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Sample records for healthy korean volunteers

  1. Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.

    Science.gov (United States)

    Park, Sunny; Hyun, Yang Jin; Kim, Yu Ran; Lee, Ju Hyun; Ryu, Sunae; Kim, Jeong Mi; Oh, Woo Yong; Na, Han Sung; Lee, Jong Gu; Seo, Doo Won; Hwang, In Yeong; Park, Zewon; Jang, In Jin; Oh, Jaeseong; Choi, Seung Eun

    2017-05-01

    The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. © 2017 The Korean Academy of Medical Sciences.

  2. Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers

    Science.gov (United States)

    Hyun, Yang Jin; Kim, Yu Ran; Kim, Jeong Mi; Na, Han Sung

    2017-01-01

    The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. Clinical trial registry at the U.S. National Institutes of Health (https://clinicaltrials.gov), number NCT02299687. PMID:28378544

  3. The effects of fexofenadine at steady-state on sleep architecture: a study using polysomnography in healthy Korean volunteers.

    Science.gov (United States)

    Lee, Ho-Won; Lee, Hae Won; Park, Dae Jin; Moon, Sung Ok; Ahn, Ju Hee; Kim, Mi Jin; Kim, Sung-Doo; Kim, Ji-Eun; Yoon, Young-Ran

    2008-07-01

    To compare the effects of a first-generation antihistamine, chlorpheniramine, with those of the second-generation antihistamine, fexofenadine, at steady-state, on nocturnal sleep architecture in healthy Korean volunteers using polysomnography and the Multiple Sleep Latency Test. We evaluated whether a genetic polymorphism of multi-drug resistance 1 gene (MDR1) could produce variations in pharmacokinetic and pharmacodynamic parameters of fexofenadine. Ten healthy male volunteers received one capsule of fexofenadine 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days, in a single-site, randomized, double-blind, two-treatment, multiple-dosing, two-way crossover study, with a washout period of 7 days. Overnight polysomnography was measured on the second night of the treatment period. The Multiple Sleep Latency Test was carried out the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping on the third day. Compared with baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, with no significant decrease in the percentage of REM sleep. No significant change in latency for REM sleep or percentage REM sleep after dosing with fexofenadine was observed. There was no significant change in the daytime sleepiness with fexofenadine and chlorpheniramine. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant. Our findings suggest that fexofenadine and chlorpheniramine at steady-state have no significant effect on nocturnal sleep variables and daytime sleepiness, when compared to baseline.

  4. Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, two-way crossover study.

    Science.gov (United States)

    Jang, Jae-Won; Seo, Ji-Hyung; Jo, Min-Ho; Lee, Young-Joo; Cho, Young-Wuk; Yim, Sung-Vin; Lee, Kyung-Tae

    2013-02-01

    Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-∞) were within the predetermined bioequivalence range (80 - 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-∞) with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference

  5. Pharmacokinetic properties and bioequivalence of 2 formulations of valsartan 160-mg tablets: A randomized, single-dose, 2-period crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Kim, Ji-Eon; Ki, Min-Hyo; Yoon, In-Soo; Cho, Hyun-Jong; Kim, Ree-Sun; Tae Kim, Geun; Kim, Dae-Duk

    2014-02-01

    The solubility of valsartan is dependent on pH and thus may cause patient variability in drug absorption and failure in bioequivalence studies; thus, increasing the solubility and release of valsartan at low pH has been suggested for a more favorable pharmacokinetic profile. However, due to this pH dependence, the change in the formulation process could alter the disintegration and/or dissolution profile of the drug, possibly making the results of bioequivalence studies misleading. The aim of this study was to assess the bioavailability and tolerability of a newly developed oral formulation of valsartan 160 mg (wet-granulation tablet) in healthy Korean male volunteers. This study was performed with the subjects under fasted conditions, using a randomized, single-dose, 2-period crossover design. Subjects were assigned to receive, in randomized order, a single dose of the test formulation and a reference formulation (valsartan 160-mg dry-granulation tablet), with a washout period of 7 days between the administrations. Blood samples were collected up to 24 hours after dosing, and pharmacokinetic parameters were determined after the plasma valsartan concentration was analyzed using UPLC-MS/MS. The dissolution studies of both formulations were conducted using USP apparatus 2 at 50 rpm with 1000 mL of phosphate buffer solution (pH, 6.8) at 37°C ± 0.5°C. Bioequivalence was defined per Korean Food and Drug Administration's regulatory criteria as 90% CIs of the geometric mean test/reference ratios of AUC0-t and Cmax within the range of 0.8 to 1.25. Tolerability was assessed using physical examination and subject interviews. Sixty subjects were enrolled (mean [SD] age [range], 23.6 [2.4] years [21-31]; height, 173.7 [6.6] cm [161-190]; and weight, 68.0 [8.7] kg [54-85]). The mean AUC0-∞ values with the test and reference tablets were 31,784 (13,844) and 32,714 (14,512) ng · h/mL, respectively; Cmax, 5094 (2061) and 5064 (1864) ng/mL; Tmax, 2.92 (1.04) and 3.08 (1

  6. Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers.

    Science.gov (United States)

    Rhim, Si-Youn; Park, Jin-Hee; Park, Yoo-Sin; Lee, Min-Ho; Kim, Dong-Sun; Shaw, Leslie M; Yang, Seok-Chul; Kang, Ju-Seop

    2009-05-01

    Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence. The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population. This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA). Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19

  7. Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Jin, Seok-Joon; Kim, Yo Han; Kim, Mi-Jo; Sung, Hyeryoung; Jang, Seong Bok; Lee, Sung Jae; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2012-09-01

    events (AEs) were reported in 8 subjects. All AEs were considered to be mild, and there were no clinically significant differences between treatment groups. The findings from this study suggest bioequivalence between revaprazan given as monotherapy and in combination with itopride in these healthy Korean male volunteers, with no clinical significant drug-drug interaction. All treatments in this study was generally well tolerated. ClinicalTrials.gov identifier: NCT0133289. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

  8. Tolerability and pharmacokinetics of avanafil, a phosphodiesterase type 5 inhibitor: a single- and multiple-dose, double-blind, randomized, placebo-controlled, dose-escalation study in healthy Korean male volunteers.

    Science.gov (United States)

    Jung, Jinah; Choi, Sangmin; Cho, Sang Heon; Ghim, Jong-Lyul; Hwang, Aekyung; Kim, Unjib; Kim, Bong Sik; Koguchi, Atsushi; Miyoshi, Shinji; Okabe, Hirotaka; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2010-06-01

    Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction. This study was conducted to meet Korean regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral doses of avanafil in healthy Korean male volunteers were assessed. A double-blind, randomized, placebo-controlled, parallel-group, dose-escalation study was conducted at the Asan Medical Center (Seoul, Korea). Subjects were randomized to receive either drug or placebo in blocks according to each dose. Subjects were randomly allocated to receive 50-, 100-, or 200-mg tablets of avanafil or placebo once daily for 7 days (avanafil:placebo, 8:2 in each dose group). Tolerability was assessed by monitoring vital signs and results of laboratory tests, 12-lead ECGs, and color discrimination tests. Blood samples of approximately 6 mL were collected in heparinized tubes before and 0.1, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after drug administration on days 1 and 7. Plasma concentrations of avanafil were measured using LC-MS/MS. Pharmacokinetic parameters of avanafil on days 1 and 7 were determined by noncompartmental analysis and compared among the 3 dose groups. Of the 32 healthy male subjects initially enrolled, 30 completed the study. The mean (SD) age, height, and weight of the participants were 23.4 (1.7) years, 175.0 (5.4) cm, and 70.3 (8.9) kg, respectively. Adverse events were reported by 20 of 25 subjects (80%) taking avanafil and by 4 of 6 (67%) taking placebo. No serious adverse events were reported, and there were no clinically relevant changes in vital signs, ECG recordings, physical examination findings, or color discrimination test results. All the adverse events resolved spontaneously. Avanafil reached a mean T(max) at 0.33 to 0.52 hour after dosing and then declined, with a mean apparent t1/2 of 5.36 to 10.66 hours. AUC and C(max) were proportional

  9. Pain perception in healthy volunteers

    DEFF Research Database (Denmark)

    Janum, Susanne; Nielsen, Signe Tellerup; Werner, Mads U

    2016-01-01

    We aimed to study the relationship between pain perception and cytokine release during systemic inflammation. We present a randomized crossover trial in healthy volunteers (n = 17) in 37 individual trials. Systemic inflammation was induced by an i.v. bolus of Escherichia coli LPS (2 ng/kg) on two...... separate trial days, with or without a nicotine patch applied 10 h previously. Pain perception at baseline, and 2 and 6 h after LPS was assessed by pressure algometry and tonic heat stimulation at an increasing temperature (45-48℃) during both trials. Compared with baseline, pain pressure threshold...... was reduced 2 and 6 h after LPS, while heat pain perception was accentuated at all testing temperatures after 2 but not 6 h. The magnitude of changes in pain perception did not correlate to cytokine release. No effect of transdermal nicotine or training status was observed. In conclusion, LPS administration...

  10. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Kim, Bo-Hyung; Kim, Kyu-Pyo; Lim, Kyoung Soo; Kim, Jung-Ryul; Yoon, Seo Hyun; Cho, Joo-Youn; Lee, Yong-Oh; Lee, Kyung-Hee; Jang, In-Jin; Shin, Sang-Goo; Yu, Kyung-Sang

    2010-02-01

    Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine. Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities, according to the drug-development guidance for fixed-dose combination formulations in Korea. This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract. An open-label, randomized, 2-period, 2-treatment, 2-sequence, single-dose crossover study was conducted in healthy Korean male volunteers. All volunteers were randomly assigned to a sequence group for the 2 treatments, which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg, separated by a 1-week washout period between the treatments. Bleeding time was determined just before dosing and at 5, 12, and 48 hours after dosing. Platelet aggregation was evaluated before dosing and at 4, 8, 26, and 48 hours after dosing. Blood samples (8 mL) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after dosing. Ticlopidine concentrations were determined by a validated method using HPLC and ultraviolet detection. Adverse events were identified using general health-related questions, vital signs, physical examinations, ECGs, and laboratory tests. A total of 24 healthy men participated in the study (mean [SD] age, 24.1 [4.3] years; weight, 66.6 [7.4] kg; height, 174.7 [5.0] cm). The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups, and changes in platelet aggregation were not significantly different between the groups. Likewise, the pharmacokinetic parameters of ticlopidine were not significantly different

  11. Uroflow measurements in healthy female volunteers.

    Science.gov (United States)

    Ahmed, Stephanie; McNanley, Anna; Perevich, Maryann; Glantz, John Christopher; Buchsbaum, Gunhilde

    2010-11-01

    : There is not currently a standard definition of "normal" for uroflowmetry parameters, particularly with respect to spontaneous voids or multiple repeated measurements within an individual. Our study aimed to describe uroflow parameters for "normal" in a group of healthy women based on repeated measurements. : Spontaneous voids of twelve healthy women were recorded over two weeks. Additionally, one prompted void per subject was recorded. Prompted voids were compared to the subjects' spontaneous voids. These voids were also compared to those of patients evaluated for urinary incontinence. Groups were compared using paired t tests. : The mean voided volume was 306 ml and the mean maximum flow rate was 49 ml/s. The prompted voids were lower in volume, maximum flow, and duration than spontaneous voids. When corrected for volume, these differences were not significant. Maximum flow rates in patients evaluated for urinary incontinence were lower than those of volunteers. : Uroflowmetry parameters vary widely between and within healthy volunteers. Prompted voids are representative of spontaneous voids. Maximum flow rates of patients evaluated for urinary incontinence were lower than those of volunteers. In a group of healthy volunteers voiding in a private, spontaneous setting, a maximum flow rate of lower than 17 ml/s (2 SDs below the mean) might be considered abnormally low.

  12. The Impact of Acculturation on Informal and Formal Volunteering of Korean Americans in the United States

    Directory of Open Access Journals (Sweden)

    Hee Soun Jang

    2016-04-01

    Full Text Available This study examines the impact of acculturation on Korean Americans’ decisions to volunteer either for secular and religious organizations or informally. The results show that language difficulty and Korean identity lower the likelihood of secular volunteering, but not of informal volunteering. Koreans who are Protestants or Catholics, and those with higher levels of education, are more likely to volunteer formally, but not informally. The findings indicate formal volunteering is strongly associated with acculturation factors, along with personal and social variables but informal volunteering appears to be independent from and not complementary of the other two types of volunteering.

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

    OpenAIRE

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

    2016-01-01

    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. ...

  14. Bioavailability of hydroxychloroquine tablets in healthy volunteers.

    OpenAIRE

    Tett, S E; Cutler, D J; Day, R O; Brown, K F

    1989-01-01

    1. Five healthy volunteers received, in a randomised crossover design study, a 155 mg oral tablet and an intravenous infusion of 155 mg racemic hydroxychloroquine (200 mg hydroxychloroquine sulphate) to assess the bioavailability of the commercially available tablet (Plaquenil, Winthrop Laboratories, Australia). 2. The terminal elimination half-life of hydroxychloroquine is more than 40 days, thus blood and urine samples were collected for 5 months following each dose to characterise adequate...

  15. How healthy are the "Healthy volunteers"? Penetrance of NAFLD in the biomedical research volunteer pool.

    Science.gov (United States)

    Takyar, Varun; Nath, Anand; Beri, Andrea; Gharib, Ahmed M; Rotman, Yaron

    2017-09-01

    Healthy volunteers are crucial for biomedical research. Inadvertent inclusion of subjects with nonalcoholic fatty liver disease (NAFLD) as controls can compromise study validity and subject safety. Given the rising prevalence of NAFLD in the general population, we sought to identify its prevalence and potential impact in volunteers for clinical trials. We conducted a cross-sectional study of subjects who were classified as healthy volunteers between 2011 and 2015 and had no known liver disease. Subjects were classified as presumed NAFLD (pNF; alanine aminotransferase [ALT] level ≥ 20 for women or ≥ 31 for men and body mass index [BMI] > 25 kg/m(2) ), healthy non-NAFLD controls (normal ALT and BMI), or indeterminate. A total of 3160 subjects participated as healthy volunteers in 149 clinical trials (1-29 trials per subject); 1732 of these subjects (55%) had a BMI > 25 kg/m(2) and 1382 (44%) had abnormal ALT. pNF was present in 881 subjects (27.9%), and these subjects were older than healthy control subjects and had higher triglycerides, low-density lipoprotein cholesterol, and HbA1c and lower high-density lipoprotein cholesterol (P healthy control subjects (4 versus 1). NAFLD is common and often overlooked in volunteers for clinical trials, despite its potential impact on subject safety and validity of study findings. Increased awareness of NAFLD prevalence and stricter ALT cutoffs may ameliorate this problem. (Hepatology 2017;66:825-833). Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  16. LSD enhances suggestibility in healthy volunteers.

    Science.gov (United States)

    Carhart-Harris, R L; Kaelen, M; Whalley, M G; Bolstridge, M; Feilding, A; Nutt, D J

    2015-02-01

    Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control. The present study sought to test the effect of LSD on suggestibility in a modern research study. Ten healthy volunteers were administered with intravenous (i.v.) LSD (40-80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for 'efficacy' (i.e. A ≈ B) and counterbalanced across conditions (i.e. 50 % completed version 'A' under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects. Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005). These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

  17. Pharmacogenetics of healthy volunteers in Puerto Rico

    Science.gov (United States)

    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

  18. Prediction of psilocybin response in healthy volunteers.

    Science.gov (United States)

    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.

  19. Prediction of psilocybin response in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Erich Studerus

    Full Text Available 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.

  20. Enhanced Absorption Study of Ginsenoside Compound K (20-O-β-(D-Glucopyranosyl-20(S-protopanaxadiol after Oral Administration of Fermented Red Ginseng Extract (HYFRG™ in Healthy Korean Volunteers and Rats

    Directory of Open Access Journals (Sweden)

    Il-Dong Choi

    2016-01-01

    Full Text Available To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD of AUC0–t and Cmax of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL, respectively; in case of Sprague Dawley rats the mean (±SD of AUC0–t and Cmax of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL, respectively. Tmax of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.

  1. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    Dose regimens in perioperative fluid management are rarely evidence based. Therefore, we investigated responses to an IV fluid infusion in healthy volunteers to assess basic physiologic effects of a fluid infusion per se. In a prospective, double-blinded, cross-randomized study, 12 healthy...... volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting...

  2. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers Udgivelsesdato: 2008...

  3. Exposure to bisphenol A is directly associated with inflammation in healthy Korean adults.

    Science.gov (United States)

    Choi, Yong Jun; Ha, Kyoung Hwa; Kim, Dae Jung

    2017-01-01

    It was recently discovered that bisphenol A (BPA) and phthalates are cardiovascular disruptors. Inflammation is central to the initiation and progression of cardiovascular disease (CVD). This study evaluated whether BPA and different phthalate metabolites are associated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in healthy Korean adults. This research is part of an ongoing, population-based study of Korean adults (30-64 years of age) conducted at the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC). The study enrolled 200 healthy volunteers (96 men, 104 women). Plasma hs-CRP was measured as an inflammation marker. BPA and five phthalate metabolites in urine were analyzed by using liquid chromatography/tandem mass spectrometry. BPA and monobenzyl phthalate (MBzP) differed significantly between the low-hs-CRP (inflammation regardless of obesity or insulin resistance.

  4. Gastric Impedance Spectroscopy in Cardiovascular Surgery Patients vs. Healthy Volunteers.

    Science.gov (United States)

    Beltran, N; Sanchez-Miranda, G; Godinez, M; Diaz, U; Sacristan, E

    2005-01-01

    Impedance spectroscopy has been proposed as a method of monitoring mucosal injury due to hypoperfusion and ischemia in the critically ill. The present study evaluates spectral differences in elective cardiovascular surgery patients compared with the impedance spectra of the gastric mucosa in healthy adults. An impedance spectroscopy probe and nasogastric tube (ISP/NGT) was placed into the stomach of 77 heart surgery and 21 healthy volunteers. The recorded impedance spectra were classified into 3 groups: group 1 for healthy volunteers; group 2 for patients with neither ischemia nor complications; and group 3 for patients with ischemia and complications during the first 3 days in the recovery unit. There were statistical differences in resistance (p<0.001) and reactance (p<0.001) among the 3 groups. The results show that impedance spectra are distinct and significantly different in patients with probable ischemic mucosal injury compared to healthy subjects, and therefore this technology may be a useful prognostic and diagnostic monitoring tool.

  5. Psychopharmacology of theobromine in healthy volunteers.

    Science.gov (United States)

    Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

    2013-07-01

    Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

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

    OpenAIRE

    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). Resul...

  7. Travoprost lowers intraocular pressure in healthy student volunteers ...

    African Journals Online (AJOL)

    We evaluated the change in diurnal intraocular pressure (IOP) induced by the instillation of single dose travoprost 0.004% and placebo into the eyes of 20 healthy African volunteers in a randomized double masked, placebo controlled, crossover, single centre study. Pulse rate, systolic and diastolic blood pressure, and ...

  8. Assessment of platelet profile of healthy volunteers in the trimesters ...

    African Journals Online (AJOL)

    Assessment of platelet profile of healthy volunteers in the trimesters of pregnancy in Benin City, Nigeria. ... Thus PDW compensates for these reductions and a lack of this compensatory increase may aggravate the effect of thrombocytopenia in pregnancy. Platelet Count, Plateletcrit, Mean Platelet Volume, Platelet ...

  9. Informed consent in healthy volunteers: Whom does it protect?

    NARCIS (Netherlands)

    Van Vliet, A.A.; Wemer, J.; Wilffert, B.; De Vroedt, J.W.P.; Jonkman, J.H.G.

    1999-01-01

    In the next decade, centres for research on the safety, tolerability or bioequivalence of new molecular entities will be confronted with numerous compounds, a narrowing time frame for performing Phase I research activities, and a growing demand for healthy volunteers for participation in

  10. Bioavailability of four oral Coenzyme Q formulations in healthy volunteers

    DEFF Research Database (Denmark)

    Weis, M.; Mortensen, S.A.; Rassing, M.R.

    1994-01-01

    The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing...

  11. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

    2016-01-01

    BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were...... collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...

  12. Normal range values for thromboelastography in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    S. Scarpelini

    2009-12-01

    Full Text Available Thromboelastography (TEG® provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG® parameters analyzed were R, K, α, MA, LY30, and coagulation index. All volunteers outside the manufacturer’s normal range underwent extensive coagulation investigations. Reference ranges for 95% for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, α: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77%, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81% specificity. Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturer’s normal values for citrated blood-kaolin had a specificity of 81% and would incorrectly identify 8.5% of the healthy volunteers as coagulopathic. This study supports the manufacturer’s recommendation that each institution should determine its own normal values before adopting TEG®, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG®.

