.

    PubMed

    Li, Xi-Ling; Shi, Qing; Jin, Wenlong; Li, Gao; Todoroki, Kenichiro; Mizuno, Hajime; Toyo'oka, Toshimasa; Min, Jun Zhe

    2016-08-01

    The presence of elevated uric acid (UA) levels is a sign of gout, that is, hyperuricemia. In this study the monitoring of the UA levels in less-invasive biological samples, such as the human fingernail, is suggested for the diagnosis and therapy of gout. Twenty-six healthy volunteers (HV) and 22 gout patients (GP) were studied. The UA was extracted from human fingernail samples, then separated on an Inertsil ODS-3 column (250 × 4.6 mm i.d., 4.0 μm, GL Sciences) by isocratic elution using methanol-74 mm phosphate buffer (pH 2.2) 2:98 (v/v). A UV detector was used to monitor the samples at 284 nm. Using the developed method, different UA concentrations were found in the GP and HV. When comparing the concentrations from GP with those from HV, a statistically significant correlation was observed between the UA (p < 0.01). In this study, the UA was confirmed as a potential biomarker for the diagnosis and therapy of gout. We have developed a novel sensitive, and simple method for the determination of UA in the fingernails of GP and HV. The human fingernail may serve as a noninvasive biosample for the diagnosis of gout. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26787501

  13. The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers.

    PubMed

    Meyer, Michael; Beyer, Diana; Vollhardt, Karin; Woischwill, Christiane; Jilma, Bernd; Wolff, Gerhard

    2007-12-01

    Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated. PMID:17876866

  14. Effect of dehusked Garcinia kola seeds on the overall pharmacokinetics of quinine in healthy Nigerian volunteers.

    PubMed

    Igbinoba, Sharon I; Onyeji, Cyprian O; Akanmu, Moses A; Soyinka, Julius O; Pullela, Srirama Sarma V V; Cook, James M; Nathaniel, Thomas I

    2015-03-01

    We investigated the effect of concurrent ingestion of Garcinia kola seed on the pharmacokinetics of quinine. In a randomized crossover study, 24 healthy Nigerian volunteers were assigned into 2 groups (A and B; n = 12 per group) on the basis of G. kola dose orally ingested. Each subject received 600 mg quinine sulfate before and after ingesting 12.5 g of G. kola once daily for 7 days (group A) or 12.5 g twice daily for 6 days and once on the seventh day (group B). Blood samples were collected and analyzed for plasma quinine and its metabolite (3-hydroxyquinine) using a validated high performance liquid chromatography method. Concurrent administration of quinine with G. kola reduced quinine tmax by 48% (group A), mean Cmax by 19% and 26% in groups A and B, respectively, and slight reduction in mean AUC0- ∞ of quinine in both groups. 3-hydroxyquinine Cmax also reduced by 29% and 32%; AUC0-∞ by 13% and 9%, respectively. The point estimates of the T/R ratio of the geometric means for all Cmax obtained and only the AUC0-∞ at a higher dose of G. kola were outside the 80%-125% bioequivalence range. In conclusion, an herb-drug interaction was noted with concurrent quinine and G. kola administration. PMID:25328082

  15. Bioequivalence assay between orally disintegrating and conventional tablet formulations in healthy volunteers.

    PubMed

    Armando, Yara Popst; Schramm, Simone Grigoleto; Silva, Marina de Freitas; Kano, Eunice Kazue; Koono, Eunice Emiko Mori; Porta, Valentina; Serra, Cristina Helena dos Reis

    2009-01-21

    The purpose of this study was to evaluate bioequivalence of two commercial 8 mg tablet formulations of ondansetrona available in the Brazilian market. In this study, a simple, rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method is described for the determination of ondansetron in human plasma samples. The method was validated over a concentration range of 2.5-60 ng/ml and used in a bioequivalence trial between orally disintegrating and conventional tablet ondansetron formulations, to assess its usefulness in this kind of study. Vonau flash (Biolab Sanus Farmacêutica, Brazil, as test formulations) and Zofran (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 8 mg dose to 23 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determinated by calculating 90% confidence interval (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmically transformed data. The 90% confidence interval for the ratio of C(max) (87.5-103.8%), AUC(0-t) (89.3-107.2%) and AUC(0-infinity) (89.7-106.0%) values for the test and reference products is within the 80-125% interval, proposed by FDA, EMEA and ANVISA. It was concluded that two ondansetron formulations are bioequivalent in their rate and extent of absorption. PMID:18848869

  16. A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.

    PubMed

    Huang, Qing; Aa, Jiye; Jia, Huning; Xin, Xiaoqing; Tao, Chunlei; Liu, Linsheng; Zou, Bingjie; Song, Qinxin; Shi, Jian; Cao, Bei; Yong, Yonghong; Wang, Guangji; Zhou, Guohua

    2015-09-01

    Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy. PMID:26216528

  17. Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers

    PubMed Central

    Markert, Christoph; Schweizer, Yvonne; Hellwig, Regina; Wirsching, Theresia; Riedel, Klaus-Dieter; Burhenne, Juergen; Weiss, Johanna; Mikus, Gerd; Haefeli, Walter E

    2014-01-01

    Aims The aim of this study was to assess the effect of the cytochrome P450 (CYP) 3A4 and organic anion-transporting polypeptide (OATP) 1B1 inhibitor clarithromycin on the pharmacokinetics of bosentan. We also aimed to evaluate the impact of CYP2C9 and SLCO1B1 (encoding for OATP1B1) genotypes and their combination. Methods We assessed the effect of the OATP and CYP3A inhibitor clarithromycin on bosentan pharmacokinetics at steady state and concurrently quantified changes of CYP3A activity using midazolam as a probe drug. Sixteen healthy volunteers received therapeutic doses of bosentan (125 mg twice daily) for 14 days and clarithromycin (500 mg twice daily) concomitantly for the last 4 days, and bosentan pharmacokinetics was assessed on days 1, 10 and 14. Results Clarithromycin significantly increased bosentan area under the plasma concentration–time curve of the dosing interval 3.7-fold and peak concentration 3.8-fold in all participants irrespective of the genotype. Clarithromycin also reduced CYP3A activity (midazolam clearance) in all participants; however, these changes were not correlated to the changes of bosentan clearance. Conclusions Clarithromycin substantially increases the exposure to bosentan, suggesting that dose reductions may be necessary. PMID:23738582

  18. Incidence of associated events during the performance of invasive procedures in healthy human volunteers

    NASA Technical Reports Server (NTRS)

    Highstead, R. Grant; Tipton, Kevin D.; Creson, Daniel L.; Wolfe, Robert R.; Ferrando, Arny A.

    2005-01-01

    Metabolic investigations often utilize arteriovenous sampling and muscle biopsy. These investigations represent some risk to the subject. We examined 369 studies performed in the General Clinical Research Center between January 1994 and May 2003 for events related to femoral catheterization and muscle biopsies. Incidents were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr, n=28). There were no clinically defined major complications associated with either procedure. The incidence of femoral catheter repositioning or reinsertion was higher in the older group (25.5 vs. 9.7%). There was no difference in the incidence of premature removal of catheters, ecchymosis or hematoma, or the persistence of pain after discharge. The occurrence of all incidents did not increase with multiple catheterizations. Muscle biopsy was associated with infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and older groups, respectively). Both procedures entail a small likelihood of a vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a loss of consciousness. These results indicate that, in skilled hands and a defined clinical setting, the incidents associated with femoral catheterization and muscle biopsy in healthy volunteers are reasonable and largely controllable.

  19. Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 in Healthy Volunteers.

    PubMed

    Vaidya, Soniya S; Khindri, Sanjeev; Maahs, Suzanne; Machineni, Surendra; Hara, Hisanori; Juan, Axel; Kaiser, Günther

    2016-07-01

    This single-dose, 4-period crossover study evaluated the pharmacokinetics (PK) of the β2 -agonist indacaterol maleate and the corticosteroid mometasone furoate (MF) after inhalation of a fixed-dose combination (QMF149, indacaterol maleate/MF, 500/400 μg) via the Twisthaler (TH) device with and without activated charcoal and postdose mouth rinsing in healthy volunteers. The PK of indacaterol maleate 300 μg inhaled via the Breezhaler (BRZ) device was also characterized. Relative bioavailability of indacaterol and MF for inhalation with versus without charcoal, based on AUClast, was 0.25 (90% confidence interval [CI], 0.18-0.35) and 0.70 (90%CI, 0.52-0.93), respectively. Thus, 25% and 70% of systemic exposure of indacaterol and MF, respectively was due to pulmonary absorption and 75% and 30%, respectively, was due to gastrointestinal absorption. Mouth rinsing reduced the systemic exposure of indacaterol by approximately 35% but had no relevant effect on the exposure of MF. Dose-normalized AUClast for indacaterol inhaled via the BRZ device was 2.3-fold higher than QMF149 via the TH device. All treatments had a good safety profile and were well tolerated. Data from this study and comparison with inhalation of indacaterol via the BRZ device suggest that the latter was more efficient than the TH device regarding lung delivery of indacaterol. PMID:27310329

  20. The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses.

    PubMed

    Posner, J; Bye, A; Dean, K; Peck, A W; Whiteman, P D

    1985-01-01

    The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions. PMID:3932079

  1. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases. PMID:23820464

  2. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

    PubMed Central

    Ikuta, Naoko; Okamoto, Hinako; Furune, Takahiro; Uekaji, Yukiko; Terao, Keiji; Uchida, Ryota; Iwamoto, Kosuke; Miyajima, Atsushi; Hirota, Takashi; Sakamoto, Norihiro

    2016-01-01

    R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA. PMID:27314343

  3. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  4. Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic resonance spectroscopy

    PubMed Central

    Conway, Michael A; Bristow, J David; Blackledge, Martin J; Rajagopalan, Bheeshma; Radda, George K

    1991-01-01

    A technique was devised for individuals to exercise prone in a magnet during magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance spectra of the heart were obtained by the phase modulated rotating frame imaging technique in six healthy volunteers during steady state dynamic quadriceps exercise. During prone exercise heart rate, blood pressure, and total body oxygen consumption were measured at increasing loads and the results were compared with those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg load the heart rate was similar and the systolic and diastolic blood pressures were higher than those during stage 1 of the Bruce protocol. The rate-pressure products were similar but the total body oxygen consumption was lower during prone exercise. There was no difference in the ratio of phosphocreatine to adenosine triphosphate during rest and exercise. Thus during exercise that produced a local cardiac stress equal to or greater than that during stage 1 of the Bruce protocol treadmill exercise, the energy requirements of the normal human myocardium were adequately supplied by oxidative phosphorylation. PMID:1993127

  5. Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic resonance spectroscopy.

    PubMed

    Conway, M A; Bristow, J D; Blackledge, M J; Rajagopalan, B; Radda, G K

    1991-01-01

    A technique was devised for individuals to exercise prone in a magnet during magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance spectra of the heart were obtained by the phase modulated rotating frame imaging technique in six healthy volunteers during steady state dynamic quadriceps exercise. During prone exercise heart rate, blood pressure, and total body oxygen consumption were measured at increasing loads and the results were compared with those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg load the heart rate was similar and the systolic and diastolic blood pressures were higher than those during stage 1 of the Bruce protocol. The rate-pressure products were similar but the total body oxygen consumption was lower during prone exercise. There was no difference in the ratio of phosphocreatine to adenosine triphosphate during rest and exercise.Thus during exercise that produced a local cardiac stress equal to or greater than that during stage 1 of the Bruce protocol treadmill exercise, the energy requirements of the normal human myocardium were adequately supplied by oxidative phosphorylation. PMID:1993127

  6. Effects of Different Therapeutic Ultrasound Waveforms on Endothelial Function in Healthy Volunteers: A Randomized Clinical Trial.

    PubMed

    Cruz, Jeferson Mendes; Hauck, Melina; Cardoso Pereira, Ana Paula; Moraes, Maicon Borges; Martins, Cassio Noronha; da Silva Paulitsch, Felipe; Plentz, Rodrigo Della Méa; Peres, William; Vargas da Silva, Antônio Marcos; Signori, Luis Ulisses

    2016-02-01

    The purpose of this study was to determine the effects of different therapeutic 1-MHz ultrasound waveforms on endothelial function before and after cyclooxygenase (COX) inhibition. Forty-two healthy volunteers aged 27.2 ± 3.8 y underwent interventions and an evaluation for endothelial function (n = 15; with COX inhibition, n = 15; duration of the vasodilator effect, n = 12) by technique flow-mediated dilation. Continuous ultrasound therapy (0.4 W/cm(2 SATA)), pulsed ultrasound therapy (20% duty cycle, 0.08 W/cm(2 SATA)) or placebo (equipment power off) was randomly applied over the brachial artery for 5 min. COX inhibition (aspirin) was carried out 30 min before treatments. In relation to the placebo, flow-mediated dilation increased by 4.8% using continuous ultrasound and by 3.4% using pulsed ultrasound. After COX, flow-mediated dilation was enhanced by 2.1% by continuous ultrasound and 2.6% by pulsed ultrasound. This vasodilation persisted for 20 min. Continuous and pulsed therapeutic 1-MHz ultrasound waveforms improved endothelial function in humans, which provided them with anti-inflammatory vascular effects. PMID:26578361

  7. Effect of food on the pharmacokinetics of rifalazil, a novel antibacterial, in healthy male volunteers.

    PubMed

    Chen, Y-X; Cabana, B; Kivel, N; Michaelis, A

    2007-07-01

    Rifalazil is a new antibiotic structurally related to rifampin but devoid of the metabolic liabilities typically associated with the rifamycin class of antibiotics. A randomized, 3-way crossover study in healthy male volunteers (n = 12) investigated the safety and pharmacokinetics of a single 25-mg oral rifalazil dose administered under a standard breakfast containing fat as 30% of calories, a high-fat breakfast containing fat as 60% of calories, and an overnight fast of 10 hours with a 21- to 28-day washout between doses. Systemic exposure to rifalazil based on Cmax, AUC(0-Tlast), and AUC(0-infinity) was increased progressively as the fat content of the test breakfast was increased from 30% to 60% compared with fasting. The confidence intervals for both fat-containing breakfasts are outside the limits of 80% to 125% allowed for food effect bioequivalence based on Cmax, AUC(0-Tlast), and AUC(0-infinity). This food effect may be a result of increased fractional absorption with increasing dietary fat content. Another striking finding was the large reduction of the pharmacokinetic intersubject variability after rifalazil administration with food. Rifalazil was safe and well tolerated under fed and fasted conditions. PMID:17463218

  8. Bioequivalence study of 8 mg ondansetron film-coated tablets in healthy Caucasian volunteers.

    PubMed

    Rudzki, P J; Kaza, M; Leś, A; Gilant, E; Ksycińska, H; Serafin-Byczak, K; Troć, M; Raszek, J; Piątkowska-Chabuda, E; Skowrońska-Smolak, M; Tarasiuk, A; Wilkowska, E; Łazowski, T

    2014-04-01

    The aim of the study was to investigate the bioequivalence of a generic product of 8 mg film-coated tablets (test) to the branded product (reference) at the same strength in order to apply for regulatory approval. The secondary objective of the study was to compare the tolerability of both products. A double blinded, randomized, cross-over, 2-period, comparative study was conducted in healthy Caucasian volunteers under fasting conditions. A single oral dose administration of the test or reference product was followed by a 7-day wash-out period. The ondansetron concentration was determined using a validated high performance liquid chromatography with a UV detection method. The 90% confidence interval of the point estimate (test over reference products) for C(max) and AUC(0-t) fell within the 80.00-125.00% acceptance range. The results of the study indicate that the film-coated tablets of Ondatron 8 mg manufactured by Tarchomińskie Zakłady Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zofran manufactured by GlaxoSmithKline Export Ltd (reference product). Both products were well tolerated. PMID:24132707

  9. The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

    PubMed Central

    Pickering, Gisèle; Kastler, Adrian; Macian, Nicolas; Pereira, Bruno; Valabrègue, Romain; Lehericy, Stéphane; Boyer, Louis; Dubray, Claude; Jean, Betty

    2015-01-01

    Background Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans. Methods and results This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter. Conclusion These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain. PMID:26229445

  10. Effect of dehusked Garcinia kola seed on the overall pharmacokinetics of quinine in healthy Nigerian volunteers

    PubMed Central

    Igbinoba, Sharon I.; Onyeji, Cyprian O.; Akanmu, Moses A.; Soyinka, Julius O.; Pullela, Srirama Sarma V.V; Cook, James M.; Nathaniel, Thomas I.

    2016-01-01

    We investigated the effect of concurrent ingestion of Garcinia kola seed on the pharmacokinetics of quinine. In a randomized crossover study, 24 healthy Nigerian volunteers were assigned into two groups (A and B; n = 12 per group) on the basis of G. kola dose orally ingested. Each subject received 600mg quinine sulphate before and after ingesting 12.5g of G. kola once daily for seven days (Group A) or 12.5g twice daily for six days and once on the seventh day (Group B). Blood samples were collected and analyzed for plasma quinine and its metabolite, (3-hydroxyquinine) using a validated HPLC method. Concurrent administration of quinine with G. kola reduced quinine tmax by 48% (group A), mean Cmax by 19% and 26% in groups A and B, and slight reduction in mean AUC0–∞ of quinine in both groups. 3-hydroxyquinine Cmax also reduced by 29% and 32%; AUC0–∞ by 13% and 9% respectively. The point estimates of the T/R ratio of the geometric means for all Cmax obtained and only the AUC0–∞ at a higher dose of G. kola were outside the 80–125% bioequivalence range. In conclusion, an herb-drug interaction was noted with concurrent quinine and G. kola administration. PMID:25328082

  11. The effects of exercise and body armor on cognitive function in healthy volunteers.

    PubMed

    Roberts, Aaron P J; Cole, Jon C

    2013-05-01

    Police officers routinely wear body armor to protect themselves against the threat posed by firearms and edged weapons, yet little is known of the cognitive effects of doing so. Two studies investigated the effects of exercise and body armor on working memory function in healthy volunteers. In study 1, male undergraduates were assigned to one of four groups: (i) brief exercise, (ii) brief exercise wearing body armor, (iii) extended exercise, and (iv) extended exercise wearing body armor. In study 2, university gym members were assigned to one of two groups: (i) wearing body armor and (ii) not wearing body armor. In both studies, heart rate and oral temperature were measured before, immediately after, and 5 minutes after exercise. The phonemic verbal fluency task and digits backward test were administered at the same time points. In both studies, a mixed analysis of variance revealed statistically significant changes to the cognitive functioning of participants. A change in cognitive strategy was observed, reflected by a decrease in executive function (switches) and an increase in nonexecutive function (cluster size). These data suggest that the cognitive effects of exercise and body armor may have profound implications for police officers' ability to make tactical decisions. PMID:23756004

  12. A Community-based Education Project: Intertidal Surveys With Student and Adult Volunteers

    NASA Astrophysics Data System (ADS)

    Muller-Parker, G.; Bingham, B. L.

    2004-12-01

    The Fidalgo Learning about the Intertidal Project (FLIP) brought together scientists, educators, students and adult volunteers (20-30 total individuals) to conduct studies of the intertidal zone of a section of Fidalgo Island, Wa. in 2003 and 2004. The project goals were to: 1) obtain basic data on diversity and abundance of intertidal species in different habitats, 2) promote public awareness and appreciation of the intertidal zone, and 3) develop a model program for volunteer participation in scientific surveys. The 2-week program began with 2 days of workshops on local intertidal organisms to teach the FLIP participants how to classify and identify the different organisms and substrates they were likely to encounter in the surveys. We provided general lectures on intertidal habitats and on the importance of the intertidal zone to coastal resources. The FLIP participants worked together on identifying organisms, practicing the use of quadrats and data collection before the surveys began. Following 4 days of field surveys, the participants signed up for workshops that included compilation and analysis of the data, photography, nature writing and algae pressing. The final activity was a public tour of the intertidal day held at a local park. 50-60 people of all ages participated. The goal was to educate the public in plant and animal identification and habitat variability as well as "beach etiquette." Successful model program elements included self-selected volunteers and attention to the composition of each survey team, with one scientist/leader per team and one adult and two students or two adults and one student per team (4-5 teams, each completing one transect per site). Program flexibility was also crucial; FLIP volunteers were not required to attend every single day and post-survey workshops were optional. Volunteers participated to different extents and for different lengths of time depending on their abilities and interests. Project ownership was important

  13. The Relationship between Ministry Satisfaction and Spiritual Maturity among Adult Church Volunteers in the Korean Presbyterian Church in South Korea

    ERIC Educational Resources Information Center

    Nho, Sung Hyun

    2012-01-01

    This quantitative study examined the relationship between ministry satisfaction and spiritual maturity among adult church volunteers in the Korean Presbyterian church in South Korea (Kosin). It also sought to investigate factors related to volunteers' job satisfaction and their spiritual maturity. Participants included 531 adult small group…

  14. Safety, Tolerability, and Pharmacokinetics of Intravenous Nemonoxacin in Healthy Chinese Volunteers

    PubMed Central

    Cao, Guo-ying; Zhang, Ying-yuan; Guo, Bei-ning; Yu, Ji-cheng; Wu, Xiao-jie; Chen, Yuan-cheng; Wu, Ju-Fang; Shi, Yao-guo

    2014-01-01

    Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at assessing the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, double-blind, placebo-controlled, dose escalating safety and tolerability study in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square crossover pharmacokinetic study in 12 subjects. The study revealed that nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related adverse events (AEs) were mild, transient, and confined to local irritation at the injection site. The pharmacokinetic study revealed that after the administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum plasma drug concentration (Cmax) values were 4.826 μg/ml, 7.152 μg/ml, and 11.029 μg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC0–72 h) were 17.05 μg · h/ml, 39.30 μg · h/ml, and 61.98 μg · h/ml. The mean elimination half-life (t1/2) was 11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear dose-response relationship between the AUC0–72 h and AUC0–∞. These findings provide further support for the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.) PMID:25092690

  15. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

    PubMed Central

    Wu, Guolan; Zheng, Yunliang; Zhou, Huili; Hu, Xingjiang; Liu, Jian; Zhai, You; Zhu, Meixiang; Wu, Lihua; Shentu, Jianzhong

    2015-01-01

    Background Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. Methods A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. Results Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration– time curve from 0 to 10 hours (AUC0–10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. Conclusion Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10

  16. Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

    PubMed Central

    Stolker, Robert Jan; Mik, Egbert

    2016-01-01

    Background The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. This study describes the first use of a clinical prototype in skin of humans. Methods The clinical prototype was tested in 30 healthy volunteers. A self-adhesive patch containing 2 mg 5-aminolevulinic acid (ALA) was applied on the skin of the anterior chest wall (sternal) for induction of mitochondrial protoporphyrin IX and was protected from light for 5 h. MitoPO2 was measured by means of oxygen-dependent delayed fluorescence of protoporphyrin IX. MitoVO2 was determined by dynamic mitoPO2 measurements on the primed skin, while locally blocking oxygen supply by applying local pressure with the measurement probe. MitoPO2 was recorded before and during a 60-s period of compression of the microcirculation, at an interval of 1 Hz. Oxygen consumption (i.e. the local oxygen disappearance rate) was calculated from the decay of the mitoPO2 slope. Results Oxygen-dependent delayed fluorescence measurements were successfully performed in the skin of 27 volunteers. The average value (± SD) of mitoPO2 was 44 ± 17 mmHg and mean mitoVO2 values were 5.8 ± 2.3 and 6.1 ± 1.6 mmHg s-1 at a skin temperature of 34°C and 40°C, respectively. No major discomfort during measurement and no long-term dermatological abnormalities were reported in a survey performed 1 month after measurements. Conclusion These results show that the clinical prototype allows measurement of mitochondrial oxygenation and oxygen consumption in humans. The development of this clinically applicable device offers opportunities for further evaluation of the technique in humans and the start of first clinical studies. PMID:27455073

  17. Effect of Slow and Fast Pranayama Training on Handgrip Strength and Endurance in Healthy Volunteers

    PubMed Central

    Thangavel, Dinesh; Gaur, Girwar Singh; Bhavanani, Ananda Balayogi; Rajajeyakumar, M.; Syam, Sunder A.

    2014-01-01

    Background: Pranayama has been assigned very important role in yogic system of exercises and is said to be much more important than yogasanas for keeping sound health. Also different pranayamas produce divergent physiological effects. Aim: To study the effect of 12 weeks training of slow and fast pranayama on handgrip strength and endurance in young, healthy volunteers of JIPMER population. Settings and Design: Present study was conducted in the Department of Physiology, JIPMER in 2011-12 (1.06.11 to 1.04.12). Materials and Methods: Total of 91 volunteer subjects were randomised into slow pranayama (SPG) (n=29), fast pranayama (FPG) (n=32) and control groups (CG) (n=30). Supervised pranayama training (SPG - Nadisodhana, Pranav pranayama and Savitri pranayama; FPG - Kapalabhati, Bhastrika and Kukkuriya pranayama) was given for 30 minutes thrice a week for 12 weeks to both slow and fast pranayama groups by certified yoga trainer. Hand grip strength (HGS) and endurance (HGE) parameters were recorded using handgrip dynamometer (Rolex, India) at baseline and after 12 weeks of pranayama training. Statistical Analysis Used: Longitudinal changes in each group were compared by using Student’s paired t-test. Delta changes in each group were analysed by ANOVA with Tukey post-hoc analysis. Results: In SPG significant improvement occurred only in HGE parameter from 83.95±45.06 to 101.62±53.87 (seconds) (p<0.001) whereas in FPG, significant improvement was observed in HGS from 33.31±9.83 to 37.9±9.41 (Kilograms) (p=0.01) as well as in HGE from 92.78±41.37 to 116.56±58.54 (seconds) (p=0.004). Using Students unpaired t-test difference between the groups in HGS is found to be 1.17±5.485 in SPG and in FPG is 4.59±7.26 (p=0.39); HGE difference in SPG is 1.77±21.17 and in FPG is 2.38±43.27 (p>0.05). Conclusion: Pranayama training decreases sympathetic activity, resulting in mental relaxation and decreased autonomic arousal thereby, decreasing force fluctuations during

  18. Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

    PubMed Central

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

    2012-01-01

    Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

  19. Investigation of cerebral haemodynamics by near-infrared spectroscopy in young healthy volunteers reveals posture-dependent spontaneous oscillations.

    PubMed

    Tachtsidis, Ilias; Elwell, Clare E; Leung, Terence S; Lee, Chuen-Wai; Smith, Martin; Delpy, David T

    2004-04-01

    Autonomic reflexes enable the cardiovascular system to respond to gravitational displacement of blood during changes in posture. Spontaneous oscillations present in the cerebral and systemic circulation of healthy subjects have demonstrated a regulatory role. This study assessed the dynamic responses of the cerebral and systemic circulation upon standing up and the posture dependence of spontaneous oscillations. In ten young healthy volunteers, blood pressure and cerebral haemodynamics were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. Oscillatory changes in the cerebral NIRS signals and the diastolic blood pressure (DBP) signal have been identified by the fast Fourier analysis. Blood pressure increased during standing and returned to basal level when volunteers sat on a chair. The mean value of cerebral tissue oxygen index (TOI) as measured by NIRS did not demonstrate any significant changes. Oscillatory changes in DBP, oxyhaemoglobin concentration [O2Hb] and TOI showed a significant increase when subjects were standing. Investigation of the low frequency component (approximately 0.1 Hz) of these fluctuations revealed posture dependence associated with activation of autonomic reflexes. Systemic and cerebral changes appeared to preserve adequate blood flow and cerebral perfusion during standing in healthy volunteers. Oscillatory changes in [O2Hb] and TOI, which may be related to the degree of cerebral sympathetic stimulation, are posture dependent in healthy subjects. PMID:15132309

  20. Effects of GUASHA on Heart Rate Variability in Healthy Male Volunteers under Normal Condition and Weightlifters after Weightlifting Training Sessions

    PubMed Central

    Wang, Xingze; Chatchawan, Uraiwan; Nakmareong, Saowanee; Silsirivanit, Atit; Wang, Yingying; Xie, Dongbei; Yang, Jinsheng; Eungpinichpong, Wichai

    2015-01-01

    Objectives. This paper aims at exploring the effects of GUASHA on heart rate variability between healthy volunteers under normal condition and weightlifters after training sessions. Methods. Ten healthy male volunteers under normal condition and 15 male weightlifters after weightlifting training sessions were recruited into two groups. Electrocardiography was recorded before and immediately after 20-minute GUASHA. HRV was calculated in both the time domain and the frequency domain. Results. Stress index was reduced, while standard deviation of N-N intervals (SDNN), proportion derived by dividing the number of interval differences of successive N-N intervals greater than 50 ms, and root mean square of successive differences (RMSSD) were enhanced after GUASHA therapy in the two groups. The changes in SDNN and RMSSD were higher in the healthy men group than in the weightlifters group. In addition, low frequency was decreased whereas high frequency was significantly increased in healthy men after the GUASHA session. Conclusions. GUASHA therapy facilitates the parasympathetic nervous activity and modulates the balance between parasympathetic and sympathetic activities in both healthy men under normal condition and weightlifters after training sessions as indicated. Although the changes of the HRV parameters were similar in both groups, the responsiveness was more pronounced in healthy men than in male weightlifters. PMID:26120346

  1. Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers*

    PubMed Central

    Vásquez, Laura; Scorza Dagert, José V.; Scorza, José V.; Vicuña-Fernández, Nelson; de Peña, Yaneira Petit; López, Sabrina; Bendezú, Herminia; Rojas, Elina; Vásquez, Libia; Pérez, Belén

    2006-01-01

    Background: Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness against clinical manifestations of leishmaniasis, an infection caused by Leishmania, a genus of flagellate protozoa comprising parasites of worldwide distribution. Approximately 1.8 million new cases are reported annually. Objective: The aim of this study was to assess the pharmacokinetics of the investigational generic SbV, Ulamina (pentachloride of antimony + N-methylglucamine), in healthy adult volunteers. Methods: In this study, SbV was administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25, 0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were collected at 6-hour intervals during the 24-hour postadministration period. Determination of trivalent antimony, SbV, and total antimony concentrations in blood and urine samples was carried out using atomic absorption spectrometry. Clinical history was reviewed and the subjects were monitored before and after administration of SbV using physical examination, weight, and hepatic- and renal-function studies. The pharmacokinetic parameters calculated were Cmax, Tmax, absorption constant (Ka), elimination constant (Kel), AUC2–24h, AUC0-∞, elimination phase (t½β), volume of distribution (Vd), and urinary excretion rate. Results: Five subjects (3 men, 2 women; mean age, 28 years [range, 18–34 years]) were included in the study. One hour after drug administration the following values were obtained: Cmax, 1.1 μg/mL; Tmax, 1.3 hours; Ka, 1.87 hours; Kel, 0.043 hours; AUC0–24h, 12.26 μg/mL · h; AUC0-∞, 19.84 μg/mL · h; t½β, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 μg/h; these were mean values for the entire study group. The single dose was well tolerated by all subjects. Conclusions: The investigational generic SbV, Ulamina, was associated with linearelimination after IM administration of a single 5-mg/kg dose. A 2-compartment pharmacokinetic model was observed in

  2. Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers.

    PubMed Central

    Looareesuwan, S; White, N J; Warrell, D A; Forgo, I; Dubach, U G; Ranalder, U B; Schwartz, D E

    1987-01-01

    1 A mefloquine hydrochloride tablet (250 mg base equivalent to 4.8 +/- 0.6 mg kg-1; mean +/- s.d.) and deuterium labelled mefloquine hydrochloride solution (250 mg base) were given to six adult male Thai patients with acute falciparum malaria and six healthy Swiss adult male volunteers (equivalent to 3.5 +/- 0.1 mg kg-1). 2 The relative bioavailability of the tablet formulation derived from comparison of the areas under the plasma concentration-time curves was similar in both groups; 87 +/- 11% and 89 +/- 10% (mean +/- s.d.). 3 The rate of drug absorption appeared to be similar in the two groups but peak plasma mefloquine concentrations were approximately three times higher in the Thai patients (1004 +/- 276 ng ml-1 for the tablet and 1085 +/- 280 ng ml-1 for the suspension) compared with the Swiss volunteers (319 +/- 73 ng ml-1 for the tablet, and 369 +/- 121 ng ml-1 for the suspension). 4 Estimates of the oral clearance CLpo of unlabelled mefloquine were significantly lower (17.5 +/- 4.4 ml h-1 kg-1) in the Thai patients compared with 28.8 +/- 3.5 ml h-1 kg-1 in the Swiss volunteers; P less than 0.05). Terminal elimination half-lives were significantly shorter in the patients (10.3 +/- 2.5 days) than in the volunteers (16.7 +/- 1.9 days; P less than 0.005). Differences of a similar magnitude were observed when comparing the pharmacokinetic parameters derived from the deuteromefloquine plasma concentrations. 5 Both genetic and disease related factors are likely to account for the large pharmacokinetic differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3304385

  3. Using “Clinical Trial Diaries” to Track Patterns of Participation for Serial Healthy Volunteers in U.S. Phase I Studies

    PubMed Central

    Edelblute, Heather B.; Fisher, Jill A.

    2015-01-01

    Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers’ Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that “clinical trial diaries” can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers’ involvement in Phase I clinical trials. PMID:25742668

  4. Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers

    PubMed Central

    Booij, L; Welfeld, K; Leyton, M; Dagher, A; Boileau, I; Sibon, I; Baker, G B; Diksic, M; Soucy, J-P; Pruessner, J C; Cawley-Fiset, E; Casey, K F; Benkelfat, C

    2016-01-01

    Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean±s.d.=22.1±3.4 years) [11C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg−1, by mouth; n=8) or placebo (3 × lactose, by mouth; n=9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P⩽0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P<0.04), and voxel-based analyses showed larger stress-induced decreases in [11C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [11C]raclopride binding, primarily in the sensorimotor striatum (P<0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked. PMID:26905412

  5. Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.

    PubMed Central

    Chen, Z R; Bochner, F; Somogyi, A

    1988-01-01

    1. The pharmacokinetics of pholcodine after two single doses and after chronic administration were studied in healthy human volunteers. 2. Six subjects received single oral doses of 20 and 60 mg of pholcodine according to a balanced cross-over design with an interval of 3 weeks between the two treatments. Blood and saliva samples and all urine were collected over 168 h after each dosage administration. Subsequently, the same subjects received 20 mg pholcodine 8 hourly orally for 10 days. Blood and saliva samples and all urine were collected during an 8 h dosing interval after the last dose on day 11. 3. Plasma, saliva and urine concentrations of pholcodine were determined by a high performance liquid chromatographic assay. 4. After the single doses, pholcodine was absorbed rapidly (tmax = 1.6 +/- 1.2 h) and eliminated slowly with a mean half-life of 50.1 +/- 4.1 h. The renal clearance of pholcodine was 137 +/- 34 ml min-1 and was inversely correlated with urine pH (r = 0.60) but not with urine flow rate. 26.2 +/- 3.3% of the dose was excreted as unchanged pholcodine after both doses. The concentration of pholcodine in saliva was 3.6 times higher than in plasma. 5. After chronic administration, the pharmacokinetics of pholcodine were not statistically different from the single dose parameters. 6. Pholcodine did not appear to undergo conjugation. The plasma protein binding was 23.5%. Morphine, in unconjugated or conjugated form, was not detected in the urine of any subject after pholcodine administration. PMID:3190994

  6. Glycine transporter type 1 occupancy by bitopertin: a positron emission tomography study in healthy volunteers.

    PubMed

    Martin-Facklam, Meret; Pizzagalli, Flavia; Zhou, Yun; Ostrowitzki, Susanne; Raymont, Vanessa; Brašić, James R; Parkar, Nikhat; Umbricht, Daniel; Dannals, Robert F; Goldwater, Ron; Wong, Dean F

    2013-02-01

    Deficient N-methyl-D-aspartate (NMDA) receptor transmission is thought to underlie schizophrenia. An approach for normalizing glutamate neurotransmission by enhancing NMDA receptor transmission is to increase glycine availability by inhibiting the glycine transporter type 1 (GlyT1). This study investigated the relationship between the plasma concentration of the glycine reuptake inhibitor bitopertin (RG1678) and brain GlyT1 occupancy. Healthy male volunteers received up to 175 mg bitopertin once daily, for 10-12 days. Three positron emission tomography scans, preceded by a single intravenous infusion of ∼30 mCi [(11)C]RO5013853, were performed: at baseline, on the last day of bitopertin treatment, and 2 days after drug discontinuation. Eighteen subjects were enrolled. At baseline, regional volume of distribution (V(T)) values were highest in the pons, thalamus, and cerebellum (1.7-2.7 ml/cm(3)) and lowest in cortical areas (∼0.8 ml/cm(3)). V(T) values were reduced to a homogeneous level following administration of 175 mg bitopertin. Occupancy values derived by a two-tissue five-parameter (2T5P) model, a simplified reference tissue model (SRTM), and a pseudoreference tissue model (PRTM) were overall comparable. At steady state, the relationship between bitopertin plasma concentration and GlyT1 occupancy derived by the 2T5P model, SRTM, and PRTM exhibited an EC(50) of ∼190, ∼200, and ∼130 ng/ml, respectively. E(max) was ∼92% independently of the model used. Bitopertin plasma concentration was a reliable predictor of occupancy because the concentration-occupancy relationship was superimposable at steady state and 2 days after drug discontinuation. These data allow understanding of the concentration-occupancy-efficacy relationship of bitopertin and support dose selection of future molecules. PMID:23132267

  7. Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.

    PubMed

    Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

    2004-01-01

    A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. PMID:14597158

  8. Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

    PubMed Central

    Toombs, Christopher F; Insko, Michael A; Wintner, Edward A; Deckwerth, Thomas L; Usansky, Helen; Jamil, Khurram; Goldstein, Brahm; Cooreman, Michael; Szabo, Csaba

    2010-01-01

    INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005–0.20 mg kg−1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1–5 min following administration of IK-1001 at 0.10 mg kg−1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S. PMID:20565454

  9. First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers.

    PubMed

    Soergel, David G; Subach, Ruth Ann; Sadler, Brian; Connell, John; Marion, Alan S; Cowan, Conrad L; Violin, Jonathan D; Lark, Michael W

    2014-03-01

    TRV130 is a G protein-biased ligand at the µ-opioid receptor. In preclinical studies it was potently analgesic while causing less respiratory depression and gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A first-in-human study was conducted with ascending doses of TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV130 was well-tolerated over the dose range 0.15 to 7 mg administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax were dose-linear, with AUC0-inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to 102.36 ng/mL across the dose range tested, with half-life of 1.6-2.7 hours. A 1.5 mg dose of TRV130 was also well-tolerated when administered as 30, 15, 5, and 1 minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6 phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused dose- and exposure-related pupil constriction, confirming central compartment µ-opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7 mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose escalation. These findings suggest that TRV130 may have a broad margin between doses causing µ-opioid receptor-mediated pharmacology and doses causing µ-opioid receptor-mediated intolerance. PMID:24122908

  10. Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers.

    PubMed

    Stewart, Julian M; Balakrishnan, Keshawadhana; Visintainer, Paul; Del Pozzi, Andrew T; Messer, Zachary R; Terilli, Courtney; Medow, Marvin S

    2016-03-15

    Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia. PMID:26801310

  11. Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers.

    PubMed

    Booij, L; Welfeld, K; Leyton, M; Dagher, A; Boileau, I; Sibon, I; Baker, G B; Diksic, M; Soucy, J-P; Pruessner, J C; Cawley-Fiset, E; Casey, K F; Benkelfat, C

    2016-01-01

    Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean ± s.d. = 22.1 ± 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 × lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ⩽ 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked. PMID:26905412

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

    PubMed Central

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

    2014-01-01

    Background The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Methods Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing. PMID:24672263

  13. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (−)-Epicatechin in healthy volunteers

    PubMed Central

    Barnett, Christopher F.; Moreno-Ulloa, Aldo; Shiva, Sruti; Ramirez-Sanchez, Israel; Taub, Pam R.; Su, Yongxuan; Ceballos, Guillermo; Dugar, Sundeep; Schreiner, George; Villarreal, Francisco

    2015-01-01

    (−)-Epicatechin ((−)-EPI), a naturally occurring flavanol has emerged as a likely candidate for cocoa-based product reported reductions in cardiometabolic risk. The present study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of purified (−)-EPI administered to healthy volunteers. In this phase I, open-label, two-part single- and multiple-dose study subjects received either a single dose (n=9) of 50, 100 or 200 mg or multiple doses (n=8) of 50 mg daily (q.d.) or twice daily (b.i.d) for 5 days. Blood was collected at 0, 0.5, 1, 2, 4 and 6 hrs after (−)-EPI administration in the single and multiple dose groups (blood collection repeated in day 5). Samples were analyzed by HPLC-HR-ESI-MS for EPI and metabolites quantification. In the q.d. and b.i.d. groups, blood samples were analyzed for NO surrogates, follistatin, platelet mitochondrial complex I, V and citrate synthase level determinations. (−)-EPI was well tolerated and readily absorbed with further phase 2 metabolism. On day 5, in the q.d. and b.i.d. groups, there were significant increases in plasma nitrite of 30 % and 17 %, respectively. In the q.d. group on day 5 vs. day 1, platelet mitochondria complexes I, IV and citrate synthase activities demonstrated a significant increase of ~ 92, 62 and 8 %, respectively. Average day 5 follistatin AUC levels were ~2.5 fold higher vs. day 1 AUC levels in the b.i.d. group. (−)-EPI was safe with no observed adverse effects and our findings suggest that increases in NO metabolites, mitochondrial enzyme function and plasma follistatin levels may underlie some of the beneficial effects of cocoa products or (−)-EPI as reported in other studies. PMID:25598082

  14. Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers.

    PubMed

    Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba

    2008-01-01

    The bioavailability of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-24h, AUC0-infinity, Cmax, t1/2, and Ke. The mean AUC0-infinity of cefixime was 45008.7 +/- 10989.9 and 45221.3 +/- 2155.7 n x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of cefixime was on average 4746.9 +/- 1284 ng/ml for the test and 4726.3 +/- 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-infinity and AUC0-24h of cefixime were in the bioequivalence range (94%-112%). Therefore, the two formulations were considered to be bioequivalent. PMID:18412024

  15. Cerebral venous blood oxygenation monitoring during hyperventilation in healthy volunteers with a novel optoacoustic system

    NASA Astrophysics Data System (ADS)

    Petrov, Andrey; Prough, Donald S.; Petrov, Irene Y.; Petrov, Yuriy; Deyo, Donald J.; Henkel, Sheryl N.; Seeton, Roger; Esenaliev, Rinat O.

    2013-03-01

    Monitoring of cerebral venous oxygenation is useful to facilitate management of patients with severe or moderate traumatic brain injury (TBI). Prompt recognition of low cerebral venous oxygenation is a key to avoiding secondary brain injury associated with brain hypoxia. In specialized clinical research centers, jugular venous bulb catheters have been used for cerebral venous oxygenation monitoring and have demonstrated that oxygen saturation < 50% (normal range is 55-75%) correlates with poor clinical outcome. We developed an optoacoustic technique for noninvasive monitoring of cerebral venous oxygenation. Recently, we designed and built a novel, medical grade optoacoustic system operating in the near-infrared spectral range for continuous, real-time oxygenation monitoring in the superior sagittal sinus (SSS), a large central cerebral vein. In this work, we designed and built a novel SSS optoacoustic probe and developed a new algorithm for SSS oxygenation measurement. The SSS signals were measured in healthy volunteers during voluntary hyperventilation, which induced changes in SSS oxygenation. Simultaneously, we measured exhaled carbon dioxide concentration (EtCO2) using capnography. Good temporal correlation between decreases in optoacoustically measured SSS oxygenation and decreases in EtCO2 was obtained. Decreases in EtCO2 from normal values (35-45 mmHg) to 20-25 mmHg resulted in SSS oxygenation decreases by 3-10%. Intersubject variability of the responses may relate to nonspecific brain activation associated with voluntary hyperventilation. The obtained data demonstrate the capability of the optoacoustic system to detect in real time minor changes in the SSS blood oxygenation.

  16. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  17. Necessity and risks of arterial blood sampling in healthy volunteer studies.

    PubMed

    Oertel, Bruno Georg; Vermehren, Johannes; Zimmermann, Michael; Huynh, Thomas Tao; Doehring, Alexandra; Ferreiros, Nerea; Senzel, Stephan; Schmitz-Rixen, Thomas; Erbe, Matthias; Geisslinger, Gerd; Harder, Sebastian; Angst, Martin S; Lötsch, Jörn

    2012-10-01

    Arterial blood sampling is necessary when drugs such as the fast-acting opioid analgesic remifentanil exhibit relevant differences between arterial and venous blood concentrations. Arterial cannulation is generally considered to be clinically safe and has thus become a standard procedure in pharmacokinetic-pharmacodynamic assessments. However, rare cases of arterial occlusions have to be considered in risk-benefit assessments of arterial sampling in pharmacokinetic studies, especially when including healthy volunteers. In an actual case, arterial occlusion requiring surgical repair was caused by a factor V Leiden thrombophilia associated genetic variant F5 1691G>A (rs6025) and aggravated by a hypoplastic radial artery. Neither risk factor had been identified prior to enrolment by routine laboratory tests such as the prothrombin time (international normalized ratio), partial thromboplastin time and the clinical Allen's test of arterial function. Re-assessment of the necessity of arterial sampling showed that none of the potential alternatives, target concentrations of computerized infusions or venous concentrations during non-steady-state and steady-state conditions could provide the arterial concentrations. Relying on venous concentrations may result in erroneous pharmacodynamic parameters. Accurate pharmacokinetic-pharmacodynamic studies relying on precisely measured blood concentrations require serial sampling techniques during both steady-state and non-steady-state conditions. However, as illustrated by the presented case, incidents involving the generally safe procedure of arterial sampling are possible, although rare. To further minimize the risks, screening of subjects for prothrombotic risks and careful assessment of the suitability of the artery should be considered in pharmacokinetic studies requiring arterial cannulation. PMID:23018527

  18. Pharmacokinetic studies in healthy volunteers on a new gastroprotective pharmaceutic form of diclofenac.

    PubMed

    De Bernardi di Valserra, M; Feletti, F; Tripodi, A S; Contos, S; Carabelli, A; Maggi, L; Germogli, R

    1993-03-01

    The pharmacokinetic properties of a new gastroprotective pharmaceutical formulation of diclofenac (CAS 15307-79-6) were investigated in twelve healthy volunteers. In this new form the diclofenac is the nucleus of sequential sucralfate-covered tablets. The experimental design was an open, random, two period balanced cross-over study. All the subjects received a single oral dose of 50 mg diclofenac contained in the new formulation or in the reference enteric-coated tablets. Plasma concentrations of diclofenac were determined at 0.5, 1, 2, 4, 6, and 8 h after drug administration using HPLC method. After administration of a diclofenac-sucralfate association diclofenac was quickly absorbed and the peak plasma concentration (0.773 +/- 0.08 microgram/ml) was achieved in about 1 h. AUC(0-infinity) value was about 1.8 micrograms/ml/h and the mean elimination half-life was 1.20 +/- 0.12 h. The pharmacokinetic profile of diclofenac-sucralfate association is similar to the values reported in previous papers for enteric-coated forms; anyway an early occurrence of the peak plasma concentration was observed for the new formulation. The new diclofenac-sucralfate association shows a different rate of absorption (namely an early and greater peak plasma concentration of diclofenac) and a similar extent of absorption (AUC(0-infinity) being not statistically different) as compared to the reference enteric-coated tablets of 50 mg diclofenac. These results could be related to the delaying and protective effect of sucralfate whose action is different from the one carried by the coat of the enteric-coated tablets. PMID:8489569

  19. Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

    PubMed Central

    Pross, Nathalie; Patat, Alain; Vivet, Philippe; Bidaut, Michelle; Fauchoux, Nicolas

    2015-01-01

    Aim The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg–1 alcohol using 40% vodka). Methods In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration. Results Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated. Conclusion SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed. PMID:25782469

  20. Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling

    PubMed Central

    Zhao, Yutong; Zhao, Jing; Donahoe, Michael P.; Barge, Suchitra; Horne, William T.; Kolls, Jay K.; McVerry, Bryan J.; Birukova, Anastasiya; Tighe, Robert M.; Foster, W. Michael; Hollingsworth, John; Ray, Anuradha; Mallampalli, Rama; Ray, Prabir; Lee, Janet S.

    2016-01-01

    Despite recent advances in understanding macrophage activation, little is known regarding how human alveolar macrophages in health calibrate its transcriptional response to canonical TLR4 activation. In this study, we examined the full spectrum of LPS activation and determined whether the transcriptomic profile of human alveolar macrophages is distinguished by a TIR-domain-containing adapter-inducing interferon-β (TRIF)-dominant type I interferon signature. Bronchoalveolar lavage macrophages were obtained from healthy volunteers, stimulated in the presence or absence of ultrapure LPS in vitro, and whole transcriptomic profiling was performed by RNA sequencing (RNA-Seq). LPS induced a robust type I interferon transcriptional response and Ingenuity Pathway Analysis predicted interferon regulatory factor (IRF)7 as the top upstream regulator of 89 known gene targets. Ubiquitin-specific peptidase (USP)-18, a negative regulator of interferon α/β responses, was among the top up-regulated genes in addition to IL10 and USP41, a novel gene with no known biological function but with high sequence homology to USP18. We determined whether IRF-7 and USP-18 can influence downstream macrophage effector cytokine production such as IL-10. We show that IRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocyte-derived macrophages, and USP-18 overexpression attenuated LPS-induced production of IL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10, and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes. These results suggest that IRF-7 and predicted downstream target USP18, both elements of a type I interferon gene signature identified by RNA-Seq, may serve to fine-tune early cytokine response by calibrating IL-10 production in human alveolar macrophages. PMID:27434537

  1. Microbiome changes in healthy volunteers treated with GSK1322322, a novel antibiotic targeting bacterial peptide deformylase.

    PubMed

    Arat, Seda; Spivak, Aaron; Van Horn, Stephanie; Thomas, Elizabeth; Traini, Christopher; Sathe, Ganesh; Livi, George P; Ingraham, Karen; Jones, Lori; Aubart, Kelly; Holmes, David J; Naderer, Odin; Brown, James R

    2015-02-01

    GSK1322322 is a novel antibacterial agent under development, and it has known antibacterial activities against multidrug-resistant respiratory and skin pathogens through its inhibition of the bacterial peptide deformylase. Here, we used next-generation sequencing (NGS) of the bacterial 16S rRNA genes from stool samples collected from 61 healthy volunteers at the predosing and end-of-study time points to determine the effects of GSK1322322 on the gastrointestinal (GI) microbiota in a phase I, randomized, double-blind, and placebo-controlled study. GSK1322322 was administered either intravenously (i.v.) only or in an oral-i.v. combination in single- and repeat-dose-escalation infusions. Analysis of the 16S rRNA sequence data found no significant changes in the relative abundances of GI operational taxonomic units (OTUs) between the prestudy and end-of-study samples for either the placebo- or i.v.-only-treated subjects. However, oral-i.v. treatment resulted in significant decreases in some bacterial taxa, the Firmicutes and Bacteroidales, and increases in others, the Betaproteobacteria, Gammaproteobacteria, and Bifidobacteriaceae. Microbiome diversity plots clearly differentiated the end-of-study oral-i.v.-dosed samples from all others collected. The changes in genome function as inferred from species composition suggest an increase in bacterial transporter and xenobiotic metabolism pathways in these samples. A phylogenetic analysis of the peptide deformylase protein sequences collected from the published genomes of clinical isolates previously tested for GSK1322322 in vitro susceptibility and GI bacterial reference genomes suggests that antibiotic target homology is one of several factors that influences the response of GI microbiota to this antibiotic. Our study shows that dosing regimen and target class are important factors when considering the impact of antibiotic usage on GI microbiota. (This clinical trial was registered at the GlaxoSmithKline Clinical Study

  2. Extent and variability of the first-pass elimination of adinazolam mesylate in healthy male volunteers.

    PubMed

    Fleishaker, J C; Friedman, H; Pollock, S R

    1991-02-01

    The pharmacokinetics of adinazolam and N-desmethyladinazolam (NDMAD) were studied in 14 healthy male volunteers who received 15 mg adinazolam mesylate orally as a solution and 5 mg adinazolam mesylate intravenously in a crossover design. Two weeks prior to the crossover study, each subject received 5 mg/kg indocyanine green (ICG) as an intravenous bolus injection to estimate liver blood flow. The absolute bioavailability (F), calculated as the dose-corrected ratio of oral to iv adinazolam area under the curve (AUC) values, was found to be 39%. NDMAD AUC values were similar following oral and iv administration, and adinazolam mean absorption time was approximately 0.77 hr. Thus, adinazolam is completely and rapidly absorbed after oral administration in man; the incomplete bioavailability is due to first-pass metabolism. Mean liver blood flow, adinazolam systemic clearance, blood/plasma ratio, and extraction ratio were 1189 ml/min, 498 ml/min, 0.70, and 0.57, respectively. The extraction ratio agrees with that calculated as 1-F (0.62), suggesting that the liver is primarily responsible for first-pass metabolism of adinazolam. The unbound fraction of adinazolam in plasma was 0.31 (range, 0.25-0.36); adinazolam free intrinsic clearance (a reflection of metabolic capacity) was 4285 ml/min (range, 2168-6312 ml/min). These results suggest that the majority of the variability in adinazolam plasma concentrations following oral administration is due to the variability in the metabolic capacity of the liver for adinazolam, rather than variability in plasma protein binding. PMID:2023863

  3. Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers

    PubMed Central

    Yao, Hsuan-Ming; Hsu, Ann; Gupta, Suneel; Modi, Nishit B.

    2016-01-01

    Objectives IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. Methods Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75–95, 36.25–145, 48.75–195, and 61.25–245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions. Results Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state. Conclusions IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption. PMID:26626430

  4. Influence of 3 antivertiginous medications on the vigilance of healthy volunteers.

    PubMed

    Schneider, D; Kiessling, B; Wieczorek, M; Bognar-Steinberg, I; Schneider, L; Claussen, C F

    2003-04-01

    In the present randomized, comparative, double-blind, 3-way crossover study, possible effects of 3 antivertiginous medications on vigilance were investigated. 30 healthy volunteers received single doses of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevert, ARL), dimenhydrinate 50 mg, or betahistine dimesylate 12 mg, in randomized order at 1-week intervals. Spontaneous brain electrical activity (EEG), acoustic late evoked potentials (ALEP) with P300, and reaction time were measured before and 90 (t90) and 180 minutes (t180) after drug intake. All 3 medications led to a delay of P300 (primary criterion) and a decrease of its amplitude. The maximum delay at t180 was found for dimenhydrinate (16.42 ms) and the lowest for betahistine (6.33 ms). Differences ARL vs dimenhydrinate and ARL vs betahistine were not statistically significant (p > 0.05). Spectral analysis of spontaneous EEG showed slight and similar decreases in the power in the a-band under dimenhydrinate and ARL (p = 0.07 and p = 0.03 with respect to baseline, respectively), but basically no change under betahistine. There was no effect on reaction time by either medication. None of the subjects reported drowsiness or any other adverse event. The findings confirm the reported suitability of P300 latency for measurement of drug effects on brain activity, but provide no indication of concomitant impairment of performance capacity by the tested drugs. Global assessment of the results suggests that the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg exerts only a minor effect on vigilance, not significantly different from betahistine, which is commonly regarded as a non-sedating antivertiginous drug PMID:12708605

  5. Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission

    PubMed Central

    Wurie, Fatima

    2013-01-01

    The size and concentration of exhaled particles may influence respiratory infection transmission risk. We assessed variation in exhaled particle production between individuals, factors associated with high production and stability over time. We measured exhaled particle production during tidal breathing in a sample of 79 healthy volunteers, using optical particle counter technology. Repeat measurements (several months after baseline) were obtained for 37 of the 79 participants.   Multilevel linear regression models of log transformed particle production measures were used to assess risk factors for high production.  Stability between measurements over time was assessed using Lin’s correlation coefficients. Ninety-nine percent of expired particles were <1μm in diameter. Considerable variation in exhaled particle production was observed between individuals and within individuals over time. Distribution of particle production was right skewed.  Approximately 90% of individuals produce <150 particles per litre in normal breathing.  A few individuals had measurements of over 1000 particles per litre (maximum 1456). Particle production increased with age (p<0.001) and was associated with high tree pollen counts. Particle production levels did not remain stable over time [rho 0.14 (95%CI -0.10, 0.38, p=0.238)]. Sub-micron particles conducive to airborne rather than droplet transmission form the great majority of exhaled particles in tidal breathing. There is a high level of variability between subjects but measurements are not stable over time. Production increases with age and may be influenced by airway inflammation caused by environmental irritants. Further research is needed to determine whether the observed variations in exhaled particle production affect transmission of respiratory infection. PMID:24555026

  6. Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.

    PubMed

    Sylvén, C; Beermann, B; Jonzon, B; Brandt, R

    1986-07-26

    In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors. PMID:3089465

  7. Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers.

    PubMed

    Jacobs, Birgit S; Colbers, Angela P H; Velthoven-Graafland, Kirsten; Schouwenberg, Bas J J W; Burger, David M

    2014-08-01

    Psychosis and other mental illnesses are common in HIV-infected patients. Olanzapine is one of the preferred antipsychotic agents for the treatment of schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown. Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir. To compensate for the induction of olanzapine metabolism by fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15 mg with fosamprenavir/ritonavir would lead to a similar area under the concentration-time curve (AUC) compared with olanzapine 10 mg alone. An open-label, randomised, two-period, cross-over, single-centre trial was conducted in 24 healthy volunteers. Subjects were randomised to one of the following treatments: (A) fosamprenavir/ritonavir 700/100 mg twice daily (b.i.d.) for 16 days with a single dose of olanzapine 15 mg on Day 13, a wash-out period of 31 days and a single dose of olanzapine 10 mg on Day 48; or (B) the same medication in reverse order. Twenty subjects completed the trial. The geometric mean ratios (90% CI) of olanzapine AUClast, maximum drug concentration (C(max)) and apparent elimination half-life (t(1/2)) when taken with fosamprenavir/ritonavir versus olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74), respectively. Fosamprenavir/ritonavir 700/100 mg b.i.d. appeared to induce olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine when combining with a ritonavir-boosted protease inhibitor. PMID:24929949

  8. Microbiome Changes in Healthy Volunteers Treated with GSK1322322, a Novel Antibiotic Targeting Bacterial Peptide Deformylase

    PubMed Central

    Arat, Seda; Spivak, Aaron; Van Horn, Stephanie; Thomas, Elizabeth; Traini, Christopher; Sathe, Ganesh; Livi, George P.; Ingraham, Karen; Jones, Lori; Aubart, Kelly; Holmes, David J.; Naderer, Odin

    2014-01-01

    GSK1322322 is a novel antibacterial agent under development, and it has known antibacterial activities against multidrug-resistant respiratory and skin pathogens through its inhibition of the bacterial peptide deformylase. Here, we used next-generation sequencing (NGS) of the bacterial 16S rRNA genes from stool samples collected from 61 healthy volunteers at the predosing and end-of-study time points to determine the effects of GSK1322322 on the gastrointestinal (GI) microbiota in a phase I, randomized, double-blind, and placebo-controlled study. GSK1322322 was administered either intravenously (i.v.) only or in an oral-i.v. combination in single- and repeat-dose-escalation infusions. Analysis of the 16S rRNA sequence data found no significant changes in the relative abundances of GI operational taxonomic units (OTUs) between the prestudy and end-of-study samples for either the placebo- or i.v.-only-treated subjects. However, oral-i.v. treatment resulted in significant decreases in some bacterial taxa, the Firmicutes and Bacteroidales, and increases in others, the Betaproteobacteria, Gammaproteobacteria, and Bifidobacteriaceae. Microbiome diversity plots clearly differentiated the end-of-study oral-i.v.-dosed samples from all others collected. The changes in genome function as inferred from species composition suggest an increase in bacterial transporter and xenobiotic metabolism pathways in these samples. A phylogenetic analysis of the peptide deformylase protein sequences collected from the published genomes of clinical isolates previously tested for GSK1322322 in vitro susceptibility and GI bacterial reference genomes suggests that antibiotic target homology is one of several factors that influences the response of GI microbiota to this antibiotic. Our study shows that dosing regimen and target class are important factors when considering the impact of antibiotic usage on GI microbiota. (This clinical trial was registered at the GlaxoSmithKline Clinical Study

  9. Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers.