  13. Proprioceptive function of the shoulder girdle in healthy volunteers.

    Science.gov (United States)

    Jerosch, J; Thorwesten, L; Steinbeck, J; Reer, R

    1996-01-01

    In 27 healthy volunteers (9 females, 18 males) we evaluated the proprioceptive function of the glenohumeral joint. The volunteers were asked to place the arm in different positions with and without visual control. The test was performed for the dominant and for the nondominant extremity. The following joint positions were measured: 50 degrees, 100 degrees, 150 degrees abduction; 50 degrees, 100 degrees, 150 degrees flexion; +45 degrees, 0 degrees, -45 degrees rotation in 90 degrees abduction. Joint position was documented with a motion-analyzing system with passive reflecting markers. The results showed significant differences between the measurements with and without visual control. Proprioception was worse below the shoulder level (50 degrees abduction, flexion). Two volunteers with generally good coordinative capabilities showed better results than the rest of the group. We observed no differences between dominant and nondominant extremities nor between males and females. Our results demonstrated low variance of the proprioceptive function of the glenohumeral joint in healthy volunteers. Our findings serve as a base for further evaluations in different patients' populations.

  14. Vascular Effects of Urocortins 2 and 3 in Healthy Volunteers

    OpenAIRE

    Venkatasubramanian, Sowmya; Griffiths, Megan E.; McLean, Steven G.; Miller, Mark R.; Luo, Rosa; Lang, Ninian N.; Newby, David E.

    2013-01-01

    Background Urocortin 2 and urocortin 3 are endogenous peptides with an emerging role in cardiovascular pathophysiology. We assessed their pharmacodynamic profile and examined the role of the endothelium in mediating their vasomotor effects in vivo in man. Methods and Results Eighteen healthy male volunteers (23?4 years) were recruited into a series of double?blind, randomized crossover studies using bilateral forearm venous occlusion plethysmography during intra?arterial urocortin 2 (3.6 to 1...

  15. Ultrasound assessment of optic nerve sheath diameter in healthy volunteers.

    Science.gov (United States)

    Goeres, Patrick; Zeiler, Frederick A; Unger, Bertram; Karakitsos, Dimitrios; Gillman, Lawrence M

    2016-02-01

    Ultrasound assessment of optic nerve sheath diameter (ONSD) has been suggested as a non-invasive measure of intracranial pressure. Numerous small studies suggest its validity; however, discrepancy exists around normal values for ONSD. In this study we sought to define a normal value range for ONSD in a population of healthy adult volunteers. ONSD was measured in healthy adult volunteers and a normal range was defined using descriptive statistics. A regression analysis was used to determine relationship between ONSD measurements and sex, age, height and weight. One hundred twenty adults were recruited (age 18-65 [mean 29.3]) with 55 male and 65 female subjects. Mean ONSD was 3.68 mm (95% confidence interval [CI], 2.85-4.40). Upon regression analysis, mean ONSD did not vary with age, weight, or height but did vary with sex. Mean ONSD measurements for men were 3.78 mm (95% CI, 3.23-4.48) compared with 3.60 mm (95% CI, 2.83-4.11) for women. This study has defined the range of ONSD in a healthy cohort of volunteers. The lack of relationship to age, weight and height is similar to other studies but this is the first study to find a difference depending on sex suggesting the possible need for separate reference ranges for men and women. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Esomeprazole reduces gastroesophageal reflux after beer consumption in healthy volunteers.

    Science.gov (United States)

    Franke, Andreas; Hepp, Caroline; Harder, Hermann; Beglinger, Christoph; Singer, Manfred V

    2008-01-01

    Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pHbeer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

  17. The Associations between Pain Sensitivity and Knee Muscle Strength in Healthy Volunteers

    DEFF Research Database (Denmark)

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie

    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...

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

    Directory of Open Access Journals (Sweden)

    Kline Joel N

    2004-09-01

    Full Text Available Abstract 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

  19. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers.

    Science.gov (United States)

    Modaghegh, Mohammad-Hadi; Shahabian, Masoud; Esmaeili, Habib-Allah; Rajbai, Omid; Hosseinzadeh, Hossein

    2008-12-01

    Saffron (Crocus sativus) stigma tablets were evaluated for short-term safety and tolerability in healthy adult volunteers. The study was a double-blind, placebo-controlled design consisting of a 1 week treatment of saffron tablets. Volunteers were divided into 3 groups of 10 each (5 males and 5 females). Group I received placebo; groups 2 and 3 received 200 and 400mg saffron tablets, respectively, for 7 days. General measures of health were recorded during the study such as hematological, biochemical and electrocardiographic parameters done in pre- and post-treatment periods. Clinical examination showed no gross changes in all volunteers after intervention. Saffron with higher dose (400mg) decreased standing systolic blood pressure and mean arterial pressures significantly. Saffron decreased slightly some hematological parameters such as red blood cells, hemoglobin, hematocrit and platelets. Saffron increased sodium, blood urea nitrogen and creatinine. This study showed that saffron tablets may change some hematological and biochemical parameters. However, these alterations were in normal ranges and they were not important clinically.

  20. Validation of a transient pain monitor in healthy volunteers.

    Science.gov (United States)

    Dualé, Christian; Dalle, Nathalie; Cardot, Jean-Michel; Martin, Alice; Boby, Henri; Bigay, Vincent; Dubray, Claude

    2011-01-01

    Transient pain in humans is usually quantified using visual analog or numeric rating scales, but no assessment method has yet been validated in real time during such stimulation. To validate a transient pain monitor, healthy volunteers submitted to stimulations generated by a CO(2) laser at graded levels of stimulation were trained to close the dominant hand around a handgrip dynamometer as strongly as they felt the pain, and the signal was computerized.The parameters recorded for each response were the peak intensity, the area under the curve, and pain expressed on a visual analog scale as a control. The volunteers underwent a second session 1 week later to assess reproducibility. The 3 parameters studied had a similar capacity to report the intensity of stimulation. The peak intensity showed many similarities with the visual analog scale, although a downward drift of the values throughout the session was observed. The area under the curve displayed a greater interindividual variability than other parameters, but it was better to assess low-intensity stimulation; a better fit for crossover designs was also suggested with the area under the curve. This study validates in human volunteers under a laser stimulation of skin the metrological properties of an electronic handgrip device to assess the intensity of transient punctuate pain (compared with visual analog scale). The transient pain monitor validated here should now be tested in the clinical context. Copyright © 2011 by American Society of Regional Anesthesia and Pain Medicine

  1. Pharmacokinetic interaction between fluoxetine and metoclopramide in healthy volunteers.

    Science.gov (United States)

    Vlase, Laurian; Leucuta, Adrian; Farcau, Dorin; Nanulescu, Mircea

    2006-09-01

    The pharmacokinetic interaction of fluoxetine with metoclopramide in healthy volunteers was evaluated. A dose of 20 mg metoclopramide in combination with 60 mg fluoxetine was administered to 24 healthy male volunteers in a two treatment study design, separated by 8 days in which the fluoxetine alone was administered as a single p.o. dose daily. Plasma concentrations of metoclopramide were determined during a 24 h period following drug administration. Metoclopramide plasma concentrations were determined by a validated HPLC method. Pharmacokinetic parameters of metoclopramide were calculated using non-compartmental analysis. In the two periods of treatment, the mean peak plasma concentrations (Cmax) were 44.02 ng/ml (metoclopramide alone) and 62.72 ng/ml (metoclopramide after pre-treatment with fluoxetine). The times taken to reach Cmax and tmax, were 1.15 h and 1.06 h, respectively. The total areas under the curve (AUC(0-infinity)) were 312.61 ng.h/ml and 590.62 ng.h/ml, respectively. The half-life values (t1/2) were 5.52 h and 8.47 h. Statistically significant differences were observed for both AUC(0-infinity) and t1/2 of metoclopramide when administered alone or after 8 days treatment with fluoxetine. The experimental data demonstrate the pharmacokinetic interaction between fluoxetine and metoclopramide and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed. Copyright 2006 John Wiley & Sons, Ltd.

  2. Intersession repeatability of acoustic rhinometry measurements in healthy volunteers.

    Science.gov (United States)

    Al Ahmari, Mohammed Dhafer; Wedzicha, Jadwiga Anna; Hurst, John Robert

    2012-09-01

    Acoustic rhinometry is a rapid, reliable and non-invasive technique for the evaluation of conditions associated with impaired nasal patency. This study aimed to examine the intersession repeatability of acoustic rhinometry measurements of unilateral and combined nasal parameters in a group of healthy volunteers. Twenty healthy volunteers were studied. In each subject, acoustic rhinometry measurements were performed on five consecutive days, with multiple recordings. Five clinically relevant parameters were measured in each session and the intersession repeatability of these measurements was expressed in terms of mean coefficient of variation, intraclass correlation coefficient and inter-item correlations. Intraclass correlation coefficients showed a high, and greater repeatability over time for all the combined (mean) values compared to the unilateral values. All intraclass correlations for combined values were ≥0.80 confirming almost perfect agreement. All intraclass correlations and inter-item correlations were associated with Pmeasurements. Acoustic rhinometry provides highly repeatable measurements of nasal patency, which is best for combined (mean) nasal parameters. This property makes it suitable for use in the diagnosis and follow-up of conditions associated with nasal obstruction, either structural or functional.

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

    Science.gov (United States)

    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 (PAmbroxol 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

  4. Tympanic displacement analysis in healthy volunteers after indomethacin administration.

    Science.gov (United States)

    Walsted, Alice; Wagner, Niels; Andersen, Kim Møller

    2002-12-01

    The aim of this study was to investigate whether a tympanic displacement analyser could detect decreases in cerebral blood flow and intracranial pressure after administration of indomethacin in healthy volunteers. In a double-blind crossover study involving 14 healthy volunteers all subjects first underwent a test-retest evaluation to investigate reproducibility followed by tests performed in sitting and supine positions to confirm intracranial-cochlear pressure transfer. In two further sessions tests were performed before and 90 min after subjects were blindly administered a suppository containing either 100 mg of indomethacin or placebo. It was found that tympanic membrane analysis performed 90 min after administration of such a suppository did not mirror the induced reduction in cerebral blood flow after administration of active drug. After administration of indomethacin eight of the subjects experienced discomfort and dizziness; after placebo none experienced subjective symptoms. After administration of indomethacin a statistically significant decrease in heart rate was demonstrated. The exponential form of the intracranial pressure-volume curve may explain why a decrease in intracranial pressure was not detected using the tympanic membrane displacement method, because the measurements were made in subjects with normal intracranial pressure. More significant findings may be found in patients with elevated intracranial pressure.

  5. Population pharmacokinetics of olprinone in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kunisawa T

    2014-03-01

    Full Text Available Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM® software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg, distribution volume of the central compartment (134 mL/kg, intercompartmental clearance (7.75 mL/minute/kg, and distribution volume of the peripheral compartment (275 mL/kg. The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive were 22.2% and 0.129 (standard deviation. The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model

  6. MDMA Impairs Response to Water Intake in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Matthew J. Baggott

    2016-01-01

    Full Text Available 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.

  7. Multiple-dose pharmacokinetics of ceftibuten in healthy volunteers.

    Science.gov (United States)

    Lin, C; Radwanski, E; Affrime, M; Cayen, M N

    1995-01-01

    The pharmacokinetics of ceftibuten, a new cephalosporin antibiotic, and its conversion product, ceftibutentrans, were studied in healthy male volunteers following daily oral administration of a 400-mg capsule for 7 days. Mean concentrations of ceftibuten in plasma obtained on day 5 were similar to those obtained on day 7. Analysis of variance indicated that the concentrations in plasma on days 5 and 7 were at steady state. The mean accumulation factor was 1.14 for day 5 and 1.13 for day 7. The half-life (2.4 h) was independent of the duration of drug administration, and the mean maximum concentration of drug in plasma was 18 to 19 micrograms/ml. Urinary excretion was the major elimination route for ceftibuten, by which 57 to 59% of the drug was excreted unchanged over a 24-h period. The amounts of ceftibuten-trans in plasma and urine were low. PMID:7726497

  8. Multiple-dose pharmacokinetics of ceftibuten in healthy volunteers.

    Science.gov (United States)

    Lin, C; Radwanski, E; Affrime, M; Cayen, M N

    1995-02-01

    The pharmacokinetics of ceftibuten, a new cephalosporin antibiotic, and its conversion product, ceftibutentrans, were studied in healthy male volunteers following daily oral administration of a 400-mg capsule for 7 days. Mean concentrations of ceftibuten in plasma obtained on day 5 were similar to those obtained on day 7. Analysis of variance indicated that the concentrations in plasma on days 5 and 7 were at steady state. The mean accumulation factor was 1.14 for day 5 and 1.13 for day 7. The half-life (2.4 h) was independent of the duration of drug administration, and the mean maximum concentration of drug in plasma was 18 to 19 micrograms/ml. Urinary excretion was the major elimination route for ceftibuten, by which 57 to 59% of the drug was excreted unchanged over a 24-h period. The amounts of ceftibuten-trans in plasma and urine were low.

  9. Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

    Science.gov (United States)

    Trépanier, Eric F.; Nafziger, Anne N.; Amsden, Guy W.

    1998-01-01

    Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident. PMID:9517954

  10. Normobaric hyperoxia alters the microcirculation in healthy volunteers.

    Science.gov (United States)

    Orbegozo Cortés, Diego; Puflea, Florin; Donadello, Katia; Taccone, Fabio Silvio; Gottin, Leonardo; Creteur, Jacques; Vincent, Jean-Louis; De Backer, Daniel

    2015-03-01

    The use of high concentrations of inhaled oxygen has been associated with adverse effects but recent data suggest a potential therapeutic role of normobaric hyperoxia (NH) in sepsis and cerebral ischemia. Hyperoxia may induce vasoconstriction and alter endothelial function, so we evaluated its effects on the microcirculation in 40 healthy adult volunteers using side-stream dark field (SDF) video-microscopy on the sublingual area and near-infrared spectroscopy (NIRS) on the thenar eminence. In a first group of volunteers (n=18), measurements were taken every 30 min: at baseline in air, during NH (close to 100% oxygen via a non-rebreathing mask) and during recovery in air. In a second group (n=22), NIRS measurements were taken in NH or ambient air on two separate days to prevent any potential influence of repeated NIRS measurements. NH significantly decreased the proportion of perfused vessels (PPV) from 92% to 66%, perfused vessel density (PVD) from 11.0 to 7.3 vessels/mm, perfused small vessel density (PSVD) from 9.0 to 5.8 vessels/mm and microvascular flow index (MFI) from 2.8 to 2.0, and increased PPV heterogeneity from 7.5% to 30.4%. Thirty minutes after return to air, PPV, PVD, PSVD and MFI remained partially altered. During NH, NIRS descending slope and NIRS muscle oxygen consumption (VO2) decreased from 8.5 to 7.9%/s and 127 to 103 units, respectively, in the first group and from 10.7 to 9.4%/s and 150 to 115 units in the second group. NH, therefore, alters the microcirculation in healthy subjects, decreasing capillary perfusion and VO2 and increasing the heterogeneity of the perfusion. Copyright © 2014. Published by Elsevier Inc.

  11. Healthy Volunteers Can Be Phenotyped Using Cutaneous Sensitization Pain Models

    Science.gov (United States)

    Rowbotham, Michael C.; Dahl, Jørgen B.

    2013-01-01

    Background Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. Methods We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models. Results Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into ‘small area’ (1st quartile [75%]) responders: 56–76% of subjects consistently fell into same ‘small-area’ or ‘large-area’ category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models. Conclusion Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models. PMID:23671631

  12. Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

    Science.gov (United States)

    Cho, Kyung-Jin; Cho, Wonkyung; Cha, Kwang-Ho; Park, Junsung; Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

    2010-01-01

    In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serum concentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC(0-4h), AUC(0 --> infinity), C(max), T(max) and T1/2 were 865.28 ng x h/ml, 873.04 ng x h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng x h/ml, 830.97 ng x h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC(0 --> infinity) and C(max) were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC(0 --> infinity) and C(max) were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.

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

    Directory of Open Access Journals (Sweden)

    Kalpana D Dhuri

    2013-01-01

    Full Text Available 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.

  14. Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

    Directory of Open Access Journals (Sweden)

    Mads U Werner

    Full Text Available BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. METHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]. Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C, the brief thermal sensitization (BTS, and the burn injury (BI models. Three studies included both the H/C and BTS models. RESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st quartile [75%] responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm and BTS (thigh models. CONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.

  15. The pharmacokinetic interaction between ivacaftor and ritonavir in healthy volunteers.

    Science.gov (United States)

    Liddy, Anne Marie; McLaughlin, Gavin; Schmitz, Susanne; D'Arcy, Deirdre M; Barry, Michael G

    2017-10-01

    The aim of this study was to determine the pharmacokinetic interaction between ivacaftor and ritonavir. A liquid chromatography mass spectrometry (LC-MS) method was developed for the measurement of ivacaftor in plasma. An open-label, sequential, cross-over study was conducted with 12 healthy volunteers. Three pharmacokinetic profiles were assessed for each volunteer: ivacaftor 150 mg alone (study A), ivacaftor 150 mg plus ritonavir 50 mg daily (study B), and ivacaftor 150 mg plus ritonavir 50 mg daily after two weeks of ritonavir 50 mg daily (study C). Addition of ritonavir 50 mg daily to ivacaftor 150 mg resulted in significant inhibition of the metabolism of ivacaftor. Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf obv ) increased significantly in both studies B and C compared to study A (GMR [95% CI] 19.71 [13.18-31.33] and 19.77 [14.0-27.93] respectively). Elimination half-life (t1/2 ) was significantly longer in both studies B and C compared to study A (GMR [95% CI] 11.14 [8.72-13.62] and 9.72 [6.68-12.85] respectively). There was no significant difference in any of the pharmacokinetic parameters between study B and study C. Ritonavir resulted in significant inhibition of the metabolism of ivacaftor. These data suggest that ritonavir may be used to inhibit the metabolism of ivacaftor in patients with cystic fibrosis (CF). Such an approach may increase the effectiveness of ivacaftor in 'poor responders' by maintaining higher plasma concentrations. It also has the potential to significantly reduce the cost of ivacaftor therapy. © 2017 The British Pharmacological Society.

  16. Study of GABA in healthy volunteers: pharmacokinetics and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Junfeng eLi

    2015-11-01

    Full Text Available 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, 2g GABA once, and 2g GABA three times/day for seven 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 transitional 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.

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

    Directory of Open Access Journals (Sweden)

    Hilal eCerit

    2015-07-01

    Full Text Available 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-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 placebo. 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 placebo 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.

  18. Pharmacokinetics and tolerance of fluconazole suppositories in healthy volunteers.

    Science.gov (United States)

    Pfaff, G; Zimmermann, T; Lach, P; Yeates, R; Simon, G; Wildfeuer, A

    1993-03-01

    Fluconazole (Diflucan, CAS 86386-73-4) suppositories offer a novel way to administer this systemically active antimycotic. The pharmacokinetics and toleration of this new formulation have now been examined in healthy adult volunteers. In crossover experiments the bioequivalence was demonstrated for 200 mg suppositories and 200 mg capsules, and for 25 mg suppositories and 25 mg fluconazole in an oral suspension. The mean bioavailability of the 200 mg suppository relative to the capsule was about 93%. The mean bioavailability of the 25 mg suppository relative to the oral suspension was 107%. Absorption of fluconazole after administration of the suppositories was, however, somewhat slower than after oral ingestion of the capsule or suspension. The pharmacokinetic parameters of the 200 mg and 25 mg suppositories suggest that the kinetics of rectally administered fluconazole are linear with dosage. Daily administration of the 200 mg suppository gives a continuous increase in the mean fluconazole plasma concentration, until steady-state is reached on about the 5th day. The systemic and local toleration of the fluconazole suppositories was good.

  19. Ketamine-dependent neuronal activation in healthy volunteers.

    Science.gov (United States)

    Höflich, Anna; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Vanicek, Thomas; Ganger, Sebastian; Spies, Marie; Windischberger, Christian; Kasper, Siegfried; Winkler, Dietmar; Lanzenberger, Rupert

    2017-04-01

    Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S ® ) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p ketamine could be revealed.

  20. Pharmacokinetics of interferon alpha-2b in healthy volunteers.

    Science.gov (United States)

    Radwanski, E; Perentesis, G; Jacobs, S; Oden, E; Affrime, M; Symchowicz, S; Zampaglione, N

    1987-01-01

    In a three-way crossover design, 12 healthy male volunteers received 5 X 10(6) IU/m2 body surface area interferon alpha-2b(IFN alpha-2b) by intravenous (IV) infusion over 30 minutes, intramuscular (IM) injections, and subcutaneous (SC) injections. Blood and urine samples were collected at specified times, and analysis of IFN alpha-2b concentrations was performed by immunoradiometric assay. "Flulike" symptoms were the most frequently reported adverse experiences and were independent of the route of administration. After a 30-minute IV infusion, IFN alpha-2b disappeared rapidly from serum, with distribution and elimination phase half-lives of 0.1 hour and 1.7 hours, respectively. Interferon alpha-2b was absorbed slowly after IM and SC administration, with similar absorption half-lives of 5.8 and 5.5 hours, respectively. The observed maximal concentrations after IM and SC administration were 42.1 IU/mL at six hours and 45.8 IU/mL at eight hours, respectively. Interferon alpha-2b was eliminated with half-lives of 2.2 hours after IM administration and 2.9 hours after SC administration. The areas under the serum concentration-time curves for the SC and IM doses were higher than those obtained for the IV infusion. Measurable amounts of IFN alpha-2b were not found in urine regardless of the route of administration.

  1. Effect of High Inspiratory Oxygen Fraction on Endothelial Dysfunction in Healthy Volunteers

    DEFF Research Database (Denmark)

    Larsen, Mikkel Hjordt Holm; Ekeløf, Sara; Kokotovic, Dunja

    2017-01-01

    It has been suggested that high inspiratory oxygen concentrations during anesthesia may be associated with higher postoperative mortality due to endothelial dysfunction. A randomized controlled crossover study was conducted with 25 healthy male volunteers. They inhaled an oxygen concentration of ...... unaffected. Inhalation of a high oxygen fraction in healthy volunteers did not result in a significant reduction of endothelial function....

  2. Korean kimchi: promoting healthy meals through cultural tradition

    Directory of Open Access Journals (Sweden)

    Nobuko Hongu

    2017-09-01

    Conclusion: The availability and many varieties of kimchi exist in the US. Despite new trends and changes in the US, kimchi continues to be a significant important staple in many Korean and non-Korean families in the US.

  3. Pharmacokinetic interaction study of ticagrelor and cyclosporine in healthy volunteers.

    Science.gov (United States)

    Teng, Renli; Kujacic, Mirjana; Hsia, Judith

    2014-08-01

    Patients with acute coronary syndrome and certain co-morbidities may receive ticagrelor, a reversibly binding P2Y(12) receptor antagonist, and cyclosporine, a commonly used immunosuppressant drug. This study assessed the potential pharmacokinetic drug-drug interaction between ticagrelor and cyclosporine. In this single-centre, open-label, three-treatment, three-period crossover study (NCT01504906), healthy volunteers (n = 26) randomly received each of three treatments: cyclosporine (600 mg single oral dose) plus ticagrelor (180 mg single oral dose); cyclosporine alone; ticagrelor alone. Treatments were separated by a washout period of ≥14 days. Plasma concentrations of ticagrelor and its active metabolite (AR-C124910XX) and blood concentrations of cyclosporine were analyzed, and pharmacokinetic parameters were calculated. Safety and tolerability were assessed. Compared with ticagrelor alone, the geometric least squares mean (LSM) ratio (90 % confidence interval [CI]) for the ticagrelor area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) was 2.83 (2.63-3.06), and the maximum plasma concentration (C(max)) was 2.30 (2.06-2.58), in the presence of cyclosporine. Co-administration of cyclosporine with ticagrelor significantly increased AR-C124910XX AUC(∞) (1.33 [1.23-1.42]) and decreased C(max) (0.85 [0.76-0.94]). Ticagrelor had no effect on cyclosporine pharmacokinetic parameters, as the 90 % CIs of the LSM ratios were all within the 0.80-1.25 no-effect range. Co-administration of ticagrelor and cyclosporine was generally well tolerated. Co-administration of cyclosporine with ticagrelor increased exposure to ticagrelor and its active metabolite and had no effect on cyclosporine pharmacokinetic parameters. The magnitude of cyclosporine's effect on ticagrelor pharmacokinetics does not warrant dose adjustment of ticagrelor.

  4. Cardiopulmonary and metabolic effects of yoga in healthy volunteers

    Directory of Open Access Journals (Sweden)

    T Satheesh Divya

    2017-01-01

    Full Text Available Background: Yoga the spiritual union of mind with the divine intelligence of the universe aims to liberate a human being from conflicts of body–mind duality. Beneficial cardiovascular and pulmonary effects of yoga are in par with aerobic exercise, even amounting to replace the exercise model. We conducted an interventional study in healthy volunteers, to analyze the impact of short-term yoga training on cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests. Materials and Methods: A sample of fifty new recruits attending the district yoga center was subject to 75 min yoga practice a day for 41 days. Basal values of cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests were recorded before yoga training and were reassessed for postyoga changes after 41 days. Results: After yoga practice there was a significant reduction in the resting heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure of the participants. Effects on autonomic function tests were variable and inconclusive. There was a significant increase in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate after yoga. A significant reduction in body mass index was observed. Effects on metabolic parameters were promising with a significant reduction in fasting blood sugar level, serum total cholesterol, serum triglycerides serum low-density lipoprotein levels, and significant increase in high-density lipoprotein. There was no significant change in thyroid function tests after yoga. Conclusion: Short-term yoga practice has no effect on thyroid functions. Yoga practice was found beneficial in maintaining physiological milieu pertaining to cardiovascular and other metabolic parameters.

  5. Evaluation of the maximum isometric tongue force of healthy volunteers.

    Science.gov (United States)

    Ulrich Sommer, J; Birk, Richard; Hörmann, Karl; Stuck, Boris A

    2014-11-01

    The forces of specific muscle groups have been well described for nearly all parts of the human body. Interestingly, data for the tongue and its forces are rare. In light of ongoing development of systems for managing the tongue (retaining, advancing, suspending or stabilizing), especially in patients with obstructive sleep apnea, knowledge of the maximum tongue force is important for the conceptual design of those systems. The maximum tongue force in a sagittal direction was documented using a custom-built device that included a tongue clamp and a piezoelectric sensor to capture force measurements. Once positioned securely in the device, participants were asked to move the tongue in a posterior sagittal direction, with maximum force, in each of three test positions. Forty-nine healthy volunteers (29 male) were included in the study. Tongue force measurements were collected three times in three different tongue positions. Thirty-three participants had repeated measurements to investigate any potential learning effect. The maximum force of the human tongue in a posterior sagittal direction showed high inter-individual variation and ranged from 3.2 to 52.4 Newton (N; mean 14.1 ± 7.5 N), when measured from a "neutral protrusion or resting" tongue position. The "retracted" and "maximal protrusion" testing positions yielded lower maximum tongue forces. Men (m) showed statistically significantly higher tongue forces than women (w) (m: 16.0 ± 8.4 N, w: 11.0 ± 4.3 N), and there was a positive correlation with BMI and a negative correlation with age. Comparing the first measurement session with the second session (per patient) showed higher mean maximum forces in the second session, but with no statistical significance. The maximum tongue force data showed substantial inter- and intra-individual variability and gender dependency. Some male individuals produced very high forces. These forces should be considered for the future conception and development of tongue

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

    National Research Council Canada - National Science Library

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

    2014-01-01

    ..., 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...

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

    National Research Council Canada - National Science Library

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

    2014-01-01

      [ProQuest: [...] denotes non US-ASCII text; see PDF] This study investigated the effect of multidose administration of danshen ethanol extract on fexofenadine pharmacokinetics in healthy volunteers...

  8. Objective measurement of cough in otherwise healthy volunteers with acute cough.

    Science.gov (United States)

    Sunger, Kanchan; Powley, William; Kelsall, Angela; Sumner, Helen; Murdoch, Robert; Smith, Jaclyn A

    2013-02-01

    Cough is one of the commonest reasons for medical consultation and acute cough associated with upper respiratory tract infections (URTIs) is a global problem. In otherwise healthy volunteers complaining of cough associated with symptoms of URTI, we aimed to assess objective and subjective measures of cough and their repeatability and perform power calculations for the design of future studies to test therapies. We studied 54 otherwise healthy volunteers with acute cough (effectiveness of novel anti-tussives.

  9. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led......, infusion of the fluid over 3 h in the morning, and additionally 24-h hospitalization under standardized conditions. Primary outcome assessments were pulmonary function (spirometry), exercise capacity (submaximal treadmill test), balance function (BalanceMaster), and weight. Infusion of 40 mL/kg of lactated...

  10. Korean kimchi: promoting healthy meals through cultural tradition

    OpenAIRE

    Nobuko Hongu; Angela S. Kim; Asuka Suzuki; Hope Wilson; Karen C. Tsui; Sunmin Park

    2017-01-01

    Background: Kimchi, a spicy traditional Korean side dish, is made with a variety of fermented vegetables, such as Napa cabbage (baechu), hot red pepper, garlic, ginger, and other spices. Throughout generations for thousands of years, kimchi has been served daily at virtually all meals in Korean households. It gives the flavors of garlic, ginger, scallions, and chili. Kimchi is an ingredient with many culinary benefits as it is commonly added to soups, noodles, and rice dishes. In addition to ...

  11. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the

  12. Pharmacokinetics of UC-isotretinoin in healthy volunteers and volunteers with biliary T-tube drainage

    Energy Technology Data Exchange (ETDEWEB)

    Colburn, W.A.; Vane, F.M.; Bugge, C.J.; Carter, D.E.; Bressler, R.; Ehmann, C.W.

    1985-05-01

    The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of UC-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as UC in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of UC were observed in the healthy subjects whereas they were not seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the UC was 90 hr. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of UC-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.

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

    OpenAIRE

    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...

  14. Risk and Emotion Among Healthy Volunteers in Clinical Trials

    Science.gov (United States)

    Cottingham, Marci D.; Fisher, Jill A.

    2017-01-01

    Theorized as objective or constructed, risk is recognized as unequally distributed across social hierarchies. Yet the process by which social forces shape risk and risk emotions remains unknown. The pharmaceutical industry depends on healthy individuals to voluntarily test early-stage, investigational drugs in exchange for financial compensation. Emblematic of risk in late modernity, Phase I testing is a rich site for examining how class and race shape configurations of emotion and risk. Using interview data from 178 healthy trial participants, this article examines emotion and risk as mutually constituting processes linked to biographical context and social structure. Biographical events like economic insecurity and incarceration influence how risk is felt by providing comparative experiences of felt risk and felt benefits. Such events, in turn, are structured by class-based and racial inequalities, linking class and race positions to primary emotional experiences of risk. PMID:28867852

  15. Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.

    Science.gov (United States)

    Pereira, R; Fidelis, S; Vanunci, M L P; Oliveira, C H; Mendes, G D; Abib, E; Moreno, R A

    2004-01-01

    To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes. The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively. Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.

  16. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

    2016-01-01

    collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...... significantly between the study days (P = 0.067). Mean (SD) t 1/2 absorption of oral melatonin was 6.0 (3.1) min. Mean t max was 40.8 (17.8) min with a median (IQR) C max of 3550.5 (2500.5-8057.5) pg ml(-1). Mean t 1/2 elimination was 53.7 (7.0) min. Median absolute bioavailability was 2.5 (1.7-4.7) %. Median C...

  17. MODULATION OF SYMPATHOVAGAL BALANCE AFTER CHANDRANADI PRANAYAMA IN HEALTHY VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    Chintala Kiran Kumar Ch, Bandi Hari Krishna, Mallikarjuna Reddy N

    2015-10-01

    Full Text Available Background and objectives: Regardless of prevailing advances in yoga research, the immediate benefit of chandranadi pranayama (CNP on heart rate variability was not explored. Therefore, in this study, we planned to study the immediate effect of CNP on heart rate, blood pressure and HRV. Methods: One hundred and ten medical students were randomly divided into two groups; control group (n=55 and CNP group (n=55. CNP group participants were individually trained to perform CNP by an experienced yoga instructor with a regularity of 6 breaths/min for five minutes. CG volunteers didn’t undergo CNP, Pre and post intervention HR, BP measurements and spectral analysis of HRV was done in both the groups. The paired student’s t test was used to determine significant differences. Results: There was a significant decrease in HR (p<0.01, BP (p<0.05, LFnu (p<0.05, LF/HF (p<0.001 and increase in HFnu (p<0.01 followed by five minutes of CNP in CNP group. Further, HR, SBP, DBP was reduced by 9.10%, 4.80%, 7.75 % respectively. HRV results showed 7.59% reduction in LFnu, 17.8% reduction in LF/HF and HF was increased by 12.37%. There were no significant changes in CG. Conclusion: It is concluded that CNP is beneficial in reducing HR, BP and to improve Sympathovagal balance. We advise that this effective method be included with the management protocol of hypertension and utilized when immediate reduction of blood pressure is required in day-to-day as well as clinical situations.

  18. Magnetic resonance elastography: feasibility of liver stiffness measurements in healthy volunteers at 3T.

    Science.gov (United States)

    Mannelli, L; Godfrey, E; Graves, M J; Patterson, A J; Beddy, P; Bowden, D; Joubert, I; Priest, A N; Lomas, D J

    2012-03-01

    To demonstrate the feasibility of obtaining liver stiffness measurements with magnetic resonance elastography (MRE) at 3T in normal healthy volunteers using the same technique that has been successfully applied at 1.5 T. The study was approved by the local ethics committee and written informed consent was obtained from all volunteers. Eleven volunteers (mean age 35 ± 9 years) with no history of gastrointestinal, hepatobiliary, or cardiovascular disease were recruited. The magnetic resonance imaging (MRI) protocol included a gradient echo-based MRE sequence using a 60 Hz pneumatic excitation. The MRE images were processed using a local frequency estimation inversion algorithm to provide quantitative stiffness maps. Adequate image quality was assessed subjectively by demonstrating the presence of visible propagating waves within the liver parenchyma underlying the driver location. Liver stiffness values were obtained using manually placed regions of interest (ROI) outlining the liver margins on the gradient echo wave images, which were then mapped onto the corresponding stiffness image. The mean stiffness values from two adjacent sections were recorded. Eleven volunteers underwent MRE. The quality of the MRE images was adequate in all the volunteers. The mean liver stiffness for the group was 2.3 ± 0.38 kPa (ranging from 1.7-2.8 kPa). This preliminary work using MRE at 3T in healthy volunteers demonstrates the feasibility of liver stiffness evaluation at 3T without modification of the approach used at 1.5 T. Adequate image quality and normal MRE values were obtained in all volunteers. The obtained stiffness values were in the range of those reported for healthy volunteers in previous studies at 1.5 T. There was good interobserver reproducibility in the stiffness measurements. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  20. Increased set shifting costs in fasted healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Heather M Bolton

    Full Text Available 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.

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

    Science.gov (United States)

    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. © The Author(s) 2015.

  2. Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

    DEFF Research Database (Denmark)

    Daugaard, D.; Thomsen, L. L.; Iversen, H. K.

    2009-01-01

    of the middle cerebral artery was measured (transcranial Doppler). Our hypothesis was disproved, as Az did not decrease GTN-induced headache. Unexpectedly but interestingly, GTN combined with Az induced more delayed headache than GTN alone. Furthermore, a migraine-like headache was observed in three volunteers......Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate...... healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 mu g kg-1 min-1 for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity...

  3. A phase I trial of Gynostemma pentaphyllum Makino in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Malee Banjob

    2007-03-01

    Full Text Available We conducted a phase I trial of Gynostemma pentaphyllum, grown in northern Thailand, to evaluate its safety in three groups of healthy volunteers. Fourteen, fifteen and fourteen volunteers respectively received the water extract of G. pentaphyllum in capsules at the doses of 50, 200 and 400 mg twice daily for two months. There were no major adverse events reported from any of the three groups throughout the study. Significant changes in hematological parameters, natural killer cell activities and the numbers of CD3+, CD4+ and CD8+ cells were not seen during taking the extract. Some biochemical parameters were significantly different from baseline data. Those values were, however, within normal limits and did not result in clinically significant conditions. Our results suggested that the water extract of G. pentaphyllum at the doses of 50, 200 or 400 mg twice daily given to healthy volunteers for two months was safe.

  4. Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers.

    Science.gov (United States)

    Yamauchi, K; Wakabayashi, H; Hashimoto, S; Teraguchi, S; Hayasawa, H; Tomita, M

    1998-01-01

    A protective effect of bovine lactoferrin (Lf) during lethal bacteraemia has been reported in mice. Also, protective effects of orally administered bovine Lf have been reported in cases of intractable stomatitis in cats and Cryptocaryon irritans infection in red sea bream. In this study, we examined the effects of orally administered bovine Lf on the immune system of healthy volunteers. Ten healthy male volunteers (age range of 31 to 55 years old) were given bovine Lf (2 g/body/day) for 4 weeks. Blood samples were drawn before, during and after administration of Lf. Phagocytic activity and superoxide production activity of polymorphonuclear leukocytes (PMN) were evaluated from the number of PMN phagocytizing polymer particles and by the dichlorofluorescein (DCFH) oxidation assay, respectively. The expression levels of CD11b, CD16 and CD56 molecules on leukocytes were quantified using flow cytometry. The phagocytic activity of PMN increased during the period of Lf administration in 3 of the 10 volunteers. In 2 of the 3 volunteers in which the phagocytic activity increased, PMN expressed CD16 at higher levels corresponding to the increase in 3 of the 10 volunteers, whereas the CD11b+ lymphocytes and CD56+ lymphocytes increased in 4 volunteers including the same 3 volunteers who showed an increase in CD16+. These results suggest that the proportion of natural killer (NK) cells among the lymphocytes might have increased in these subjects. It was demonstrated that the phagocytic activity or superoxide production activity of PMN or the proportions of CD11b+, CD16+ and CD56+ in lymphocytes was influenced by Lf administration in 7 of the 10 volunteers, while the effects of Lf on the immune system differed in individual cases. These results suggest that Lf administration may influence primary activation of the host defense system.

  5. [Quantitative study of phonation by aerophonoscopy: Reproducibility study on healthy volunteers].

    Science.gov (United States)

    Ganry, L; Blot, P; Balandier, S; Bouric, J-M; Sabouni, W; Corre, P; Khonsari, R H

    2016-04-01

    The aerophonoscope allows for recording buccal and nasal airflow during breathing and speech and the sounds emitted by the patient. It is known to be useful in the postoperative follow-up of cleft lip and palate children, but there are currently no studies that quantitatively validate its reliability in pathological or non-pathological situations. The aim of our study was to measure the reliability of aerophonoscopic measures in adult healthy volunteers. A quantitative evaluation of the reliability of aerophonoscopy has been carried out in 30 healthy adult volunteers by measuring its inter- and intra-individual reproducibility and its sensibility in relation with the degree of the velopharyngeal sphincter constriction using a test-retest protocol. The aerophonoscope allows for inter- and intra-individual reproducible measures in healthy adult volunteers. Its sensibility to velopharyngeal sphincter constriction is good in healthy adult volunteers. The interest of aerophonoscopy in the treatment strategy of cleft lip and palate patients remains unclear. More reliable quantitative data would be of major interest to determine whether this device is suitable for the follow-up of cleft lips and palate patients or not. This would also allow for planning a second soft-palate operation and for assessing the efficacy of revision surgery such as superior or inferior pedicled pharyngoplasty. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Correlation between midazolam and lignocaine pharmacokinetics and MEGX formation in healthy volunteers

    NARCIS (Netherlands)

    Swart, Eleonora L; van der Hoven, Ben; Groeneveld, A B Johan; Touw, Daniel J; Danhof, Meindert

    AIMS: The objectives of the present investigation were: (a) to determine the correlation between lignocaine and midazolam pharmacokinetics following intravenous administration in healthy volunteers, (b) to determine the effects of treatment with an inhibitor of CYP3A4 (erythromycin) on this

  7. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers.

    Science.gov (United States)

    Saha, Madhusudan; Parveen, Irin; Shil, Bimal Chandra; Saha, Shasanka Kumar; Banik, Ranjit Kumar; Majumder, Monojit; Salam, Mahjuba Umme; Islam, Asm Nazmul

    2016-01-01

    To see the prevalence of lactose intolerance (LI) and related symptoms following oral lactose challenge in healthy volunteers. Symptoms of abdominal pain, nausea, borborygmi, flatulence, and diarrhea were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 25 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥ 1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM), i.e., LI. A total of 166 volunteers (123 males, 43 females) with a mean age 34.78 ± 11.45 years participated in this study. Lactose intolerance was found among 85.54% (n = 142, M = 104, F = 38). The main symptoms of LI were diarrhea (n = 83, 58.4.0%), borborygmi (n = 81, 57.04%), abdominal pain (n = 35, 24.65%), and flatulence (n = 27, 19.0%). Lactose intolerance among healthy adults may be common in Bangladesh. Diarrhea and borborygmi were mostly associated symptoms of LI. Saha M, Parveen I, Shil BC, Saha SK, Banik RK, Majumder M, Salam MU, Nazmul Islam ASM. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers. Euroasian J Hepato-Gastroenterol 2016;6(1):5-7.

  8. In-vivo Kinetics of Silymarin (Milk Thistle) on Healthy Male Volunteers

    African Journals Online (AJOL)

    In-vivo Kinetics of Silymarin (Milk Thistle) on Healthy Male Volunteers. M Usman, M Ahmad, AU Madni, NAW Asghar, M Akhtar, M Atif, M Qamar-uz-zaman. Abstract. Purpose: The study was aimed at evaluating the in vivo kinetics of silymarin tablets, a product with antihepatotoxic and free radical scavenging activities.