    PubMed

    Abdallah, R M; Alam, S M; Awaad, F M; Dham, R; El-Kersh, A; El-Laithy, A; Shalby, M H; Shihabeddin, M; El-Walily, A F; Yacout, M; Zaman, Q

    2002-04-01

    An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice. PMID:12056535

  10. Brain Targeted Transcranial Administration of Diazepam and Shortening of Sleep Latency in Healthy Human Volunteers

    PubMed Central

    Pathirana, W.; Gunasekera, S. M.; Constantine, G. R.; Perera, Sanja; Perera, B. M.; Kamaladiwela, R.

    2011-01-01

    Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted

  11. First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.

    PubMed

    Stevens, Misty W; Henry, Ralph L; Owens, S Michael; Schutz, Ralph; Gentry, W Brooks

    2014-01-01

    This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17-19 d in the 3 highest dose groups and volume of distribution of 5-6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration. PMID:25484042

  12. Absolute bioavailability, pharmacokinetics, and urinary excretion of the novel antimigraine agent almotriptan in healthy male volunteers.

    PubMed

    Jansat, Josep M; Costa, Joan; Salvà, Pau; Fernandez, Francisco J; Martinez-Tobed, Antonio

    2002-12-01

    Absolute bioavailability, pharmacokinetics, and urinary excretion of almotriptan, a novel 5-HT(1B/1D) receptor agonist, were studied in 18 healthy males following single intravenous (i.v.) (3 mg), subcutaneous (s.c.) (6 mg), and oral (25 mg) doses. Volunteers received each dose in a randomized sequence separated by a 7-day washout. Blood and urine samples for pharmacokinetic evaluations were taken for up to 24 hours after dosing. The disposition kinetics of almotriptan after i.v. and s.c. administration showed biphasic decline described by a two-compartment model. The fastest disposition phase was well observed, although estimates of the rate constant showed high variability. After s.c. administration of almotriptan, the bioavailability was 100% with a time to maximum plasma concentration (tmax) of 5 to 15 minutes, whereas after oral administration, the bioavailability was about 70% with a tmax of 1.5 to 3.0 hours. No significant differences were observed between administration routes in the elimination half-life (t(1/2), obtaining mean values ranging from 3.4 to 3.6 hours. The volume of distribution, total clearance, and t(1/2) indicated that almotriptan was extensively distributed and rapidly cleared from the body irrespective of dose or route of administration. The primary route of elimination was renal clearance (approximately 50%-60% of total body clearance). About 65% of the i.v. and s.c. dose and 45% of the oral dose were excreted unchanged in urine in 24 hours, with nearly 90% of this in the first 12 hours. Renal clearance was approximately 2- to 3-fold that of the glomerular filtration rate in man, suggesting that almotriptan is eliminated in part by renal tubular secretion. PMID:12463724

  13. Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling.

    PubMed

    Pinilla-Vera, Miguel; Xiong, Zeyu; Zhao, Yutong; Zhao, Jing; Donahoe, Michael P; Barge, Suchitra; Horne, William T; Kolls, Jay K; McVerry, Bryan J; Birukova, Anastasiya; Tighe, Robert M; Foster, W Michael; Hollingsworth, John; Ray, Anuradha; Mallampalli, Rama; Ray, Prabir; Lee, Janet S

    2016-01-01

    Despite recent advances in understanding macrophage activation, little is known regarding how human alveolar macrophages in health calibrate its transcriptional response to canonical TLR4 activation. In this study, we examined the full spectrum of LPS activation and determined whether the transcriptomic profile of human alveolar macrophages is distinguished by a TIR-domain-containing adapter-inducing interferon-β (TRIF)-dominant type I interferon signature. Bronchoalveolar lavage macrophages were obtained from healthy volunteers, stimulated in the presence or absence of ultrapure LPS in vitro, and whole transcriptomic profiling was performed by RNA sequencing (RNA-Seq). LPS induced a robust type I interferon transcriptional response and Ingenuity Pathway Analysis predicted interferon regulatory factor (IRF)7 as the top upstream regulator of 89 known gene targets. Ubiquitin-specific peptidase (USP)-18, a negative regulator of interferon α/β responses, was among the top up-regulated genes in addition to IL10 and USP41, a novel gene with no known biological function but with high sequence homology to USP18. We determined whether IRF-7 and USP-18 can influence downstream macrophage effector cytokine production such as IL-10. We show that IRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocyte-derived macrophages, and USP-18 overexpression attenuated LPS-induced production of IL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10, and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes. These results suggest that IRF-7 and predicted downstream target USP18, both elements of a type I interferon gene signature identified by RNA-Seq, may serve to fine-tune early cytokine response by calibrating IL-10 production in human alveolar macrophages. PMID:27434537

  14. Effect of Fast and Slow Pranayama Practice on Cognitive Functions In Healthy Volunteers

    PubMed Central

    Sharma, Vivek Kumar; M., Rajajeyakumar; S., Velkumary; Subramanian, Senthil Kumar; Bhavanani, Ananda B.; Madanmohan; Sahai, Ajit; Thangavel, Dinesh

    2014-01-01

    Objectives: To compare the cumulative effect of commonly practised slow and fast pranayama on cognitive functions in healthy volunteers. Settings and Design: 84 participants who were in self-reported good health, who were in the age group of 18-25 years, who were randomized to fast pranayama, slow pranayama and control group with 28 participants in each group. Material and Methods: Fast pranayama included kapalabhati, bhastrika and kukkuriya. Slow pranayama included nadishodhana, Pranav and Savitri. Respective pranayama training was given for 35 minutes, three times per week, for a duration of 12 weeks under the supervision of a certified yoga trainer. Parameters were recorded before and after 12 weeks of intervention: Perceived stress scale (PSS), BMI, waist to hip ratio and cognitive parameters-letter cancellation test, trail making tests A and B, forward and reverse digit spans and auditory and visual reaction times for red light and green light. Statistical Analysis: Inter–group comparison was done by one way ANOVA and intra-group comparison was done by paired t-test. Results and Conclusion: Executive functions, PSS and reaction time improved significantly in both fast and slow pranayama groups, except reverse digit span, which showed an improvement only in fast pranayama group. In addition, percentage reduction in reaction time was significantly more in the fast pranayama group as compared to that in slow pranayama group. Both types of pranayamas are beneficial for cognitive functions, but fast pranayama has additional effects on executive function of manipulation in auditory working memory, central neural processing and sensory-motor performance. PMID:24596711

  15. Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers.

    PubMed

    Hou, R H; Langley, R W; Szabadi, E; Bradshaw, C M

    2007-08-01

    Arousal is regulated by the interplay between wakefulness- and sleep-promoting nuclei. Major wakefulness-promoting nuclei are the histaminergic tuberomamillary nucleus (TMN) of the hypothalamus and the noradrenergic locus coeruleus (LC) of the pons, which also play a role in autonomic regulation. First generation antihistamines, such as diphenhydramine, are likely to cause sedation by blocking excitatory H1 histamine receptors in the cerebral cortex, and the anti-narcolepsy drug modafinil may promote wakefulness by activating the locus coeruleus. We compared the effects of single doses of diphenhydramine (75 mg) and modafinil (200 mg) on arousal and autonomic functions in 16 healthy male volunteers, using a placebo-controlled, balanced, double-blind design. Arousal was assessed by critical flicker fusion frequency (CFFF), visual analogue scales (VAS) and pupillary fatigue waves (Pupillographic Sleepiness Test (PST)). Autonomic functions measured included resting pupil diameter, light and darkness reflex responses, blood pressure, heart rate and salivation. Data were analysed with ANOVA, with multiple comparisons. Diphenhydramine had sedative effects as shown by reductions in CFFF, VAS alertness ratings and increases of the indices of pupillary fatigue. Modafinil had alerting effects as indicated by reductions in the measures of pupillary fatigue. Comparison of pre-post medication changes in pupil diameter showed a decrease after diphenhydramine and an increase after modafinil. Diphenhydramine reduced salivation, and modafinil increased systolic blood pressure. In conclusion, diphenhydramine and modafinil evoked opposite effects on arousal and sympathetic functions, which are likely to reflect their interaction with the central histaminergic and noradrenergic systems. Hyposalivation by diphenhydramine is likely to be due to its additional anticholinergic property. PMID:17092978

  16. Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers.

    PubMed

    Vargas Pelaez, Alvaro F; Gao, Zhaohui; Ahmad, Tariq A; Leuenberger, Urs A; Proctor, David N; Maman, Stephan R; Muller, Matthew D

    2016-05-01

    Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α-adrenergic receptors and β-adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat-free mass and were infused slowly to achieve steady-state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat-by-beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low-dose, steady-state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when

  17. Bioequivalence study of two imatinib formulations after single-dose administration in healthy Korean male volunteers.

    PubMed

    Jung, J A; Kim, N; Yang, J-S; Kim, T-e; Kim, J-R; Song, G-S; Kim, H; Ko, J W; Huh, W

    2014-12-01

    Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 μg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 μg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · μg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated. PMID:24549963

  18. Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.

    PubMed

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21355446

  19. Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers.

    PubMed

    Seng, Kok-Yong; Hee, Kim-Hor; Soon, Gaik-Hong; Chew, Nicholas; Khoo, Saye H; Lee, Lawrence Soon-U

    2015-11-01

    In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH. PMID:26282412

  20. Population Pharmacokinetic Analysis of Isoniazid, Acetylisoniazid, and Isonicotinic Acid in Healthy Volunteers

    PubMed Central

    Seng, Kok-Yong; Hee, Kim-Hor; Soon, Gaik-Hong; Chew, Nicholas; Khoo, Saye H.

    2015-01-01

    In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH. PMID:26282412

  1. Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers.

    PubMed

    Guarnieri, Regina V; Ribeiro, Rafaela L; de Souza, Altay A Lino; Galduróz, José Carlos F; Covolan, Luciene; Bueno, Orlando F A

    2016-01-01

    Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model. PMID:27047394

  2. The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma.

    PubMed

    Tao, Jianfei; Jiang, Peng; Peng, Chengcheng; Li, Min; Liu, Runhui; Zhang, Weidong

    2016-07-15

    To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-∞), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice. PMID:26830535

  3. Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers

    PubMed Central

    Guarnieri, Regina V.; Ribeiro, Rafaela L.; de Souza, Altay A. Lino; Galduróz, José Carlos F.; Covolan, Luciene; Bueno, Orlando F. A.

    2016-01-01

    Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model. PMID:27047394

  4. Comparative bioequivalence study of a new levothyroxine solution versus a reference L-thyroxine solution in normal healthy volunteers.

    PubMed

    Chassard, D; Kerihuel, J C; Caplain, H; Tran Quang, N; Thebault, J J

    1991-01-01

    A bioequivalence study between a new Levothyroxine solution and a reference solution was performed in 12 healthy volunteers after one single 3000 g oral administration. Administrations were done according to a cross-over schedule with a three week wash-out period. Plasma profile of Levothyroxine was determined for 72 hours, clinical tolerance being appreciated for 10 days after each administration. No statistical difference was reported for pharmacokinetic parameters and clinical tolerance was good. PMID:1820903

  5. The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility

    PubMed Central

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen; Østervig, Rebecca; Asghar, Mohammad Sohail; Dahl, Jørgen Berg

    2016-01-01

    Introduction Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min) in healthy volunteers. Material and Methods Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min.), and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied. Results For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006). Conclusions We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers. Trial Registration clinicaltrials.gov NCT02166164 PMID:27167119

  6. Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers

    PubMed Central

    Del Tacca, Mario; Pasqualetti, Giuseppe; Di Paolo, Antonello; Virdis, Agostino; Massimetti, Gabriele; Gori, Giovanni; Versari, Daniele; Taddei, Stefano; Blandizzi, Corrado

    2009-01-01

    AIMS There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug. METHODS Two generic amoxicillin products (generic A and B) were selected among four fast-release tablet formulations available on the Italian market. Twenty-four healthy adult volunteers of either sex participated to a single-dose, randomized, three-treatment, crossover, single-blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high-performance liquid chromatography. RESULTS Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of Cmax ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation. CONCLUSIONS These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for Cmax on the basis of single-dose pharmacokinetic assessment. PMID:19660001

  7. Precursors of Hypertensive Heart Phenotype Develop in Healthy Adults

    PubMed Central

    de Marvao, Antonio; Dawes, Timothy J.W.; Shi, Wenzhe; Durighel, Giuliana; Rueckert, Daniel; Cook, Stuart A.; O’Regan, Declan P.

    2015-01-01

    Objectives This study used high-resolution 3-dimensional cardiac magnetic resonance to define the anatomical and functional left ventricular (LV) properties associated with increasing systolic blood pressure (SBP) in a drug-naïve cohort. Background LV hypertrophy and remodeling occur in response to hemodynamic stress but little is known about how these phenotypic changes are initiated in the general population. Methods In this study, 1,258 volunteers (54% women, mean age 40.6 ± 12.8 years) without self-reported cardiovascular disease underwent 3-dimensional cardiac magnetic resonance combined with computational modeling. The relationship between SBP and wall thickness (WT), relative WT, end-systolic wall stress (WS), and fractional wall thickening were analyzed using 3-dimensional regression models adjusted for body surface area, sex, race, age, and multiple testing. Significantly associated points in the LV model (p < 0.05) were identified and the relationship with SBP reported as mean β coefficients. Results There was a continuous relationship between SBP and asymmetric concentric hypertrophic adaptation of the septum and anterior wall that was associated with normalization of wall stress. In the lateral wall an increase in wall stress with rising SBP was not balanced by a commensurate hypertrophic relationship. In normotensives, SBP was positively associated with WT (β = 0.09) and relative WT (β = 0.07) in the septal and anterior walls, and this regional hypertrophic relationship was progressively stronger among pre-hypertensives (β = 0.10) and hypertensives (β = 0.30). Conclusions These findings show that the precursors of the hypertensive heart phenotype can be traced to healthy normotensive adults and that an independent and continuous relationship exists between adverse LV remodeling and SBP in a low-risk population. These adaptations show distinct regional variations with concentric hypertrophy of the septum and eccentric hypertrophy of the

  8. Modafinil Increases the Latency of Response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial

    PubMed Central

    Mohamed, Ahmed Dahir; Lewis, Chris Roberts

    2014-01-01

    Background Modafinil is a medication licensed for the treatment of narcolepsy. However, it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning. Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers, numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks. Interestingly, several clinical and preclinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times. This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil. The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test (HSCT). Methodology Sixty-four healthy volunteers received either a single dose (200 mg) of modafinil (n = 32) or placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT. Principal Findings Participants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo. However, participants in both groups made a similar number of errors on each of these measures, indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo. Conclusions This study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT, a task that is highly sensitive to prefrontal executive function, without enhancing

  9. Nasal PMN response to repeated challenge with endotoxin in healthy volunteers**

    EPA Science Inventory

    Abstract Rationale: We have employed nasal challenge with Iipopolysaccharid (lPS) followed by nasal lavage (NU to experimentally induce and examine upper airway inflammation in human volunteers.It is unclear however whether adaptation within individuals occurs following repeated ...

  10. Brain areas activated by uncertain reward-based decision-making in healthy volunteers

    PubMed Central

    Guo, Zongjun; Chen, Juan; Liu, Shien; Li, Yuhuan; Sun, Bo; Gao, Zhenbo

    2013-01-01

    Reward-based decision-making has been found to activate several brain areas, including the ventrolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to analyze the location and intensity of activation during the reward-based decision-making task, with respect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ‘risk’ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during ambiguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbitofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, inferior parietal lobule, and cerebellar posterior lobe exhibited greater activation in the ‘risk’ than in the ‘certain’ condition (P < 0.05). The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ‘ambiguous’ condition compared to the ‘risk’ condition (P < 0.05). The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during decision-making about uncertain rewards. Thus, we observed different levels and regions of

  11. Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers

    PubMed Central

    2014-01-01

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O3), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m3), O3 (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O3 (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O3 and DE decreased FEV1 (17.6%) to a greater extent than O3 alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O3 and DE exposures were summed together and compared to the combined DE and O3 exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O3 exposure than the individuals’ matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O3 and DE exposure can be observed showing a greater than additive manner. In addition, O3-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological

  12. A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

    PubMed

    Yannovits, N; Zintzaras, E; Pouli, A; Koukoulis, G; Lyberi, S; Savari, E; Potamianos, S; Triposkiadis, F; Stefanidis, I; Zartaloudis, E; Benakis, A

    2006-01-01

    Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0

  13. Interaction potential of Carmegliptin with P-glycoprotein (Pgp) transporter in healthy volunteers

    PubMed Central

    Kuhlmann, Olaf; Carlile, David; Noe, Johannes; Bentley, Darren

    2014-01-01

    Objective The primary objective of this study was to investigate the interaction potential of carmegliptin with P-glycoprotein transporter in vitro and in vivo. A secondary objective was to investigate the safety and tolerability of carmegliptin alone or co-administered with verapamil. Research design and methods The inhibition potential of carmegliptin was tested in vitro and in a non-randomized open-label study in 16 healthy male volunteers. On day 1 a single dose of carmegliptin (150 mg) was given, followed by a single dose of verapamil (80 mg) on day 7, on day 10 a single dose of carmegliptin (150 mg) together with verapamil (80 mg t.i.d.), and verapamil (80 mg t.i.d.) on days 11–14. Finally, on day 15 a single dose of 150 mg carmegliptin together with 80 mg t.i.d. verapamil was administered. Pharmacokinetic and safety parameters were assessed. Results Carmegliptin showed in vitro a low cell permeability and was a good substrate for human MDR1 cells. When carmegliptin was taken with verapamil, the mean exposure and Cmax to carmegliptin increased by 29% and 53%, respectively. Increases in exposure were slightly greater on the sixth day of verapamil dosing than on the first day. Verapamil Cmax was 17% lower on average when given with carmegliptin than when verapamil was taken alone, and similar trends were apparent in corresponding norverapamil pharmacokinetics. All reported adverse events (n = 28) were mild in intensity, and verapamil had no apparent effect on the pattern or incidence of events. Conclusions In vitro, carmegliptin is a substrate but not an inhibitor of human Pgp. Consistently, the co-administration of carmegliptin with verapamil altered the pharmacokinetics of carmegliptin slightly and moderately increased the exposure. Peak exposure of verapamil and its metabolite norverapamil tended to be lower when co-administered with carmegliptin. The combination of carmegliptin and verapamil was generally well tolerated. Although the

  14. Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers

    PubMed Central

    SERGIDES, CHRISTAKIS; CHIRILĂ, MARINELA; SILVESTRO, LUIGI; PITTA, DAPHNE; PITTAS, ANDREAS

    2016-01-01

    Over the past few decades, trans-resveratrol has received widespread attention as a preventive agent for numerous diseases. Several studies have demonstrated that it has significant biological and pharmacological properties. Trans-resveratrol has been reported to possess anti-oxidant, anti-inflammatory, anticarcinogenic, antidiabetic, anti-aging, cardioprotective and neuroprotective properties, which can be relevant in chronic diseases and longevity in humans. The aim of the present study was to investigate the rate and extend of absorption, and also the safety of resveratrol following a single 500 mg oral dose. This was an open label, single dose, one period, bioavailability study in 15 healthy volunteers under fasting conditions. Blood samples were collected at predefined time points up to 24 h after resveratrol administration, and plasma concentrations of resveratrol and its conjugated (glucuronated and sulphated) metabolites were determined using a validated high performance liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters, including Cmax, AUC0-t, AUC0-inf, Tmax, T1/2 and MRT, were determined from plasma concentration-time profiles and found to be in good agreement with previously reported data. Cmax and AUC0-inf were lower for resveratrol when compared with the values for its glucuronated and sulphated metabolites. Cmax for resveratrol, glucuronated resveratrol and sulphated resveratrol were 71.2±42.4 ng/ml, 4,083.9±1,704.4 ng/ml and 1,516.0±639.0 ng/ml, respectively, while the AUC0-inf values were 179.1±79.1 ng/ml, 39,732.4±16,145.6 ng/ml and 14,441.7±7,593.2 ng/ml, respectively. No adverse reactions associated with resveratrol were reported during the study. The plasma concentrations of resveratrol (free and conjugated) were in agreement with those mentioned in the literature, and were adequate to promote the pharmacological activities of resveratrol. In conclusion, resveratrol 500 mg tablets were well-tolerated by all

  15. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers.

    PubMed

    Mustapha, A; Yakasai, I A; Aguye, I A

    1996-01-01

    The influence of Tamarindus indica L. fruit extract incorporated in a traditional meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6 healthy volunteers. There was a statistically significant increase in the plasma levels of aspirin and salicylic acid, respectively, when the meal containing Tamarindus indica fruit extract was administered with the aspirin tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/- 0.21 mg/ml (P < 0.05); 14.03 +/- 0.11 mg/ml.h to 86.51 +/- 0.21 mg/ml.h (P < 0.085) and 1.04 +/- 0.12 h to 1.50 +/- 0.44 h (P < 0.05) respectively. There was no change in the tmax (0.50 +/- 0.17 h) but there was a decrease in the kel from 0.633 +/- 0.22 to 0.463 +/- 0.29 (P < 0.05). Similarly, the Cmax, AUC0-6h and kel for salicylic acid rose from 43.84 +/- 0.21 mg/ml to 68.19 +/- 0.71 mg/ml (P < 0.05); 171.59 +/- 0.07 mg/ml.h to 266.22 +/- 0.21 mg/ml/.h (P < 0.05) and 7.37 +/- 0.29 to 19.30 +/- 0.21 (P < 0.05), respectively. The tmax decreased from 2.0 +/- 0.18 h to 1.0 +/- 0.08 h (P < 0.05) and t1/2 from 0.25 +/- 0.21 h to 0.184 +/- 0.11 h (P < 0.05). The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of aspirin. PMID:8980919

  16. Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.

    PubMed

    Garba, M; Yakasai, I A; Bakare, M T; Munir, H Y

    2003-01-01

    The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-ibuprofen and carboxy-ibuprofen respectively, when the meal containing Tamarindus indica fruit extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The C(max), AUC(0-6 hr) and Ka for ibuprofen increased from 38 +/- 0.70 microg/ml to 42 +/- 0.98 microg/ml (p > 0.05); and 28.03 +/- 2.40 microg/ml x hr to 56.51 +/- 0.16 microg/ml x hr (p < 0.05) and 1.048 +/- 0.02hr(-1) to 2.781 +/- 0.11 hr(-1) (p < 0.05) respectively. There was no change in the t(max) (120.00 +/- 0.43m) but there was a decrease in the k(el) from 0.63 +/- 0.20 hr(-1) to 0.46 +/- 0.11 hr(-1) (p<0.05). Similarly the C(max), AUC(0-6 h) and Ka for hydroxy-ibuprofen rose from 43 +/- 0.76 microg/ml to 45 +/- 0.16 microg/ml (p < 0.05); 39.04 +/- 2.30 microg/ml x hr to 59.49 +/- 2.39 microg/ml.hr in (p < 0.05) and 1.498 +/- 0.79hr(-1) to 3.442 +/- 0.23 hr(-1) (p < 0.05) respectively; while the C(max), AUC(0-6 h) and Ka for carboxy-ibuprofen rose from 48 +/- 0.7 microg/ml to 51 +/- 0.16 microg/ml (p < 0.05); 41.972 +/- 0.68 microg/ml x hr to 63.948 +/- 0.12 microg/ml x hr (p < 0.05) and 1.649 +/- 0.08 hr(-1) to 4.187 +/- 0.42 hr(-1) (p < 0.05) respectively. The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of Ibuprofen. PMID:14527090

  17. Early effects of erythropoietin on serum hepcidin and serum iron bioavailability in healthy volunteers.

    PubMed

    Lainé, Fabrice; Laviolle, Bruno; Ropert, Martine; Bouguen, Guillaume; Morcet, Jeff; Hamon, Catherine; Massart, Catherine; Westermann, Mark; Deugnier, Yves; Loréal, Olivier

    2012-04-01

    Hepcidin regulates plasma iron bioavailability and subsequently iron availability for erythropoiesis. rHuEPO has been reported to decrease hepcidin expression in case of repeated subcutaneous injections. Thus, hepcidin level measurement could be a candidate marker for detection of rHuEPO abuse. However, when used for doping, rHuEPO can be injected intravenously and the scheme of injection is unknown. Our aim was to evaluate the early effects of a single intravenous rHuEPO injection on serum hepcidin levels. Fourteen male healthy volunteers received one intravenous injection of 50 U/Kg of rHuEPO during a placebo-controlled, randomized, double-blind, cross-over study. Serum hepcidin, quantified by a competitive ELISA method and iron parameters was then evaluated for 24 h. Serum levels of hepcidin were significantly increased 4 h after rHuEPO injection when compared with placebo injection (78.3 ± 55.5 vs. 57.5 ± 34.6 ng/ml, respectively; +36%, p < 0.05), whereas iron and transferrin saturation dramatically decreased 12 h after rHuEPO injection when compared with placebo injection (9.2 ± 3.5 vs. 15.8 ± 4.2 μg/l, respectively; -42%, p < 0.05 and 14.8 ± 5.0 vs. 26.3 ± 6.4%, respectively; -44%, p < 0.05). In addition, 12 and 24 h after rHuEPO injection serum hepcidin levels were lower compared with placebo injection (41.6 ± 27.4 vs. 56.6 ± 28.1 ng/ml after 12 h; -27%, p < 0.05 and 26.0 ± 29.6 vs. 81.2 ± 29.4 ng/ml after 24 h; -68%, p < 0.05). Intravenous injection of recombinant EPO induces a precocious and transient increase of serum hepcidin leading to a transient decrease of iron bioavailability. The transitory increase and dynamics of its concentration make difficult the practical use of hepcidin to detect rHuEPO doping. PMID:21818622

  18. Pharmacokinetics and pharmacodynamics of recombinant human interferon-beta in healthy male volunteers.

    PubMed

    Salmon, P; Le Cotonnec, J Y; Galazka, A; Abdul-Ahad, A; Darragh, A

    1996-10-01

    The pharmacokinetics and pharmacodynamics of recombinant human interferon-beta (rHuIFN-beta 1a) were assessed following administration to 12 healthy male volunteers. Each subject received, in a double-blind, balanced, random-order, crossover sequence, single doses of 6 MIU of rHuIFN-beta 1a (Rebif) i.v., i.m., and s.c. or matching placebo on four occasions separated by washout periods of 1 week. Blood samples were collected at preset times for the measurement of serum IFN-beta levels and of intracellular 2'-5'-oligoadenylate synthetase levels. Blood pressure, sitting heart rate, respiratory rate, oral body temperature, and tolerance were monitored regularly. All administrations of rHuIFN-beta 1a were well tolerated, although about half of the subjects had a flu-like syndrome, as expected. After i.v. bolus injection, the pharmacokinetics of rHuIFN-beta 1a were well described by a classic two-compartment model. Mean total clearance of rHuIFN-beta 1a was about 100 L.h-1. The distribution half-life was 5 min, and the terminal half-life was approximately 5 h. After i.m. or s.c. injection, serum IFN-beta profiles were rather flat, and about one sixth of the administered dose was available systemically. Extent and duration of clinical and biologic effects were independent of the route of administration and of the IFN-beta serum levels. Biologic pharmacodynamic effects persisted even when IFN-beta serum levels had returned to baseline and were still significantly elevated 3 days after a single dose. Because of the independence of the extent and duration of clinical and biologic pharmacodynamic effects from the route of administration and from the IFN-beta serum levels, the s.c route of administration is preferred in indications in which primarily an immunomodulatory action is sought. Predominantly antiviral and antiproliferative activity is enhanced by the i.v. route to provide adequate drug levels at the site of pathology, although its application is limited on practical

  19. Pharmacokinetics and Pharmacodynamics of Multiple-Dose Intravenous Nemonoxacin in Healthy Chinese Volunteers

    PubMed Central

    Wu, Xiao-jie; Guo, Bei-ning; Zhang, Ying-yuan; Yu, Ji-cheng; Cao, Guo-ying; Chen, Yuan-cheng; Zhu, De-mei; Ye, Xin-yu; Wu, Ju-fang; Shi, Yao-guo; Chang, Li-wen; Chang, Yu-ting; Tsai, Cheng-yuan

    2014-01-01

    This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n = 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n = 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean ± SD) at steady state (Cmax_ss) were 9.60 ± 1.84 and 11.04 ± 2.18 μg/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0–24_ss) were 44.03 ± 8.62 and 65.82 ± 10.78 μg · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ± 1.47, 8.17 ± 1.76, and 9.96 ± 2.23 μg/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0–24_ss values were 40.46 ± 9.52, 54.17 ± 12.10, and 71.34 ± 17.79 μg · h/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was ≤1 mg/liter. It is suggested that all of the studied intravenous nemonoxacin dosing regimens should have favorable clinical and microbiological efficacies in future clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.) PMID:25534726

  20. The effect of food on cabergoline pharmacokinetics and tolerability in healthy volunteers.

    PubMed

    Persiani, S; Rocchetti, M; Pacciarini, M A; Holt, B; Toon, S; Strolin-Benedetti, M