  9. Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

    DEFF Research Database (Denmark)

    Daugaard, D.; Thomsen, L. L.; Iversen, H. K.

    2009-01-01

    Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate...

  10. Effect of tumor necrosis factor-alpha infusion on the incretin effect in healthy volunteers

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumor necrosis factor-alpha (TNF-α). Whereas TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce...

  11. Comparison of intrabrachial and finger blood pressure in healthy elderly volunteers

    NARCIS (Netherlands)

    Rongen, G. A.; Bos, W. J.; Lenders, J. W.; van Montfrans, G. A.; van Lier, H. J.; van Goudoever, J.; Wesseling, K. H.; Thien, T.

    1995-01-01

    This study was performed to compare continuous Finapres (FIN) and intrabrachial (IAP) blood pressure in healthy elderly volunteers. Fifteen elderly subjects (age 71 to 83) without cardiovascular disease and an intraarterial mean (range) systolic and diastolic blood pressure of 162 (122 to 195) and

  12. Quantification of theophylline-induced eosinopenia and hypokalaemia in healthy volunteers

    NARCIS (Netherlands)

    Braat, M. C.; Jonkers, R. E.; Bel, E. H.; van Boxtel, C. J.

    1992-01-01

    The relationship between theophylline pharmacokinetics and its eosinopenic and hypokalaemic effects were studied in 6 healthy volunteers after an oral dose of theophylline 250 mg. The mean peak theophylline concentration (Cmax) of 8.33 +/- 2.16 mg/L occurred 1.02 +/- 0.26 h after ingestion. The

  13. Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction.

    NARCIS (Netherlands)

    Cools, R.; Robinson, O.J.; Sahakian, B.

    2008-01-01

    Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for

  14. The OxyMask™ development and performance in healthy volunteers

    Directory of Open Access Journals (Sweden)

    James E Paul

    2008-12-01

    Full Text Available James E Paul1, Horia Hangan2, Julius Hajgato31Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 2Faculty of Engineering, The University of Western Ontario, London, ON, Canada; 3Southmedic Inc., Barrie, ON, CanadaBackground: 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.Keywords: oxygen, oxygen masks, oxygen therapy, OxyMask™, OxyArm™, clinical trial, computational fluid dynamics (CFD, equipment design, biomedical engineering

  15. Development of a Korean Diet Score (KDS) and its application assessing adherence to Korean healthy diet based on the Korean Food Guide Wheels.

    Science.gov (United States)

    Lee, Myoungsook; Chae, Soo Wan; Cha, Youn-Soo; Cho, Mi Sook; Oh, Hea Young; Kim, Mi Kyung

    2013-02-01

    The most critical point in the assessment of adherence to dietary guidelines is the development of a practical definition for adherence, such as a dietary pattern score. The purpose of this study was to develop the Korean Diet Score (KDS) based on the Korean Food Balance Wheel and to examine the association of KDS with various lifestyle characteristics and biochemical factors. The dietary data of 5,320 subjects from the 4th Korean National Health and Nutritional Examination Survey were used for the final analysis. The food guide was composed of six food group categories; 'grain dishes', 'fish and meat dishes', 'vegetable dishes', 'fruits', 'milk' and 'oils and sugars'. Based on the recommended serving numbers for each group, the scores measuring adherence to this food guide were calculated from the dietary information from the 24-hour dietary recall questionnaire, and then its correlation with various characteristics was assessed. KDS was significantly associated with several clinical, lifestyle and socioeconomic factors as well as diagnosed disease history. The higher quintile group of KDS showed a significantly lower level in fasting blood glucose, systolic blood pressure, triglycerides, current smoking and drinking as well as higher leisure time activity, house income and education. Furthermore, the KDS quintile group of women was inversely associated with hypertension, osteoporosis and diabetes. A higher KDS quintile was characterized with a higher intake of several critical nutrients, such as Ca, Fe and vitamins as well as a desirable nutrition balance such as the ratio of macronutrients. Our results demonstrate that KDS is a beneficial tool in assessing the adherence to a healthy diet based on the Korean dietary guidelines. We suggest that KDS could be a useful indicator for evaluating the dietary balance of the Korean population.

  16. Multiple-Dose Pharmacokinetics of Ceftibuten in Healthy Adults and Geriatric Volunteers.

    Science.gov (United States)

    Radwanski, Elaine; Teal, Marilyn; Affrime, Melton; Cayen, Mitchell; Lin, Chin-Chung

    1994-06-01

    The steady-state pharmacokinetics of ceftibuten, an orally active cephalosporin were investigated in 12 healthy male volunteers (19--38 years) and in 12 geriatric volunteers (65--76 years). Each received one 200-mg ceftibuten capsule every 12 h on days 1--3 and one capsule in the morning on day 4. Plasma and urine samples were collected at various times on days 1--4 and assayed by high-pressure liquid chromatographic method for ceftibuten and ceftibuten-trans, a conversion product. The T(max) for ceftibuten and ceftibuten-trans occurred at about 2 and 3 h, respectively, in both populations. The C(max) and AUC((0--12 h)) ranged from 10.8 to 12.4 &mgr;g ml(minus sign1) and from 47.5 to 55.1 &mgr;g h ml(minus sign1), respectively, for normal volunteers compared to 12.9--17.5 &mgr;g ml(minus sign1) and 62.3--87.1 &mgr;g h ml(minus sign1), respectively, for geriatric volunteers. The respective values for ceftibuten-trans in normal and geriatric volunteers were 1.3 and 1.3 &mgr;g ml(minus sign1), respectively, and 6.9--8.2 and 5.9--9.8 &mgr;g h ml(minus sign1). At steady state, the C(max) and AUC((0--12 h)) of ceftibuten-trans were about 10--11% and 13--16% those of ceftibuten in normal volunteers and about 8--9% and 9--11% those of ceftibuten, respectively, in geriatric volunteers. The accumulation factor of ceftibuten in normal volunteers was 1.1 as compared to 1.3 in geriatric volunteers. The terminal phase half-life was 2.5 h in healthy volunteers and 3.2 h in geriatric volunteers. Urinary excretion appeared to be the major route of elimination in both populations accounting for more than 90% of the dose recovered in the urine during the dosing interval. The results of this study demonstrate that ceftibuten, 200 mg given twice a day, is safe and well tolerated, is well absorbed, and that steady-state is achieved on days 3 and 4. There is some accumulation in the elderly, but dosage regimen based on age is not warranted.

  17. MR elastography: Spleen stiffness measurements in healthy volunteers--preliminary experience.

    Science.gov (United States)

    Mannelli, Lorenzo; Godfrey, Edmund; Joubert, Ilse; Patterson, Andrew J; Graves, Martin J; Gallagher, Ferdia A; Lomas, David J

    2010-08-01

    The purpose of this article is to establish the range of normal splenic stiffness in healthy volunteers using MR elastography (MRE) and to investigate any correlation with physiologic parameters and driver position. Sixteen volunteers (mean [+/- SD] age, 37 +/- 9 years) with no history of gastrointestinal, hepatobiliary, or cardiovascular disease were recruited. The MRI protocol included T2-weighted axial and gradient-echo MRE sequences using steady-state 60-Hz excitation. Two MRE acquisitions were performed, one with the driver placed on the right side of the abdomen and the other with the driver placed on the left side. Volunteers' body mass index (BMI), arterial mean blood pressure, age, spleen volume, and liver stiffness were also determined. Two radiologists independently measured the spleen stiffness on the MRE inversion images. The correlations between spleen stiffness and BMI, arterial mean blood pressure, age, spleen volume, and liver stiffness were quantified. Sixteen volunteers underwent MRE. With the driver placed on the right side of the abdomen, the mean splenic stiffness was 3,565 +/- 586 Pa (range, 2,353-4,442 Pa); with the driver on the left side of the abdomen, the mean splenic stiffness was significantly (p 0.05) These preliminary results in a small number of healthy volunteers show that spleen stiffness is not significantly correlated with BMI, arterial mean blood pressure, spleen volume, or liver stiffness. A significant difference was observed using different driver positions.

  18. Effects of different sleep deprivation protocols on sleep perception in healthy volunteers.

    Science.gov (United States)

    Goulart, Leonardo I; Pinto, Luciano R; Perlis, Michael L; Martins, Raquel; Caboclo, Luis Otavio; Tufik, Sergio; Andersen, Monica L

    2014-10-01

    To investigate whether different protocols of sleep deprivation modify sleep perception. The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI). There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period (P sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Dixon quantitative chemical shift MRI for bone marrow evaluation in the lumbar spine: a reproducibility study in healthy volunteers

    NARCIS (Netherlands)

    Maas, M.; Akkerman, E. M.; Venema, H. W.; Stoker, J.; den Heeten, G. J.

    2001-01-01

    PURPOSE: The purpose of this work was to explore the reproducibility of fat-fraction measurements using Dixon quantitative chemical shift imaging (QCSI) in the lumbar spine (L3, L4, and L5) of healthy volunteers. METHOD: Sixteen healthy volunteers were examined at 1.5 T two times to obtain a

  20. Comparison of 24-hour urinary citrate excretion in stone formers and healthy volunteers

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Goodarzi

    2012-01-01

    Full Text Available Low urinary citrate excretion is a risk factor in stone formers (SF. This study aimed to measure the urinary citrate excretion in SF and healthy volunteers at our center from 12 June 2008 to 20 August 2009. There were 28 SF patients (18 males and ten females and 27 (18 males and nine females age-matched healthy adult volunteers who participated in this study. Both groups had a similar living environment, extrinsic factors, diet and genetic descent. After collecting 24-h urine, citrate was measured using an enzymatic kit. Routine urinalysis and 24-h creatinine and uric acid were also performed. There was a significant difference in urinary citrate excretion level among SF (mean 310, SD 260 mg/L and normal volunteer subjects (mean 800, SD 300 mg/L. By applying the previously defined normal values (320 mg/24 h of urinary citrate in the local population, 43% of the SF in our study group was hypocitric, and none among the controls. We conclude that prevalence of hypocitraturia in stone formers was higher than that in healthy volunteers in our population.

  1. Effects of magnesium sulphate on cerebral haemodynamics in healthy volunteers: a transcranial Doppler study.

    Science.gov (United States)

    Sherman, R; Armory, P; Moody, P; Hope, T; Mahajan, R P

    2003-08-01

    Magnesium is increasingly being considered as a neuroprotective agent. We aimed to study its effects on middle cerebral artery blood flow velocity (V(mca)), cerebral autoregulation and cerebral vascular reactivity to carbon dioxide (CRCO(2)) in healthy volunteers. Fifteen healthy volunteers were recruited. Using transcranial Doppler ultrasonography, V(mca) was recorded continuously. The strength of autoregulation was assessed by the transient hyperaemic response test, and the CRCO(2) was measured by assessing changes in V(mca) to the induced changes in end-tidal carbon dioxide. I.V. infusion of magnesium sulphate was then started (loading dose of 16 mmol followed by an infusion at the rate of 2.7 mmol h(-1)) for 45 min. The cerebral haemodynamic variables were measured again near the end of the infusion of magnesium sulphate. Total serum magnesium levels were doubled by the infusion regimen. However, there were no significant changes in V(mca), strength of autoregulation, or CRCO(2). Five of the volunteers reported marked nausea and two developed significant hypotension during the loading dose. Infusion of magnesium sulphate, in a dose that doubles its concentration in plasma, does not affect V(mca), strength of autoregulation or CRCO(2) in healthy volunteers. However, it can be associated with nausea and hypotension.

  2. Axial traction magnetic resonance imaging (MRI) of the glenohumeral joint in healthy volunteers: initial experience.

    Science.gov (United States)

    Garwood, Elisabeth R; Souza, Richard B; Zhang, Amy; Zhang, Alan L; Ma, C Benjamin; Link, Thomas M; Motamedi, Daria

    Evaluate technical feasibility and potential applications of glenohumeral (GH) joint axial traction magnetic resonance imaging (MRI) in healthy volunteers. Eleven shoulders were imaged in neutral and with 4kg axial traction at 3T. Quantitative measurements were assessed. Axial traction was well tolerated. There was statistically significant widening of the superior GH joint space (p=0.002) and acromial angle (p=0.017) with traction. Inter-rater agreement was high. GH joint axial traction MRI is technically feasible and well tolerated in volunteers. Traction of the capsule, widening of the superior GH joint space and acromial angle were observed. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Guski, Louise Schow

    2017-01-01

    concentrations of enalapril and the active metabolite enalaprilat were measured. The volunteers were divided into six different groups according to their genetic profile of CES1: Group 1 (controls, n=16) with two CES1 copies without non-synonymous SNPs in the exons; group 2 (n=5) with four copies of CES1; group......The present study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time points, plasma...

  4. Age dependent white matter lesions and brain volume changes in healthy volunteers

    DEFF Research Database (Denmark)

    Christiansen, P; Larsson, H B; Thomsen, C

    1994-01-01

    was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males......The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles...

  5. The reliability of topographic measurements from navigated transcranial magnetic stimulation in healthy volunteers and tumor patients.

    Science.gov (United States)

    Zdunczyk, Anna; Fleischmann, Robert; Schulz, Juliane; Vajkoczy, Peter; Picht, Thomas

    2013-07-01

    Navigated transcranial magnetic stimulation (nTMS) is increasingly being used for preoperative mapping of the motor cortex. Any new technology should undergo rigorous validation before being widely adopted in routine clinical practice. The aim of this experimental study was to assess the intraexaminer and interexaminer reliability of topographic mapping with nTMS. nTMS mapping of the motor cortex for the first dorsal interosseous (FDI) muscle was performed by an expert and a novice examiner, twice in ten healthy volunteers and once in ten tumor patients. The distances between the centers-of-gravity and hotspots were calculated, as were coefficients of variation. This study also compared orthogonal versus variable orientation of the stimulation coil. The mean (range) distance between centers-of-gravity for the expert examiner in the test-retest protocol with healthy volunteers was 4.40 (1.86-7.68) mm. The mean (range) distance between centers-of-gravity for the expert vs. novice examiner was 4.89 (2.39-9.22) mm. There were no significant differences in this result between healthy volunteers and tumor patients. nTMS is sufficiently reliable for clinical use, but examiners should make efforts to minimize sources of error. The reliability of nTMS in tumor patients appears comparable to healthy subjects.

  6. Transient Elastographic Values of Healthy Volunteers in a Tertiary Care Hospital

    Directory of Open Access Journals (Sweden)

    Bhupendra Kumar Basnet

    2014-03-01

    Full Text Available Introduction:Transient elastography is a very promising non invasive procedure to determine liver stiffness for diagnosis of fibrosis in various chronic liver diseases. However, studies on normal values of liver stiffness in apparently healthy subjects are still few. We aimed to determine liver stiffness values in healthy Nepalese volunteers. Methods:Transient elastography (FibroScanR, Echosens, Paris, France was performed to find out liver stiffness values in 45 apparently healthy volunteers after explaining study protocol. Complete medical examination with routine laboratory tests was performed. Subjects with normal liver biochemistries and normal liver ultrasonography were taken for analysis. Results:Mean liver stiffness value of study subjects was 4.24±0.70 kPa. Liver stiffness value was found higher in males than in females (4.32±0.74 vs 4.07±0.61 kPa, respectively, P=0.26 but not statistically significant. Similarly, comparison between age and liver stiffness also showed positive correlation (r=0.211 but not statistically significant (P=0.164 Conclusions: Our study showed that the mean liver stiffness value was 4.24±0.70 kPa in our population and influence of age, gender and body mass index were not significant. Keywords: chronic liver disease; FibroScanR; healthy volunteers; liver stiffness valve; transient elastography.

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

    Science.gov (United States)

    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.

  8. Effect of calyx capsule-ethanol extract Hibiscus sabdariffa L. on renal function of healthy volunteers

    Science.gov (United States)

    Harun, N.; Darmawan, E.; Nurani, L. H.

    2017-11-01

    Hibiscus sabdariffa contains flavonoid, triterpenoid, anthocyanin which function as immunostimulant. H. sabdariffa is considered safe for animal renal; nonetheless, there are known side effects of which need to be further investigated for human renal. This research aims to investigate the effect of calyx capsule-ethanol extract H. sabdariffa for renal function of healthy male and female for 30 days period by monitoring Scr and Clcr component in their blood samples. The method of this experimental research was by pre and post-treatment by involving 20 healthy volunteers who have met inclusion and exclusion criteria. The volunteers have completed the informed consent for this experiment. Furthermore, volunteers were divided into two groups (10 male and 10 female). Each group was given orally 500 mg of calyx capsule-ethanol extract H. sabdariffa per day for 30 days period. Blood tests were taken on day 0, day 30 after consuming the capsule and day 45 (15 days after the last day of capsule intake) in order to measure the Scr and Clcr concentration in the blood samples by using Jaffe dan Cockcroft-Gault method. The results of each sampling day were further analyzed statistically and compared using Repeated ANOVA dan Friedman test. The results suggest that there was a difference in the renal function on day 0, 30 and 45 samplings. However, there was no significant difference in Scr dan Clcr concentrations on female and male volunteers (p>0.05). Specifically, the type of gender affects Scr concentration (p0.05). In addition, age and Body Mass Index (BMI) does not affect Scr and Clcr concentrations (p>0.05). The side effects discovered through the monitoring increased in mixturition and bloatedness. Calyx capsule-ethanol extract H. sabdariffa does not affect on renal function of healthy volunteers.

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

    Science.gov (United States)

    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 (phyperkyphosis 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.

  10. Population pharmacokinetics of halofantrine in healthy volunteers and patients with symptomatic falciparum malaria.

    Science.gov (United States)

    Klein, Kerenaftali; Aarons, Leon; Ter Kuile, Feiko O; Nosten, Francois; White, Nick J; Edstein, Michael D; Teja-Isavadharm, Paktiya

    2012-11-01

    To investigate the population pharmacokinetics of the antimalarial halofantrine (HF) in healthy volunteers and patients with symptomatic falciparum malaria. Healthy volunteer data were obtained from six volunteers who received three different doses of HF (250, 500 and 1000 mg) after an overnight fast with a washout period of at least 6 weeks between doses. Patient data (n = 188) were obtained from randomised controlled trials conducted on the Thai-Burmese border in the early 1990s. They were either assigned to receive a total HF dose of 24 mg/kg (8 mg/kg every 6 h for 24 h) or 72 mg/kg (8 mg/kg every 6 to 10 h for 3 days). The population pharmacokinetics of HF were evaluated using non-linear mixed effects modelling with a two-compartment model with first-order absorption. The population estimates of apparent clearance (CL), volume of compartment one (V1), distributional clearance (CLD) and volume of compartment two (V2) of HF in healthy volunteers were 2453 l/day (102 l/h), 2386 l, 716 l/day (29.8 l/h) and 2641 l, respectively. The population estimates of the PK parameters in patients were 429 l/day (17.9 l/h), 729 l, 178 l/day (7.42 l/h) and 1351 l, respectively. All PK parameters were significantly related to body weight and some were related to sex, sampling method, pre-treatment parasite density and whether patients vomited or not. When the two datasets were analysed jointly using a maximum likelihood method, the population estimates in patients were 196 l/day (8.17 l/h), 161 l, 65 l/day (2.71 l/h) and 89 l, respectively, and the parameters were significantly related to body weight and sex. Bayesian analysis of the patient data, with a diffuse prior based on the healthy volunteer data analysis results, yielded the population estimates 354 l/day (14.8 l/h), 728 l, 162 l/day (6.75 l/h) and 1939 l, respectively. The pharmacokinetic properties of HF in patients with malaria are affected by several demographic variables as well as other relevant covariates. Apparent

  11. Acute effects of Delta-9-Tetrahydrocannabinol on performance monitoring in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Desiree eSpronk

    2011-09-01

    Full Text Available Rationale: The error-related negativity (ERN is a negative event-related potential that occurs immediately after an erroneous response and is thought to reflect human performance monitoring. Delta-9-Tetrahydrocannabinol (THC administration in healthy volunteers has been linked to impaired performance monitoring in behavioral studies, but to date no studies have examined the effects of cannabinoids on the ERN. Methods: EEG data from 10 healthy volunteers was recorded during execution of a speeded choice reaction time task (Flankers task after administration of THC or placebo vapor in a double-blind randomized crossover design. Results: The findings of this study show that the ERN was significantly reduced after administration of THC. The behavioral outcomes on the Flankers task showed no indications of drug-induced impairments.Discussion: The diminished ERN reflects impairments in the process of performance monitoring. The task design was not optimized to find behavioral effects. The study shows that cannabinoids impair performance monitoring.

  12. Associations between personality traits and CCK-4-induced panic attacks in healthy volunteers.

    Science.gov (United States)

    Tõru, Innar; Aluoja, Anu; Võhma, Ulle; Raag, Mait; Vasar, Veiko; Maron, Eduard; Shlik, Jakov

    2010-07-30

    In this study we examined how personality disposition may affect the response to cholecystokinin tetrapeptide (CCK-4; 50 microg) challenge in healthy volunteers (n=105). Personality traits were assessed with the Swedish universities Scales of Personality (SSP). Statistical methods employed were correlation analysis and logistic regression. The results showed that the occurrence of CCK-4-induced panic attacks was best predicted by baseline diastolic blood pressure, preceding anxiety and SSP-defined traits of lack of assertiveness, detachment, embitterment and verbal aggression. Significant interactions were noted between the above mentioned variables, modifying their individual effects. For different subsets of CCK-4-induced symptoms, the traits of physical aggression, irritability, somatic anxiety and stress susceptibility also appeared related to panic manifestations. These findings suggest that some personality traits and their interactions may influence vulnerability to CCK-4-induced panic attacks in healthy volunteers. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers.

    Science.gov (United States)

    Guarnieri, Regina V; Buratto, Luciano G; Gomes, Carlos F A; Ribeiro, Rafaela L; de Souza, Altay A Lino; Stein, Lilian M; Galduróz, José C; Bueno, Orlando F A

    2017-01-01

    Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Effect of eslicarbazepine acetate and oxcarbazepine on cognition and psychomotor function in healthy volunteers.

    Science.gov (United States)

    Milovan, Denise; Almeida, Luis; Romach, Myroslava K; Nunes, Teresa; Rocha, José Francisco; Sokowloska, Marta; Sellers, Edward M; Soares-da-Silva, Patrício

    2010-08-01

    The results of two single-blind studies conducted to evaluate the cognitive and psychomotor effects of eslicarbazepine acetate and oxcarbazepine following single and repeated administration in healthy volunteers are reported. The cognitive and psychomotor evaluation consisted of several computerized and paper-and-pencil measures. Eslicarbazepine acetate and oxcarbazepine had similar overall cognitive profiles and did not cause clinically relevant cognitive impairment. The incidence of adverse events was lower with eslicarbazepine acetate than with oxcarbazepine. Copyright 2010. Published by Elsevier Inc.

  15. Hemodynamic changes caused by acupuncture in healthy volunteers: a prospective, single-arm exploratory clinical study

    OpenAIRE

    Kim, Tae-Hun; Ku, Boncho; Bae, Jang-Han; Shin, Jae-Young; Jun, Min-Ho; Kang, Jung Won; Kim, Junghwan; Lee, Jun-Hwan; Kim, Jaeuk U.

    2017-01-01

    Background Radial pressure pulse wave (RPPW) examination has been a key diagnostic component of traditional Chinese medicine. The objective of this study was to investigate the changes in RPPW along with various hemodynamic variables after acupuncture stimulation and to examine the validity of pulse diagnosis as a modern diagnostic tool. Methods We conducted acupuncture stimulation at both ST36 acupuncture points in 25 healthy volunteers. We simultaneously assessed the RPPW by pulse tonometry...

  16. Omeprazole preferentially inhibits the metabolism of (+)-(S)-citalopram in healthy volunteers

    Science.gov (United States)

    Rocha, Adriana; Coelho, Eduardo B; Sampaio, Stefânia A; Lanchote, Vera L

    2010-01-01

    AIM The study assessed the influence of omeprazole on the kinetic disposition of the (+)-(S)-citalopram (CITA) and (−)-(R)-CITA enantiomers in healthy volunteers. METHODS In a cross-over study, healthy volunteers (n = 9) phenotyped as extensive metabolizers of CYP2C19 and CYP2D6 and with an oral midazolam clearance ranging from 10.9 to 149.3 ml min−1 kg−1 received a single dose of racemic CITA (20 mg orally) in combination or not with omeprazole (20 mg day−1 for 18 days). Serial blood samples were collected up to 240 h after CITA administration. CITA and demethylcitalopram (DCITA) enantiomers were analyzed by LC-MS/MS using a Chiralcel® OD-R column. RESULTS The kinetic disposition of CITA was enantioselective in the absence of treatment with omeprazole, with the observation of a greater proportion of plasma (−)-(R)-CITA [AUC S : R ratio of 0.53 (95% CI 0.41, 0.66) for CITA and 1.08 (95% CI 0.80, 1.76) for DCITA] than (+)-(S)-CITA. Racemic CITA administration to healthy volunteers in combination with omeprazole showed a loss of enantioselectivity in CITA pharmacokinetics with an increase of approximately 120% in plasma (+)-(S)-CITA concentrations [AUC S : R ratio of 0.95 (95% CI 0.72, 1.10) for CITA and 0.95 (95% CI 0.44, 1.72) for DCITA]. CONCLUSIONS The administration of multiple doses of omeprazole preferentially inhibited (+)-(S)-CITA metabolism in healthy volunteers. Although omeprazole increased plasma concentrations of (+)-(S)-CITA by approximately 120%, it is difficult to evaluate the clinical outcome because the range of plasma CITA concentrations related to maximum efficacy and minimum risk of adverse effects has not been established. PMID:20642546

  17. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial

    OpenAIRE

    Grubben, M.J.; Boers, G.H.; Blom, H J; Broekhuizen, R; Jong, de, JJA Joost; Rijt, van, L.; Katan, M. B.

    2000-01-01

    Background: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. Objective: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. Design: Sixty-four healthy volunteers (31 men and...

  18. Cine MRI of Tracheal Dynamics in Healthy Volunteers and Patients With Tracheobronchomalacia.

    Science.gov (United States)

    Ciet, Pierluigi; Boiselle, Phillip M; Heidinger, Benedikt; Andrinopoulou, Eleni-Rosalina; O'Donnel, Carl; Alsop, David C; Litmanovich, Diana E

    2017-10-01

    Bronchoscopy and MDCT are routinely used to assess tracheobronchomalacia (TBM). Recently, dynamic MRI (cine MRI) has been proposed as a radiation-free alternative to MDCT. In this study, we tested cine MRI assessment of airway dynamics during various breathing conditions and compared cine MRI and MDCT measurements in healthy volunteers and patients with suspected TBM. Cine MRI was found to be a technically feasible alternative to MDCT for assessing central airway dynamics.

  19. Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI

    DEFF Research Database (Denmark)

    Nilsson, Matias; Poulsen, Jakob L; Brock, Christina

    2016-01-01

    Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale....../ascending colon by 41% (P =0.005) and in the transverse colon by 20% (P= 0.005). No associations were detected between questionnaire scores and colorectal volumes. Conclusion Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies...

  20. Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers.

    Science.gov (United States)

    Fenoll-Palomares, C; Muñoz Montagud, J V; Sanchiz, V; Herreros, B; Hernández, V; Mínguez, M; Benages, A

    2004-11-01

    To assess the salivary flow rate, pH, and buffer capacity of healthy volunteers, and their relationships with age, gender, obesity, smoking, and alcohol consumption, and to establish the lower-end value of normal salivary flow (oligosialia). A prospective study was conducted in 159 healthy volunteers (age > 18 years, absence of medical conditions that could decrease salivary flow). Unstimulated whole saliva was collected during ten minutes, and salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and bicarbonate concentration was considered the lower limit of normality. Median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than 44 years was associated with higher flow rates (OR 2.10). Compared with women, men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81). Bicarbonate concentration correlated with salivary flow rate. The lower-end values of normal flow rate and bicarbonate concentration were 0.15 ml/min and 1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol consumption did not influence salivary parameters. In healthy volunteers, salivary flow rate depends on age and gender, and correlates with buffer capacity. Obesity, smoking, and alcohol use do not influence salivary secretion.

  1. Assessment of bone age in prepubertal healthy Korean children: Comparison among the Korean standard bone age chart, Greulich-Pyle method, and Tanner-Whitehouse method

    Energy Technology Data Exchange (ETDEWEB)

    Kim Jeong Rye; Lee, Young Seok; Yu, Jee Suk [Dankook University Hospital, Cheonan(Korea, Republic of)

    2015-02-15

    To compare the reliability of the Greulich-Pyle (GP) method, Tanner-Whitehouse 3 (TW3) method and Korean standard bone age chart (KS) in the evaluation of bone age of prepubertal healthy Korean children. Left hand-wrist radiographs of 212 prepubertal healthy Korean children aged 7 to 12 years, obtained for the evaluation of the traumatic injury in emergency department, were analyzed by two observers. Bone age was estimated using the GP method, TW3 method and KS, and was calculated in months. The correlation between bone age measured by each method and chronological age of each child was analyzed using Pearson correlation coefficient, scatterplot. The three methods were compared using one-way analysis of variance. Significant correlations were found between chronological age and bone age estimated by all three methods in whole group and in each gender (R2 ranged from 0.87 to 0.9, p < 0.01). Although bone age estimated by KS was slightly closer to chronological age than those estimated by the GP and TW3 methods, the difference between three methods was not statistically significant (p > 0.01). The KS, GP, and TW3 methods show good reliability in the evaluation of bone age of prepubertal healthy Korean children without significant difference between them. Any are useful for evaluation of bone age in prepubertal healthy Korean children.

  2. Assessment of bone age in prepubertal healthy Korean children: comparison among the Korean standard bone age chart, Greulich-Pyle method, and Tanner-Whitehouse method.

    Science.gov (United States)

    Kim, Jeong Rye; Lee, Young Seok; Yu, Jeesuk

    2015-01-01

    To compare the reliability of the Greulich-Pyle (GP) method, Tanner-Whitehouse 3 (TW3) method and Korean standard bone age chart (KS) in the evaluation of bone age of prepubertal healthy Korean children. Left hand-wrist radiographs of 212 prepubertal healthy Korean children aged 7 to 12 years, obtained for the evaluation of the traumatic injury in emergency department, were analyzed by two observers. Bone age was estimated using the GP method, TW3 method and KS, and was calculated in months. The correlation between bone age measured by each method and chronological age of each child was analyzed using Pearson correlation coefficient, scatterplot. The three methods were compared using one-way analysis of variance. Significant correlations were found between chronological age and bone age estimated by all three methods in whole group and in each gender (R(2) ranged from 0.87 to 0.9, p 0.01). The KS, GP, and TW3 methods show good reliability in the evaluation of bone age of prepubertal healthy Korean children without significant difference between them. Any are useful for evaluation of bone age in prepubertal healthy Korean children.

  3. Association between Frequency of Breakfast Consumption and Academic Performance in Healthy Korean Adolescents

    OpenAIRE

    Wi-Young so

    2013-01-01

    Background The purpose of this study was to examine whether the frequency of breakfast consumption was related to academic performance in healthy Korean adolescents. Methods: We analyzed data from the seventh Korea Youth Risk Behavior Web-based Survey conducted in 2011, in which 75,643 adolescents from school grades 7?12 participated. We assessed the association between the frequency of breakfast consumption (per week) and academic performance using multivariate logistic regression analysis a...

  4. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  5. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.

    Science.gov (United States)

    Raut, Ashwinikumar A; Rege, Nirmala N; Tadvi, Firoz M; Solanki, Punita V; Kene, Kirti R; Shirolkar, Sudatta G; Pandey, Shefali N; Vaidya, Rama A; Vaidya, Ashok B

    2012-07-01

    Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  6. Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.

    Science.gov (United States)

    Kraehenmann, Rainer; Preller, Katrin H; Scheidegger, Milan; Pokorny, Thomas; Bosch, Oliver G; Seifritz, Erich; Vollenweider, Franz X

    2015-10-15

    The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change. This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state. These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Haunting Phantom on the Way to the Korean Reunification? The Chinese People’s Volunteer Armyin the Korean War and Its Legal Questions

    National Research Council Canada - National Science Library

    Eric Yong Joong Lee

    2014-01-01

    Although relationships among the former belligerent parties of the Korean War have changed drastically over the decades, the parties still remain under the armistice system because the Korean War is not over legally...

  8. What if Institutional Review Boards (IRBs treated healthy volunteers in clinical trials as their clients?

    Directory of Open Access Journals (Sweden)

    Martin Tolich

    2010-12-01

    Full Text Available Objectives: To understand the motivations of university students volunteering for clinical trials in New Zealand and their comprehension of risk. Methods: An ethnography using both direct observation and unstructured interviews of student volunteers in two New Zealand clinical trial companies.Subjects: Eighteen volunteers who participated in one of three separate clinical trials were interviewed. Thirteen of the eighteen trialists had been involved in previous clinical trials. Results: 1 These university students share similarities with economically disadvantaged minorities – they do not actively engage with the informed consent process, and they arrive at the trial ready to consent. 2 Word of mouth endorsements from incumbent trialists are the main factor influencing students’ decision-making process. 3 The trialists’ assessment of harm focused more on the food they were required to ingest than on the research drug.Discussion: Economic disadvantage is not a necessary precondition for volunteers to arrive at a clinical trial ready to consent. These university students were motivated to consent via informal networks sharing information about these lucrative trials. Trialists’ definition of harm may be broader than that of ethics committees. Ethics committees could employ a post-study questionnaire to evaluate healthy volunteers’ experience of the trial.

  9. Feasibility of using 3D MR elastography to determine pancreatic stiffness in healthy volunteers.

    Science.gov (United States)

    Shi, Yu; Glaser, Kevin J; Venkatesh, Sudhakar K; Ben-Abraham, Ephraim I; Ehman, Richard L

    2015-02-01

    To evaluate the feasibility of using three-dimensional (3D) MR elastography (MRE) to determine the stiffness of the pancreas in healthy volunteers. Twenty healthy volunteers underwent 1.5 Tesla MRE exams using an accelerated echo planar imaging (EPI) pulse sequence with low-frequency vibrations (40 and 60 Hz). Stiffness was calculated with a 3D direct inversion algorithm. The mean shear stiffness in five pancreatic subregions (uncinate, head, neck, body, and tail) and the corresponding liver stiffness were calculated. The intrasubject coefficient of variation (CV) was calculated as a measure of the reproducibility for each volunteer. The mean shear stiffness (average of values obtained in different pancreatic subregions) was (1.15 ± 0.17) kPa at 40 Hz, and (2.09 ± 0.33) kPa at 60 Hz. The corresponding liver stiffness was higher than the pancreas stiffness at 40 Hz ([1.60 ± 0.21] kPa, mean pancreas-to-liver stiffness ratio: 0.72), but similar at 60Hz ([2.12 ± 0.23) kPa, mean ratio: 0.95). The mean intrasubject CV for each pancreatic subregion was lower at 40 Hz than 60 Hz (P measurements throughout the pancreas, with more consistent data acquired at 40 Hz. © 2014 Wiley Periodicals, Inc.

  10. Failure in evoking the trigeminal cardiac reflex by mandibular stretching in healthy volunteers.

    Science.gov (United States)

    De Innocentiis, Carlo; Caputi, Cristiano Giovannni; Pinto, Filomena; Quintiliani, Stefania; Meccariello, Armando; Renda, Giulia; Di Nicola, Marta; De Caterina, Raffaele; D'Attilio, Michele

    2015-03-01

    Stimulation of trigeminal sensory afferences has been reported to evoke hypotension and bradycardia, a phenomenon known as the trigeminal cardiac reflex. We attempted to evoke such a reflex through cycles of alternate mandibular stretching in healthy volunteers, as previously reported, for its possible therapeutic exploitation. In Phase 1 of the study, 10 healthy volunteers [5 male, 5 female, age (mean ± SD) 27±2 years)] underwent 2 randomized sessions of automated monitoring, every 6 minutes, of systolic blood pressure (SBP), diastolic (D) BP, and heart rate (HR), with a one-week interval, either with mandibular stretching (12 minutes with a spring device fitted in the mouth), or nothing (control). Observation was prolonged for 180 minute after the end of the stretching. In Phase 2, 7 other volunteers (4 male and 3 female, age 24±1.3 years) repeated the protocol with a sampling interval of 2 minutes until the end of stretching. Baseline levels of SBP, DBP and HR were similar in the test and control sessions. There was a progressive fall of BP and HR as a function of time during the test session. With stretching: SBP changed from 119.2±10.1 to 118.1±10.1 to 115.8±10.5 mmHg, at baseline, end of stretching and 180 minutes after, respectively, pmeasurements, we could not detect significant BP or HR effects of repeated mandibular stretching.

  11. Mildronate treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers.

    Science.gov (United States)

    Liepinsh, Edgars; Konrade, Ilze; Skapare, Elina; Pugovics, Osvalds; Grinberga, Solveiga; Kuka, Janis; Kalvinsh, Ivars; Dambrova, Maija

    2011-09-01

    In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and γ-butyrobetaine in healthy volunteers. Mildronate was administered perorally, at a dosage of 500mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, γ-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method. After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of γ-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and γ-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20µm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate. Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  12. Age dependent white matter lesions and brain volume changes in healthy volunteers

    DEFF Research Database (Denmark)

    Christiansen, P; Larsson, H B; Thomsen, C

    1994-01-01

    The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles was meas......The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles...... was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males...... and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles...

  13. Lanreotide inhibits human jejunal secretion induced by prostaglandin E1 in healthy volunteers.

    Science.gov (United States)

    Sobhani, I; René, E; Ramdani, A; Bayod, F; Sabbagh, L C; Thomas, F; Mignon, M

    1996-02-01

    1. Somatostatin inhibits hormonal secretions in the gastrointestinal tract. Somatostatin analogues are used in the treatment of VIPome-related watery diarrhoea. In addition, more than 10% of patients with AIDS suffer from diarrhoea likely due to the increased intestinal secretion of water and ions. However, the direct effect of somatostatin on the flux of water and ions in the intestine has not been, so far, analyzed in vivo. The aim of the present study was to evaluate the effect of lanreotide, a somatostatin analogue, on the movements of water and ions in the jejunum in man. 2. Accordingly, 10 healthy volunteers (age 18-35 years, mean 27) and two patients with AIDS (26 and 33 years) suffering from water diarrhoea (> 800 ml day-1) underwent intestinal perfusion using a four lumen tube with proximal occluding balloon. The segment tested was 25 cm long. The jejunum was infused by an isotonic control saline solution containing polyethylene glycol (PEG) as nonabsorbable marker. Basal jejunal secretions were measured in all subjects. Prostaglandin E1 (PGE1) was administered intraluminally to stimulate jejunal secretion in healthy volunteers. The effect of intravenous lanreotide on the jejunal PGE1-induced secretions of water and electrolytes was analysed in healthy subjects and on the basal secretions in AIDS patients. Each period was analyzed on the basis of three (10 min) successive intestinal juice collections after 20-30 min equilibration time. The antisecretory effect of lanreotide was evaluated in each subject as the difference between fluxes compared to the control period. 3. In healthy volunteers, PGE1 induced secretion of H2O, Na+, K+ and Cl- in the jejunum and lanreotide reduced significantly PGE1-induced response. In both AIDS patients basal fluxes of water and ions were reduced by lanreotide in a dose-dependent manner. 4. Somatostatin can reduce stimulated-jejunal secretion of ions and water in normal subjects and may improve water diarrhoea in AIDS

  14. Less healthy dietary pattern is associated with smoking in Korean men according to nationally representative data.

    Science.gov (United States)

    Suh, Sang-Yeon; Lee, Ju Hyun; Park, Sang Shin; Seo, Ah-Ram; Ahn, Hong-Yup; Bae, Woo Kyung; Lee, Yong Joo; Yim, Eunji

    2013-06-01

    The relationship between smoking and nutrient intake has been widely investigated in several countries. However, Korea presents a population with a smoking rate of approximately 50% and dietary consumption of unique foods. Thus, the aim of this study was to evaluate the association of dietary patterns with smoking in Korean men using a nationally representative sample. The study subjects were comprised of 4,851 Korean men over 19 yr of age who participated in the fourth Korean National Health and Nutrition Examination Survey. Dietary data were assessed by the 24-hr recall method. The smoking group comprised 2,136 men (46.6%). Five dietary patterns were derived using factor analysis: 'sugar & fat', 'vegetables & seafood', 'meat & drinks', 'grains & eggs', and 'potatoes, fruits and dairy products.' Current smokers showed a more significant 'sugar & fat' pattern (P = 0.001) while significantly less of the 'vegetables & seafood' and 'potatoes, fruits and dairy products' patterns (P = 0.011, P Korean male smokers showed less healthy dietary patterns than nonsmokers. Thus, the result of this study underlines the need for health professionals to also provide advice on dietary patterns when counseling patients on smoking cessation.

  15. Corpus cavernosum electromyography during morning naps in healthy volunteers: further evidence that corpus cavernosum potentials reflect sympathetically mediated activity.

    NARCIS (Netherlands)

    Jiang, X.; Meuleman, E.J.H.; Wijkstra, H.; Wagner, G.