    1996-07-01

    The effect of food on the pharmacokinetics and tolerability of cabergoline in man was investigated. For this purpose an open, randomized, single-dose study was conducted in 12 healthy male volunteers who received 1 mg cabergoline as tablets both under fasting conditions and after a breakfast containing a substantial amount of carbohydrates, fat, and proteins, in a crossover fashion. The two treatments were separated by a 4 week washout period. Plasma and urine were collected up to 336 and 168 h respectively after administration and cabergoline concentration was measured in both fluids using a validated radioimmunoassay. Tolerability assessment included haematology, blood chemistry, and urinalysis, blood pressure and heart rate measurements, and ECG. Under both fasting and fed conditions low but persistent cabergoline plasma levels were observed in the present study up to 2 weeks after drug intake, in agreement with the long-lasting prolactin-lowering activity of the drug. In subjects receiving cabergoline under fed or fasting conditions, Cmax values averaged 44 and 54 pg mL(-1), AUC(0-336 h) averaged 6392 and 5331 pg h mL(-1), Ae(0-168 h) averaged 12.7 and 11.9 micrograms, and t1/2 averaged 109.7 and 101.3 h, respectively. No statistically significant difference was found when Cmax, AUC(0-336 h), t1/2, and Ae(0-168 h) from subjects treated under fasting and fed conditions were compared. Median tmax values in subjects treated under fasting or fed conditions were identical (2.5 h). The statistical analysis applied to the parameters chosen to evaluate the variations in the blood pressure profiles observed either supine or standing did not show any significant difference between the fed and fasting conditions. Heart rate values were not significantly modified after cabergoline under either fed or fasting conditions. Laboratory evaluation showed some minor deviations from normal, which were not clinically relevant (only one subject showed an occasional and transient

  1. Doppler ultrasonography measurement of hepatic hemodynamics during Valsalva maneuver: healthy volunteer study

    PubMed Central

    2015-01-01

    Purpose: The aim of our study was to assess the hemodynamic change of liver during the Valsalva maneuver using Doppler ultrasonography. Methods: Thirty healthy men volunteers were enrolled (mean age, 25.5±3.64 years). The diameter, minimal and maximal velocities, and volume flow of intrahepatic inferior vena cava (IVC), middle hepatic vein (MHV), and right main portal vein (RMPV) was measured during both rest and Valsalva maneuver. These changes were compared using paired t-test. Results: The mean diameters (cm) of the intrahepatic IVC at rest and Valsalva maneuver were 1.94±0.40 versus 0.56±0.66 (P<0.001). The mean diameter (cm), minimal velocity (cm/sec), maximal velocity (cm/sec), and volume flow (mL/min) of MHV at rest and Valsalva maneuver were 0.60±0.15 versus 0.38±0.20 (P<0.001), -7.98±5.47 versus 25.74±13.13 (P<0.001), 21.34±6.89 versus 35.12±19.95 (P=0.002), and 106.94±97.65 versus 153.90±151.80 (P=0.014), respectively. Those of RMPV at rest and Valsalva maneuver were 0.78±0.21 versus 0.76±0.20 (P=0.485), 20.21±8.22 versus 18.73±7.43 (P=0.351), 26.79±8.85 versus 24.93±9.91 (P=0.275), and 391.52±265.63 versus 378.43±239.36 (P=0.315), respectively. Conclusion: The blood flow velocity and volume flow of MHV increased significantly during Valsalva maneuver. These findings suggest that hepatic vein might play an important role to maintain venous return to the heart during the maneuver. PMID:25327526

  2. Approximate Quantification in Young, Healthy Older Adults', and Alzheimer Patients

    ERIC Educational Resources Information Center

    Gandini, Delphine; Lemaire, Patrick; Michel, Bernard Francois

    2009-01-01

    Forty young adults, 40 healthy older adults, and 39 probable AD patients were asked to estimate small (e.g., 25) and large (e.g., 60) collections of dots in a choice condition and in two no-choice conditions. Participants could choose between benchmark and anchoring strategies on each collection of dots in the choice condition and were required to…

  3. Story Processing Ability in Cognitively Healthy Younger and Older Adults

    ERIC Educational Resources Information Center

    Wright, Heather Harris; Capilouto, Gilson J.; Srinivasan, Cidambi; Fergadiotis, Gerasimos

    2011-01-01

    Purpose: The purpose of the study was to examine the relationships among measures of comprehension and production for stories depicted in wordless pictures books and measures of memory and attention for 2 age groups. Method: Sixty cognitively healthy adults participated. They consisted of two groups--young adults (20-29 years of age) and older…

  4. Population pharmacokinetics of zonisamide after oral administration in healthy Chinese volunteers.

    PubMed

    Qiu, Xuewen; Dai, Qing; Sun, Fengjun; Liu, Yao; Yang, Bo; Xiang, Rongfeng; Yu, Mingjie; Xiong, Lirong; Bi, Shanshan; Lu, Wei; Chen, Yongchuan; Xia, Peiyuan

    2016-05-01

    To develop a population-based pharmacokinetic model for the oral antiepileptic drug zonisamide using a cohort of healthy (nonepileptic) subjects and evaluate the effect of individual factors on the pharmacokinetics of zonisamide. 30 young adults (21-39 years) in good health were randomly assigned to 3 equal groups (1:1 sex ratio) for single-dose administration of zonisamide at 200 mg, 300 mg, or 400 mg. An additional 9 subjects (22-24 years) were administered once daily zonisamide at 300 mg for 14 days, and comprised the multiple dosing group. Venous blood samples were collected for analysis prior to (baseline, 0 hours) and after (1-300 hours) drug administration, providing 607 total samples used to build the pharmacokinetic model. The population pharmacokinetic analysis was performed by ICON's nonlinear mixed-effect modeling (NONMEM) software. Validation of the final model was carried out by nonparametric bootstrapping and visual predictive check. The zonisamide pharmacokinetics was best described by a two-compartment model with first-order elimination. In the final model, the estimated value of clearance (CL) was 23.25 L/h, the volume of distribution of the central compartment (Vc) was 34.50 L, the intercompartmental clearance (Q) was 20.22 L/h, and the Ka was 0.026 h(-1). The peripheral volume of distribution (Vp) was 1,429 L for single dose and 1,003 L for multiple doses. Body weight was the significant covariate affecting CL, Vc, Vp, and Q. Otherwise, female subjects had a lower Q than male subjects. The pharmacokinetics of zonisamide after oral administration could be described using a linear first-order elimination two-compartment model, which may provide a reference for clinical use of zonisamide in Chinese adults. PMID:27007995

  5. Stopped hearts, amputated toes and NASA: contemporary legends among healthy volunteers in US phase I clinical trials

    PubMed Central

    Fisher, Jill A.

    2015-01-01

    The first stage of testing new pharmaceuticals in humans is referred to as a phase I clinical trial. The purpose of these studies is to test the safety of the drugs and to establish appropriate doses that can later be given to patients. Most of these studies are conducted under controlled, in-patient conditions using healthy volunteers who are paid for their participation. To explore healthy volunteers’ experiences in clinical trials, an ethnographic study was conducted at six in-patient phase I clinics in the USA. In addition to the observation of clinic activities (from informed consent procedures to dosing to blood draws), 268 semi-structured interviews were conducted, 33 with clinic staff and 235 with healthy volunteers. Drawing on this dataset, this article explores healthy volunteers’ exchange of contemporary legends about phase I clinical trials. In addition to potentially scaring the listener and communicating distrust in the medical community, these incredible stories help participants cope with perceived stigma and establish a gradient of risk of trial participation, creating potential boundaries to their participation in medical research. The article argues that contemporary legends play a productive role in society, shaping how people view themselves and others and influencing their decisions about risky activities. PMID:25601069

  6. Tolerability of intramuscular and intradermal delivery by CELLECTRA® adaptive constant current electroporation device in healthy volunteers

    PubMed Central

    Diehl, Malissa C; Lee, Jessica C; Daniels, Stephen E; Tebas, Pablo; Khan, Amir S; Giffear, Mary; Sardesai, Niranjan Y; Bagarazzi, Mark L

    2013-01-01

    DNA vaccines are being developed as a potentially safe and effective immunization platform. However, translation of DNA vaccines into a clinical setting has produced results that have fallen short of those generated in a preclinical setting. Various strategies are being developed to address this lack of potency, including improvements in delivery methods. Electroporation (EP) creates transient increases in cell membrane permeability, thus enhancing DNA uptake and leading to a more robust immune response. Here, we report on the safety and tolerability of delivering sterile saline via intramuscular (IM) or intradermal (ID) injection followed by in vivo electroporation using the CELLECTRA® adaptive constant current device in healthy adults from two open-label studies. Pain, as assessed by VAS, was highest immediately after EP but diminishes by about 50% within 5 min. Mean VAS scores appear to correlate with the amount of energy delivered and depth of needle insertion, especially for intramuscular EP. Mean scores did not exceed 7 out of 10 or 3 out of 10 for IM and ID EP, respectively. The majority of adverse events included mild to moderate injection site reactions that resolved within one day. No deaths or serious adverse events were reported during the course of either study. Overall, injection followed by EP with the CELLECTRA® device was well-tolerated and no significant safety concerns were identified. These studies support the further development of electroporation as a vaccine delivery method to enhance immunogenicity, particularly for diseases in which traditional vaccination approaches are ineffective. PMID:24051434

  7. A randomized control trial of the effect of yoga on verbal aggressiveness in normal healthy volunteers

    PubMed Central

    Deshpande, Sudheer; Nagendra, H R; Raghuram, Nagarathna

    2008-01-01

    Objective: To study the effect of yoga on verbal aggressiveness in normal healthy adults. Methods: Of the 1228 persons who attended introductory lectures, 226 subjects of both sexes who satisfied the inclusion and exclusion criteria and who consented to participate in the study were randomly allocated into two groups. These 226 subjects were between the ages of 17 and 62 years and 173/226 completed the eight weeks of intervention. The Yoga (Y) group practised an integrated yoga module that included asanas, pranayama, meditation, notional correction, and devotional sessions. The control group practised mild to moderate physical exercises (PE). Both groups had supervised practices (by trained experts) for one hour daily, six days a week for eight weeks. Verbal Aggressiveness was assessed before and after eight weeks using the self-administered Verbal Aggressive Scale. Results: The baseline score of the two groups did not differ significantly (P = 0.66). There was a significant decrease in verbal aggressiveness in the yoga group (P = 0.01 paired samples t-test) with a nonsignificant increase in the PE group. ANCOVA using pre- values as covariates showed a significant difference between the groups (P = 0.013). RMANOVA for interaction between the sexes or age groups in change scores were not significant. Conclusions: This study has demonstrated that an eight week intervention of an integrated yoga module decreased verbal aggressiveness in the yoga group (in males and those below 25 years of age), with a nonsignificant increase in the PE group. PMID:21829289

  8. No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers.

    PubMed

    Spence, Rebecca; Mandagere, Arun; Harrison, Brooke; Dufton, Christopher; Boinpally, Ramesh

    2009-12-01

    Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (PK) interactions between these two drugs were assessed in a crossover study in 26 healthy adults. Single-dose PK of ambrisentan (10 mg) and its metabolite, 4-hydroxymethyl ambrisentan, were determined in the absence and presence of multiple doses of tadalafil (40 mg QD). Similarly, single-dose PK of tadalafil (40 mg) were evaluated in the absence and presence of multiple doses of ambrisentan (10 mg QD). In the presence of tadalafil, ambrisentan maximum plasma concentration (C(max)) was similar (105.0% [90% CI: 95.9-115.0%]) and systemic exposure (AUC(0-infinity)) was slightly decreased (87.5% [84.0-91.2%]), compared with ambrisentan alone. Similar changes were observed with 4-hydroxymethyl ambrisentan. Tadalafil C(max) (100.6% [94.4-107.1%]) and AUC(0-infinity) (100.2% [92.6-108.4%]) showed no difference in the absence and presence of ambrisentan. The safety profile of the drugs combined was similar to that of either drug alone. No dose adjustments should be necessary when these drugs are coadministered. These results are in contrast to previous reports that the sulfonamide-based ERA bosentan can cause marked decreases in the exposure of tadalafil. PMID:19455620

  9. The effect of Ginkgo biloba on memory in healthy male volunteers.

    PubMed

    Moulton, P L; Boyko, L N; Fitzpatrick, J L; Petros, T V

    2001-07-01

    The purpose of this study was to investigate possible effects of Ginkgo biloba, a widely used herbal extract, on memory. This study incorporated a double-blind, placebo-controlled design, which used 30 healthy male subjects in each of two groups. The treatment group received two 60-mg tablets of BioGinkgo (27/7) [corrected] daily for 5 days, while the placebo group received a placebo. On the fifth day, after a 2-h waiting period, all subjects were given the Sternberg Memory Scanning Test [Q. J. Exp. Psychol. 27 (1975) 1.], a reaction time control test, the vocabulary and digit span subtests of the WAIS-R [Wechsler D. Manual for the Wechsler adult intelligence scale - revised. New York: Psychological Corporation, 1981.], a reading span test [J. Verbal Learn. Verbal Behav. 19 (1980) 450.] and a prose recall test [Discourse Proc. 13 (1990) 387.]. Blood pressure, heart rate and side effects were also monitored throughout the study. Nonsignificant results were found on all interactions involving treatment group on all tests except the Sternberg Memory Scanning Test. The extract appeared to be safe but largely ineffective in enhancing memory. PMID:11495672

  10. The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

    PubMed Central

    García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L.; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

    2005-01-01

    Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of ΔCTXΦ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain

  11. The Influence of Arm Positioning on Ultrasonic Visualization of the Subclavian Vein: An Anatomical Ultrasound Study in Healthy Volunteers.

    PubMed

    Sadek, Meriem; Roger, Claire; Bastide, Sophie; Jeannes, Pascal; Solecki, Kamila; de Jong, Audrey; Buzançais, Gautier; Elotmani, Loubna; Ripart, Jacques; Lefrant, Jean Yves; Bobbia, Xavier; Muller, Laurent

    2016-07-01

    We hypothesized that placing the arm in 90° abduction, through 90° flexion and 90° external rotation, could improve ultrasound visualization of the subclavian vein. In 49 healthy volunteers, a single operator performed a view of the subclavian vein in neutral position and abduction position. A second blinded operator measured the cross-sectional area of the subclavian vein. Abduction position increased the cross-sectional area of the subclavian vein from 124 ± 46 (mean ± SD) to 162 ± 58 mm (P = 0.001). An increase of the cross-sectional area of ≥50% was observed in 41% volunteers (95% confidence interval, 27%-56%, n = 20); this technique offers an alternative approach (maybe safer) for ultrasound-guided catheterization of the subclavian vein. PMID:27149016

  12. Effect of fluvoxamine on the pharmokinetics of zolpidem: a two-treatment period study in healthy volunteers.

    PubMed

    Vlase, Laurian; Popa, Adina; Neag, Maria; Muntean, Dana; Achim, Marcela; Leucuţa, Sorin Emilian

    2012-01-01

    1. Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and fluvoxamine in healthy volunteers. 2. The study consisted of two periods: Period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem; and Period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 100 mg fluvoxamine. Between the two periods, the subjects were treated for 6 days with a single daily dose of 100 mg fluvoxamine. 3. Pharmacokinetic parameters of zolpidem given in each treatment period were calculated using non-compartmental analysis and the data from two periods were compared to determine statistically significant differences. 4. In the two periods of treatments, the mean peak plasma concentrations (C(max)) were 56.4 ± 25.6 ng/mL (zolpidem alone) and 67.3 ± 25.8 ng/mL (zolpidem after pretreatment with fluvoxamine). The t(max), times taken to reach C(max), were 0.83 ± 0.44 and 1.26 ± 0.74 h, respectively, and the total areas under the curve (AUC(0-∞)) were 200.9 ± 116.8 and 512.0 ± 354.6 ng h/mL, respectively. The half-life of zolpidem was 2.24 ± 0.81 h when given alone and 4.99 ± 2.92 h after pretreatment with fluvoxamine. 5. Fluvoxamine interacts with zolpidem in healthy volunteers and increases its exposure by approximately 150%. The experimental data showed the pharmacokinetic interaction between zolpidem and fluvoxamine, and suggest that the observed interaction might be clinically significant, but its relevance has to be confirmed. PMID:21985609

  13. Tongue Adiposity and Strength in Healthy Older Adults

    PubMed Central

    Butler, Susan G.; Lintzenich, Catherine Rees; Leng, Xiaoyan; Stuart, Andrew; Feng, Xin; Carr, J. Jeffrey; Kritchevsky, Stephen B.

    2012-01-01

    Objectives/Hypothesis To identify treatable risk factors for aspiration in older adults—particularly those associated with sarcopenia – we examined tongue composition. We hypothesized that 1) isometric and swallowing posterior tongue strength would positively correlate with posterior tongue adiposity, and 2) healthy older adults who aspirate would have greater tongue adiposity than healthy older adults who did not aspirate. Study Design Prospective Methods Participants were 40 healthy adults, comprised of 20 aspirators (Mean age = 78 years) and 20 non-aspirators (Mean age = 81 years), as identified via flexible endoscopic evaluation of swallowing. Measures of maximal isometric posterior tongue strength and posterior swallowing tongue strength were acquired via tongue manometry. An index of posterior tongue adiposity was acquired via computed tomography for a 1 cm region of interest. Result(s) Posterior tongue adiposity was correlated with posterior tongue isometric (r = .32, p = 0.05) but not swallowing pressures (p > 0.05) as examined with separate partial correlation analyses. Tongue adiposity did not significantly differ as a function of age, gender, or aspiration status (p > 0.05). Conclusion(s) Lower posterior isometric tongue strength was associated with greater posterior tongue adiposity. However, aspiration in healthy older adults was not affected by posterior tongue adiposity. This finding offers insight into the roles of tongue composition and strength in healthy older adults. PMID:22522371

  14. A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers.

    PubMed

    Bailey, Jayne E; Kendrick, Adrian; Diaper, Alison; Potokar, John P; Nutt, David J

    2007-01-01

    The inhalation of 7.5% carbon dioxide (CO2) in healthy subjects produces an increase in blood pressure and heart rate, and increased feelings of anxiety, fear and tension (Bailey et al. 2005). As this state is similar to that of general anxiety rather than panic, we further validated this by examining the effects of anxiolytic medication. Two separate studies in healthy volunteers are described; study one is a double-blind, placebo-controlled study of a single dose of 2 mg lorazepam and study two describes the effects of 21 days of treatment with paroxetine. Gas challenges were air and 7.5% CO2 inhaled for 20 minutes, delivered on day 0 (before treatment) and day 21 (after treatment) in the paroxetine study. Subjective effects were measured using visual analogue scales and questionnaires. When compared with placebo, lorazepam 2 mg significantly reduced peak CO2-induced subjective fear, feelings of wanting to leave, tension and worry. In the paroxetine study, when compared with day 0, day 21 showed a significantly attenuated peak CO2-induced nervousness and a trend for reduced ratings of anxiety, fear, feel like leaving, tense and worried. In these studies we have shown that this CO2 model of anxiety is sensitive to lorazepam and to a lesser extent paroxetine. This gives support to its utility as an experimental model of general anxiety disorder in healthy volunteers. PMID:16533865

  15. In vitro T-cell profile induced by BCG Moreau in healthy Brazilian volunteers.

    PubMed

    Ponte, C; Peres, L; Marinho, S; Lima, J; Siqueira, M; Pedro, T; De Luca, P; Cascabulho, C; Castello-Branco, L R; Antas, P R Z

    2015-01-01

    Tuberculosis (TB) remains the world's leading cause of morbidity and mortality. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine currently in use, its efficacy is highly variable. It has been suggested that early antigenic presentation is a pivotal event leading to a better immune response in TB vaccine models. To investigate this further, we compared in vitro cell-mediated immune responses in the context of early sensitization with TB (i.e. healthy adults vaccinated with BCG when they were young, HD; n = 25) to those in its absence (i.e., newborns with naïve immunity to TB, UV; n = 10) by challenging mononuclear cells with BCG Moreau. After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. In addition, supernatants were assayed for a broad range of cytokines using an array system. The HD group showed robust reactivity to Protein Purified Derivative and BCG while the naïve, UV group did not. Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. Otherwise, only the UV group showed expression of CD25dim+ as an activation marker dependent on BCG infection. In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. Taken together, our results highlight critical roles of early sensitization with TB in mounting cell-mediated immune responses. PMID:25483636

  16. Mass balance and metabolism of the antimalarial pyronaridine in healthy volunteers.

    PubMed

    Morris, Carrie A; Dueker, Stephen R; Lohstroh, Peter N; Wang, Li-Quan; Fang, Xin-Ping; Jung, Donald; Lopez-Lazaro, Luis; Baker, Mark; Duparc, Stephan; Borghini-Fuhrer, Isabelle; Pokorny, Rolf; Shin, Jang-Sik; Fleckenstein, Lawrence

    2015-03-01

    This was a single dose mass balance and metabolite characterization study of the antimalarial agent pyronaridine. Six healthy male adults were administered a single oral dose of 720 mg pyronaridine tetraphosphate with 800 nCi of radiolabeled (14)C-pyronaridine. Urine and feces were continuously collected through 168 h post-dose, with intermittent 48 h collection periods thereafter through 2064 h post-dose. Drug recovery was computed for analyzed samples and interpolated for intervening time periods in which collection did not occur. Blood samples were obtained to evaluate the pharmacokinetics of total radioactivity and of the parent compound. Total radioactivity in urine, feces, and blood samples was determined by accelerator mass spectrometry (AMS); parent concentrations in blood were determined with LC/MS. Metabolite identification based on blood, urine, and feces samples was conducted using a combination of LC + AMS for identifying radiopeaks, followed by LC/MS/MS for identity confirmation/elucidation. The mean cumulative drug recovery in the urine and feces was 23.7 and 47.8 %, respectively, with an average total recovery of 71.5 %. Total radioactivity was slowly eliminated from blood, with a mean half-life of 33.5 days, substantially longer than the mean parent compound half-life of 5.03 days. Total radioactivity remained detectable in urine and feces collected in the final sampling period, suggesting ongoing elimination. Nine primary and four secondary metabolites of pyronaridine were identified. This study revealed that pyronaridine and its metabolites are eliminated by both the urinary and fecal routes over an extended period of time, and that multiple, varied pathways characterize pyronaridine metabolism. PMID:24590312

  17. Adult Volunteers. A Handbook for Teacher-Librarians in the Vancouver School Board to Provide Assistance to Teacher-Librarians Who Are Establishing Adult Volunteer Programs, [and] to Suggest Ideas for Teacher-Librarians Who Wish to Enlarge or Enhance Their Volunteer Programs.

    ERIC Educational Resources Information Center

    Vancouver School Board (British Columbia).

    Guidelines are presented for establishing, enhancing, and evaluating adult volunteer programs in school library resource centers, especially those in Vancouver, Canada. It is noted that in 1982 over 200 adults volunteered their time to work on a regular basis with teacher-librarians in Vancouver. Sections include: (1) a rationale for establishing…

  18. LC-MS Method for Studying the Pharmacokinetics and Bioequivalence of Clonidine Hydrochloride in Healthy Male Volunteers

    PubMed Central

    Danafar, Hossein; Hamidi, Mehrdad

    2016-01-01

    Background: A simple and sensitive high performance liquid chromatography-electrospray ionization mass spectrometry method has been evaluated for the assignment of clonidine hydrochloride in human plasma. Methods: The mobile phase composed of acetonitrile-water 60:40 (v/v) and 0.2% formic acid 20 μl of sample was chromatographically analyzed using a repacked ZORBAX-XDB-ODS C18 column (2.1 mm×30 mm, 3.5 μ). Detection of analytes was achieved by tandem mass spectrometry with Electrospray Ionization (ESI) interface in positive ion mode operated under the multiple-reaction monitoring mode (m/z 230.0 →213). Sample pretreatment consisted of a one-step Protein Precipitation (PPT) with methanol and perchloric acid (HClO4) of 0.10 ml plasma. Results: Standard curve was linear (r=0.998) over the concentration range of 0.01–10.0 ng/ml and showed suitable accuracy and precision. The Limit of Quantification (LOQ) was 0.01 ng/ml. The mean (SD) Cmax, Tmax, AUC0–t and AUC0–∞ values after administration of the test and reference formulations, respectively, were in this manner: 6.16 (0.32) versus 6.21 (0.07) ng/ml, 30.12 (0.86) versus 30.13 (0.73) hr, 290.37 (1.13) versus 293.39 (1.22) ng/ml/hr, and 350.17 (1.98) versus 352.96 (1.67) ng/ml/hr. The mean (SD) t1/2 was 120.12 (1.90) hr for the test formulation and 120.96 (1.54) hr for the reference formulation. No statistical differences were showed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. Conclusion: The method is rapid, simple, very steady and precise for the separation, assignment, pharmacokinetic and bioavailability evaluation of clonidine in healthy Iranian adult male volunteers. PMID:27141268

  19. CONTROLLED EXPOSURES OF HEALTHY AND ASTHMATIC VOLUNTEERS TO CONCENTRATED AMBIENT PARTICLES IN METROPOLITAN LOS ANGELES

    EPA Science Inventory

    Investigators expect to use a Harvard ambient particle concentrator to assess the effects of exposure to concentrated ambient particles (CAPs) on healthy and asthmatic people.  12 healthy individuals and 12 individuals with mild asthma will be exposed to either filtere...

  20. Randomized, Double-Blind Clinical Trial to Assess the Acute Diuretic Effect of Equisetum arvense (Field Horsetail) in Healthy Volunteers.

    PubMed

    Carneiro, Danilo Maciel; Freire, Ramias Calixto; Honório, Tereza Cristina de Deus; Zoghaib, Iury; Cardoso, Fabiana Fernandes de S E Silva; Tresvenzol, Leonice Manrique F; de Paula, José Realino; Sousa, Ana Luiza Lima; Jardim, Paulo César Brandão Veiga; da Cunha, Luiz Carlos

    2014-01-01

    In this double-blind, randomized clinical trial, 36 healthy male volunteers were randomly distributed into three groups (n = 12) that underwent a three-step treatment. For four consecutive days, we alternately administered a standardized dried extract of Equisetum arvense (EADE, 900 mg/day), placebo (corn starch, 900 mg/day), or hydrochlorothiazide (25 mg/day), separated by a 10-day washout period. Each volunteer served as his own control, and the groups' results were compared. We repeated the same evaluation after each stage of treatment to evaluate the safety of the drug. The diuretic effect of EADE was assessed by monitoring the volunteers' water balance over a 24 h period. The E. arvense extract produced a diuretic effect that was stronger than that of the negative control and was equivalent to that of hydrochlorothiazide without causing significant changes in the elimination of electrolytes. There was no significant increase in the urinary elimination of catabolites. Rare minor adverse events were reported. The clinical examinations and laboratory tests showed no changes before or after the experiment, suggesting that the drug is safe for acute use. Further research is needed to better clarify the mechanism of diuretic action and the other possible pharmacological actions of this phytomedicine. PMID:24723963

  1. Effect of different surgical positions on the cerebral venous drainage: a pilot study using healthy volunteers.

    PubMed

    Yeoh, T Y; Tan, A; Manninen, P; Chan, V W S; Venkatraghavan, L

    2016-07-01

    Excessive neck flexion and rotation in certain surgical positions may cause kinking of the internal jugular vein that obstructs cerebral venous blood flow and results in elevated intracranial pressure. The objective of this study was to measure internal jugular vein flow and identify potential impediments to venous flow in supine, prone, and park bench positions using non-anaesthetised volunteers. Twenty-seven volunteers were recruited. Venous flow rate was derived from ultrasound measurements of the vessel cross-sectional area and flow velocity. Change from supine to prone position produced a significant increase in both jugular vein cross-sectional areas without affecting venous flows. In the right park bench position, the right internal jugular vein cross-sectional area decreased from 1.2 to 0.9 cm(2) (p = 0.027) without substantive changes in mean venous flow rate (p = 0.91) when compared with supine. In summary, the internal jugular vein flow was not compromised by either prone or park bench positions in non-anaesthetised volunteers, and careful positioning may prevent kinking of the jugular vein. Further studies in anaesthetised and ventilated patients are needed to validate these results for clinical practice. PMID:27160870

  2. Preliminary study of relationships between hypnotic susceptibility and personality disorder functioning styles in healthy volunteers and personality disorder patients

    PubMed Central

    2011-01-01

    Background Hypnotic susceptibility is one of the stable characteristics of individuals, but not closely related to the personality traits such as those measured by the five-factor model in the general population. Whether it is related to the personality disorder functioning styles remains unanswered. Methods In 77 patients with personality disorders and 154 healthy volunteers, we administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSSC) and the Parker Personality Measure (PERM) tests. Results Patients with personality disorders showed higher passing rates on SHSSC Dream and Posthypnotic Amnesia items. No significant correlation was found in healthy volunteers. In the patients however, SHSSC Taste hallucination (β = 0.26) and Anosmia to Ammonia (β = -0.23) were significantly correlated with the PERM Borderline style; SHSSC Posthypnotic Amnesia was correlated with the PERM Schizoid style (β = 0.25) but negatively the PERM Narcissistic style (β = -0.23). Conclusions Our results provide limited evidence that could help to understand the abnormal cognitions in personality disorders, such as their hallucination and memory distortions. PMID:21801440

  3. The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers

    PubMed Central

    Gasior, Maciej; Toyn, Jeremy H.; Wang, Jun-Sheng; Hong, Quan; Berisha, Flora; Furlong, Michael T.; Raybon, Joseph; Lentz, Kimberley A.; Sweeney, Francis; Zheng, Naiyu; Akinsanya, Billy; Berman, Robert M.; Thompson, Lorin A.; Olson, Richard E.; Morrison, John; Drexler, Dieter M.; Macor, John E.; Albright, Charlie F.; Ahlijanian, Michael K.; AbuTarif, Malaz

    2016-01-01

    The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a γ-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Aβ39, Aβ40, and Aβ42 while increasing Aβ37 and Aβ38, thereby providing evidence of γ-secretase enzyme modulation rather than inhibition. In plasma, reductions in Aβ40 and Aβ42 were observed with no change in total Aβ; in CSF, modest decreases in total Aβ were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Aβ42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Aβ lowering in Alzheimer’s disease, this study demonstrates that γ-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer’s disease and other indications. PMID:27189973

  4. The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers.

    PubMed

    Soares, Holly D; Gasior, Maciej; Toyn, Jeremy H; Wang, Jun-Sheng; Hong, Quan; Berisha, Flora; Furlong, Michael T; Raybon, Joseph; Lentz, Kimberley A; Sweeney, Francis; Zheng, Naiyu; Akinsanya, Billy; Berman, Robert M; Thompson, Lorin A; Olson, Richard E; Morrison, John; Drexler, Dieter M; Macor, John E; Albright, Charlie F; Ahlijanian, Michael K; AbuTarif, Malaz

    2016-07-01

    The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a γ-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Aβ39, Aβ40, and Aβ42 while increasing Aβ37 and Aβ38, thereby providing evidence of γ-secretase enzyme modulation rather than inhibition. In plasma, reductions in Aβ40 and Aβ42 were observed with no change in total Aβ; in CSF, modest decreases in total Aβ were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Aβ42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Aβ lowering in Alzheimer's disease, this study demonstrates that γ-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer's disease and other indications. PMID:27189973

  5. The Associations between Pain Sensitivity and Knee Muscle Strength in Healthy Volunteers: A Cross-Sectional Study

    PubMed Central

    Graven-Nielsen, Thomas; Bliddal, Henning

    2013-01-01

    Objectives. To investigate associations between muscle strength and pain sensitivity among healthy volunteers and associations between different pain sensitivity measures. Methods. Twenty-eight healthy volunteers (21 females) participated. Pressure pain thresholds (PPTs) were obtained from 1) computer-controlled pressure algometry on the vastus lateralis and deltoid muscles and on the infrapatellar fat pad and 2) computerized cuff pressure algometry applied on the lower leg. Deep-tissue pain sensitivity (intensity and duration) was assessed by hypertonic saline injections into the vastus lateralis, deltoid, and infrapatellar fat pad. Quadriceps and hamstring muscle strength was assessed isometrically at 60-degree knee flexion using a dynamometer. Associations between pain sensitivity and muscle strength were investigated using multiple regressions including age, gender, and body mass index as covariates. Results. Knee extension strength was associated with computer-controlled PPT on the vastus lateralis muscle. Computer-controlled PPTs were significantly correlated between sites (r > 0.72) and with cuff PPT (r > 0.4). Saline induced pain intensity and duration were correlated between sites (r > 0.39) and with all PPTs (r < −0.41). Conclusions. Pressure pain thresholds at the vastus lateralis are positively associated with knee extensor muscle strength. Different pain sensitivity assessment methods are generally correlated. The cuff PPT and evoked infrapatellar pain seem to reflect the general pain sensitivity. This trial is registered with ClinicalTrials.gov: NCT01351558. PMID:24167727

  6. Sphenopalatine Ganglion Acupuncture Improves Nasal Ventilation and Modulates Autonomic Nervous Activity in Healthy Volunteers: A Randomized Controlled Study

    PubMed Central

    Wang, Kuiji; Chen, Luquan; Wang, Yang; Wang, Chengshuo; Zhang, Luo

    2016-01-01

    The study aimed to assess the effects of Sphenopalatine ganglion (SPG) acupuncture on nasal ventilation function and autonomic nervous system in health volunteers. 39 healthy subjects were randomly assigned to either active SPG acupuncture group (AA group) or sham-SPG acupuncture group (SA group). All subjects were assessed for self-reported nasal ventilation, nasal patency (nasal airway resistance (NAR) and nasal cavity volume (NCV), exhaled nasal nitric oxide (nNO), and neuropeptides (substance P(SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY)) in nasal secretions at baseline, 30 minutes, 2 hours, and 24 hours after acupuncture. Significantly more subjects in AA group reported improvements in nasal ventilation at all time points after acupuncture, compared to SA group. NAR and NCV were also significantly lower in AA group than SA group. The level of nNO in AA group was significantly decreased after 24 hours compared to SA group. The level of NPY was significantly increased in AA group at 30 minutes and 2 hours compared to baseline and SA group. The levels of SP and VIP were not significantly different in the two groups. We concluded that SPG acupuncture could help to improve nasal ventilation by increasing sympathetic nerve excitability in healthy volunteers. PMID:27425415

  7. Sphenopalatine Ganglion Acupuncture Improves Nasal Ventilation and Modulates Autonomic Nervous Activity in Healthy Volunteers: A Randomized Controlled Study.