    2005-01-01

    PURPOSE: We assessed the practicability of corpus cavernosum (CC) electromyography (EMG) in volunteers during morning naps in the laboratory and further validated this method. MATERIALS AND METHODS: A total of 11 healthy volunteers with a mean age of 23.8 years (range 19 to 31) were included. CC-EMG

  16. Corpus cavernosum electromyography during morning naps in healthy volunteers: further evidence that corpus cavernosum potentials reflect sympathetically mediated activity

    NARCIS (Netherlands)

    Jiang, Xiaogang; Meuleman, Eric J. H.; Wijkstra, Hessel; Wagner, Gorm

    2005-01-01

    PURPOSE: We assessed the practicability of corpus cavernosum (CC) electromyography (EMG) in volunteers during morning naps in the laboratory and further validated this method. MATERIALS AND METHODS: A total of 11 healthy volunteers with a mean age of 23.8 years (range 19 to 31) were included. CC-EMG

  17. Effect of Needling at CV-12 (Zhongwan on Blood Glucose Levels in Healthy Volunteers: A Pilot Randomized Placebo Controlled Trial

    Directory of Open Access Journals (Sweden)

    Sriloy Mohanty

    2016-12-01

    Conclusion: The result of this study suggests that although 20 minutes of needling at CV-12 without stimulation produced a mild reduction in RBG levels in healthy volunteers, it did not produce a statistically significant result.

  18. Quantitative Evaluation of Trabecular Bone Structure by Calcaneus MR Images Texture Analysis of Healthy Volunteers and Osteoporotic Subjects

    National Research Council Canada - National Science Library

    Herlidou, S

    2001-01-01

    The aim of this study is to evaluate, in vivo, trabecular bone structure of the calcaneus of healthy volunteers and osteoporotic patients by texture analysis of MR images Automated methods of texture...

  19. The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Harder-Lauridsen, Nina Majlund; Benatti, Fabiana Braga

    2016-01-01

    Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest...... affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile...... in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated...

  20. Effects of Blueberry and Cranberry Juice Consumption on the Plasma Antioxidant Capacity of Healthy Female Volunteers

    DEFF Research Database (Denmark)

    Pedersen(Vægter), Christian Bjerggaard; Kyle, J; Jenkinson, AM

    2000-01-01

    OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml...... of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also...... obtained four hours after consuming the juice. RESULTS: Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60...

  1. Skin sensitivity to rocuronium and vecuronium: a randomized controlled prick-testing study in healthy volunteers.

    Science.gov (United States)

    Dhonneur, Gilles; Combes, Xavier; Chassard, Didier; Merle, Jean Claude

    2004-04-01

    Prick tests are frequently used for the authentication of neuromuscular blocking drugs (NMBDs) as causative drugs for anaphylactic reactions during anesthesia. Unfortunately, the actual threshold concentration for skin testing remains debatable for most NMBDs. We studied the flare and wheal responses to prick tests with rocuronium and vecuronium. Thirty healthy, nonatopic, anesthesia-naive male and female volunteers (14 men and 16 women) from 18 to 40 yr of age were assigned randomly to receive a total of 10 prick tests-4 ascending dilutions (1:1000, 1:100, 1:10, and 1) of rocuronium and vecuronium and 2 controls-on both forearms. An assessor blinded to the assignment monitored systemic and skin responses to NMBDs and measured wheal and flare surfaces immediately after and 15 min after prick tests. None of the volunteers experienced any immediate systemic or cutaneous responses to rocuronium or vecuronium. Although a dilution of 1:1000 of both NMBDs failed to promote any skin response at 15 min, 50% and 40% of the subjects had a positive skin reaction to undiluted rocuronium and vecuronium, respectively. We demonstrated a sex effect related to smaller threshold concentration-induced cutaneous reactions in female volunteers to both muscle relaxants. Our observation questions the reliability of prick testing with undiluted solutions of rocuronium and vecuronium for the diagnosis of allergy. Building concentration-skin response curves to prick tests with rocuronium and vecuronium in healthy, nonatopic, anesthesia-naive male and female volunteers demonstrated that the nonreactive concentration for both muscle relaxants is the 1:1000 dilution of the stock solutions. Our observation calls into question the past practice of prick-testing skin for sensitivity to neuromuscular blocking drugs by using undiluted solutions.

  2. The effect of gluten on intestinal fermentation, gastric and gallbladder emptying in healthy volunteers.

    Science.gov (United States)

    Di Stefano, Michele; Carnevale Maffè, Gabriella; Bergonzi, Manuela; Mengoli, Caterina; Formagnana, Pietro; Di Sabatino, Antonio; Corazza, Gino Roberto

    2015-09-01

    The relationship between gluten ingestion and gastrointestinal tract function is a matter of debate. We analysed the effect of gluten on gastric and gallbladder emptying and intestinal fermentation in healthy volunteers. Ultrasound measurement of gastric and gallbladder emptying after both gluten-containing and gluten-free meals was performed in 18 volunteers (8 women, age 25.0±2.5 years; BMI 22±1.9). Breath hydrogen excretion after a gluten-containing meal, a gluten-free meal and a gluten-free meal with added gluten powder was measured in 16 volunteers (10 women, age 25.2±2.7 years; BMI 22±1.8). The severity of symptoms was monitored. Gluten presence in the meals was not recognised. Gastric emptying time was 81.6±13.8min after gluten-containing and 73.9±21.6min after gluten-free meals (p=0.11). Percentage ejection fraction after gluten-containing meals was 60±9% and 60.6±6% after gluten-free meals (p=0.68). Peak and cumulative hydrogen excretion were significantly higher after gluten-containing than after gluten-free meals (peak: 12.5±7.3 vs 6.5±5.1 parts-per-million, pgluten powder to the gluten-free meal did not modify fermentation. Symptoms were mild and not different after the meals. In healthy volunteers, gluten may induce gastrointestinal alterations. Further studies are needed to clarify which patients could benefit from dietary modification. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Pharmacokinetics of Single-Dose and Multi-Dose of Lovastatin/Niacin ER Tablet in Healthy Volunteers

    OpenAIRE

    Yan-yan Jia; Song Ying; Chen-tao Lu; Jing Yang; Li-kun Ding; Ai-dong Wen; Yan-rong Zhu

    2012-01-01

    An extended-release (ER) niacin and lovastatin fixed-dose combination has been developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The purpose of the present study was to examine the drug interaction between niacin and lovastatin after multi-dose oral administration of lovastatin/niacin ER combination in healthy Chinese volunteers. A single-center, randomized, open-label, 5-period crossover study was conducted in thirty healthy volunteers aged 18 to 45 years wi...

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

    Directory of Open Access Journals (Sweden)

    Elisângela Colpo

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  6. Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers

    DEFF Research Database (Denmark)

    Christensen, Mette Marie Hougaard; Højlund, Kurt; Hother-Nielsen, Ole

    2015-01-01

    PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1). METHODS: The study was conducted as part of a randomized cross-over trial. Thirty......-four healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9 with two reduced-function alleles) were included. In one of the study periods, they were titrated to steady-state with 1 g metformin twice daily. RESULTS: Neither AUC(0-12), C(max) nor Cl(renal) were...... statistically significantly affected by the number of reduced-function alleles (0, 1 or 2) in OCT1: (AUC(0-12): 0, 1, 2: 14, 13 and 14 h ng/L (P = 0.61)); (C(max): 0, 1, 2: 2192, 1934 and 2233 ng/mL, (P = 0.26)) and (Cl(renal): 0, 1, 2: 31, 28 and 30 L/h (P = 0.57)) CONCLUSIONS: In a cohort of healthy...

  7. Rectal visceral sensitivity in women with irritable bowel syndrome without psychiatric comorbidity compared with healthy volunteers.

    Science.gov (United States)

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

    2009-01-01

    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. We wanted to examine rectal visceral sensitivity in IBS patients without comorbid psychiatric disorders, IBS patients with phobic anxiety and healthy volunteers. 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. 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. 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.

  8. Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers.

    Science.gov (United States)

    Müller, U; Rowe, J B; Rittman, T; Lewis, C; Robbins, T W; Sahakian, B J

    2013-01-01

    Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. A double-blind placebo-controlled parallel design study evaluated the effect of 200 mg of modafinil (N = 32) or placebo (N = 32) in non-sleep deprived healthy volunteers. Non-verbal tests of divergent and convergent thinking were used to measure creativity. A new measure of task motivation was used, together with more levels of difficulty on neuropsychological tests from the CANTAB battery. Improvements under modafinil were seen on spatial working memory, planning and decision making at the most difficult levels, as well as visual pattern recognition memory following delay. Subjective ratings of enjoyment of task performance were significantly greater under modafinil compared with placebo, but mood ratings overall were not affected. The effects of modafinil on creativity were inconsistent and did not reach statistical significance. Modafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Pharmacokinetic Properties of Nintedanib in Healthy Volunteers and Patients With Advanced Cancer.

    Science.gov (United States)

    Dallinger, Claudia; Trommeshauser, Dirk; Marzin, Kristell; Liesener, Andre; Kaiser, Rolf; Stopfer, Peter

    2016-11-01

    Nintedanib, a triple angiokinase inhibitor, has undergone clinical investigation for the treatment of solid tumors and idiopathic pulmonary fibrosis. Nintedanib (Vargatef® ) plus docetaxel is approved in the EU for the treatment of patients with adenocarcinoma non-small cell lung cancer (NSCLC) after first-line chemotherapy, and as monotherapy (Ofev® ) in the United States and EU for the treatment of patients with idiopathic pulmonary fibrosis. Pharmacokinetics (PK) of nintedanib after oral single and multiple doses and intravenous (IV) administration were assessed using 3 data sets: (1) an absolute bioavailability trial that enrolled 30 healthy volunteers; (2) a pooled data analysis of 4 studies that enrolled a total of 107 healthy volunteers; and (3) a pooled data analysis of 4 studies that enrolled a total of 149 patients with advanced cancer. In the absolute bioavailability trial of healthy volunteers, nintedanib showed a high total clearance (geometric mean 1390 mL/min) and a high volume of distribution at steady state (Vss  = 1050 L). Urinary excretion of IV nintedanib was about 1% of dose; renal clearance was about 20 mL/min and therefore negligible. There was no deviation from dose proportionality after IV administration in the dose range tested. Absolute bioavailability of oral nintedanib (100 mg capsule) relative to IV dosing (4-hour infusion, 6 mg) was slightly below 5%. Nintedanib was quickly absorbed after oral administration. It underwent rapid and extensive first-pass metabolism and followed at least biphasic disposition kinetics. In advanced cancer patients, steady state was reached at the latest at 7 days for twice-daily dosing. Nintedanib's PK was time-independent; accumulation after repeated administration was negligible. © 2016, The American College of Clinical Pharmacology.

  10. Credibility and comprehension of healthy volunteers in lengthy inpatient drug studies.

    Science.gov (United States)

    Apseloff, Glen; Kitzmiller, Joseph P; Tishler, Carl L

    2013-01-01

    Early clinical trials rely upon paid healthy volunteers. Concern has been raised regarding the characteristics of these individuals, how well they understand their rights and the risks of clinical research, and how they may be influenced by manipulation or coercion. Therefore, we investigated (1) the motivations of subjects in clinical trials, (2) how well these individuals comprehend a consent form they sign, and (3) the effect of the stipend on the reliability of information reported by volunteers in clinical trials. Thirty healthy subjects (age, 21-45 years) in a long-duration clinical trial were administered a questionnaire gathering demographic information and testing their comprehension of the consent form. In a separate chart review of 10 clinical trials, 374 subjects were studied to determine their reliability in reporting abnormalities in their medical history and in reporting adverse events, and an association was examined between the incidence of unreliable reporting and the stipend paid to them for participating in the clinical trial. A large percentage of subjects who were enrolled in the long-duration clinical trial failed to comprehend a variety of basic concepts related to the consent form and their participation in the drug study. The chart review demonstrated that subjects who are paid larger stipends may not be more likely to report abnormalities on their medical history. Further studies should be undertaken with larger numbers of subjects enrolled in clinical trials, and possible associations between demographic data (eg, income, level of education, number of previous studies) and the reliability of information provided by normal healthy research volunteers should be examined.

  11. Effects of dexamethasone coadministered with oseltamivir on the pharmacokinetics of oseltamivir in healthy volunteers.

    Science.gov (United States)

    Jang, Kyungho; Kim, Min-Kyoung; Oh, Jaeseong; Lee, SeungHwan; Cho, Joo-Youn; Yu, Kyung-Sang; Choi, Tai Kiu; Lee, Sang-Hyuk; Lim, Kyoung Soo

    2017-01-01

    Oseltamivir is widely used in the treatment and prophylaxis of influenza A and B viral infections. It is ingested as an oral prodrug that is rapidly metabolized by carboxylesterase 1 (CES1) to its active form, oseltamivir carboxylate. Dexamethasone is also used in the treatment of acute respiratory distress syndrome, a severe complication of influenza; however, its influence on the pharmacokinetics (PK) of oseltamivir is controversial. The aim of this study was to investigate the effects of coadministering oseltamivir and dexamethasone on the PK of oseltamivir in healthy volunteers. An open-label, two-period, one-sequence, multiple-dose study was conducted in 19 healthy male volunteers. Oseltamivir (75 mg) was orally administered on Day 1 and Day 8, and dexamethasone (1.5 mg) was administered once daily from Day 3 to Day 8. Serial blood and urine samples were collected for PK analysis of oseltamivir and oseltamivir carboxylate on Day 1 and Day 8. Oseltamivir and oseltamivir carboxylate concentrations in plasma and urine were determined using liquid chromatography-tandem mass spectrometry. Area under the plasma concentration-time curve (AUC) of oseltamivir and oseltamivir carboxylate decreased after dexamethasone treatment for 6 days. The geometric mean ratio (90% confidence interval) of the metabolic ratio (oseltamivir carboxylate AUC0-48h/oseltamivir AUC0-48h) was 0.92 (0.87-0.97). The amount of unchanged oseltamivir excreted in urine increased by 14% after dexamethasone treatments. Coadministration of dexamethasone with oseltamivir slightly decreased systemic exposure to oseltamivir and oseltamivir carboxylate in healthy volunteers. This result suggests that CES1 is inhibited by dexamethasone in humans. However, coadministration of oseltamivir and dexamethasone did not appear to have a clinically relevant effect on the PK of oseltamivir; based on these results, dexamethasone can be coadministered with oseltamivir.

  12. Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers

    Science.gov (United States)

    Müller, U.; Rowe, J.B.; Rittman, T.; Lewis, C.; Robbins, T.W.; Sahakian, B.J.

    2013-01-01

    Background Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. Methods A double-blind placebo-controlled parallel design study evaluated the effect of 200 mg of modafinil (N = 32) or placebo (N = 32) in non-sleep deprived healthy volunteers. Non-verbal tests of divergent and convergent thinking were used to measure creativity. A new measure of task motivation was used, together with more levels of difficulty on neuropsychological tests from the CANTAB battery. Results Improvements under modafinil were seen on spatial working memory, planning and decision making at the most difficult levels, as well as visual pattern recognition memory following delay. Subjective ratings of enjoyment of task performance were significantly greater under modafinil compared with placebo, but mood ratings overall were not affected. The effects of modafinil on creativity were inconsistent and did not reach statistical significance. Conclusions Modafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals. This article is part of a Special Issue entitled ‘Cognitive Enhancers’. PMID:22820554

  13. Gas chromatographic-mass spectrometric determination of levodropropizine plasma levels in healthy volunteers.

    Science.gov (United States)

    Zaratin, P; De Angelis, L; Cattabeni, F

    1988-08-01

    A gas chromatographic-mass spectrometric method for the qualitative and quantitative analysis of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526) in plasma is described. The method proved to be highly selective and sensitive. Drug concentrations as low as 5 ng/ml could be measured. Levodropropizine plasma levels were measured in 6 healthy volunteers after administration of an acute 60 mg dose. Peak concentrations were reached between 40 and 60 min and measurable amounts of drug were present till 8 h after administration.

  14. Linearity of levodropropizine, a new antitussive drug, in the healthy volunteer.

    Science.gov (United States)

    Borsa, M; Glavenna, G; Ferrari, M P; Canali, S; Giachetti, C; Zanolo, G

    1991-01-01

    The object of this study was to determine whether the pharmacokinetics of levodropropizine were linear. Twelve healthy adult male volunteers received oral doses use of 30, 60 and 90 mg of levodropropizine. A cross-over design was used. With the exception of Cmax, and AUC the pharmacokinetics of levodropropizine in the dose range studied are similar. The relationship between the doses and AUCs and the statistical comparison of AUCs (Anova test and Westlake test) confirm that in the range 30-90 mg the plasma pharmacokinetics of levodropropizine are linear.

  15. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Petersen, Karin Lottrup

    2006-01-01

    In most published studies women are more sensitive to experimental pain than men. Enhanced central pain processing in women has been suggested, but psychosocial factors might also have affected the findings. Data from five completed healthy volunteer studies were analyzed to investigate gender...... differences in development of secondary hyperalgesia. Cutaneous hyperalgesia was induced with the heat/capsaicin sensitization model. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation after heat and capsaicin sensitization, rating of pain during heat...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  17. Long-lasting patch reactions to gold sodium thiosulfate occurs frequently in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Klaus E; Jensen, Charlotte D

    2007-01-01

    In a skin irritancy study in healthy volunteers with 3 metal salts, aqueous gold sodium thiosulfate (GSTS) in a dilution series caused unexpectedly frequent and strong patch test reactions on volar forearm skin in 22 of 31 participants (71%). The reactions showed morphological features consistent...... of skin and/or mucosal complaints related to exposure to gold items. The results indicate that inclusion of GSTS in routine patch testing may cause problems regarding interpretation and clinical relevance of positive GSTS patch tests, which fulfil the clinical criteria of a contact allergy....

  18. Smoking cession decreases mean platelet volume in healthy Korean populations.

    Science.gov (United States)

    Cho, S Y; You, E; Lee, H J; Lee, W I; Park, T S

    2014-01-01

    Smoking is considered as a major modifiable risk factor for cardiovascular diseases. It has been shown that smoking cessation drops the risk of cardiovascular diseases such as myocardial infarction and also improves platelet function. Because mean platelet volume (MPV) is a simple and convenient indicator for platelet activation, we planned to investigate the effect of smoking status on MPV in healthy populations. This study was conducted on 398 individuals who visited our hospital for regular medical check-ups and were confirmed not to have diabetes or hypertension. MPV was measured using EDTA blood on an Advia 2120 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) within 2 hours. Present smokers showed higher MPV levels than present non-smokers. When MPV was compared by taking previous smoking history and present smoking status into account, the smoking cessation group showed significantly lower MPV levels than other groups. Because this finding was significant only in the female group, the change in MPV according to smoking status was found to be different by gender. We carefully suggest that smoking cessation can lower the risk of cardiovascular diseases through the change in MPV, which can be more effective for women than men.

  19. Comparison of spinal alignment, muscular strength, and quality of life between women with postmenopausal osteoporosis and healthy volunteers.

    Science.gov (United States)

    Miyakoshi, N; Kudo, D; Hongo, M; Kasukawa, Y; Ishikawa, Y; Shimada, Y

    2017-11-01

    This study compared spinal alignment, muscular strength, and quality of life (QOL) between women with postmenopausal osteoporosis and healthy volunteers. The results indicated that lower QOL in osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean muscle mass, and generalized muscle weakness. Increased spinal kyphosis is common in patients with osteoporosis and negatively impacts quality of life (QOL). Muscular strength is also important for QOL in patients with osteoporosis. However, spinal kyphosis and muscle weakness also occur in healthy individuals with advancing age. The purposes of this study were thus to compare spinal alignment, muscular strength, and QOL between women with postmenopausal osteoporosis and healthy volunteers. Participants comprised 236 female patients with postmenopausal osteoporosis (mean age, 68.7 years) and 93 healthy volunteer women (mean age, 71.0 years). Body mass index (BMI), angles of spinal kyphosis, back extensor strength, grip strength, and QOL were compared between groups. BMI, back extensor strength, and grip strength were significantly higher in the volunteer group than in the osteoporosis group (p osteoporosis group than in the volunteer group (p osteoporosis group than in the volunteer group (p osteoporosis group than in the volunteer group (p osteoporosis group (p osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean muscle mass, and generalized muscle weakness.

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

    Science.gov (United States)

    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. Copyright © 2013 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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

    To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans. 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. 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. 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.

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

    Science.gov (United States)

    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) 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

  3. Effects of the Red Bull energy drink on cognitive function and mood in healthy young volunteers.

    Science.gov (United States)

    Wesnes, Keith A; Brooker, Helen; Watson, Anthony W; Bal, Wendy; Okello, Edward

    2017-02-01

    The present study compared the cognitive and mood effects of two commercially available products, Red Bull energy drink 250 mL and Red Bull Sugarfree energy drink 250 mL, together with a matching placebo 250 mL. Twenty-four healthy young volunteers took part in a randomised, placebo controlled, double-blind, three-way cross-over study. Cognitive function was assessed using an integrated set of nine computerised tests of attention, working and episodic memory. On each study day the volunteers received a standardised breakfast prior to completing a baseline performance on cognitive tests and mood scales, followed by the consumption of the study drink. The cognitive tests and scales were then re-administered at 30, 60 and 90 min post-dose. Red Bull was found to produce significant improvements over both the Sugarfree version and the placebo drink on two composite scores from the six working and episodic memory tests; one combining the 12 accuracy measures from the six tasks and the other the average speed of correct responses from the working memory and episodic recognition memory tasks. These improvements were in the range of a medium effect size, which reflects a substantial enhancement to memory in young volunteers.

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

    DEFF Research Database (Denmark)

    Guo, Song; Gøtze, Jens Peter; Jeppesen, Jørgen L

    2015-01-01

    ) 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......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...

  5. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus

    2012-01-01

    of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction...... and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses...... of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development...

  6. The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

    DEFF Research Database (Denmark)

    Petersen, Astrid Heide; Kohler, Gerd; Korsatko, Stefan

    2008-01-01

    What is already known about this subject * Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans. What this paper adds * This report is the first to investigate the effect...... of exercise on the absorption of inhaled insulin. * In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged...... overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

  7. Quantitative MRI comparison of systemic hemodynamics in Mustard/Senning repaired patients and healthy volunteers at rest

    Energy Technology Data Exchange (ETDEWEB)

    Laffon, Eric [Service de Medecine Nucleaire, Hopital du Haut-Leveque, 33604, Pessac (France); Laboratoire de Physiologie Cellulaire Respiratoire, INSERM EMI 0356, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076, Bordeaux Cedex (France); Jimenez, Maria; Choussat, Alain [Service de Cardiologie, Hopital du Haut-Leveque, 33604, Pessac (France); Latrabe, Valerie [Service de Radiologie, Hopital du Haut-Leveque, 33604, Pessac (France); Ducassou, Dominique [Service de Medecine Nucleaire, Hopital du Haut-Leveque, 33604, Pessac (France); Marthan, Roger [Laboratoire de Physiologie Cellulaire Respiratoire, INSERM EMI 0356, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076, Bordeaux Cedex (France); Laurent, Francois [Service de Radiologie, Hopital du Haut-Leveque, 33604, Pessac (France)

    2004-05-01

    The purpose of the present study was to non-invasively compare ascending aortic blood flow and cross-sectional area (CSA) variations vs time in Mustard or Senning repaired (MSR) patients against those of healthy volunteers at rest. Velocity-encoded MR imaging was performed in 10 male patients (age range 18-24 years, median age 20.5 years) late after a Mustard or Senning correction, and in 10 male healthy volunteers (age range 21-25 years, median age 22.5 years), at the upper part of the ascending aorta. Both aortic cross-sectional area (CSA) and blood-flow variations were recorded over a complete cardiac cycle, with a 30-ms time of resolution. The body-surface area (BSA), the mean CSA over the systolic phase, and the BSA-normalized systemic ventricle power and work were significantly lower in the patient series compared with those of the volunteer series. The BSA-normalized right ventricle (RV) power and work of MSR patients were equal to 87 and 83% on average of those of the left ventricle (LV) of healthy volunteers. We conclude that, at rest, the mechanical performance of the systemic RV in MSR patients is significantly lower than that of the LV in healthy volunteers. Furthermore, the significantly lower aortic CSA found in MSR patients than in healthy volunteers may reveal an increase in the vasomotor tone. (orig.)

  8. Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.

    Science.gov (United States)

    Chotsiri, Palang; Wattanakul, Thanaporn; Hoglund, Richard M; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Blessborn, Daniel; Jittamala, Podjanee; White, Nicholas J; Day, Nicholas P J; Tarning, Joel

    2017-12-01

    The aims of the present study were to evaluate the pharmacokinetic properties of dihydroartemisinin (DHA) and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers. The population pharmacokinetic properties of DHA and piperaquine were assessed in 16 healthy Thai adults using an open-label, randomized, crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling. The developed models described DHA and piperaquine population pharmacokinetics accurately. Concomitant treatment with primaquine did not affect the pharmacokinetic properties of DHA or piperaquine. A linear pharmacokinetic-pharmacodynamic model described satisfactorily the relationship between the individually corrected QT intervals and piperaquine concentrations; the population mean QT interval increased by 4.17 ms per 100 ng ml-1 increase in piperaquine plasma concentration. Simulations from the final model showed that monthly and bimonthly mass drug administration in healthy subjects would result in median maximum QT interval prolongations of 18.9 ms and 16.8 ms, respectively, and would be very unlikely to result in prolongation of more than 50 ms. A single low dose of primaquine can be added safely to the existing DHA-piperaquine treatment in areas of multiresistant Plasmodium falciparum malaria. Pharmacokinetic-pharmacodynamic modelling and simulation in healthy adult volunteers suggested that therapeutic doses of DHA-piperaquine in the prevention or treatment of P. falciparum malaria are unlikely to be associated with dangerous QT prolongation. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  9. A novel model for the pharmacokinetic studies of bevacizumab and etanercept in healthy volunteers and patients.

    Science.gov (United States)

    Li, Meizhen; Qiang, Wei; Hu, Li; Wang, Lei; Cheng, Zeneng

    2017-12-01

    Therapeutic monoclonal antibodies (mAbs) have been successfully applied to treat various diseases and shown a promising prospect in medical treatment. MAbs have some unique characteristics when compared with small chemical drugs, and their pharmacokinetic (PK) properties are much more complex than those of small chemical drugs, whose eliminations are usually linear. In this study, a new model was established through taking into account the mechanisms of the elimination of mAbs. The proposed model was applied to the modeling and simulation of two kinds of mAbs, including bevacizumab and etanercept, in PK studies of healthy volunteers and eligible patients, and the classical linear compartment model was set as control. The goodness-of-fit of the fitting concentration-time curve of mAbs was calculated to verify the accuracy of both models during the modeling and simulation. The accuracy of the proposed model was better than that of classical linear compartment model in healthy volunteers and even much better in patients. The proposed model demonstrates a stronger ability in the modeling and simulation of mAbs, and may provide a new option for the PK studies of those reagents. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Caffeine and taurine containing energy drink increases left ventricular contractility in healthy volunteers.

    Science.gov (United States)

    Doerner, Jonas M; Kuetting, Daniel L; Luetkens, Julian A; Naehle, Claas P; Dabir, Darius; Homsi, Rami; Nadal, Jennifer; Schild, Hans H; Thomas, Daniel K

    2015-03-01

    To investigate the impact of a caffeine and taurine containing energy drink (ED) on myocardial contractility in healthy volunteers using cardiac MR and cardiac MR based strain analysis. 32 healthy volunteers (mean age 28 years) were investigated before and 1 h after consumption of a caffeine and taurine containing ED. For assessment of global cardiac functional parameters balanced SSFP-Cine imaging was performed, whereas CSPAMM tagging was used to evaluate global and regional myocardial strain. In addition, ten randomly chosen subjects were investigated once more using a caffeine only protocol to further evaluate the effect of caffeine solely. Heart rate and blood pressure were recorded throughout all studies. ED consumption led to a significant increase in peak systolic strain (PSS) and peak systolic strain rate (PSSR) 1 h after consumption (PSS: w/o ED -22.8 ± 2.1%; w ED -24.3 ± 2.4%, P = taurine containing ED results in a subtle, but significant increase of myocardial contractility 1 h after consumption.

  11. Effects of unoprostone on diurnal variation of intraocular pressure in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Inoue K

    2011-07-01

    Full Text Available Kenji Inoue1, Kei Noguchi1, Masato Wakakura1, Goji Tomita21Inouye Eye Hospital, Tokyo; 22nd Department of Ophthalmology, Toho University School of Medicine, Tokyo, JapanPurpose: To prospectively evaluate the diurnal variation of intraocular pressure (IOP during unoprostone treatment in 13 healthy volunteers.Method: IOP was measured by Goldmann applanation tonometry by the same observer every 3 hours from 9 am to 9 am the next morning. Unoprostone was then instilled at 9 am and 9 pm daily for 1 month. After 1 month, IOP was measured again with unoprostone instilled at 9 am and 9 pm during IOP measurement. We then compared the average daily IOP before and after the treatment (paired t-test.Results: After 1 month of treatment, the average IOP decreased at every time point but one (12 pm, 3 pm, 6 pm, 9 pm, 12 am, 3 am, and 9 am, but not at 6 am. There were no adverse reactions and none of the subjects discontinued unoprostone.Conclusion: The hypotensive effects of unoprostone persist throughout the day, but this study suggests that the effects may be weaker at nighttime and early in the morning.Keywords: unoprostone, intraocular pressure, diurnal variation, healthy volunteer

  12. Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers.

    Science.gov (United States)

    Cadroy, Yves; Pillard, Fabien; Sakariassen, Kjell S; Thalamas, Claire; Boneu, Bernard; Riviere, Daniel

    2002-09-01

    We have investigated the effect of moderate and strenuous exercise on experimental arterial thrombus formation in men. Thrombogenesis was measured in 15 sedentary healthy male volunteers at rest or immediately after two standardized exercise tests performed for 30 min on a bicycle ergometer. The exercises were performed at a constant load corresponding to either 50 or 70% maximal oxygen uptake. Thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native nonanticoagulated blood for 3 min. The shear rate at the collagen surface was 2,600 s(-1). Platelet and fibrin deposition was quantified by immunoenzymatic methods. The results show that moderate exercise did not affect arterial thrombus formation. In contrast, platelet thrombus formation on collagen was increased on the average by 20% after 30 min at 70% maximal oxygen uptake (P = 0.03). Fibrin deposition on collagen remained unchanged with exercise, regardless of its intensity. Thus, with the use of a clinically relevant human experimental model of thrombosis, the present study suggests that exercise of heavy intensity may increase the risk for arterial thrombogenesis in sedentary young healthy male volunteers.

  13. Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion.

    Science.gov (United States)

    Smit, B; Smulders, Y M; Eringa, E C; Gelissen, H P M M; Girbes, A R J; de Grooth, H J S; Schotman, H H M; Scheffer, P G; Oudemans-van Straaten, H M; Spoelstra-de Man, A M E

    2017-12-06

    To determine the human dose-response relationship between a stepwise increase in arterial oxygen tension and its associated changes in oxygen delivery and sublingual microcirculatory perfusion METHODS: Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20 kPa, 40 kPa, 60 kPa and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume-clamp method. At the end of each period, the sublingual microcirculation was assessed by Sidestream Darkfield Imaging RESULTS: Systemic oxygen delivery was unchanged throughout the study (Pslope =0.8). Perfused vessel density decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18, Pslope =0.001). Cardiac index decreased linearly (max -10%, SD10, Pslope <0.001) due to a reduction in heart rate (max -10%, SD7, Pslope =0.009). There were no changes in stroke volume or mean arterial pressure. Most changes became apparent above an arterial oxygen tension of 20 kPa CONCLUSIONS: In healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic oxygen delivery. Sublingual microcirculatory perfused vessel density decreased in a dose-dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Recognition of facial emotion and perceived parental bonding styles in healthy volunteers and personality disorder patients.

    Science.gov (United States)

    Zheng, Leilei; Chai, Hao; Chen, Wanzhen; Yu, Rongrong; He, Wei; Jiang, Zhengyan; Yu, Shaohua; Li, Huichun; Wang, Wei

    2011-12-01

    Early parental bonding experiences play a role in emotion recognition and expression in later adulthood, and patients with personality disorder frequently experience inappropriate parental bonding styles, therefore the aim of the present study was to explore whether parental bonding style is correlated with recognition of facial emotion in personality disorder patients. The Parental Bonding Instrument (PBI) and the Matsumoto and Ekman Japanese and Caucasian Facial Expressions of Emotion (JACFEE) photo set tests were carried out in 289 participants. Patients scored lower on parental Care but higher on parental Freedom Control and Autonomy Denial subscales, and they displayed less accuracy when recognizing contempt, disgust and happiness than the healthy volunteers. In healthy volunteers, maternal Autonomy Denial significantly predicted accuracy when recognizing fear, and maternal Care predicted the accuracy of recognizing sadness. In patients, paternal Care negatively predicted the accuracy of recognizing anger, paternal Freedom Control predicted the perceived intensity of contempt, maternal Care predicted the accuracy of recognizing sadness, and the intensity of disgust. Parenting bonding styles have an impact on the decoding process and sensitivity when recognizing facial emotions, especially in personality disorder patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

  15. Minimal variation in anti-A and -B titers among healthy volunteers over time

    DEFF Research Database (Denmark)

    Sprogøe, Ulrik; Yazer, Mark; Rasmussen, Mads Hvidkjær

    2017-01-01

    measurements on the same donor are required to ensure that each donation produces a low titer product. METHODS: The anti-A and/or -B titers were measured on 56 healthy adult volunteers (47 blood donors; 9 blood center personnel) every three months for 12 consecutive months using an automated solid phase...... titer measurements from all 56 volunteers were combined as appropriate, the highest overall combined SD was 0.47 titer steps for IgG anti-A. This value corresponds to a 95% confidence interval for intra-individual variation in this antibody’s titer over 12 months of 0.96 titer steps. Thus, based on one...... measurement, an IgG anti-A with a titer step of, for example, 6 would be expected to be in the range of titer step 5 to titer step 7 over the course of one year with 95% probability. CONCLUSION: The titers of anti-A and/or -B among healthy adults are stable over at least one year. This suggests that repeated...

  16. Effect of Modulated Electrohyperthermia on the Pharmacokinetics of Oral Transmucosal Fentanyl Citrate in Healthy Volunteers.

    Science.gov (United States)

    Lee, Sun Young; Kim, Min-Gul

    2016-12-01

    This study aimed to determine whether changes occur in fentanyl absorption and disposition when administered in conjunction with modulated electrohyperthermia (mEHT) treatment. A randomized, single-dose, crossover, open-label study was used to investigate the effect of mEHT on the pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing. Geometric mean ratios (ratio of fentanyl with mEHT to fentanyl alone) for the Cmax and AUC0-last were 1.20 (90% CI, 1.09-1.32) and 1.15 (90% CI, 0.99-1.33), respectively. The mean temperature of the abdominal skin surface increased by approximately 4°C. There was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with mEHT, and it is not necessary to modify the dosing regimen. cris.nih.go,kr Identifier: KCT0001286. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  17. Evaluation of antioxidant potential of Rasayana drugs in healthy human volunteers.

    Science.gov (United States)

    Kuchewar, Vaishali V; Borkar, Mangal A; Nisargandha, Milind A

    2014-01-01

    It is increasingly being realized that many of today's diseases are due to "oxidative stress" that results from an imbalance between formation and neutralization of free radicals. Rasayana Chikitsa is a unique branch of Ayurveda. The word Rasayana means the way for attaining excellent Rasadi Dhatus. Several medicinal plants have been described as Rasayanas in Ayurveda. Ashwagandha and Guduchi are the best among the Rasayanas described by Charaka. To study the efficacy of Ashwagandha and Guduchi in oxidative stress in healthy volunteers. The study was carried out on 30 healthy volunteers after obtaining written informed consent. They were randomly distributed in three groups. Each group was treated with three different colored capsules containing Ashwagandha, Guduchi and placebo in the dose of 1 capsule (500 mg) twice a day for 6 months. The parameters such as hemoglobin%, Erythorcyte Sedimentation Rate (ESR), Malondialdehyde (MDA), Super-Oxide Dismutase (SOD) level, etc., were assessed before and after treatment. The Student's t-test was applied to assess significant variations in all of the studied parameters. In this study, there was a significant increase in SOD level and decrease in MDA level in Ashwagandha and Guduchi groups. Ashwagandha and Guduchi may be helpful in preventing the oxidative stress and premature aging.

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

    Science.gov (United States)

    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.

  19. Distribution and respiratory activity of mycobacteria in household water system of healthy volunteers in Japan.

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    Tomoaki Ichijo

    Full Text Available 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.

  20. PAIN THRESHOLD MEASUREMENTS IN HIGH AND LOW ALTITUDE AMONG HEALTHY VOLUNTEER ADULTS: A COMPARATIVE STUDY

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    Nashwa S. Hamed

    2016-12-01

    Full Text Available Background: Majority of high altitude residents have certain clinical, physiological, anatomical and biochemical changes. Pain threshold is one of the numerable changes that may occur due to chronic hypoxia. The aim of this research was to study the long term effects of high altitude exposure on pain perception among healthy volunteer subjects. Methods: This is an observational case-control study. Two groups of healthy volunteer subjects, highland group (n=242 and lowland group (n=242 in two different cities. Assessment methods used were: Pressure algometer, was measured bilaterally three times on ten body points and Situational pain scale, which is 18 items self-report questionnaire measuring the mental representation of pain intensity in imaginary painful situations. Results: pain sensitivity was lower in highlanders compared to lowlanders (p<0.0005. While the participants’ attitudes towards imaginary painful situations trough SPS showed lesser pain sensitivity in highlanders compared to lowlanders in 72% from the total scale items. Conclusion: According to the results of the current study, pressure pain threshold is higher (pain sensitivity is lower in highlanders compared to lowlanders. And attitudes towards imaginary painful situations are lower in highland population compared to lowland population as a long-term effect of chronic hypoxia.

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

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    Furong Qiu

    2014-01-01

    Full Text Available 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.

  2. Arterial Injury and Endothelial Repair: Rapid Recovery of Function after Mechanical Injury in Healthy Volunteers

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    Lindsey Tilling

    2014-01-01

    Full Text Available Objective. Previous studies suggest a protracted course of recovery after mechanical endothelial injury; confounders may include degree of injury and concomitant endothelial dysfunction. We sought to define the time course of endothelial function recovery using flow-mediated dilation (FMD, after ischaemia-reperfusion (IR and mechanical injury in patients and healthy volunteers. The contribution of circulating CD133+/CD34+/VEGFR2+ “endothelial progenitor” (EPC or repair cells to endothelial repair was also examined. Methods. 28 healthy volunteers aged 18–35 years underwent transient forearm ischaemia induced by cuff inflation around the proximal biceps and radial artery mechanical injury induced by inserting a wire through a cannula. A more severe mechanical injury was induced using an arterial sheath and catheter inserted into the radial artery of 18 patients undergoing angiography. Results. IR and mechanical injury produced immediate impairment of FMD (from 6.5 ± 1.2% to 2.9 ± 2.2% and from 7.4 ± 2.3% to 1.5 ± 1.6% for IR and injury, resp., each P<0.001 but recovered within 6 hours and 2 days, respectively. FMD took up to 4 months to recover in patients. Circulating EPC did not change significantly during the injury/recovery period in all subjects. Conclusions. Recovery of endothelial function after IR and mechanical injury is rapid and not associated with a change in circulating EPC.

  3. Variability in sublingual microvessel density and flow measurements in healthy volunteers.

    Science.gov (United States)

    Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

    2009-02-01

    As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

  4. The silicon content of beer and its bioavailability in healthy volunteers.

    Science.gov (United States)

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Elliott, Hazel; Walker, Caroline; Mehta, Payal; Shoukru, Sera; Thompson, Richard P H; Powell, Jonathan J

    2004-03-01

    Dietary Si, as soluble orthosilicic acid (OSA), may be important for the growth and development of bone and connective tissue. Beer appears to be a major contributor to Si intake, although the Si content of beer and its bioavailability in human subjects have not been well established. Here we investigated the Si content of different beers and then estimated Si absorption from beer in healthy volunteers. The Si content of seventy-six different beers was estimated using inductively coupled plasma optical emission spectrometry and one of the beers, used in the ingestion study, was ultrafiltered to determine OSA content. Next, following the ingestion of 0.6 litres beer (22.5 mg Si; 4.6 % (v/v) ethanol), serum and urinary Si levels were measured in nine healthy volunteers over a 6 h period. A solution of OSA was similarly investigated as a positive control and water and 4.6 % ethanol as negative controls. The mean Si level of beer was 19.2 (sd 6.6) mg/l; the median Si level was 18.0 mg/l. There was no significant difference in the Si levels of the different beers by geographical origin or type of beer. Serum and urinary Si levels increased considerably following the ingestion of beer or a solution of OSA but not with the ingestion of either 4.6 % ethanol or water. The ultrafilterability of Si from beer (about 80 %) and its absorption in volunteers (about 55 %) was comparable with that of a solution of OSA suggesting that Si in beer is present chiefly in a monomeric form and is readily bioavailable.