    PubMed

    Wang, Kuiji; Chen, Luquan; Wang, Yang; Wang, Chengshuo; Zhang, Luo

    2016-01-01

    The study aimed to assess the effects of Sphenopalatine ganglion (SPG) acupuncture on nasal ventilation function and autonomic nervous system in health volunteers. 39 healthy subjects were randomly assigned to either active SPG acupuncture group (AA group) or sham-SPG acupuncture group (SA group). All subjects were assessed for self-reported nasal ventilation, nasal patency (nasal airway resistance (NAR) and nasal cavity volume (NCV), exhaled nasal nitric oxide (nNO), and neuropeptides (substance P(SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY)) in nasal secretions at baseline, 30 minutes, 2 hours, and 24 hours after acupuncture. Significantly more subjects in AA group reported improvements in nasal ventilation at all time points after acupuncture, compared to SA group. NAR and NCV were also significantly lower in AA group than SA group. The level of nNO in AA group was significantly decreased after 24 hours compared to SA group. The level of NPY was significantly increased in AA group at 30 minutes and 2 hours compared to baseline and SA group. The levels of SP and VIP were not significantly different in the two groups. We concluded that SPG acupuncture could help to improve nasal ventilation by increasing sympathetic nerve excitability in healthy volunteers. PMID:27425415

  8. Modulation of alpha-interferon's antiviral and clinical effects by aspirin, acetaminophen, and prednisone in healthy volunteers.

    PubMed

    Hendrix, C W; Petty, B G; Woods, A; Kuwahara, S K; Witter, F R; Soo, W; Griffin, D E; Lietman, P S

    1995-10-01

    The magnitude and duration of the antiviral and clinical effect of alpha-interferon was measured in healthy volunteers. A single 3 million unit intramuscular dose of interferon was given either alone (controls) or after 72 h of concomitant medications. These medications included either aspirin (650 mg every 4 h), acetaminophen (650 mg every 4 h), or prednisone (40 mg per day). Peripheral blood mononuclear cells were assayed for resistance to vesicular stomatitis virus infection and induction of 2'-5'-oligoadenylate synthetase activity as evidence of interferon's antiviral effect. Co-administration of acetaminophen increased both antiviral parameters by more than 70% (P < 0.05) and reduced symptoms after interferon dosing, compared to controls. Aspirin and prednisone did not demonstrate any significant differences from controls in antiviral effect. As a group, acetaminophen, aspirin, and prednisone reduced the clinical symptoms by 47% compared to controls (P = 0.03) after interferon dosing, although individual drug comparisons failed to reach statistical significance. Independent of treatment group, the changes in antiviral markers after interferon dosing correlated closely with each other (r = 0.72, P < 0.001), but neither correlated with symptoms or fever (r < 0.30, P > 0.05). Acetaminophen enhances the antiviral effects of a single intramuscular dose of alpha-interferon, considering the parameters measured in these healthy volunteers. PMID:8585766

  9. A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

    PubMed

    Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

    2014-07-01

    This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. PMID:27128838

  10. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria.

    PubMed

    Yago, Marc R; Frymoyer, Adam; Benet, Leslie Z; Smelick, Gillian S; Frassetto, Lynda A; Ding, Xiao; Dean, Brian; Salphati, Laurent; Budha, Nageshwar; Jin, Jin Y; Dresser, Mark J; Ware, Joseph A

    2014-11-01

    Many orally administered, small-molecule, targeted anticancer drugs, such as dasatinib, exhibit pH-dependent solubility and reduced drug exposure when given with acid-reducing agents. We previously demonstrated that betaine hydrochloride (BHCl) can transiently re-acidify gastric pH in healthy volunteers with drug-induced hypochlorhydria. In this randomized, single-dose, three-way crossover study, healthy volunteers received dasatinib (100 mg) alone, after pretreatment with rabeprazole, and with 1500 mg BHCl after rabeprazole pretreatment, to determine if BHCl can enhance dasatinib absorption in hypochlorhydric conditions. Rabeprazole (20 mg b.i.d.) significantly reduced dasatinib Cmax and AUC0-∞ by 92 and 78%, respectively. However, coadministration of BHCl significantly increased dasatinib Cmax and AUC0-∞ by 15- and 6.7-fold, restoring them to 105 and 121%, respectively, of the control (dasatinib alone). Therefore, BHCl reversed the impact of hypochlorhydria on dasatinib drug exposure and may be an effective strategy to mitigate potential drug-drug interactions for drugs that exhibit pH-dependent solubility and are administered orally under hypochlorhydric conditions. PMID:25274610

  11. Subjective assessment of palatability, digestibility and emotions in healthy volunteers after ingestion of an iced dessert: preliminary report.

    PubMed

    Garzaro, M; Raimondo, L; Nadalin, J; Pecorari, G; Giordano, C

    2010-01-01

    Dietary habits can be influenced by several factors such as emotional status and food palatability represented by food smell, taste, texture, appearance and temperature. The aim of this study is to assess the palatability and digestibility of a coffee-flavored iced dessert ingested at the end of a standardized meal and its impact on emotional status in a sample of 30 healthy female volunteers. Thirty healthy female volunteers, after ENT and psychological assessment, were asked to fill in a Psycho-Emotional Questionnaire to assess their basal emotional pattern before the consumption of an iced coffee-flavored dessert after a standard meal. After the meal they filled in an Organoleptic-Sensory questionnaire, a Dynamic Digeribility questionnaire and again a Psycho-Emotional Questionnaire. In our study, most of the subjects found the tested coffee-flavoured iced dessert pleasant according to the Organoleptic-Sensorial Questionnaire (OSQ), in terms of taste, aspect, texture and smell; moreover, in 29 subjects the Dynamic Digestibility Questionnaire (DDQ) resulted in a good digestive experience. By means of the Psycho-Emotional Questionnaire (PEQ), an improvement of feelings and mood, associated with good data of digestibility and palatability was recorded. Although this observation is not statistically significant, the results seem to show a positive correlation between pleasure in eating such a product and emotional status. These data are preliminary and need further investigations on a larger population, in order to confirm this association, also in a mixed population, comparing male and female eating behaviour. PMID:21122277

  12. The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir in healthy volunteers

    PubMed Central

    Garg, Varun; Chandorkar, Gurudatt; Yang, Yijun; Adda, Nathalie; McNair, Lindsay; Alves, Katia; Smith, Frances; Heeswijk, Rolf P G

    2013-01-01

    AIM To evaluate the effects of ketoconazole, rifampicin and efavirenz on the pharmacokinetics of telaprevir in healthy volunteers. METHOD Results from three clinical studies are described. (1) Volunteers received a single 750 mg dose telaprevir with and without a single 400 mg dose ketoconazole. (2) Volunteers received (a) 1250 mg telaprevir followed by three 750 mg doses given every 8 h and (b) four 1250 mg telaprevir doses given every 8 h, with a single 400 mg dose ketoconazole given with the fourth dose of telaprevir. (3) Volunteers received either a single 750 mg dose telaprevir with or without 600 mg once daily rifampicin, or 750 mg every 8 h telaprevir with and without 600 mg once daily efavirenz. RESULTS A single 400 mg dose of ketoconazole increased single dose telaprevir exposure: the geometric least-squares mean ratio (GLSMR, with 90% confidence limits) was 1.24 (1.10, 1.41) for Cmax and 1.62 (1.45, 1.81) for AUC(0,∞). However, after multiple doses of telaprevir, there was no discernible effect of ketoconazole on telaprevir exposure. Co-administration of rifampicin at steady-state markedly reduced single dose telaprevir exposure with GLSMRs of 0.14 (0.11, 0.18) for Cmax and 0.08 (0.07, 0.11) for AUC(0,∞), whereas efavirenz had a smaller effect on telaprevir exposure when both drugs were co-administered at steady-state, with GLSMRs of 0.91 (0.81, 1.02) for Cmax, 0.53 (0.44, 0.65) for Cmin, and 0.74 (0.65, 0.84) for AUC(0,8 h). CONCLUSION CYP3A inducers, rifampicin and efavirenz, can reduce telaprevir exposure to varying degrees based on their potency. The effect of ketoconazole as an inhibitor of telaprevir metabolism is more pronounced after a single dose of telaprevir than after repeated administration. PMID:22642697

  13. Postural sway following cryotherapy in healthy adults.

    PubMed

    Fukuchi, Claudiane A; Duarte, Marcos; Stefanyshyn, Darren J

    2014-01-01

    In light of the wide use of cryotherapy and its potential negative effects on postural stability, little is known about how postural sway is affected, particularly when the whole lower limb is immersed. The purpose of this study was to analyze the influence of cryotherapy on postural sway in healthy males. Twenty-six subjects were randomly assigned into two intervention groups: control (tepid water at ∼26°C) or ice (cold water at ∼11°C). Postural sway was measured through the center of pressure (COP) position while they stood on a force plate during bipedal (70 s) and unipedal (40 s) conditions before and after the subjects were immersed in a water tub up to the umbilical level for 20 min. COP standard deviation (SD) and COP velocity were analyzed in the anterior-posterior (AP) and medial-lateral (ML) directions. Statistical analysis showed that in the bipedal condition cryotherapy increased the COP SD and COP velocity in the ML direction. During the unipedal condition, a higher COP velocity in the AP and ML directions was also reported. Our findings indicate that cryotherapy by immersing the whole lower limb should be used with caution before engaging in challenging postural control activities. PMID:24631278

  14. Factors affecting leukocyte count in healthy adults.

    PubMed

    Carel, R S; Eviatar, J

    1985-09-01

    The relationships between white blood cell (WBC) count, smoking, and other health variables were determined among 35,000 apparently healthy men and women. The effect of smoking on the WBC count was greater than that of all other variables. The leukocyte level and the variance in WBC count values increased with increased smoking intensity. The relationship between smoking intensity and leukocyte level is expressed quantitatively by the following regression equation: WBC (10(3)/mm3) = 7.1 + 0.05(SM), where SM has seven values according to the smoking level. Multiple regression analysis with additional variables other than smoking did not much improve the predictive value of the equation. The effect of smoking on WBC count could be only partially explained by an inflammatory process, e.g., chronic bronchitis. Relationships of statistical significance (but mostly with r values of less than 0.10) were found between WBC count and the following variables: hemoglobin, heart rate, weight (or Quetelet index), cholesterol, uric acid, creatinine, sex, ethnic origin, systolic blood pressure, height, blood sugar, and diastolic blood pressure. The normal WBC count range for smokers differs from that of nonsmokers and is shifted to the right according to the smoking level. This may have both a diagnostic and prognostic significance in different clinical settings. PMID:4070192

  15. Effect of Carum carvi, a herbal bioenhancer on pharmacokinetics of antitubercular drugs: A study in healthy human volunteers

    PubMed Central

    Choudhary, Naiyma; Khajuria, Vijay; Gillani, Zahid H.; Tandon, Vishal R.; Arora, Ekta

    2014-01-01

    Aim and Objectives: The present study was undertaken in 20 healthy human volunteers to evaluate the effect of a herbal bioenhancer, Carum carvi on pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in fixed dose combination (FDC). Materials and Methods: It was a prospective, two-period, open-label, cross-over experiment on 20 healthy human male volunteers. The volunteers were administered a single dose of FDC containing rifampicin (450 mg), isoniazid (300 mg), and pyrazinamide (1000 mg) and after 10 days washout period the same FDC along with C. carvi extract (100 mg) was administered. Blood samples were collected at different time-points and analyzed by high-performance liquid chromatography (HPLC). Detailed pharmacokinetic parameters were calculated, which included Cmax, area under curve (AUC), time to reach maximum plasma concentration (Tmax), clearance (Cl), volume of distribution (Vd), and half-life (t½). Results: Additions of C. carvi extract lead to increase in plasma levels of rifampicin, isoniazid, and pyrazinamide. The bioavailability indices Cmax of rifampicin increased from 4.57 ± 0.19 to 5.95 ± 0.19 (P = 0.000) and AUC increased from 40.11 ± 1.69 to 53.01 ± 1.88 (P = 0.000). Similarly, Cmax of isoniazid increased from 2.66 ± 0.16 to 3.62 ± 0.16 (P = 0.000) and AUC from 17.72 ± 0.78 to 22.87 ± 0.94 (P = 0.000). The bioavailability indices of pyrazinamide also revealed an increase in Cmax from 18.81 ± 0.79 to 25.06 ± 1.14 (P = 0.000) and AUC from 107.65 ± 4.42 to 137.71 ± 5.92 (P = 0.000), respectively. Conclusion: C. carvi acts as a bioenhancer and modifies the kinetics of antitubercular treatment (ATT) favorably. PMID:24741485

  16. Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

    PubMed

    Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

    2014-07-01

    We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values. PMID:24788075

  17. Predicting future years of healthy life for older adults.

    PubMed

    Diehr, P; Patrick, D L; Bild, D E; Burke, G L; Williamson, J D

    1998-04-01

    Cost-effectiveness studies often need to compare the cost of a program to the lifetime benefits of the program, but estimates of lifetime benefits are not routinely available, especially for older adults. We used data from two large longitudinal studies of older adults (ages 65-100) to estimate transition probabilities from one health state to another, and used those probabilities to estimate the mean additional years of healthy life that an older adult of specified age, sex, and health status would experience. We found, for example, that 65-year-old women in excellent health can expect 16.8 years of healthy life in the future, compared to only 8.5 years for women in poor health. We also provide estimates of discounted years of healthy life and future life expectancy. These estimates may be used to extend the effective length of the study period in cost-effectiveness studies, to examine the impact of chronic diseases or risk factors on years of healthy life, or to investigate the relationship of years of life to years of healthy life. Several applications are described. PMID:9539891

  18. Modulation, Adaptation, and Control of Orofacial Pathways in Healthy Adults

    ERIC Educational Resources Information Center

    Estep, Meredith E.

    2009-01-01

    Although the healthy adult possesses a large repertoire of coordinative strategies for oromotor behaviors, a range of nonverbal, speech-like movements can be observed during speech. The extent of overlap among sensorimotor speech and nonspeech neural correlates and the role of neuromodulatory inputs generated during oromotor behaviors are unknown.…

  19. Understanding Arthritis Promoting Healthy Lifestyles for Older Adults

    ERIC Educational Resources Information Center

    Tremethick, Mary Jane; Hogan, Patricia I.; Coleman, Barb; Adams, Kady

    2010-01-01

    One of the goals of "Healthy People 2010" is to decrease the incidence of limitation in physical activity due to arthritis. Physical education, recreation, and dance professionals can play an important role in meeting this objective by addressing barriers to physical activity and exercise in older adults with arthritis, and by successfully…

  20. Promoting Healthy Aging in Adults with Developmental Disabilities

    ERIC Educational Resources Information Center

    Heller, Tamar; Sorensen, Amy

    2013-01-01

    This article reviews the research on health promotion for adults aging with developmental disabilities. First, it examines barriers to healthy aging, including health behaviors and access to health screenings and services. Second, it reviews the research on health promotion interventions, including physical activity interventions, health education…

  1. Predictive Accuracy of Exercise Stress Testing the Healthy Adult.

    ERIC Educational Resources Information Center

    Lamont, Linda S.

    1981-01-01

    Exercise stress testing provides information on the aerobic capacity, heart rate, and blood pressure responses to graded exercises of a healthy adult. The reliability of exercise tests as a diagnostic procedure is discussed in relation to sensitivity and specificity and predictive accuracy. (JN)

  2. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

    PubMed

    Pastore, Robert L; Brooks, Judith T; Carbone, John W

    2015-06-01

    Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations. PMID:26003334

  3. Arrhythmias Seen in Baseline 24-Hour Holter ECG Recordings in Healthy Normal Volunteers During Phase 1 Clinical Trials.

    PubMed

    Hingorani, Pooja; Karnad, Dilip R; Rohekar, Prashant; Kerkar, Vaibhav; Lokhandwala, Yash Y; Kothari, Snehal

    2016-07-01

    Regulatory agencies encourage sponsors to submit 24-hour ambulatory ECG data for assessing cardiac safety of new drugs, and some arrhythmias, hitherto considered rare, have been observed in some early-phase studies. Interpretation of these observations is difficult given the dearth of published data on the prevalence of cardiac arrhythmias seen during 24-hour continuous ECG monitoring in healthy volunteers (HV) from clinical trials. We analyzed drug-free ambulatory ECG recordings from 1273 HV (1000 males, 273 females; age 18-65 years) from 22 phase 1 studies that were analyzed in a core ECG laboratory; all subjects had normal screening ECGs. Supraventricular arrhythmias such as supraventricular premature complexes were observed in 60.8% of healthy volunteers, supraventricular tachycardia in 2.2%, and atrial fibrillation in 0.1%. Ventricular arrhythmias included premature ventricular complexes (PVCs) in 43.4%, >200 PVCs per 24 hours in 3.3%, multifocal PVCs in 5.3%, nonsustained ventricular tachycardia in 0.7%, and accelerated idioventricular rhythm in 0.3%. Bradyarrhythmias included sinus pause >3 seconds in 0.3%, and second-degree AV block in 2.4%. Complete heart block and torsades de pointes were not seen in any subject. Based on the observed incidence, we estimated the maximum number of healthy subjects in whom these arrhythmias may be seen as a matter of chance in studies with smaller sample sizes if the study drug has no arrhythmogenic effect. Our results and these estimates could help interpret whether cardiac arrhythmias observed in early-phase studies are due to chance or possibly are a drug effect. PMID:26626443

  4. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers

    PubMed Central

    Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-01-01

    Abstract Background: There are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure. Methods: We observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named “Fill & Flush Drainage Method” was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff. Results: We measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85). Conclusions: NIRFLI, a transparent sphygmomanometer cuff and the “Fill and Flush” manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature. PMID:27167187

  5. Antiplatelet effects of dietary nitrate in healthy volunteers: involvement of cGMP and influence of sex.

    PubMed

    Velmurugan, Shanti; Kapil, Vikas; Ghosh, Suborno M; Davies, Sheridan; McKnight, Andrew; Aboud, Zainab; Khambata, Rayomand S; Webb, Andrew J; Poole, Alastair; Ahluwalia, Amrita

    2013-12-01

    Ingestion of vegetables rich in inorganic nitrate has emerged as an effective method, via the formation of a nitrite intermediate, for acutely elevating vascular NO levels. As such a number of beneficial effects of dietary nitrate ingestion have been demonstrated including the suggestion that platelet reactivity is reduced. In this study we investigated whether inorganic nitrate supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen. We conducted two randomised crossover studies each in 24 (12 of each sex) healthy subjects assessing the acute effects of dietary nitrate (250 ml beetroot juice) or potassium nitrate capsules (KNO3, 8 mmol) vs placebo control on platelet reactivity. Inorganic nitrate ingested either from a dietary source or via supplementation raised circulating nitrate and nitrite levels in both sexes and attenuated ex vivo platelet aggregation responses to ADP and, albeit to a lesser extent, collagen but not epinephrine in male but not female volunteers. These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cGMP levels. In addition, we show that nitrite reduction to NO occurs at the level of the erythrocyte and not the platelet. In summary, our results demonstrate that inorganic nitrate ingestion, whether via the diet or through supplementation, causes a modest decrease in platelet reactivity in healthy males but not females. Our studies provide strong support for further clinical trials investigating the potential of dietary nitrate as an adjunct to current antiplatelet therapies to prevent atherothrombotic complications. Moreover, our observations highlight a previously unknown sexual dimorphism in platelet reactivity to NO and intimate a greater dependence of males on the NO-soluble guanylate cyclase pathway in limiting thrombotic potential. PMID:23806384

  6. Antiplatelet effects of dietary nitrate in healthy volunteers: Involvement of cGMP and influence of sex☆

    PubMed Central

    Velmurugan, Shanti; Kapil, Vikas; Ghosh, Suborno M.; Davies, Sheridan; McKnight, Andrew; Aboud, Zainab; Khambata, Rayomand S.; Webb, Andrew J.; Poole, Alastair; Ahluwalia, Amrita

    2013-01-01

    Ingestion of vegetables rich in inorganic nitrate has emerged as an effective method, via the formation of a nitrite intermediate, for acutely elevating vascular NO levels. As such a number of beneficial effects of dietary nitrate ingestion have been demonstrated including the suggestion that platelet reactivity is reduced. In this study we investigated whether inorganic nitrate supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen. We conducted two randomised crossover studies each in 24 (12 of each sex) healthy subjects assessing the acute effects of dietary nitrate (250 ml beetroot juice) or potassium nitrate capsules (KNO3, 8 mmol) vs placebo control on platelet reactivity. Inorganic nitrate ingested either from a dietary source or via supplementation raised circulating nitrate and nitrite levels in both sexes and attenuated ex vivo platelet aggregation responses to ADP and, albeit to a lesser extent, collagen but not epinephrine in male but not female volunteers. These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cGMP levels. In addition, we show that nitrite reduction to NO occurs at the level of the erythrocyte and not the platelet. In summary, our results demonstrate that inorganic nitrate ingestion, whether via the diet or through supplementation, causes a modest decrease in platelet reactivity in healthy males but not females. Our studies provide strong support for further clinical trials investigating the potential of dietary nitrate as an adjunct to current antiplatelet therapies to prevent atherothrombotic complications. Moreover, our observations highlight a previously unknown sexual dimorphism in platelet reactivity to NO and intimate a greater dependence of males on the NO-soluble guanylate cyclase pathway in limiting thrombotic potential. PMID:23806384

  7. The effect of prone positioning with surgical bolsters on liver blood flow in healthy volunteers.

    PubMed

    Chikhani, M; Evans, D L; Blatcher, A W; Jackson, A P; Guha, I N; Aithal, G P; Moppett, I K

    2016-05-01

    This study sought to identify changes in hepatic flood flow and cardiac output during prone positioning on surgical bolsters in awake volunteers, and was prompted by a local incident of significant hepatic dysfunction following surgery in the prone position. Cardiac output was determined using the non-invasive Peñáz technique, and plasma disappearance rate of indocyanine green (ICG-PDR) was measured as a surrogate maker for hepatic blood flow along with serum hepatic enzyme assays. Measurements were made after one hour in supine, prone and returned supine positions. Ten volunteers completed the study. There were significant changes in the disappearance rate of indocyanine green, which decreased this from mean (SD) 31.1 (9.70) supine to 19.6 (4.37)%.min prone, respectively (p = 0.02), increasing on return to the supine position to 24.6 (5.54)%.min (p = 0.019). Cardiac output was also significantly reduced when changing from the supine to the prone position, from mean (SD) 4.7 (1.0 to 3.5 (1.1) (l.min(-1) ), respectively (p = 0.002). We demonstrated an acute and reversible change in both hepatocellular function and cardiac output associated with the prone position. PMID:26948476

  8. Activity Levels in Healthy Older Adults: Implications for Joint Arthroplasty

    PubMed Central

    Thorp, Laura E.; Orozco, Diego; Block, Joel A.; Sumner, Dale R.; Wimmer, Markus A.

    2012-01-01

    This work evaluated activity levels in a group of healthy older adults to establish a target activity level for adults of similar age after total joint arthroplasty (TJA). With the decreasing age of TJA patients, it is essential to have a reference for activity level in younger patients as activity level affects quality of life and implant design. 54 asymptomatic, healthy older adults with no clinical evidence of lower extremity OA participated. The main outcome measure, average daily step count, was measured using an accelerometer-based activity monitor. On average the group took 8813 ± 3611 steps per day, approximately 4000 more steps per day than has been previously reported in patients following total joint arthroplasty. The present work provides a reference for activity after joint arthroplasty which is relevant given the projected number of people under the age of 65 who will undergo joint arthroplasty in the coming years. PMID:23577274

  9. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

    PubMed Central

    2010-01-01

    Background Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no

  10. Respiratory effects of fine and ultrafine particles from indoor sources--a randomized sham-controlled exposure study of healthy volunteers.

    PubMed

    Soppa, Vanessa J; Schins, Roel P F; Hennig, Frauke; Hellack, Bryan; Quass, Ulrich; Kaminski, Heinz; Kuhlbusch, Thomas A J; Hoffmann, Barbara; Weinmayr, Gudrun

    2014-07-01

    Particulate air pollution is linked to impaired respiratory health. We analyzed particle emissions from common indoor sources (candles burning (CB), toasting bread (TB), frying sausages (FS)) and lung function in 55 healthy volunteers (mean age 33.0 years) in a randomized cross-over controlled exposure study. Lung-deposited particle surface area concentration (PSC), size-specific particle number concentration (PNC) up to 10 µm, and particle mass concentration (PMC) of PM1, PM2.5 and PM10 were determined during exposure (2 h). FEV1, FVC and MEF25%-75% was measured before, 4 h and 24 h after exposure. Wilcoxon-rank sum tests (comparing exposure scenarios) and mixed linear regression using particle concentrations and adjusting for personal characteristics, travel time and transportation means before exposure sessions were performed. While no effect was seen comparing the exposure scenarios and in the unadjusted model, inverse associations were found for PMC from CB and FS in relation to FEV1 and MEF25%-75%. with a change in 10 µg/m3 in PM2.5 from CB being associated with a change in FEV1 of -19 mL (95%-confidence interval:-43; 5) after 4 h. PMC from TB and PNC of UFP were not associated with lung function changes, but PSC from CB was. Elevated indoor fine particles from certain sources may be associated with small decreases in lung function in healthy adults. PMID:25000149

  11. Effect of NR-Salacia on post-prandial hyperglycemia: A randomized double blind, placebo-controlled, crossover study in healthy volunteers

    PubMed Central

    Koteshwar, Pravina; Raveendra, Kadur Ramamurthy; Allan, Joseph Joshua; Goudar, Krishnagouda Shankargouda; Venkateshwarlu, Kudiganti; Agarwal, Amit

    2013-01-01

    Background: Salacia chinensis (S. chinensis) is widely distributed in India and Sri Lanka. Most of the species of genus Salacia are known to have effects on blood glucose levels; however, the effects of S. chinensis on glucose levels are seldom reported. Objective: To evaluate the oral hypoglycemic activity of NR- Salacia (1000 mg extract of S. chinensis) in healthy adults. Materials and Methods: Randomized, double-blind, placebo-controlled, cross-over study was conducted in healthy volunteers. Single dose of NR-Salacia (1000 mg extract of Salacia chinensis) and placebo were administered before carbohydrate-rich diet. A 6-point plasma glucose profile was performed at different time intervals up to 180 min. Results: NR-Salacia treatment significantly lowered plasma glucose level at 90 min, and the percentage reduction in glucose concentration was found to be 13.32 as compared to placebo group. A 33.85% decrease in the plasma glucose positive incremental area under curve (AUC) (0 to 180 min) was observed in comparison to placebo. No adverse events were recorded throughout the study period, except for some mild cases of abdominal discomforts like cramping and distention, vomiting, and headache in both placebo and NR-Salacia-treated groups. Conclusion: The study findings revealed that NR-Salacia lowered the post-prandial plasma glucose levels after a carbohydrate-rich meal and can be used as an oral hypoglycemic agent. PMID:24124287

  12. Respiratory Effects of Fine and Ultrafine Particles from Indoor Sources—A Randomized Sham-Controlled Exposure Study of Healthy Volunteers

    PubMed Central

    Soppa, Vanessa J.; Schins, Roel P. F.; Hennig, Frauke; Hellack, Bryan; Quass, Ulrich; Kaminski, Heinz; Kuhlbusch, Thomas A. J.; Hoffmann, Barbara; Weinmayr, Gudrun

    2014-01-01

    Particulate air pollution is linked to impaired respiratory health. We analyzed particle emissions from common indoor sources (candles burning (CB), toasting bread (TB), frying sausages (FS)) and lung function in 55 healthy volunteers (mean age 33.0 years) in a randomized cross-over controlled exposure study. Lung-deposited particle surface area concentration (PSC), size-specific particle number concentration (PNC) up to 10 µm, and particle mass concentration (PMC) of PM1, PM2.5 and PM10 were determined during exposure (2 h). FEV1, FVC and MEF25%–75% was measured before, 4 h and 24 h after exposure. Wilcoxon-rank sum tests (comparing exposure scenarios) and mixed linear regression using particle concentrations and adjusting for personal characteristics, travel time and transportation means before exposure sessions were performed. While no effect was seen comparing the exposure scenarios and in the unadjusted model, inverse associations were found for PMC from CB and FS in relation to FEV1 and MEF25%–75%. with a change in 10 µg/m3 in PM2.5 from CB being associated with a change in FEV1 of −19 mL (95%-confidence interval:−43; 5) after 4 h. PMC from TB and PNC of UFP were not associated with lung function changes, but PSC from CB was. Elevated indoor fine particles from certain sources may be associated with small decreases in lung function in healthy adults. PMID:25000149

  13. Pharmacokinetics and tolerability of single oral doses of 882C87, a potent, new anti-varicella-zoster virus agent, in healthy volunteers.

    PubMed Central

    Peck, R W; Weatherley, B C; Wootton, R; Crome, P; Holdich, T A; Posner, J

    1995-01-01

    882C87 is a nucleoside analog with potent, specific activity against varicella-zoster virus. It is approximately seven times as potent as acyclovir with an in vitro 50% inhibitory concentration of 1 to 2 microM. The tolerability and pharmacokinetics of single doses of 882C87 have been investigated in a series of studies with healthy young and elderly adult volunteers. The young received 50 to 1,600 mg, and the elderly received 50 and 100 mg. Concentrations of 882C87 and its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5PU), in plasma and urine were assayed by an automated sequential trace enrichment of dialysate-high-performance liquid chromatography procedure, and noncompartmental pharmacokinetic parameters were derived from the data. Concentrations of 882C87 in plasma increased proportionally for doses of up to 400 mg, but after higher doses the increase was less than dose proportional. In young adults, after 200, 400, and 1,600 mg, the maximum concentrations of the drug in plasma were 9.0, 16.3, and 34.7 microM, respectively, and the areas under the concentration-time curve (AUC) from 0 h to infinity were 166.6, 333.7, and 822.9 microM.h, respectively. Elimination half-life was 11.3 to 13.0 h after 50 to 400 mg, increasing to 15.3 h after 1,600 mg, associated with a small decrease in renal clearance. In healthy elderly volunteers concentrations of 882C87 in plasma after 50 and 100 mg were similar to those in young adults after twice the dose; apparent clearance and renal clearance were significantly reduced, and half-life was significantly longer at 15 h. Administration of 882C87 with food produced a small, nonsignificant reduction in mean AUC from 0 h to infinity, but in subjects with a low fasting AUC there was an increase after food and in subjects with a high fasting AUC there was a decrease. Concentrations of 5PU in plasma were one-third to one-half those of 882C87 and, in most subjects, were not dose proportional. There was a lag of at least

  14. Respiratory responses to laboratory-generation acid fog in healthy and asthmatic volunteers

    SciTech Connect

    Avol, E.L.; Linn, W.S.; Hackney, J.D. )

    1987-01-01

    The authors discuss a program to provide a first step towards assessing acute health-related effects of acid fog exposure. Polluted ambient fog was simulated in a laboratory exposure chamber. Volunteer subjects were purposely exposed and studied during periods of exercise and rest while in the challenge atmosphere. Respiratory responses were measured by methods used to assess effects of irritant gases and dry'' respirable aerosols. When a pilot study showed no obvious unfavorable effects with ambient-like pollution conditions, the exposure concentrations for the present study were extended into the occupational range, well above ambient levels. Sulfuric acid was selected for use as the test pollutant, based upon previous research experience and the availability of fog data documenting its presence during ambient fog episodes.

  15. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers

    NASA Technical Reports Server (NTRS)

    Firstenberg, M. S.; Levine, B. D.; Garcia, M. J.; Greenberg, N. L.; Cardon, L.; Morehead, A. J.; Zuckerman, J.; Thomas, J. D.

    2000-01-01

    OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

  16. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI: initial results in animals and healthy volunteers.

    PubMed

    Dregely, Isabel; Ruset, Iulian C; Mata, Jaime F; Ketel, Jeffrey; Ketel, Steve; Distelbrink, Jan; Altes, Talissa A; Mugler, John P; Wilson Miller, G; William Hersman, F; Ruppert, Kai

    2012-04-01

    Hyperpolarized xenon-129 is a noninvasive contrast agent for lung MRI, which upon inhalation dissolves in parenchymal structures, thus mirroring the gas-exchange process for oxygen in the lung. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI is an implementation of the XTC MRI technique in four dimensions (three spatial dimensions plus exchange time). The aim of this study was to evaluate the sensitivity of MXTC MRI for the detection of microstructural deformations of the healthy lung in response to gravity-induced tissue compression and the degree of lung inflation. MXTC MRI was performed in four rabbits and in three healthy human volunteers. Two lung function parameters, one related to tissue- to alveolar-volume ratio and the other to average septal-wall thickness, were determined regionally. A significant gradient in MXTC MRI parameters, consistent with gravity-induced lung tissue deformation in the supine imaging position, was found at low lung volumes. At high lung volumes, parameters were generally lower and the gradient in parameter values was less pronounced. Results show that MXTC MRI permits the quantification of subtle changes in healthy lung microstructure. Further, only structures participating in gas exchange are represented in MXTC MRI data, which potentially makes the technique especially sensitive to pathological changes in lung microstructure affecting gas exchange. PMID:22213334

  17. INTERACTIVE VIDEO DANCE GAMES FOR HEALTHY OLDER ADULTS

    PubMed Central

    STUDENSKI, S.; PERERA, S.; HILE, E.; KELLER, V.; SPADOLA-BOGARD, J.; GARCIA, J.

    2016-01-01

    Background Physical activity promotes health in older adults but participation rates are low. Interactive video dance games can increase activity in young persons but have not been designed for use with older adults. The purpose of this research was to evaluate healthy older adults’ interest and participation in a dance game adapted for an older user. Methods Healthy older adults were recruited from 3 senior living settings and offered three months of training and supervision using a video dance game designed for older people. Before and after the program, data was collected on vital signs, physical function and self reported quality of life. Feedback was obtained during and after training. Results Of 36 persons who entered (mean age 80.1 ± 5.4 years, 83 % female), 25 completed the study. Completers were healthier than non completers. Completers showed gains in narrow walk time, self-reported balance confidence and mental health. While there were no serious adverse events, 4 of 11 non completers withdrew due to musculoskeletal complaints. Conclusions Adapted Interactive video dance is feasible for some healthy older adults and may help achieve physical activity goals. PMID:21125204

  18. Volunteering as a Pathway to Productive and Social Engagement among Older Adults

    ERIC Educational Resources Information Center

    Morrow-Howell, Nancy; Lee, Yung Soo; McCrary, Stacey; McBride, Amanda

    2014-01-01

    Introduction: Research on outcomes of volunteering in later life largely focuses on the health of volunteers. This is in contrast to studies of youth, where attention is directed toward the effects of volunteering on subsequent productive and citizen behaviors. In this study, we examined the effects of volunteering on subsequent social and civic…

  19. T cell subset profile in healthy Zambian adults at the University Teaching Hospital

    PubMed Central

    Chisenga, Caroline Cleopatra; Kelly, Paul

    2016-01-01

    Introduction Symptom-free human immunodeficiency virus antibody-negative Zambian adults (51 subjects, aged 20 to 62 years, 33.3% women and 66.7% men) were studied to establish T cell subset reference ranges. Methods We carried out across sectional study at the University Teaching Hospital, Lusaka. Blood samples were collected from healthy donor volunteers from hospital health care staff, between February and March 2015. Immunopheno typing was undertaken to characterize Tcell subsets using the markers CD3, CD4, CD8, α4β7, Ki67, CD25, CCR7, CD54RA, CD57, CD28, CD27 and HLA-DR. Results Among 51 volunteers, Women had significantly higher absolute CD4 count (median 1042; IQR 864, 1270) than in men (671; 545, 899) (p=0.003). Women also had more CD4 cells expressing homing, naïve, effector and effector memory T cell subsets compared to men. However, in the CD8 population, only the effector cells were significantly different with women expressing more than the males. Conclusion We provide early reference range for T cell subsets in Zambian adults and conclude that among the African women some T cell subsets are higher than men. PMID:27231509

  20. Pharmacokinetic parameters of nandrolone (19-nortestosterone) after intramuscular administration of nandrolone decanoate (Deca-Durabolin) to healthy volunteers.

    PubMed

    Wijnand, H P; Bosch, A M; Donker, C W

    1985-01-01

    Nandrolone decanoate (Deca-Durabolin) was injected intramuscularly into healthy volunteers. One group of females received one injection of 100 mg and three groups of males received one injection of 200 mg, two repeat injections of 100 mg or four repeat injections of 50 mg respectively. The serum levels of nandrolone (19-nortestosterone) were determined by radioimmunoassay and used to estimate pharmacokinetic parameters. The following pharmacokinetic parameters were found: a mean half-life of 6 days for the release of the ester from the muscular injection depot into the general circulation; a mean half-life of 4.3 h for the combined processes of hydrolysis of nandrolone decanoate and of distribution and elimination of nandrolone; a mean nandrolone serum clearance of 1.55 1 X h-1 X kg-1. The half-life of hydrolysis of nandrolone decanoate in serum was of the order of one hour or less. The data are consistent with linear kinetics. PMID:3865478

  1. Study on Yang-Xu Using Body Constitution Questionnaire and Blood Variables in Healthy Volunteers

    PubMed Central

    Chen, Hong-Jhang; Lin, Yii-Jeng; Wu, Pei-Chen; Hsu, Wei-Hsiang; Hu, Wan-Chung; Wu, Trong-Neng; Chen, Fang-Pey; Lin, Yun-Lian

    2016-01-01

    Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC. PMID:27340421

  2. Effect of a modified guar gum preparation on glucose and lipid levels in diabetics and healthy volunteers.

    PubMed

    Smith, U; Holm, G

    1982-10-01

    Six healthy volunteers and 17 diabetics (6 insulin-dependent and 11 diet- and tablet-treated) were treated with a special processed, palatable guar gum (10 g b.i.d. immediately before meals) for periods of one or three weeks or, in some cases, up to 13 weeks. A standardized test meal was given to study the effect of the fiber on postprandial glucose levels. Ten g guar was stirred in water and taken immediately before the test meal. The postprandial blood glucose levels were similar in the healthy volunteers but significantly lower in the diabetics following treatment with guar for one and three weeks, respectively. Furthermore, the fasting blood glucose levels were significantly lower in the diabetics after three, but not one, weeks of treatment. The lower postprandial glucose levels were coupled with attenuated and delayed insulin levels in accordance with an effect of guar gum on the rate of carbohydrate absorption. The cholesterol levels were on average reduced with 14% in the diabetics following three weeks' treatment with guar. The higher the initial cholesterol level, the greater the reduction in cholesterol; 26% reduction was achieved in four patients with initial levels above 7 mM. The alpha-lipoprotein cholesterol levels were not significantly changed, thus an increase in the alpha-lipoprotein cholesterol/total serum cholesterol ratio was obtained. Neither plasma triglycerides nor body weights altered during treatment. The reported side-effects were as expected and were usually mild and transient (e.g. increased flatulence). The data show that guar gum also reduces postprandial glucose levels on a long-term basis and may improve the diabetic control. Additionally, treatment with this fiber leads to a concentration-dependent decrease in cholesterol levels. PMID:6297515

  3. Near-infrared spectroscopy extended with indocyanine green dye dilution for cerebral blood flow measurement: Median values in healthy volunteers

    NASA Astrophysics Data System (ADS)

    Mudra, R.; Muroi, C.; Niederer, P.; Keller, E.

    2008-09-01

    The cerebral blood flow (CBF) is an important vital parameter in neurointensive care. Currently, there is no non-invasive method for its measurement that can easily be applied at the bedside. A new tool to determine CBF is based on near-infrared spectroscopy (NIRS) applied together with indocyanine green (ICG) dye dilution. From a bilateral measurement on selected regions on the head of infrared (IR) absorption at various wavelengths during the dilution maneuver, the vascular perfusion characteristics of the two brain hemispheres can be determined in terms of mean transit time (mtt) of ICG, cerebral blood volume (CBV) and CBF. So far, on nine healthy volunteers, NIRS ICG dye dilution bihemispheric measurements were performed, which yielded to mtt given as median (range) of 9.3 s (5.1-16.3 s), CBV of 3.5 ml/100 g (1.7-4.1 ml/100 g), and CBF of 18.2 ml/(100 g×min) [11.1-48.6 ml/(100 g×min)]. Additionally, the blood flow index (BFI) was calculated with BFI= 13.8 mg/(100 g×s) [6.6-15.2 mg/(100 g×s)]. The Spearman rank correlation coefficient between CBF and BFI was RS = 0.76. However, as the Bland & Altman plot between CBFNIRS and the CBFBFI documents, the limits of agreement are rather wide (21.9±6.7). Under physiological conditions in healthy volunteers, no differences could be detected between the hemispheres.

  4. Different effects of the selective serotonin reuptake inhibitors fluvoxamine, paroxetine, and sertraline on the pharmacokinetics of fexofenadine in healthy volunteers.

    PubMed

    Saruwatari, Junji; Yasui-Furukori, Norio; Niioka, Takenori; Akamine, Yumiko; Takashima, Ayaka; Kaneko, Sunao; Uno, Tsukasa

    2012-04-01

    Although the interaction between selective serotonin reuptake inhibitors (SSRIs) and other drugs is important in the treatment of depression, there have been few studies of SSRIs concerning transporter-mediated interactions in humans. The objective of this study was to evaluate the in vivo effects of commonly used SSRIs on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate.Twelve healthy volunteers (3 females and 9 males) were enrolled in this study. Each subject received a 60-mg dose of fexofenadine orally at baseline. Afterward, they were randomly assigned to receive 3 treatments with a 60-mg dose of fexofenadine after a 7-day treatment with fluvoxamine (50 mg/d), paroxetine (20 mg/d), or sertraline (50 mg/d), with 2-week intervals between the agents.Fluvoxamine pretreatment significantly increased the maximum plasma concentration, the area under the concentration time curves, and the 24-hour urinary fexofenadine excretion by 66% (P = 0.004), 78% (P = 0.029), and 78% (P < 0.001), respectively, without prolonging its elimination half-life. Paroxetine extended the elimination half-life of fexofenadine by 45% (P = 0.042), and it increased the 24-hour urinary fexofenadine excretion by 55% (P = 0.002). Sertraline did not alter any of the pharmacokinetic parameters of fexofenadine.This is the first report of the different effects of 3 commonly used SSRIs on fexofenadine pharmacokinetics in humans. Our 7-day, repeated-dose clinical study in healthy volunteers indicates that fluvoxamine and paroxetine, but not sertraline, may impact the patient exposure to fexofenadine, which is likely the result of P-glycoprotein inhibition in the small intestine and/or the liver. PMID:22367658

  5. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers

    PubMed Central

    Barbour, April M; Sarov-Blat, Lea; Cai, Gengqian; Fossler, Michael J; Sprecher, Dennis L; Graggaber, Johann; McGeoch, Adam T; Maison, Jo; Cheriyan, Joseph

    2013-01-01

    Aims The purpose of this study was to establish safety and tolerability of a single intravenous (IV) infusion of a p38 mitogen-activated protein kinase inhibitor, losmapimod, to obtain therapeutic levels rapidly for a potential acute coronary syndrome indication. Pharmacokinetics (PK) following IV dosing were characterized, and pharmacokinetic/pharmacodynamic (PK/PD) relationships between losmapimod and phosphorylated heat shock protein 27 (pHSP27) and high-sensitivity C-reactive protein were explored. Methods Healthy volunteers received 1 mg losmapimod IV over 15 min (n = 4) or 3 mg IV over 15 min followed by a washout period and then 15 mg orally (PO; n = 12). Pharmacokinetic parameters were calculated by noncompartmental methods. The PK/PD relationships were explored using modelling and simulation. Results There were no deaths, nonfatal serious adverse events or adverse events leading to withdrawal. Headache was the only adverse event reported more than once (n = 3 following oral dosing). Following 3 mg IV and 15 mg PO, Cmax was 59.4 and 45.9 μg l−1 and AUC0–∞ was 171.1 and 528.0 μg h l−1, respectively. Absolute oral bioavailability was 0.62 [90% confidence interval (CI) 0.56, 0.68]. Following 3 mg IV and 15 mg PO, maximal reductions in pHSP27 were 44% (95% CI 38%, 50%) and 55% (95% CI 50%, 59%) occurring at 30 min and 4 h, respectively. There was a 17% decrease (95% CI 9%, 24%) in high-sensitivity C-reactive protein 24 h following oral dosing. A direct-link maximal inhibitory effect model related plasma concentrations to pHSP27 concentrations. Conclusions A single IV infusion of losmapimod in healthy volunteers was safe and well tolerated, and may potentially serve as an initial loading dose in acute coronary syndrome as rapid exposure is achieved. PMID:23215699

  6. Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized placebo-controlled drug-drug interaction study.

    PubMed

    Spyker, Daniel A; Cassella, James V; Stoltz, Randall R; Yeung, Paul P

    2015-12-01

    Pharmacodynamic effects and safety of single-dose inhaled loxapine administered via the Staccato(®) system and intramuscular (IM) lorazepam in combination versus each agent alone were compared in a randomized, double-blind, crossover study in healthy volunteers. Subjects received: inhaled loxapine 10 mg + IM lorazepam 1 mg; inhaled loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo in random order, each separated by a 3-day washout. Primary endpoints were maximum effect (minimum value) and area under the curve (AUC) from baseline to 2 h post treatment for respirations/min and pulse oximetry. Least-squares means (90% confidence interval [CI]) for concomitant treatment versus each agent alone were derived and equivalence (no difference) confirmed if the 90% CI was within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 20.4 years; 61% male) completed the study. There was no difference between inhaled loxapine + IM lorazepam and either agent alone on respiration or pulse oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min ratios. BP and HR were no different for inhaled loxapine + IM lorazepam and each agent alone over a 12-h postdose period. Although the central nervous system sedative effects were observed for each treatment in healthy volunteers, the effect was greater following concomitant lorazepam 1 mg IM + inhaled loxapine 10 mg administration. There were no deaths, serious AEs, premature discontinuations due to AEs, or treatment-related AEs. PMID:27022468

  7. Effects of Oral Lycopene Supplementation on Vascular Function in Patients with Cardiovascular Disease and Healthy Volunteers: A Randomised Controlled Trial

    PubMed Central

    Gajendragadkar, Parag R.; Hubsch, Annette; Mäki-Petäjä, Kaisa M.; Serg, Martin; Wilkinson, Ian B.; Cheriyan, Joseph

    2014-01-01

    Aims The mechanisms by which a ‘Mediterranean diet’ reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV). Methods and Results We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine (basal nitric oxide (NO) synthase activity) were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: −45% to −10%, P = 0.008), despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: −1.6 to −0.9 mmol/L, P<0.001). Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: −30% to +30%, P = 0.85), also suggesting lycopene improved endothelial function. Conclusions Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. Trial Registration ClinicalTrials.gov NCT01100385 PMID:24911964

  8. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers.

    PubMed

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2013-01-01

    The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1-5; 200 mg bid Days 6-9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1-10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2-9) with either ticagrelor (200 mg bid Days 4-8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5-9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (Cmax), median time to Cmax (tmax), or mean area under the plasma concentration-time curve for the dosing interval (AUC0-τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean Cmax and AUC0-τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor. PMID:23249161

  9. A parallel design study to assess the bioequivalence of generic and branded hydroxychloroquine sulfate tablets in healthy volunteers.

    PubMed

    Liu, Y-M; Chen, Q; Zhang, M-Q; Liu, G-Y; Jia, J-Y; Pu, H-H; Liu, Y; Hu, C-Y; Lu, C; Wang, W; Cao, W-E; Song, B; Song, Y-X; Zhu, J-M; Yu, C

    2012-12-01

    Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first introduced as an antimalarial, and subsequently applied to the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers, especially in a Chinese population is limited, and this study was conducted to provide support for a generic product to obtain marketing authorization in China.The aim of the present study was to compare the pharmacokinetics and assess bioequivalence of a new generic test and the branded reference hydroxychloroquine sulfate tablets in healthy volunteers.This was a parallel, open-label, randomized, single-dose, 1-period fasting study. 54 healthy subjects were randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of the test or the reference formulation. 15 blood samples were collected and whole blood concentrations of HCQ were determined by a validated liquid chromatography-isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24 values were used to test for bioequivalence. The 2 formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%. Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events.54 healthy subjects were enrolled and completed the study (mean [SD] age, height, body weight, and BMI were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27 subjects per group. No formulation or sequence effects were observed. The mean values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6 and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The 90% CIs of the ratios of Cmax and AUC0

  10. Management of Recurrent Urinary Tract Infections in Healthy Adult Women

    PubMed Central

    Hickling, Duane R; Nitti, Victor W

    2013-01-01

    Recurrence after urinary tract infection (rUTI) is common in adult women. The majority of recurrences are believed to be reinfection from extraurinary sources such as the rectum or vagina. However, uropathogenic Escherichia coli are now known to invade urothelial cells and form quiescent intracellular bacterial reservoirs. Management of women with frequent symptomatic rUTI can be particularly vexing for both patients and their treating physicians. This review addresses available and promising management strategies for rUTI in healthy adult women. PMID:24082842

  11. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Avol, E.L.

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m/sup 3/. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m/sup 3/. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  12. Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers

    PubMed Central

    Alolga, Raphael N.; Fan, Yong; Zhang, Gang; Li, Jin; Zhao, Yi-Jing; Lelu Kakila, Jimmy; Chen, Yan; Li, Ping; Qi, Lian-Wen

    2015-01-01

    K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4–10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects. PMID:26268432

  13. Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers.

    PubMed

    Alolga, Raphael N; Fan, Yong; Zhang, Gang; Li, Jin; Zhao, Yi-Jing; Lelu Kakila, Jimmy; Chen, Yan; Li, Ping; Qi, Lian-Wen

    2015-01-01

    K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4-10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects. PMID:26268432

  14. Effects of orthosis on balance and gait in healthy adults

    PubMed Central

    Kim, Myung-Joon; Choi, Yeong-Deok; Lee, Jung-Ho

    2015-01-01

    [Purpose] This study evaluated the effects of an oral orthosis that can change body alignment on the balance ability and gait of healthy adults. [Subjects and Methods] The subjects of this study were 21 University students. A gait analyzer was used to analyze the subjects’ balance ability and gait quality. Two walking speeds were used: 2 km/h, a comfortable speed, and 4 km/h, a slightly faster walking speed. [Results] The step length, and base of gait at 2 km/h differed significantly after the intervention. The total step time and step length increased significantly after the intervention. Furthermore, the total base of gait decreased significantly after the intervention. The step times of the left lower limb at 4 km/h differed significantly after the intervention. [Conclusion] The oral orthosis tested positively affects the balance ability and gait of healthy adults. PMID:26180365

  15. Healthy Older Adults Have Insufficient Hip Range of Motion and Plantar Flexor Strength to Walk Like Healthy Young Adults

    PubMed Central

    Anderson, Dennis E.; Madigan, Michael L.

    2014-01-01

    Limited plantar flexor strength and hip extension range of motion (ROM) in older adults are believed to underlie common age-related differences in gait. However, no studies of age-related differences in gait have quantified the percentage of strength and ROM used during gait. We examined peak hip angles, hip torques and plantar flexor torques, and corresponding estimates of functional capacity utilized (FCU), which we define as the percentage of available strength or joint ROM used, in ten young and ten older healthy adults walking under self-selected and controlled (slow and fast) conditions. Older adults walked with about 30% smaller hip extension angle, 28% larger hip flexion angle, 34% more hip extensor torque in the slow condition, and 12% less plantar flexor torque in the fast condition than young adults. Older adults had higher FCU than young adults for hip flexion angle (47% vs. 34%) and hip extensor torque (48% vs. 27%). FCUs for plantar flexor torque (both age groups) and hip extension angle (older adults in all conditions; young adults in self-selected gait) were not significantly <100%, and were higher than for other measures examined. Older adults lacked sufficient hip extension ROM to walk with a hip extension angle as large as that of young adults. Similarly, in the fast gait condition older adults lacked the strength to match the plantar flexor torque produced by young adults. This supports the hypothesis that hip extension ROM and plantar flexor strength are limiting factors in gait and contribute to age-related differences in gait. PMID:24461576

  16. Ultrasonographic Measurement of the Thickness of Axillary Recess Capsule in Healthy Volunteers

    PubMed Central

    2016-01-01

    Objective To evaluate the inter-rater and intra-rater reliability of ultrasonographic measurements of axillary recess (AR) thickness in healthy individuals, and to analyze the factors affecting the thickness of the AR capsule. Methods We recruited 20 healthy individuals (10 male, 10 female) with a mean age of 37 years (standard deviation ±10). Two physiatrists (an experienced and a novice rater) independently investigated the AR thickness in three rounds. The AR thickness was measured for each individual at three shoulder abduction angles (50°, 70°, and 90°). Intra-class correlation (ICC) coefficients were used to assess the reproducibility of each measurement. Results Excellent intra-rater reliability coefficients were observed at the three shoulder abduction angles, in the analysis of both raters. The inter-rater reliability coefficient was also was excellent in both studies. There were significant differences in the AR thickness, according to the angle of shoulder abduction. The AR was thicker at 50° than at 70° and 90° (all p<0.001), and the AR was thicker at 70° than at 90° (p<0.001). Height (r=0.62, p=0.003) and body mass index (r=0.52, p=0.019) were positively correlated with AR thickness. Males had a thicker AR capsule than females at all three angles (all p<0.001). Conclusion Ultrasonographic measurements of AR thickness in healthy individuals demonstrate excellent intra-rater and inter-rater reliability. AR thickness may depend on anthropometric variables and position of the shoulder. PMID:27446788

  17. Evaluation of peak cough flow in Brazilian healthy adults

    PubMed Central

    2012-01-01

    Introduction In this study we aimed to evaluate the peak cough flow (PCF) in healthy Brazilian subjects. Methods We evaluated 484 healthy subjects between 18 and 40 years old. Subjects were seated and oriented were asked to perform a maximal inspiration followed by a quick, short and explosive expiration on the peak flow meter. Three measures were carried out and recorded the average of the three results for each individual. Results The PCF values ranged between 240 and 500 L/min. The PCF values were lower in females than in males. The PCF was inversely proportional to age. Conclusion The values for Brazilian adult healthy subjects regarding PCF were between 240 and 500 L/min. PMID:23021434

  18. Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

    PubMed

    Bell, David; Gordon, Brian J; Lavery, Anita; Megaw, Katie; Kinney, Michael O; Harbinson, Mark T

    2016-02-01

    Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy. PMID:26767798

  19. On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers

    PubMed Central

    Vermeeren, Annemiek; Sun, Hong; Vuurman, Eric F.P.M.; Jongen, Stefan; Van Leeuwen, Cees J.; Van Oers, Anita C.M.; Palcza, John; Li, Xiadong; Laethem, Tine; Heirman, Ingeborg; Bautmans, An; Troyer, Matthew D.; Wrishko, Rebecca; McCrea, Jacqueline

    2015-01-01

    Study Objective: To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg. Design: Double-blind, placebo-controlled, 4-period crossover study. Setting: Maastricht University, The Netherlands. Participants: 28 healthy volunteers (15 females), aged 23 to 64 years. Interventions: Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo. Measurements: Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment. Results: Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < −2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests—all following suvorexant—stop prematurely due to self-reported somnolence. Conclusions: As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests. Clinical Trial Registration: clinicaltrials.gov NCT01311882. Citation: Vermeeren A, Sun H, Vuurman EF, Jongen S, Van Leeuwen CJ, Van Oers AC, Palcza J, Li X, Laethem T, Heirman I, Bautmans A, Troyer MD, Wrishko R, McCrea J. On-the-road driving performance the morning after bedtime use of suvorexant 20 and 40 mg: a study in non

  20. Influence of ethinyloestradiol propanolsulphonate on serum bile acids in healthy volunteers.

    PubMed

    Barth, Astrid; Klinger, Gottwalt; Rost, Michael

    2003-06-01

    The present work was done to clarify the relevance of altered serum bile acid (BA) profile in healthy women after the administration of the depot oestrogen ethinyloestradiol propanolsulphonate (EES). In the serum of 20 healthy women before and two times after oral EES application, 11 free and 14 taurine- and glycine-conjugated BA were analysed by HPLC with postcolumn derivatisation and fluorescence detection. EES significantly enhanced the total serum BA concentration and that of taurine-conjugated BAs, more pronounced the secondary BAs taurodeoxycholic, tauroursodeoxycholic and taurolithocholic acid. These secondary BAs are produced in the intestine by bacteria due to 7alpha-dehydroxylation of the primary BAs cholic and chenodeoxycholic acid. Because of unchanged free BAs, also produced by intestinal bacteria due to deconjugation, the results were interpreted as a sign of disturbed transport of BAs into the liver. Inhibition of the liver Na(+)-bile salt co-transporter (Ntcp) in the sinusoidal membrane by ethinyloestradiol, formed from the prodrug EES, may be responsible for the altered BA profile in serum. PMID:12877349

  1. Blood and breath levels of selected volatile organic compounds in healthy volunteers

    PubMed Central

    King, Julian; Klieber, Martin; Unterkofler, Karl; Hinterhuber, Hartmann; Baumann, Matthias

    2016-01-01

    Gas chromatography with mass spectrometric detection (GC-MS) was used to identify and quantify volatile organic compounds in the blood and breath of healthy individuals. Blood and breath volatiles were preconcentrated using headspace solid phase micro-extraction (HS-SPME) and needle trap devices (NTDs), respectively. The study involved a group of 28 healthy test subjects and resulted in the quantification of a total of 74 compounds in both types of samples. The concentrations of the species under study varied between 0.01 and 6700 nmol L−1 in blood and between 0.02 and 2500 ppb in exhaled air. Limits of detection (LOD) ranged from 0.01 to 270 nmol L−1 for blood compounds and from 0.01 to 0.7 ppb for breath species. Relative standard deviations for both measurement regimes varied from 1.5 to 14%. The predominant chemical classes among the compounds quantified were hydrocarbons (24), ketones (10), terpenes (8), heterocyclic compounds (7) and aromatic compounds (7). Twelve analytes were found to be highly present in both blood and exhaled air (with incidence rates higher than 80%) and for 32 species significant differences (Wilcoxon signed-rank test) between room air and exhaled breath were observed. By comparing blood, room air and breath levels in parallel, a tentative classification of volatiles into endogenous and exogenous compounds can be achieved. PMID:23435188

  2. Functional capacity in healthy volunteers before and following beta-blockade with controlled-release metoprolol.

    PubMed

    Rønnevik, P K; Nordrehaug, J E; von der Lippe, G

    1995-01-01

    The effects of the beta 1-selective beta-adrenergic blocker metoprolol on physiological responses, exercise capacity and gas exchange parameters were measured in healthy men using different graded bicycle exercise protocols on separate days before and following administration of 200 mg controlled-release metoprolol. Eleven men performed in randomised order maximal cardiopulmonary exercise testing on 50-W/6-min stage, 50-W/3-min stage and ramp (15-W/min-1) protocols. Peak heart rate and peak heart rate-blood pressure products were similar on all exercise protocols, and were significantly reduced by metoprolol. Submaximal and peak oxygen consumption were similar before and following beta-adrenoceptor blockade. Depending on the exercise protocol applied, an insignificant decrease of 4-10% in maximal cumulated exercise capacity (work-rate x time integral) was observed following administration of metoprolol. It is concluded that in healthy men evaluated with different exercise protocols the beta 1-selective controlled-release beta-adrenoceptor blocker metoprolol does not influence exercise capacity despite a marked reduction of heart rate and rate-pressure product. PMID:7589026

  3. Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers.

    PubMed

    Kleessen, Brigitta; Schwarz, Sandra; Boehm, Anke; Fuhrmann, H; Richter, A; Henle, T; Krueger, Monika

    2007-09-01

    A study was conducted to test the effects of Jerusalem artichoke inulin (JA) or chicory inulin (CH) in snack bars on composition of faecal microbiota, concentration of faecal SCFA, bowel habit and gastrointestinal symptoms. Forty-five volunteers participated in a double-blind, randomized, placebo-controlled, parallel-group study. At the end of a 7 d run-in period, subjects were randomly assigned to three groups of fifteen subjects each, consuming either snack bars with CH or JA, or snack bars without fructans (placebo); for 7 d (adaptation period), they ingested one snack bar per day (7.7 g fructan/d) and continued for 14 d with two snack bars per day. The composition of the microbiota was monitored weekly. The consumption of CH or JA increased counts of bifidobacteria (+1.2 log10 in 21 d) and reduced Bacteroides/Prevotella in number and the Clostridium histolyticum/C. lituseburense group in frequency at the end of intervention (P < 0.05). No changes in concentration of faecal SCFA were observed. Consumption of snack bars resulted in a slight increase in stool frequency. Stool consistency was slightly affected in subjects consuming two snack bars containing CH or JA per day (P < 0.05). Consumption of CH or JA resulted in mild and sometimes moderate flatulence in a few subjects compared to placebo (P < 0.05). No structural differences were detected between CH and JA before and after processing. In conclusion, adaptation on increased doses of CH or JA in bakery products stimulates the growth of bifidobacteria and may contribute to the suppression of potential pathogenic bacteria. PMID:17445348

  4. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. PMID:24373522

  5. The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers

    PubMed Central

    Mobarrez, Fariborz; Antoniewicz, Lukasz; Bosson, Jenny A.; Kuhl, Jeanette; Pisetsky, David S.; Lundbäck, Magnus

    2014-01-01

    Background Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall. PMID:24587320

  6. Impact of UGT2B17 Gene Deletion on the Pharmacokinetics of 17-Hydroexemestane in Healthy Volunteers.

    PubMed

    Chen, Shanly M; Atchley, Daniel H; Murphy, Michael A; Gurley, Bill J; Kamdem, Landry K

    2016-07-01

    Exemestane is an aromatase inhibitor drug used for the treatment of hormone-dependent breast cancer. 17-Hydroexemestane, the major and biologically active metabolite of exemestane in humans, is eliminated via glucuronidation by the polymorphic UGT2B17 phase II drug-metabolizing enzyme. Previous microsomal studies have shown that UGT2B17 gene deletion affects the intrinsic hepatic clearances of 17-hydroexemestane in vitro. In this open-label study we set out to assess the effect of UGT2B17 gene deletion on the pharmacokinetics of 17-hydroexemestane in healthy female volunteers with and without UGT2B17. To achieve this goal, 14 healthy postmenopausal women (8 carriers of the homozygous UGT2B17 wild-type allele and 6 carriers of the homozygous UGT2B17 gene-deletion allele) were enrolled and invited to receive a single 25-mg oral dose of exemestane. Pharmacokinetics was assessed over 72 hours postdosing. Our results showed that there were statistically significant differences in plasma 17-hydroexemestane AUC0-∞ (P = .0007) and urine 17-hydroexemestane C24h (P = .001) between UGT2B17 genotype groups. Our data suggest that UGT2B17 gene deletion influences 17-hydroexemestane pharmacokinetics in humans. PMID:26608382

  7. Microdosing of a Carbon-14 Labeled Protein in Healthy Volunteers Accurately Predicts Its Pharmacokinetics at Therapeutic Dosages.

    PubMed

    Vlaming, M L H; van Duijn, E; Dillingh, M R; Brands, R; Windhorst, A D; Hendrikse, N H; Bosgra, S; Burggraaf, J; de Koning, M C; Fidder, A; Mocking, J A J; Sandman, H; de Ligt, R A F; Fabriek, B O; Pasman, W J; Seinen, W; Alves, T; Carrondo, M; Peixoto, C; Peeters, P A M; Vaes, W H J

    2015-08-01

    Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early in the drug development process by the use of microdosing in a small group of healthy subjects combined with ultrasensitive accelerator mass spectrometry (AMS). After only minimal preclinical testing, we performed a first-in-human phase 0/phase 1 trial with a human recombinant therapeutic protein (RESCuing Alkaline Phosphatase, human recombinant placental alkaline phosphatase [hRESCAP]) to assess its safety and kinetics. Pharmacokinetic analysis showed dose linearity from microdose (53 μg) [(14) C]-hRESCAP to therapeutic doses (up to 5.3 mg) of the protein in healthy volunteers. This study demonstrates the value of a microdosing approach in a very small cohort for accelerating the clinical development of NBEs. PMID:25869840

  8. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants

    PubMed Central

    Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-01-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP. PMID:23685775

  9. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants.

    PubMed

    Ibáñez, Agustín; Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-07-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP. PMID:23685775

  10. Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers.

    PubMed

    Lenuzza, Natacha; Duval, Xavier; Nicolas, Grégory; Thévenot, Etienne; Job, Sylvie; Videau, Orianne; Narjoz, Céline; Loriot, Marie-Anne; Beaune, Philippe; Becquemont, Laurent; Mentré, France; Funck-Brentano, Christian; Alavoine, Loubna; Arnaud, Philippe; Delaforge, Marcel; Bénech, Henri

    2016-04-01

    This phase I, pilot clinical study was designed to evaluate the safety and the pharmacokinetic (PK) profiles of the CIME (Metabolic Identity Card) combination of ten drugs, with a view to its use as a phenotyping cocktail. Ten healthy Caucasian subjects were orally dosed with the CIME combination (caffeine-CYP1A2, repaglinide-CYP2C8, tolbutamide-CYP2C9, omeprazole-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A, acetaminophen-UGT1A1, 6&9 and 2B15, digoxin-P-gp, rosuvastatin-OATP1B1&3 and memantine-active renal transport). Blood was collected over 3 days and on day 7. CIME probes and relevant metabolites were assayed by LC-MS/MS and PK parameters were calculated. Main results were: (1) good safety with reversible mild or moderate adverse effects, (2) an analytical method able to quantify simultaneously the 10 probes and the major metabolites, (3) calculation of PK parameters for all probes in general agreed with published values, and (4) identification of the low CYP2D6 metabolizer. This pilot study showed that the CIME combination was well tolerated and that its pharmacokinetics could be accurately measured in healthy volunteers. This combination can now confidently be checked for sensitivity and specificity and for lack of interaction to be validated as a phenotyping cocktail. PMID:25465228

  11. Seroprevalence of Hepatitis B and C Infections among Healthy Volunteer Blood Donors in the Central California Valley

    PubMed Central

    Atla, Pradeep R.; Ameer, Adnan; Sadiq, Humaira; Sadler, Patrick C.

    2013-01-01

    Background/Aims The Central California Valley has a diverse population with significant proportions of Hispanics and Asians. This cross-sectional study was conducted to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in healthy blood donors in the Valley. Methods A total of 217,738 voluntary blood donors were identified between 2006 and 2010 (36,795 first-time donors; 180,943 repeat donors). Results Among the first-time donors, the HBV and HCV prevalence was 0.28% and 0.52%, respectively. Higher HBV prevalence seen in Asians (3%) followed by Caucasians (0.05%), African Americans (0.15%), and Hispanics (0.05%). Hmong had a HBV prevalence of 7.63% with a peak prevalence of 8.76% among the 16- to 35-year-old age group. Highest HCV prevalence in Native Americans (2.8) followed by Caucasians (0.59%), Hispanics (0.45%), African Americans (0.38%), and Asians (0.2%). Conclusions Ethnic disparities persist with regard to the prevalence of HBV and HCV in the Central California Valley. The reported prevalence may be an underestimate because our study enrolled healthy volunteer blood donors only. The development of aggressive public health measures to evaluate the true prevalence of HBV and HCV and to identify those in need of HBV and HCV prevention measures and therapy is critically important. PMID:23423771

  12. The Relationship between T1 Sagittal Angle and Sagittal Balance: A Retrospective Study of 119 Healthy Volunteers

    PubMed Central

    Li, Ming

    2016-01-01

    T1 sagittal angle has been reported to be used as a parameter for assessing sagittal balance and cervical lordosis. However, no study has been performed to explore the relationship between T1 sagittal angle and sagittal balance, and whether T1 sagittal angle could be used for osteotomy guidelines remains unknown. The aim of our study is to explore the relationship between T1 sagittal angle and sagittal balance, determine the predictors for T1 sagittal angle, and determine whether T1 sagittal angle could be used for osteotomy guidelines to restore sagittal balance. Medical records of healthy volunteers in our outpatient clinic from January 2014 to August 2015 were reviewed, and their standing full-spine lateral radiographs were evaluated. Demographic and radiological parameters were collected and analyzed, including age, gender, T1 sagittal angle, maxTK, maxLL, SS, PT, and PI. Correlation coefficients between T1 sagittal angle and other spinopelvic parameters were determined. In addition, multiple regression analysis was performed to establish predictive radiographic parameters for T1 sagittal angle as the primary contributors. A total of 119 healthy volunteers were recruited in our study with a mean age of 34.7 years. It was found that T1 sagittal angle was correlated with maxTK with very good significance (r = 0.697, P<0.001), maxLL with weak significance (r = 0.206, P = 0.024), SS with weak significance (r = 0.237, P = 0.009), PI with very weak significance (r = 0.189, P = 0.039), SVA with moderate significance (r = 0.445, P<0.001), TPA with weak significance (r = 0.207, P = 0.023), and T1SPI with weak significance (r = 0.309, P = 0.001). The result of multiple regression analysis showed that T1 sagittal angle could be predicted by using the following regression equation: T1 sagittal angle = 0.6 * maxTK—0.2 * maxLL + 8. In the healthy population, T1 sagittal angle could be considered as a useful parameter for sagittal balance; however, it could not be

  13. Disposition, metabolism and mass balance of delafloxacin in healthy human volunteers following intravenous administration.

    PubMed

    McEwen, Andrew; Lawrence, Laura; Hoover, Randy; Stevens, Lloyd; Mair, Stuart; Ford, Gill; Williams, Dylan; Wood, Stuart

    2015-01-01

    1. The pharmacokinetics and disposition of delafloxacin was investigated following a single intravenous (300 mg, 100 µCi) dose to healthy male subjects. 2. Mean Cmax, AUC0-∞, Tmax and t1/2 values for delafloxacin were 8.98 µg/mL, 21.31 µg h/mL, 1 h and 2.35 h, respectively, after intravenous dosing. 3. Radioactivity was predominantly excreted via the kidney with 66% of the radioactive dose recovered in the urine. Approximately 29% of the radioactivity was recovered in the faeces, giving an overall mean recovery of 94% administered radioactivity. 4. The predominant circulating components were identified as delafloxacin and a direct glucuronide conjugate of delafloxacin. PMID:25986539

  14. Impact of Integrated Amrita Meditation Technique on Adrenaline and Cortisol Levels in Healthy Volunteers

    PubMed Central

    Vandana, Balakrishnan; Vaidyanathan, Kannan; Saraswathy, Lakshmiy Ammal; Sundaram, Karimassery Ramaiyer; Kumar, Harish

    2011-01-01

    The objective was to find out the effect of Integrated Amrita Meditation Technique (IAM) on the stress hormones: adrenaline and cortisol. One hundred and fifty healthy subjects were randomized into three groups. Blood was collected at 0 hour, 48 hours, 2 months, and 8 months after the first visit. Adrenaline was analyzed by ELISA and cortisol by Chemiluminescent method. In the IAM, PMR and control groups 44, 44, and 36 came, respectively, for the baseline visit. Within group, cortisol and adrenaline levels reduced in the IAM 48 hours onwards and the fall sustained until 8 months (P < .05). ANCOVA (Repeated measures) on adrenaline taking the four levels of observation showed a highly significant (P = .001) drop in the IAM group. The mean cortisol values between groups were not statistically significant (P = .138). IAM Technique was effective in reducing adrenaline and cortisol levels within group comparisons. PMID:21318156

  15. Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine.

    PubMed

    Wöhrl, Stefan; Hemmer, Wolfgang; Focke, Margarete; Rappersberger, Klemens; Jarisch, Reinhart

    2004-01-01

    Histamine in food at non-toxic doses has been proposed to be a major cause of food intolerance causing symptoms like diarrhea, hypotension, headache, pruritus and flush ("histamine intolerance"). Histamine-rich foods such as cheese, sausages, sauerkraut, tuna, tomatoes, and alcoholic beverages may contain histamine up to 500 mg/kg. We conducted a randomized, double-blind, placebo-controlled cross-over study in 10 healthy females (age range 22-36 years, mean 29.1 +/- 5.4) who were hospitalized and challenged on two consecutive days with placebo (peppermint tea) or 75 mg of pure histamine (equaling 124 mg histamine dihydrochloride, dissolved in peppermint tea). Objective parameters (heart rate, blood pressure, skin temperature, peak flow) as well as a total clinical symptom score using a standardized protocol were recorded at baseline, 10, 20, 40, 80 minutes, and 24 hours. The subjects received a histamine-free diet also low in allergen 24 hours before hospitalization and over the whole observation period. Blood samples were drawn at baseline, 10, 20, 40, and 80 minutes, and histamine and the histamine-degrading enzyme diamine oxidase (DAO) were determined. After histamine challenge, 5 of 10 subjects showed no reaction. One individual experienced tachycardia, mild hypotension after 20 minutes, sneezing, itching of the nose, and rhinorrhea after 60 minutes. Four subjects experienced delayed symptoms like diarrhea (4x), flatulence (3x), headache (3x), pruritus (2x) and ocular symptoms (1x) starting 3 to 24 hours after provocation. No subject reacted to placebo. No changes were observed in histamine and DAO levels within the first 80 minutes in non-reactors as well as reactors. There was no difference in challenge with histamine versus challenge with placebo. We conclude that 75 mg of pure liquid oral histamine--a dose found in normal meals--can provoke immediate as well as delayed symptoms in 50% of healthy females without a history of food intolerance. PMID:15603203

  16. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis

    PubMed Central

    McRae, Marc P.

    2013-01-01

    Objective Betaine supplementation has been shown to be an effective agent for decreasing plasma homocysteine in healthy adults. Studies in healthy volunteers show that 6 g/d of betaine lowers plasma homocysteine concentrations by 5% to 20%. The purpose of this study was to perform a meta-analysis of randomized placebo-controlled trials that used daily betaine supplementation to identify the range in betaine's effects on lowering homocysteine. Methods Five randomized controlled trials published between 2002 and 2010 were identified using MEDLINE and a manual search. All 5 studies used health adult participants who were supplemented with at least 4 g/d of betaine for between 6 and 24 weeks. A meta-analysis was carried out using a random-effects model, and the overall effect size was calculated for changes in plasma homocysteine. Results The pooled estimate of effect for betaine supplementation on plasma homocysteine was a reduction of 1.23 μmol/L, which was statistically significant (95% confidence interval, − 1.61 to − 0.85; P = .01). Conclusion Supplementation with at least 4g/d of betaine for a minimum of 6 weeks can lower plasma homocysteine. PMID:23997720

  17. An acute intake of plant stanol esters alters immune-related pathways in the jejunum of healthy volunteers.

    PubMed

    De Smet, Els; Mensink, Ronald P; Boekschoten, Mark V; de Ridder, Rogier; Germeraad, Wilfred T V; Wolfs, Tim G A M; Plat, Jogchum

    2015-03-14

    Plant sterols and stanols inhibit intestinal cholesterol absorption and consequently lower serum LDL-cholesterol (LDL-C) concentrations. The underlying mechanisms are not yet known. In vitro and animal studies have suggested that changes in intestinal sterol metabolism are attributed to the LDL-C-lowering effects of plant stanol esters. However, similar studies in human subjects are lacking. Therefore, we examined the effects of an acute intake of plant stanol esters on gene expression profiles of the upper small intestine in healthy volunteers. In a double-blind cross-over design, fourteen healthy subjects (eight female and six male; age 21-55 years), with a BMI ranging from 21 to 29 kg/m², received in random order a shake with or without plant stanol esters (4 g). At 5 h after consumption of the shake, biopsies were taken from the duodenum (around the papilla of Vater) and from the jejunum (20 cm distal from the papilla of Vater). Microarray analysis showed that the expression profiles of genes involved in sterol metabolism were not altered. Surprisingly, the pathways involved in T-cell functions were down-regulated in the jejunum. Furthermore, immunohistochemical analysis showed that the number of CD3 (cluster of differentiation number 3), CD4 (cluster of differentiation number 4) and Foxp3⁺ (forkhead box P3-positive) cells was reduced in the plant stanol ester condition compared with the control condition, which is in line with the microarray data. The physiological and functional consequences of the plant stanol ester-induced reduction of intestinal T-cell-based immune activity in healthy subjects deserve further investigation. PMID:25683704

  18. A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

    PubMed

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

    2016-07-01

    Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner. PMID:26950553

  19. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia. PMID:25559494

  20. To Make Their Journey Better: Research-Focused Aspirations for Preparing Adult Volunteers for Facilitating Positive Youth Development

    ERIC Educational Resources Information Center

    Kirby, Joshua Aaron

    2010-01-01

    This basic interpretive qualitative research study explored the personal and professional backgrounds, training experiences, perspectives, and perceptions held by adult volunteers serving as crew advisors in the Venturing program of the Boy Scouts of America (BSA). Venturing is the BSA's adventure oriented youth development program for coeds age…

  1. Nutrition Risk in Home-Bound Older Adults: Using Dietician-Trained and Supervised Nutrition Volunteers for Screening and Intervention

    ERIC Educational Resources Information Center

    Laforest, Sophie; Goldin, Benita; Nour, Kareen; Roy, Marie-Andree; Payette, Helene

    2007-01-01

    Nutrition screening and early intervention in home-bound older adults are key to preventing unfavourable health outcomes and functional decline. This pilot study's objectives were (a) to test the reliability of the Elderly Nutrition Screening Tool (ENS [C]) when administered by dietician-trained and supervised nutrition volunteers, and (b) to…

  2. Cerebellar contributions to neurological soft signs in healthy young adults.

    PubMed

    Hirjak, Dusan; Thomann, Philipp A; Kubera, Katharina M; Stieltjes, Bram; Wolf, Robert C

    2016-02-01

    Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons. PMID:25708455

  3. Safety and pharmacokinetics of multiple doses of aclidinium bromide administered twice daily in healthy volunteers.

    PubMed

    Lasseter, K; Dilzer, S; Jansat, J M; Garcia Gil, E; Caracta, C F; Ortiz, S

    2012-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and increased cholinergic tone. The global initiative for chronic obstructive lung disease (GOLD) guidelines recommend long-acting anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel, long-acting muscarinic antagonist developed for the treatment of COPD. A phase I, randomized, single-blind, multiple-dose clinical trial was conducted to assess the safety and pharmacokinetics (PK) of multiple doses of twice-daily (BID) aclidinium in healthy subjects. Thirty healthy male and female subjects received aclidinium 200 μg, 400 μg, 800 μg, or placebo twice daily for 7 days. Subjects were randomized to 1 of 3 cohorts and 10 subjects in each cohort were randomized (8:2) to either aclidinium or placebo groups. Safety was assessed via adverse events (AEs), laboratory evaluations, vital signs, and ECGs. Plasma samples were obtained at multiple time points throughout the study and analyzed for aclidinium and its inactive acid and alcohol metabolites using a fully validated method of liquid chromatography coupled with tandem mass spectrometry. A total of 9 treatment-emergent AEs were reported (1, placebo; 3, aclidinium 400 μg; 5, aclidinium 800 μg), all of which were mild in severity. No serious AEs were reported. There were no clinically meaningful changes in laboratory parameters or vital signs. PK parameters on Day 7 following BID dosing of aclidinium showed that steady state was achieved for aclidinium and its metabolites. On Days 1 and 7, maximum plasma concentrations (Cmax) of aclidinium were generally observed at the first PK time point (5 min postdose) and rapidly declined, with plasma concentrations generally less than 10% of Cmax by 6 h postdose in all aclidinium groups. Mean effective t(½) after the evening dose on Day 7 ranged from 4.6 to 7.0 h for aclidinium 400 μg and 800 μg, similar to the terminal t(½) observed on Day 1 (4.5-5.9 h

  4. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.

    PubMed

    Li, Zhaoping; Henning, Susanne M; Lee, Ru-Po; Lu, Qing-Yi; Summanen, Paula H; Thames, Gail; Corbett, Karen; Downes, Julia; Tseng, Chi-Hong; Finegold, Sydney M; Heber, David

    2015-08-01

    The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota. PMID:26189645

  5. Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers

    PubMed Central

    Polotsky, Vsevolod Y.; Bevans-Fonti, Shannon; Grigoryev, Dmitry N.; Punjabi, Naresh M.

    2015-01-01

    Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea. PMID:26657991

  6. Variability in the pharmacokinetics and pharmacodynamics of low dose aspirin in healthy male volunteers.

    PubMed

    Benedek, I H; Joshi, A S; Pieniaszek, H J; King, S Y; Kornhauser, D M

    1995-12-01

    Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin (acetylsalicylic acid; ASA) are limited. This single-center study was designed to determine the rate and extent of oral absorption of 80-mg ASA tablets in healthy, young male subjects and to assess the intra- and inter-subject variability of ASA pharmacokinetics and platelet aggregation effects. Ten subjects each received a single, open-label, oral 80-mg ASA dose on three separate days. Each dose was separated by a 2-week washout interval. Blood samples for pharmacokinetic determinations of ASA and its metabolite, salicylic acid (SA) and platelet aggregation studies were obtained at scheduled timepoints before and up to 24 hours after each dose. Peak plasma ASA levels of 1 microgram/mL were achieved within 30 minutes. Peak plasma SA levels of approximately 4 micrograms/mL were attained in 1 hour. The terminal half-lives (t1/2) of ASA and SA were 0.4 and 2.1 hours, respectively. Both ASA and SA pharmacokinetics and the platelet aggregation response to ASA exhibited considerable intra- and inter-subject variability. Inhibition of platelet aggregation was found to relate with ASA area under the plasma concentration versus time curve (AUC). PMID:8750369

  7. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection. PMID:25697709

  8. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

    PubMed Central

    Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

    2011-01-01

    Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

  9. Modafinil affects mood, but not cognitive function, in healthy young volunteers.

    PubMed

    Randall, Delia C; Shneerson, John M; Plaha, Komal K; File, Sandra E

    2003-04-01

    Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double-blind study we examined its effects in 30 healthy, non sleep-deprived students (19 men and 11 women, aged 19-23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post-treatment change in the factor measuring 'somatic anxiety' and in individual ratings of 'shaking', 'palpitations', 'dizziness', 'restlessness', 'muscular tension', 'physical tiredness' and 'irritability', which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the 'psychological anxiety' and the 'aggressive mood' factors (as measured from the Bond and Lader scales). PMID:12672167

  10. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

    PubMed

    Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

    2013-01-01

    In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. PMID:22651957

  11. Lack of effect of flunarizine on the pharmacokinetics and pharmacodynamics of sumatriptan in healthy volunteers.

    PubMed Central

    Van Hecken, A M; Depré, M; De Schepper, P J; Fowler, P A; Lacey, L F; Durham, J M

    1992-01-01

    Twenty-four healthy subjects completed a double-blind, placebo controlled, parallel group study to evaluate the effect of treatment with flunarizine on the pharmacokinetics and pharmacodynamics of sumatriptan, a 5HT1-like agonist. Subjects received a single oral 200 mg dose of sumatriptan on the eighth day of a once daily treatment with either flunarizine 10 mg or matching placebo. There were no significant differences between treatments in relation to Cmax (82.3 ng ml-1 in the absence and 81.4 ng ml-1 in the presence of flunarizine), AUC (368 ng ml-1 h in the absence and 360 ng ml-1 in the presence) and elimination half-life (2.2 h in the absence and 2.4 h in the presence of flunarizine) of sumatriptan. Similarly pretreatment with flunarizine was not found to have any clinically significant effect on the pharmacodynamics of sumatriptan as measured by pulse rate, blood pressure and ECG. PMID:1321655

  12. Adrenergic Effect on Cytokine Release After Ex Vivo Healthy Volunteers' Whole Blood LPS Stimulation.

    PubMed

    Papandreou, Vasiliki; Kavrochorianou, Nadia; Katsoulas, Theodoros; Myrianthefs, Pavlos; Venetsanou, Kyriaki; Baltopoulos, George

    2016-06-01

    Catecholamines are molecules with immunomodulatory properties in health and disease. Several studies showed the effect of catecholamines when administered to restore hemodynamic stability in septic patients. This study investigates the effect of norepinephrine and dobutamine on whole blood cytokine release after ex vivo lipopolysaccharide (LPS) stimulation. Whole blood collected from healthy individuals was stimulated with LPS, in the presence of norepinephrine or dobutamine at different concentrations, with or without metoprolol, a β1 receptor antagonist. Cytokine measurement was performed in isolated cell culture supernatants with ELISA. Results are expressed as mean ± SEM and compared with Mann-Whitney rank-sum test. Both norepinephrine and dobutamine significantly reduced TNF-α and IL-6 production after ex vivo LPS stimulation of whole blood in a dose-dependent manner, and this effect was partially reversed by the presence of metoprolol. Norepinephrine and dobutamine reduce the LPS-induced production of pro-inflammatory cytokines, thus possibly contributing to altered balance between the inflammatory and anti-inflammatory responses, which are vital for a successful host response to severe disease, shock, and sepsis. PMID:27037808

  13. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

    PubMed Central

    Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

    2013-01-01

    Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

  14. Assessing efficacy of non-opioid analgesics in experimental pain models in healthy volunteers: an updated review

    PubMed Central

    Staahl, Camilla; Olesen, Anne Estrup; Andresen, Trine; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr

    2009-01-01

    AIM Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTS Nonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N-methyl-D-aspartate antagonists exemplified by ketamine generally needed strong, long-lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol attenuated pain in only a few models. CONCLUSIONS Pain induction and assessment are very important for the sensitivity of the pain models. Generally, experimental pain models need to be designed with careful consideration of the pharmacological mechanisms and pharmacokinetics of analgesics. The drawback with the different study designs is also discussed. This knowledge can aid the decisions that need to be taken when designing experimental pain studies for compounds entering Phase I and II trials. PMID:19740390

  15. Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers.

    PubMed Central

    Nakashima, M; Uematsu, T; Kosuge, K; Umemura, K; Hakusui, H; Tanaka, M

    1995-01-01

    The pharmacokinetics and tolerance of DU-6859a, 7-[(7S)-7-amino-5-azaspiro[2,4]heptan-5-yl]-8-chloro-6-fluor o-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid sesquihydrate, were investigated in healthy male Japanese volunteers after single (25, 50, 100, and 200 mg) and multiple (100 mg three times a day for 6 days plus once a day on the 7th day and 50 mg every 12 h for 13 doses) oral doses. DU-6859a was well tolerated at all doses, and all 36 subjects completed the study; mild transient soft stool in five volunteers and mild transient diarrhea in one volunteer on the multiple-dose (100 mg three times a day) study were the only side effects reported. No drug crystals were observed in the urine after the single 200-mg dose and the 100-mg three times a day regimen. DU-6859a was rapidly absorbed in the fasted state. The mean maximum concentration in serum (Cmax) ranged from 0.29 to 1.86 micrograms/ml for the 25- to 200-mg dose, and the mean time to reach Cmax ranged from 1.0 to 1.3 h. The terminal half-life ranged from 4.4 to 5.0 h. The area under the curve increased dose dependently. The serum protein binding of the drug was approximately 50%. The apparent volume of distribution clearly exceeded 1 liter/kg, suggesting good tissue penetration. Within 48 h, the cumulative urinary recovery of unchanged drug amounted to 69 to 74% of the dose administered, while fecal excretion up to 48 h after the 200-mg dose accounted for ca. 3% of the dose. Food intake did not affect the rate and extend of absorption of DU-6859a to a clinically significant extent. During multiple oral dosing, the accumulation of the drug in serum was close to the theoretically predicted values, which indicated that there was virtually no drug accumulation. PMID:7695301

  16. Complete Blood Count Reference Intervals for Healthy Han Chinese Adults

    PubMed Central

    Mu, Runqing; Guo, Wei; Qiao, Rui; Chen, Wenxiang; Jiang, Hong; Ma, Yueyun; Shang, Hong

    2015-01-01

    Background Complete blood count (CBC) reference intervals are important to diagnose diseases, screen blood donors, and assess overall health. However, current reference intervals established by older instruments and technologies and those from American and European populations are not suitable for Chinese samples due to ethnic, dietary, and lifestyle differences. The aim of this multicenter collaborative study was to establish CBC reference intervals for healthy Han Chinese adults. Methods A total of 4,642 healthy individuals (2,136 males and 2,506 females) were recruited from six clinical centers in China (Shenyang, Beijing, Shanghai, Guangzhou, Chengdu, and Xi’an). Blood samples collected in K2EDTA anticoagulant tubes were analyzed. Analysis of variance was performed to determine differences in consensus intervals according to the use of data from the combined sample and selected samples. Results Median and mean platelet counts from the Chengdu center were significantly lower than those from other centers. Red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) values were higher in males than in females at all ages. Other CBC parameters showed no significant instrument-, region-, age-, or sex-dependent difference. Thalassemia carriers were found to affect the lower or upper limit of different RBC profiles. Conclusion We were able to establish consensus intervals for CBC parameters in healthy Han Chinese adults. RBC, HGB, and HCT intervals were established for each sex. The reference interval for platelets for the Chengdu center should be established independently. PMID:25769040

  17. A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States

    PubMed Central

    Gadiko, Chaitanya; Tippabhotla, Sudhakar Koundinya; Thota, Satyanarayana; Battula, Ramakrishna; Khan, Sohel Md.; Vobalaboina, Venkateswarlu

    2013-01-01

    To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period crossover studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment arms (test or reference) separated by a washout period of 28 days. Blood samples were collected up to 72 h post-dose and plasma samples were analyzed for donepezil using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI of Cmax and AUC0-72 were 82.50–90.10 and 92.38–98.60, respectively. Corresponding values in the fed study were 91.82–98.05 and 97.27–100.27. Based on the results, the test product (donepezil) met the US regulatory criteria of bioequivalence relative to the reference product (Aricept®) under both fasting and fed conditions. PMID:24106673

  18. Lactobacillus isolates from healthy volunteers exert immunomodulatory effects on activated peripheral blood mononuclear cells

    PubMed Central

    Sun, Keyi; Xie, Chao; Xu, Donghua; Yang, Xiaofan; Tang, James; Ji, Xiaohui

    2013-01-01

    As probiotics in the gut, Lactobacilli are believed to play important roles in the development and maintenance of both the mucosal and systemic immune system of the host. This study was aimed to investigate the immuno-modulatory function of candiate lactobacilli on T cells. Lactobacilli were isolated from healthy human feces and the microbiological characteristics were identified by API 50 CHL and randomly amplified polymorphic DNA (RAPD) assays. Anti-CD3 antibody activated peripheral blood mononuclear cells (PBMCs) were treated by viable, heat-killed lactobacilli and genomic DNA of lactobacilli, and cytokine profiles were tested by ELISA. Isolated lactobacilli C44 and C48 were identified as L. acidophilus and L. paracacei, which have properties of acid and bile tolerance and inhibitor effects on pathogens. Viable and heat-killed C44 and C48 induced low levels of proinflammatory cytokines (TNF-α, IL-6 and IL-8) and high levels of IFN-γ and IL-12p70 in PBMCs. In anti-CD3 antibody activated PBMCs, viable and heat-killed C44 increased Th2 cytokine levels (IL-5, IL-6 and IL-10), and simultaneously enhanced Th1 responses by inducing IFN-γ and IL-12p70 production. Different from that of lactabacillus strains, their genomic DNA induced low levels of IL-12p70, IFN-γ and proinflammatory cytokines in PBMCs with or without anti-CD3 antibody activation. These results provided in vitro evidence that the genomic DNA of strains of C44 and C48, especially C44, induced weaker inflammation, and may be potentially applied for treating allergic diseases. PMID:23554802

  19. Urinary thrombomodulin and catecholamine levels are interrelated in healthy volunteers immersed in cold and warm water

    PubMed Central

    Pakanen, Lasse; Pääkkönen, Tiina; Ikäheimo, Tiina M; Rintamäki, Hannu; Leppäluoto, Juhani; Kaija, Helena; Kortelainen, Marja-Leena; Rautio, Arja; Porvari, Katja

    2016-01-01

    ABSTRACT Severe hypothermia has been shown to influence the levels of catecholamines and thrombomodulin, an endothelial protein essentially involved in the regulation of haemostasis and inflammation. A link between thrombomodulin and catecholamines during cold exposure has also been previously suggested. The aim of this study was to assess the influence of short-term cold exposure without hypothermia on catecholamines and the circulating and urinary thrombomodulin levels. Seven healthy male subjects were immersed in cold water (+10°C) for 10 minutes followed by a 20-minute immersion in +28°C water. Warm water immersion was performed separately for each subject (+30°C for 30 minutes). Thrombomodulin and catecholamine concentrations were measured from pre- and post-immersion (up to 23 hours) samples. In urine, the thrombomodulin level correlated strongly with adrenaline (ρ = 0.806) and noradrenaline (ρ = 0.760) levels. There were no significant differences in thrombomodulin levels between immersion temperatures. Post-immersion urinary thrombomodulin levels were significantly lower than the pre-immersion level at both immersion temperatures. Median concentrations of plasma noradrenaline and urinary adrenaline were higher after exposure to +10°C than to +30°C. Thus, further evidence of the association between thrombomodulin and catecholamines was gained in a physiologically relevant setting in humans. Additionally, it is evident that a short-term cold exposure was not able to elicit changes in the thrombomodulin levels in a follow-up period of up to 23 hours. These findings provide further understanding of the physiological responses to cold during immersion, and of the potential influence of stress on haemostatic and inflammatory responses.

  20. Comparative bioavailability of two cefadroxil products using serum and urine data in healthy human volunteers.

    PubMed

    Otoom, S; Hasan, M; Najib, N

    2004-07-01

    1. The aim of the present study was to assess the bioequivalence of two cefadroxil products, namely Ultracef (a reference product) in the form of a 500 mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA) and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk Pharmaceutical Manufacturing, Tabuk, Saudi Arabia). 2. The study was performed under US Food and Drug Administration (FDA) guidelines (http://www.fda.gov/cder) on 24 healthy male subjects. Both products were administered orally as a single dose (1 x 500 mg capsule) separated by a 1 week washout period. Following oral administration, blood and urine samples were obtained and analysed for cefadroxil concentrations using a sensitive and specific HPLC assay. 3. There were no statistically significant differences between the two products in either the mean concentration-time profiles or the cumulative urinary excretion of cefadroxil at various times. Similarly, no statistical significance was observed in the pharmacokinetic parameters reflecting rate and extent of drug absorption. The relative extent of drug absorption, assessed by calculating the area under the curve (AUC) ratio for Roxil/Ultracef for 10 h and for infinity was 0.94 with 90% confidence limits (CL) of 0.91-0.98. In agreement with serum data, the average ratio (Roxil/Ultracef) of the cumulative amount of cefadroxil excreted in urine 10 h after the dose was found to be 0.97, with 90% CL of 0.88-1.05. The CL of the AUC and cumulative urinary excretion ratios are within the FDA accepted limits for bioequivalent products (0.80-1.25). 4. These findings show that serum and urine data of cefadroxil are in agreement and indicate that Roxil (the test product) and Ultracef (the reference product) are bioequivalent in terms of the rate and extent of drug absorption. PMID:15236630

  1. Cefotaxime Resistant Escherichia coli Collected from a Healthy Volunteer; Characterisation and the Effect of Plasmid Loss

    PubMed Central

    Kirchner, Miranda; AbuOun, Manal; Mafura, Muriel; Bagnall, Mary; Hunt, Theresa; Thomas, Christopher; Weile, Jan; Anjum, Muna F.

    2013-01-01

    In this study 6 CTX-M positive E. coli isolates collected during a clinical study examining the effect of antibiotic use in a human trial were analysed. The aim of the study was to analyse these isolates and assess the effect of full or partial loss of plasmid genes on bacterial fitness and pathogenicity. A DNA array was utilised to assess resistance and virulence gene carriage. Plasmids were characterised by PCR-based replicon typing and addiction system multiplex PCR. A phenotypic array and insect virulence model were utilised to assess the effect of plasmid-loss in E. coli of a large multi-resistance plasmid. All six E. coli carrying blaCTX-M-14 were detected from a single participant and were identical by pulse field gel electrophoresis and MLST. Plasmid profiling and arrays indicated absence of a large multi-drug resistance (MDR) F-replicon plasmid carrying blaTEM, aadA4, strA, strB, dfrA17/19, sul1, and tetB from one isolate. Although this isolate partially retained the plasmid it showed altered fitness characteristics e.g. inability to respire in presence of antiseptics, similar to a plasmid-cured strain. However, unlike the plasmid-cured or plasmid harbouring strains, the survival rate for Galleria mellonella infected by the former strain was approximately 5-times lower, indicating other possible changes accompanying partial plasmid loss. In conclusion, our results demonstrated that an apparently healthy individual can harbour blaCTX-M-14 E. coli strains. In one such strain, isolated from the same individual, partial absence of a large MDR plasmid resulted in altered fitness and virulence characteristics, which may have implications in the ability of this strain to infect and any subsequent treatment. PMID:24386342

  2. High-dose diazepam facilitates core cooling during cold saline infusion in healthy volunteers.

    PubMed

    Hostler, David; Northington, William E; Callaway, Clifton W

    2009-08-01

    Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, cardiac arrest, or exertional heat illness. While infusion of cold normal saline is a simple and inexpensive method for reducing core temperature, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesized that intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and reduce core body temperature more than the administration of cold saline alone. Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline. Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH), 10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin temperature, and oxygen consumption. Data for the main outcomes were analyzed with generalized estimating equations to identify differences in group, time, or a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/- 0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3 (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x time interaction was observed for core temperature and oxygen consumption (p < 0.001). Administration of high-dose diazepam resulted in decreased oxygen consumption during cold saline infusion, suggesting that 20 mg of intravenous diazepam may reduce the shivering threshold without compromising respiratory or cardiovascular function. PMID:19767791

  3. Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers.

    PubMed

    Chen, Lin-Zhi; Jungnik, Arvid; Mao, Yanping; Philip, Elsy; Sharp, Dale; Unseld, Anna; Seman, Leo; Woerle, Hans-Jürgen; Macha, Sreeraj

    2015-01-01

    1. The absorption, biotransformation and excretion of empagliflozin, an SGLT2 inhibitor, were evaluated in eight healthy subjects following a single 50 mg oral dose of empagliflozin containing ∼100 µCi [(14)C]-empagliflozin. 2. Radioactivity was rapidly absorbed, with plasma levels peaking 1 h post-dose. Total exposure was lower in blood versus plasma, consistent with moderate (28.6-36.8%) red blood cell partitioning. Protein binding was 80.3-86.2%. 3. Most of the radioactive dose was recovered in urine (54.4%) and faeces (41.1%). Unchanged empagliflozin was the most abundant drug-related component in plasma, representing 75.5-77.4% of plasma radioactivity and 79.6% plasma radioactivity AUC0-12 h. Unchanged empagliflozin was the most abundant drug-related component in urine and faeces, representing 43.5% (23.7% of dose) and 82.9% (34.1% of dose) of radioactivity in urine and faeces, respectively. Six metabolites were identified in plasma: three glucuronide conjugates representing 4.7-7.1% of AUC0-12 h and three less abundant metabolites (<0.2-1.9% AUC0-12 h). The most abundant metabolites in urine were two glucuronide conjugates (7.8-13.2% of dose) and in faeces was a tetrahydrofuran ring-opened carboxylic acid metabolite (1.9% of dose). 4. To conclude, empagliflozin was rapidly absorbed and excreted primarily unchanged in urine and faeces. Unchanged parent was the major drug-related component in plasma. Metabolism was primarily via glucuronide conjugation. PMID:25547626

  4. Effect of Regular Gum Chewing on Levels of Anxiety, Mood, and Fatigue in Healthy Young Adults

    PubMed Central

    Sasaki-Otomaru, Akiyo; Sakuma, Yumiko; Mochizuki, Yoshiko; Ishida, Sadayo; Kanoya, Yuka; Sato, Chifumi

    2011-01-01

    Introduction: The effect of regular gum chewing on psychological status is unknown. The purpose of this study was to examine the effect of gum chewing for fourteen days on psychological status and physical and mental fatigue in healthy young adults. Methods: We assigned 50 volunteers randomly to an intervention group (n = 26) and a control group (n = 24). Participants in the intervention group were requested to chew the gum twice per a day for fourteen days. The volunteers were required to complete a questionnaire related to lifestyle for baseline assessment. The State-Trait Anxiety Inventory (STAI), the Profile of Mood State (POMS), the World Health Organization Quality of Life 26, and assessment of physical and mental fatigue by visual analog scale were used at baseline, 2 weeks (after intervention), and 4 weeks (follow-up). Results: At 2 weeks, the score of state anxiety was significantly lower in the intervention group than the control group. The intervention participants’ scores of depression-dejection, fatigue and confusion in POMS were better than the control group scores. Mental fatigue were also relieved after the intervention. At 4 weeks, there were no significant differences between both groups. Conclusion: Fourteen days’ gum chewing may improve the levels of anxiety, mood and fatigue. PMID:21866229

  5. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    SciTech Connect

    Galtier, F.; Mura, T.; Raynaud de Mauverger, E.; Chevassus, H.; Farret, A.; Gagnol, J.-P.; Costa, F.; Dupuy, A.; and others

    2012-09-15

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK

  6. Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers.

    PubMed

    Handley, Rowena; Mondelli, Valeria; Zelaya, Fernando; Marques, Tiago; Taylor, Heather; Reinders, Antje A T S; Chaddock, Christopher; McQueen, Grant; Hubbard, Kathryn; Papadopoulos, Andrew; Williams, Steve; McGuire, Philip; Pariante, Carmine; Dazzan, Paola

    2016-07-01

    This randomized within-subject, double blind study aimed to compare the effects of a single dose of two different antipsychotics (haloperidol and aripiprazole) on cortisol, interleukin (IL)-6 and hippocampal regional Cerebral Blood Flow (rCBF) in the same 17 healthy male individuals. Subjects received a single dose of haloperidol (3mg), aripiprazole (10mg) and placebo, in a randomized order on three study appointments. We measured salivary cortisol levels at multiple time points, IL-6 levels from plasma samples, and resting cerebral blood flow (rCBF), using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T). We found significantly lower cortisol levels in the haloperidol condition (F(2,32)=5.78, p=0.007), than in either placebo (p=0.013; CI=0.45, 0.406) or aripiprazole (p=0.037; CI=-0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=0.048) in comparison with placebo (p=0.02; CI=0.14, 1.8), but not with aripiprazole. Finally, we found a greater rCBF in the right (peak voxel: T=6.47, p<0.0001) and left (peak voxel T=5.17, p<0.01) hippocampus following haloperidol compared with placebo, and at trend level also in the left hippocampus following aripiprazole compared with placebo (T=4.07, p=0.057). These differences in hippocampal rCBF after both antipsychotics were no longer evident (haloperidol) or present at trend level (aripiprazole), after controlling for cortisol and IL-6 levels. Our findings suggest that haloperidol can directly regulate the hypothalamic-pituitary-adrenal (HPA) axis and immune system through a pharmacological action via D2 receptor antagonism. Finally, our data suggest that the increased hippocampal rCBF is a manifestation of the reduction in IL-6 and cortisol which follows the administration of haloperidol. PMID:27112637

  7. Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II.

    PubMed Central

    Gans, R O; Bilo, H J; von Maarschalkerweerd, W W; Heine, R J; Nauta, J J; Donker, A J

    1991-01-01

    Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension. In these conditions an increased cardiovascular reactivity to noradrenaline (NA) and angiotensin II (AII) can be observed. Using the euglycemic clamp technique, we determined the cardiovascular reactivity to graded infusions of NA and AII in nine healthy males before (Bas), and 1 and 6 h after infusion of insulin (50 mU/kg per h) was started. On separate days control experiments were carried out to control for any circadian variation. Insulin led to a decrease of the amount of circulating NA necessary to increase the diastolic blood pressure (DBP) 20 mmHg (actual experiment [mean +/- SEM]: Bas, 23.1 +/- 5.0; 1 h, 14.8 +/- 3.0; and 6 h, 12.3 +/- 3.1; and control experiment: Bas, 20.7 +/- 5.0; 1 h, 18.6 +/- 3.5; and 6 h, 17.3 +/- 3.3 nmol/liter; Bas vs. 1 and 6 h: P less than 0.05). Although the amount of NA infused to raise DBP 20 mmHg showed a similar decline after 1 h of insulin infusion, no such change from baseline could be observed at 6 h. This appeared to be due to an increase in NA clearance with more prolonged insulin infusion. Insulin exerted no effect on the amount of AII infused to increase DBP 20 mmHg (actual experiment: Bas, 27.6 +/- 6.4; 1 h, 28.8 +/- 10.0; and 6 h, 21.2 +/- 5.3; and control experiment: Bas, 33.6 +/- 5.7; 1 h, 34.2 +/- 6.1; and 6 h, 23.4 +/- 4.7 ng/kg/min; NS). We did observe a circadian variation in AII reactivity. Whether the increase in cardiovascular responsiveness to NA after administration of insulin contributes to the elevation in blood pressure frequently observed in patients with insulin resistance remains to be proven. PMID:1864961

  8. Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers.

    PubMed

    Holz, O; Tan, L; Schaumann, F; Müller, M; Scholl, D; Hidi, R; McLeod, A; Krug, N; Hohlfeld, J M

    2015-12-01

    Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 h (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 h post LPS challenge. While the cytokine response was more pronounced at 6 h, the influx of neutrophils and monocytes dominated at 24 h; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 h after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 h and cytokine variables at 6 h. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine). PMID:26545873

  9. Ethyl glucuronide concentrations in hair: a controlled alcohol-dosing study in healthy volunteers.

    PubMed

    L Crunelle, Cleo; Cappelle, Delphine; Yegles, Michel; De Doncker, Mireille; Michielsen, Peter; Dom, Geert; van Nuijs, Alexander L N; Maudens, Kristof E; Covaci, Adrian; Neels, Hugo

    2016-03-01

    Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of ≥7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the non-drinking group had median EtG concentrations of 0.5 pg/mg hair (interquartile range (IQR) 1.7 pg/mg; range < 0.21-4.5 pg/mg). Participants consuming 100 and 150 g alcohol per week showed median EtG concentrations of 5.6 pg/mg hair (IQR 4.7 pg/mg; range 2.0-9.8 pg/mg) and 11.3 pg/mg hair (IQR 5.0 pg/mg; range 7.7-38.9 pg/mg), respectively. Hair EtG concentrations between the three study groups differed significantly from one another (p < 0.001). Hair EtG concentrations can be used to differentiate between repeated (low-to-moderate) amounts of alcohol consumed over a long time period. For the assessment of repeated alcohol use, we propose that the current cut-off of 7 pg/mg could be re-evaluated. PMID:26549114

  10. Bioequivalence Comparison of Two Formulations of Fixed-Dose Combination Glimepiride/Metformin (2/500 mg)Tablets in Healthy Volunteers

    PubMed Central

    Jung, Sang-hoon; Chae, Jung-woo; Song, Byung-jeong; Kwona, Kwang-il

    2014-01-01

    Glimepiride/metformin (2/500 mg) is an oral antihyperglycemic agent for the treatment of type 2 diabetes. A generic glimepiride/metformin (2/500 mg) fixed-dose combination (FDC) tablet was developed recently. This study was designed to collect data for submission to Korean regulatory authorities to allow the marketing of the test formulation. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. This single-dose, randomized, double-blind, two-way crossover trial was conducted at Bestian Medical Center in Bucheon, Korea. In total, 40 male Korean volunteers were enrolled. The subjects were randomized to receive an FDC tablet containing the glimepiride/metformin (2/500 mg) test or reference formulation, and pharmacokinetic(PK) parameters were measured. After a 1-week washout period, the other formulation was administered and the PK parameters were measured again. The Cmax and AUCt were determined from blood samples obtained at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 h after drug administration. Bioequivalence was considered established if the 90% CIs of the geometric mean ratios(GMRs) of the test-to-reference formulations for Cmax and AUCt were within the predetermined regulatory range of 80-125%. In total, 40 healthy male subjects were enrolled and completed the study (mean [SD] age, 23.2[2.26]years[range, 19-30years];weight, 68.95[8.30]Kg[range, 52.0-87.0 Kg]; and height, 175.4[5.34] cm[range, 164-189 cm]). The GMRs(90% CI) of the glimepiride Cmax and AUCt were 1.006(0.947-1.069) and 1.010(0.953-1.071), respectively. For metformin, the values were 1.019(0.959-1.083) and 1.035(0.989-1.084), respectively. The test and reference formulations had similar PK parameters. The test formulation of glimepiride/metformin (2/500 mg) FDC tablets met the Korean regulatory criteria for bioequivalence. PMID:25237332

  11. The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

    PubMed Central

    Ekwaru, John Paul; Zwicker, Jennifer D.; Holick, Michael F.; Giovannucci, Edward; Veugelers, Paul J.

    2014-01-01

    Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets. PMID:25372709

  12. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran.

    PubMed

    Glund, Stephan; Moschetti, Viktoria; Norris, Stephen; Stangier, Joachim; Schmohl, Michael; van Ryn, Joanne; Lang, Benjamin; Ramael, Steven; Reilly, Paul

    2015-05-01

    Idarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as a specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18-45 years received between 20 mg and 8 g idarucizumab as a 1-hour intravenous infusion in 10 sequential dose groups, or 1, 2 or 4 g idarucizumab as a 5-minute infusion. Subjects within each dose group were randomised 3:1 to idarucizumab or placebo. A total of 110 randomised subjects received study drug (27 placebo, 83 idarucizumab). Peak and total exposure to idarucizumab increased proportionally with dose. Maximum plasma concentrations were achieved near the end of infusion, followed by a rapid decline, with an initial idarucizumab half-life of ~45 minutes. For the 5-minute infusions, this resulted in a reduction of plasma concentrations to less than 5 % of peak within 4 hours. Idarucizumab (in the absence of dabigatran) had no effect on coagulation parameters or endogenous thrombin potential. Overall adverse event (AE) frequency was similar for idarucizumab and placebo, and no relationship with idarucizumab dose was observed. Drug-related AEs (primary endpoint) were rare (occurring in 2 placebo and 3 idarucizumab subjects) and were mostly of mild intensity; none of them resulted in study discontinuation. In conclusion, the pharmacokinetic profile of idarucizumab meets the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. Idarucizumab was safe and well tolerated in healthy males. PMID:25789661

  13. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers - A Double-Blind Sham-Controlled Crossover Study

    PubMed Central

    Kortekaas, Rudie; Konopka, Karl-Heinz; Harbers, Marten; van der Hoeven, Johannes H.; van Wijhe, Marten; Aleman, André; Maurits, Natasha M.

    2013-01-01

    The ‘complex neural pulse’TM (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP) or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT) measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. Trial Registration Dutch Cochrane Centre NTR1093 PMID:23620795

  14. Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers.

    PubMed

    Wiers, Corinde E; Shokri-Kojori, Ehsan; Cabrera, Elizabeth; Cunningham, Samantha; Wong, Christopher; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D

    2016-03-23

    Positron emission tomography (PET) studies in animals and humans have shown that social status is associated with striatal dopamine D2/D3 receptor (D2/D3R) availability. That is, higher social hierarchy and higher scores on questionnaires assessing social status correlated positively with striatal D2/D3R availability in animals and humans respectively. Furthermore, subordinate monkeys were vulnerable to cocaine self-administration, suggesting that alternations in social hierarchy can change D2/D3R availability and vulnerability to cocaine use. Here, we investigated whether socioeconomic status (SES) measured with the Hollingshead scale is associated with striatal D2D/3R availability using [(11)C]raclopride PET in 38 cocaine abusers and 42 healthy controls matched for age and education. Compared to controls, cocaine abusers showed lower D2/D3R availability in the caudate, putamen and ventral striatum (all p≤0.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<0.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=0.35, p=0.024) and putamen (r=0.39, p=0.011) but not in ventral striatum (p=0.61); all corrected for age. The study confirms that SES is associated with striatal D2/D3R availability in healthy human volunteers. However, reductions in D2/D3R availability in cocaine abusers may be driven by factors other than SES such as chronic cocaine exposure. PMID:26828302

  15. Strategies of Healthy Adults Walking on a Laterally Oscillating Treadmill

    NASA Technical Reports Server (NTRS)

    Brady, Rachel A.; Peters, Brian T.; Bloomberg, Jacob J.

    2008-01-01

    We mounted a treadmill on top of a six degree-of-freedom motion base platform to investigate locomotor responses produced by healthy adults introduced to a dynamic walking surface. The experiment examined self-selected strategies employed by participants when exposed to continuous, sinusoidal lateral motion of the support surface while walking. Torso translation and step width were used to classify responses used to stabilize gait in a novel, dynamic environment. Two response categories emerged. Participants tended to either fix themselves in space (FIS), allowing the treadbelt to move laterally beneath them, or they fixed themselves to the base (FTB), moving laterally as the motion base oscillated. The degree of fixation in both extremes varied across participants. This finding suggests that normal adults have innate and varied preferences for reacquiring gait stability, some depending more heavily on vision (FIS group) and others on proprioception (FTB group). Keywords: Human locomotion, Unstable surface, Treadmill, Adaptation, Stability

  16. Evaluation of inhaler handling-errors, inhaler perception and preference with Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: a single site, single visit crossover study (Finhaler)

    PubMed Central

    Sandler, Niklas; Holländer, Jenny; Långström, Disa; Santtila, Pekka; Saukkonen, Anni; Torvinen, Saku

    2016-01-01

    Introduction Correct inhaler technique and device preference are positively correlated with improved adherence and clinical outcomes. This study was designed to investigate inhaler technique mastery and device preference for three different dry powder inhalers, Spiromax, Easyhaler and Turbuhaler. Methods This was a single site, single visit, crossover study assessing device mastery, handling errors and preference using empty Spiromax, Easyhaler and Turbuhaler devices in healthy adult Finnish volunteers. Inhaler naïve adult participants were observed by healthcare professionals (HCPs) to evaluate the proportion of participants achieving device mastery (defined as an absence of HCP observed errors) using a three-step approach: (1) intuitive use (with no instructions), (2) after reading the patient information leaflet and (3) after HCP instruction. HCPs monitored and recorded errors based on device-specific handling error checklists. At the end of the study, participants completed a device preference questionnaire and rated their satisfaction with the three devices. Results Spiromax was correctly used by 37.5% and 93.3% of participants in steps 1 and 2, respectively, compared with 0% and 58.3% with Easyhaler, and 9.2% and 76.7% with Turbuhaler. All three devices showed high mastery (>95%) in step 3. The most common error reported with Spiromax was related to the orientation of the device. Not shaking the device was the most common error with Easyhaler. Errors in priming the device were the most common with Turbuhaler. Spiromax, Easyhaler and Turbuhaler were rated as the ‘easiest device to use’ by 73.1%, 12.6% and 14.3% of participants, respectively. The HCP instructions clearly improved the use of all devices. Conclusion Higher levels of device mastery, including intuitive/ease of use, were reported by naïve users when using Spiromax compared with Easyhaler and Turbuhaler. PMID:27026804

  17. Effects of therapeutic and supratherapeutic doses of oral tedizolid phosphate on cardiac repolarisation in healthy volunteers: a randomised controlled study.

    PubMed

    Flanagan, Shawn; Litwin, Jeffrey; Fang, Edward; Prokocimer, Philippe

    2016-07-01

    Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively. This was a four-way crossover study with 48 subjects randomly assigned to receive therapeutic and supratherapeutic doses of tedizolid phosphate, moxifloxacin (positive control for QT interval prolongation) and placebo (negative control). A continuous 12-lead ECG was recorded from 1 h before drug administration to 23 h after administration. Adverse events, which were generally mild, occurred most frequently with moxifloxacin or with a supratherapeutic dose of tedizolid phosphate; however, all treatments were well tolerated. This study demonstrated that therapeutic or supratherapeutic doses of the antibacterial tedizolid had no clinically significant effect on QT interval in healthy adults [ClinicalTrials.gov registration no.: NCT01461460]. PMID:27342387