  5. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

    Science.gov (United States)

    Gota, Vikram S; Maru, Girish B; Soni, Tejal G; Gandhi, Tejal R; Kochar, Nitin; Agarwal, Manish G

    2010-02-24

    Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

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

    Science.gov (United States)

    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

  7. Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Xi-Qing Yan

    2013-03-01

    Full Text Available The pharmacokinetics (PK of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg and a multiple oral dose (90 mg d-1×6 d administration. The effect of food on the PK of one single oral dose (360 mg was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0. All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064 of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.Embora a farmacocinética (PK do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma

  8. Diversity of Duodenal and Rectal Microbiota in Biopsy Tissues and Luminal Contents in Healthy Volunteers.

    Science.gov (United States)

    Li, Gangping; Yang, Min; Zhou, Kan; Zhang, Lei; Tian, Lugao; Lv, Shangze; Jin, Yu; Qian, Wei; Xiong, Hanhua; Lin, Rong; Fu, Yu; Hou, Xiaohua

    2015-07-01

    The diverse microbial communities that colonize distinct segments of the gastrointestinal tract are intimately related to aspects of physiology and the pathology of human health. However, most recent studies have focused on the rectal or fecal microbiota, and the microbial signature of the duodenum is poorly studied. In this study, we compared the microbiota in duodenal and rectal samples to illustrate the characteristic microbial signatures of the duodenum in healthy adults. Nine healthy volunteers donated biopsies and luminal contents from the duodenum and rectum. To determine the composition and diversity of the microbiota, 454- pyrosequencing of bacterial 16S rRNA was performed and multiple bioinformatics analyses were applied. The α-diversity and phylogenetic diversity of the microbiota in the duodenal samples were higher than those of the rectal samples. There was higher biodiversity among the microbiota isolated from rectal biopsies than feces. Proteobacteria were more highly represented in the duodenum than in the rectum, both in the biopsies and in the luminal contents from the healthy volunteers (38.7% versus 12.5%, 33.2% versus 5.0%, respectively). Acinetobacter and Prevotella were dominant in the duodenum, whereas Bacteroides and Prevotella were dominant in the rectum. Additionally, the percentage of OTUs shared in biopsy groups was far higher than in the luminal group (43.0% versus 26.8%) and a greater number of genera was shared among the biopsies than the luminal contents. Duodenal samples demonstrated greater biological diversity and possessed a unique microbial signature compared with the rectum. The mucosa-associated microbiota was more relatively conserved than luminal samples.

  9. Effects of dexamethasone coadministered with oseltamivir on the pharmacokinetics of oseltamivir in healthy volunteers

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    Jang K

    2017-03-01

    Full Text Available Kyungho Jang,1,2,* Min-Kyoung Kim,3,4,* Jaeseong Oh,1 SeungHwan Lee,1 Joo-Youn Cho,1 Kyung-Sang Yu,1 Tai Kiu Choi,3 Sang-Hyuk Lee,3,4 Kyoung Soo Lim4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, 3Department of Psychiatry, 4Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea *These authors contributed equally to this work Purpose: Oseltamivir is widely used in the treatment and prophylaxis of influenza A and B viral infections. It is ingested as an oral prodrug that is rapidly metabolized by carboxylesterase 1 (CES1 to its active form, oseltamivir carboxylate. Dexamethasone is also used in the treatment of acute respiratory distress syndrome, a severe complication of influenza; however, its influence on the pharmacokinetics (PK of oseltamivir is controversial. The aim of this study was to investigate the effects of coadministering oseltamivir and dexamethasone on the PK of oseltamivir in healthy volunteers. Methods: An open-label, two-period, one-sequence, multiple-dose study was conducted in 19 healthy male volunteers. Oseltamivir (75 mg was orally administered on Day 1 and Day 8, and dexamethasone (1.5 mg was administered once daily from Day 3 to Day 8. Serial blood and urine samples were collected for PK analysis of oseltamivir and oseltamivir carboxylate on Day 1 and Day 8. Oseltamivir and oseltamivir carboxylate concentrations in plasma and urine were determined using liquid chromatography–tandem mass spectrometry. Results: Area under the plasma concentration–time curve (AUC of oseltamivir and oseltamivir carboxylate decreased after dexamethasone treatment for 6 days. The geometric mean ratio (90% confidence interval of the metabolic ratio

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

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    Brott DA

    2014-02-01

    Full Text Available David A Brott,1 Scott H Adler,1 Ramin Arani,2 Susan C Lovick,3 Mark Pinches,4 Stephen T Furlong1 1Translational Patient Safety and Enabling Sciences, AstraZeneca Pharmaceuticals, 2AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 3AstraZeneca Pharmaceuticals, 4Global Safety Assessment, AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, UK 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

  11. Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers.

    Science.gov (United States)

    Buś-Kwaśnik, Katarzyna; Rudzki, Piotr J; Ksycińska, Hanna; Leś, Andrzej; Serafin-Byczak, Krystyna; Raszek, Jerzy; Bielak, Agnieszka; Wybraniec, Andrzej; Płatek, Anna E; Szymański, Filip M; Łazowski, Tomasz

    2017-01-01

    Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure. The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.5 mg of bisoprolol (Bisocard® - the medicinal product) to the original medicinal product (Concor Cor 2.5® - the reference). A randomised, open-label, two-period, crossover, single-dose, relative bioavailability study was conducted in fasted healthy Caucasian volunteers. A single 10-mg oral dose (four tablets of 2.5 mg) of the test or reference product was followed by a 14-day wash-out period, after which the subjects received the alternative product. Blood was sampled within a period of 60 h post administration in pre-specified time points. Bisoprolol concentrations were determined by a validated LC-MS/MS method. The products were considered bioequivalent if the 90% confidence interval (CI) of the log-transformed geometric mean ratios (test vs. reference) for AUC(0-t), AUC(0-∞), and Cmax were within 80-125% limits. Adverse events were monitored during the study based on the subject claims and clinical parameters. Twenty-six healthy male and female volunteers (mean age ca. 29 years; body mass index 22.7 kg/m²) were in-cluded in the study, and 24 completed the clinical part. The geometric mean ratios (test/reference) for the log-transformed AUC(0-t), AUC(0-∞), and Cmax were 95.16% (90% CI 92.52-97.87%), 95.08% (90% CI 92.40-97.83%), and 100.00% (90% CI 94.83-105.45%), respectively. There were no significant differences in the pharmacokinetic parameters between the test and reference formulations. No serious adverse events were reported. The results of this single-dose study in healthy Caucasian volunteers indicate that Bisocard®; 2.5 mg film-coated tablets are bioequivalent to the reference product - Concor Cor 2.5®; 2.5 mg film-coated tablets. Both

  12. Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers

    Science.gov (United States)

    Lei, He-Ping; Ji, Wei; Lin, Jian; Chen, Hao; Tan, Zhi-Rong; Hu, Dong-Li; Liu, Li-Juan; Zhou, Hong-Hao

    2009-01-01

    AIMS To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. METHODS Fourteen healthy male volunteers (age range 19–25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day−1 (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion. RESULTS Ginkgo biloba extract administration resulted in no significant effects on the AUC0–∞ of bupropion and hydroxybupropion. Bupropion mean AUC0–∞ value was 1.4 µg·h ml−1[95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 µg·h ml−1 (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC0–∞ value was 8.2 µg·h ml−1 (95% CI 6.5, 10.4) before G. biloba administration and 8.7 µg·h ml−1 (95% CI 7.1, 10.6) after treatment. The Cmax of hydroxybupropion increased from 221.8 ng ml−1 (95% CI 176.6, 278.6) to 272.7 ng ml−1 (95% CI 215.0, 345.8) (P = 0.038) and the t1/2 of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000). CONCLUSIONS Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t1/2 and increase the Cmax of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion. PMID:19694739

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

    Directory of Open Access Journals (Sweden)

    Raimond eLozda

    2014-04-01

    Full Text Available 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 emphasise 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.

  14. Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Pickering G

    2016-12-01

    Full Text Available Gisèle Pickering,1–3 Nicolas Macian,1,2 Claude Dubray,1–3 Bruno Pereira4 1University Hospital, CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, 2Inserm, CIC 1405, UMR Neurodol 1107, 3Clermont Université, Laboratoire de Pharmacologie, Faculté de médecine, 4CHU de Clermont-Ferrand, Délégation Recherche Clinique Innovation, Clermont-Ferrand, France Background: Acetaminophen (APAP, paracetamol mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467 was carried out from May 30, 2011 to July 12, 2011. Methods: Forty healthy volunteers were included and analyzed. Nociceptive thresholds, core temperature (body temperature, and a battery of cognitive tests were recorded before and after oral APAP (2 g or placebo: Information sampling task for predecisional processing, Stockings of Cambridge for spatial memory, reaction time, delayed matching of sample, and pattern recognition memory tests. Analysis of variance for repeated measures adapted to crossover design was performed and a two-tailed type I error was fixed at 5%. Results: APAP improved information sampling task (diminution of the number of errors, latency to open boxes, and increased number of opened boxes; all P<0.05. Spatial planning and working memory initial thinking time were decreased (P=0.04. All other tests were not modified by APAP. APAP had an antinociceptive effect (P<0.01 and body temperature did not change. Conclusion: This study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance

  15. Pharmacokinetic interaction studies of atosiban with labetalol or betamethasone in healthy female volunteers.

    Science.gov (United States)

    Rasmussen, Birgitte Buur; Larsen, Lotte Seiding; Senderovitz, Thomas

    2005-11-01

    In two separate trials, we studied the concomitant administration of atosiban with labetalol and betamethasone to determine any possibility of a clinically relevant pharmacokinetic interaction. Study 1 was an open-label, single dose atosiban, multiple dose labetalol, interaction study. Study 2 was an open-label, randomised, three-period crossover pharmacokinetic study. The studies were carried out at the Clinical Pharmacology Unit of AAI Deutschland GmbH & Co KG, Neu-Ulm, Germany. The study population consisted of healthy female volunteers. In Study 1, 14 healthy female volunteers participated. On study day 1, a 12-hour intravenous infusion of 114.75 mg atosiban was administered; on days 2-4, participants received labetalol orally (100 mg twice daily), and on study day 5 they received the combined treatment. In Study 2, a total of 18 healthy female volunteers received, on three separate occasions, a 12-hour intravenous infusion of 114.75 mg atosiban, a single intramuscular injection of 12 mg betamethasone or the two drugs in combination. For Study 1, the outcome parameter for atosiban was area under the plasma concentration-time curve (AUC); the study parameters for labetalol were AUC, maximum plasma concentration (C(max)) and time to C(max) (t(max)). In Study 2, AUC, C(max) and time to C(max) (t(max)) were assessed for atosiban and betamethasone. Labetalol had no clinically relevant influence on the bioavailability (AUC) of atosiban. For labetalol, the co-administration with atosiban did not affect the extent of bioavailability, however, C(max) decreased by 36% and t(max) increased by 45 minutes. The C(min) was not affected by atosiban. The betamethasone and atosiban combination led to similar mean plasma concentration-time curves as the administration of each substance alone. Pharmacokinetic parameters (AUC, C(max), t(max)) did not differ markedly between treatments and all 90% CIs for ratios between treatments were fully within limits (80-125%). The co

  16. Distribution of coronary calcium score in healthy middle-aged Korean

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Kyu Ok; Kim, Min Jung; Choi, Byoung Wook; Kim, Jung Ho; Noh, Ki Suh; Kim, Si Yon; Ko, Heung Kyu; Suh, Il [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-11-01

    To determine the prevalence and degree of CAC (coronary artery calcification) in appearently healthy middle-aged Koreans, and the relation of CAC to risk factors for atherosclerosis. A total of 289 apparently healthy personnel at Yonsei University (male: 170, female:119, age: mean(SD=54.9{+-}7.1 years)) underwent EBT (electron bean tomography). The risk factors for athero-sclerosis, which included diabetes mellitus, hypertension, smoking, a family history of precocious onset, obesity, hyperlipidemia, and high intraperitoneal fat, were scrutinized. One hundred and sixty-eight subjects (58%) had at least one risk factor. The CAC score was calculated for all subjects and for each coronary artery separately and was then analyzed by age and sex and in relation to the risk factors. The prevalence of CAC was 40% in men and 18.5% in women (mean score:29.7 vs. 9.9). The number of individuals who had one, two, or more than two risk factors was 141,41, and 19, respectively. The number of risk factors and the prevalence and score of CAC were significantly correlated (p=0.01, 0.02 respectively). The number of individuals with no risk factor, with without CAC, was 58(20.1%) and 103(35.6%), respectively, while the number with some risk factor, with or without CAC, was 38(13.1%) and 90(31.1%), respectively. The CAC score was significantly higher in the presence of hypertension, low HDL, or obesity(p=0.001, 0.049, and 0.068, respectively). Smoking appeared to have a borderline effect on the calcium score(p=0.118). This study should provide useful information for interpreting CAC scores and establishing a treatment strategy for Koreans. The comparison of our results with other studies will enable a better understanding of the process and risk factors of atherosclerosis in Koreans.

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

    Science.gov (United States)

    Teng, Renli; Butler, Kathleen

    2013-01-01

    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. 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. Compared with ticagrelor alone, diltiazem co-administration significantly increased the mean maximum concentration (C max) and mean area under the plasma concentration-time curve (AUC) for ticagrelor by 69% and 174%, respectively. Diltiazem co-administration reduced C max by 38% but had no significant effect on AUC for AR-C124910XX. C max 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. 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.

  18. Disposition kinetics of selenium in healthy volunteers following therapeutic shampoo treatment.

    Science.gov (United States)

    Noisel, Nolwenn; Bouchard, Michèle; Carrier, Gaétan

    2010-05-01

    This study was aimed at documenting the kinetic time courses of selenium (Se) in accessible biological matrices of volunteers following controlled applications of therapeutic shampoo containing Se, to better elucidate the mechanisms by which shampoo-Se accumulates in hair and hence estimate the contribution of this source to total Se body burden. Ten healthy volunteers were exposed to Se-shampoo three times a week over a month. Blood, hair and toenail concentrations along with daily urinary excretions were repeatedly measured over an 18-month period following the onset of application. Over the entire study period, blood concentrations of Se (range: 127-233μg/l) and daily urinary excretions (range: 11.9-150μg/d) remained within baseline range of the general population. Conversely, during shampoo application, mean Se concentrations in hair reached transitional levels of 89μg/g while, following cessation of treatment, a mono-exponential decrease was observed with a mean half-life of 4.5 weeks. Two of the volunteers also exhibited an increase in toenail concentrations of Se during the study period. Results show that Se-shampoo does not contribute significantly to total Se body burden, as assessed from blood and urine levels. Differences observed between blood and urine time courses as compared to hair profiles and the presence of Se on hair grown before treatment indicates an adsorption on hair; however, the gradual decrease in Se concentrations in successive centimeters of hair grown following the application period suggests a concomitant absorption from the scalp during treatment with subsequent excretion in hair. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Association of PEAR1 rs12041331 polymorphism and pharmacodynamics of ticagrelor in healthy Chinese volunteers.

    Science.gov (United States)

    Li, Mupeng; Hu, Yaodong; Wen, Zhipeng; Li, Huilan; Hu, Xiaolei; Zhang, Yanjiao; Zhang, Zanling; Xiao, Jian; Tang, Jie; Chen, Xiaoping

    2017-12-01

    1. Genetic polymorphisms in platelet endothelial aggregation receptor 1 (PEAR1) were associated with responsiveness to aspirin and P2Y12 receptor antagonists. This study aimed to investigate whether PEAR1 polymorphism is associated with ticagrelor pharmacodynamics in healthy Chinese subjects. 2. The in vitro inhibition of platelet aggregation (IPA) was evaluated before and after ticagrelor incubated with platelet-rich plasma from 196 healthy Chinese male subjects. Eight polymorphisms at PEAR1 locus were genotyped. Eighteen volunteers (six in each rs12041331 genotype group) were randomly selected. After a single oral 180 mg dose of ticagrelor, plasma levels of ticagrelor and the active metabolite AR-C124910XX were measured and pharmacodynamics parameters including IPA and VASP-platelet reactivity index (PRI) were assessed. 3. No significant difference in ticagrelor pharmacokinetics among rs12041331 genotype was observed. As compared with rs12041331 G allele carriers, AA homozygotes exhibited increased IPA after 15 μM ticagrelor incubation (p ticagrelor administration (p ticagrelor incubation as compared to T allele carriers (p ticagrelor pharmacodynamics in healthy Chinese subjects.

  20. Effects of Oxytocin on Attention to Emotional Faces in Healthy Volunteers and Highly Socially Anxious Males

    Science.gov (United States)

    Nathan, Pradeep J.; Auyeung, Bonnie; Mogg, Karin; Bradley, Brendan P.; Sule, Akeem; Müller, Ulrich; Dudas, Robert B.; Sahakian, Barbara J.; Baron-Cohen, Simon

    2015-01-01

    Background: Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans. Methods: This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli. Results: In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed. Conclusions: These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety. PMID:25552432

  1. Cervical spine segmental vertebral motion in healthy volunteers feigning restriction of neck flexion and extension.

    Science.gov (United States)

    Puglisi, Filadelfio; Strimpakos, Nikolaos; Papathanasiou, Matthildi; Kapreli, Eleni; Bonelli, Aurelio; Sgambetterra, Sergio; Ferrari, Robert

    2007-09-01

    The purpose of this study was to obtain comparative data concerning the percentage contribution of segmental cervical vertebral motion to the cervical range of motion (ROM) in healthy volunteers under two conditions: (1) normal, voluntary neck flexion and extension and (2) feigned restriction of neck flexion and extension. Each healthy subject's angular motion over forward cervical flexion and extension was measured first by X-ray analysis during normal, voluntary motion. Then the subjects were asked to pretend that they had a 50% restricted neck range due to pain or stiffness and thus to move in both flexion and extension only as far as about 50% of their normal range. A total of 26 healthy subjects (ten males and sixteen females, age 28.7+/-7.7 years) participated. The total angular motion from C2 to C7 was normal in the unrestricted condition and was significantly reduced in the feigned restriction condition (pneck flexion and extension, a shift occurred in the pattern of how each segment contributes to the total angular range. A greater percentage contribution was made by C2-C3 and C3-C4 than under normal conditions (Pneck range (pneck ROM affects the percentage contribution of the functional units C2-C3 to C6-C7 by showing a higher percentage contribution of the upper cervical segments and less contribution to the angular rotation by the lowest cervical segment. Feigners of restricted neck range thus produce a pattern different from nonfeigning subjects.

  2. Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males.

    Science.gov (United States)

    Clark-Elford, Rebecca; Nathan, Pradeep J; Auyeung, Bonnie; Mogg, Karin; Bradley, Brendan P; Sule, Akeem; Müller, Ulrich; Dudas, Robert B; Sahakian, Barbara J; Baron-Cohen, Simon

    2014-10-31

    Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans. This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli. In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed. These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety. © The Author 2014. Published by Oxford University Press on behalf of CINP.

  3. Abdominal obesity and structure and function of the heart in healthy male Koreans: The ARIRANG study.

    Science.gov (United States)

    Son, Jung-Woo; Sung, Joong Kyung; Lee, Jun-Won; Youn, Young Jin; Ahn, Min-Soo; Ahn, Sung Gyun; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan; Koh, Sang Baek; Kim, Jang-Young

    2016-09-01

    Although central obesity is a more powerful predictor of cardiovascular disease (CVD) than general obesity, there is limited information on structural and functional changes of the heart in central obesity. Therefore, we evaluated the association between abdominal obesity and geometric and functional changes of the heart in healthy males. A total of 1460 healthy males aged 40 to 70 years without known CVD from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population were included. All individuals underwent conventional 2-dimensional echocardiography and tissue Doppler imaging to measure left atrial (LA) and left ventricle (LV) geometry and function. Increasing tertiles of waist circumference (WC) were associated with stepwise increases in LA volume, LV end-diastolic dimension, LV mass to height, deceleration time of E wave, and lower E/A ratio (all P trends 89 cm) to the lowest tertile (obesity may be a stronger predictor than general obesity of geometric and functional changes in the LV and LA.

  4. Plasma levels and pharmacokinetics of single and multiple dose of tetrazepam in healthy volunteers.

    Science.gov (United States)

    Bun, H; Philip, F; Berger, Y; Necciari, J; Al-Mallah, N R; Serradimign, A; Cano, J P

    1987-02-01

    The pharmacokinetics of tetrazepam (Myolastan, Musaril), were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg and repeated administration for 5 consecutive days of 50 mg at 12-h intervals, in tablet form. Tetrazepam was measured in plasma using a selective and sensitive GLC method. Tetrazepam is rapidly absorbed after oral administration with a peak plasma level of 0.49 +/- 0.10 mg/l at 0.94 +/- 0.47 h. The drug is widely distributed in the organism with an apparent volume of distribution of 6.7 +/- 2.1 l/kg. Tetrazepam is eliminated with a half-life of 22 +/- 4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed. No differences were observed between the pharmacokinetic values after a single dose or after repeated administration.

  5. Effect of dimeticone and pepsin on the bioavailability of metoclopramide in healthy volunteers.

    Science.gov (United States)

    do Nascimento, D F; Silva Leite, A L A e; de Moraes, R A; Camarão, G C; Bezerra, F A F; de Moraes, M O; de Moraes, M E A

    2014-10-01

    To assess the effect of dimeticone and pepsin on the bioavailability of metoclopramide (CAS 7232-21-5) in healthy volunteers. The study was conducted using a randomized, open, 2-period crossover design. The volunteers received single administration of 7-mg conventional metoclopramide capsule and a formulation containing metoclopramide (7 mg) plus dimeticone (40 mg) and pepsin (50 mg), with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Plasma metoclopramide concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The pharmacokinetics parameters AUC(last) and C(max) were obtained from the metoclopramide plasma concentration vs. time curves. Metoclopramide's association was bioequivalent to conventional capsule; 90% CIs for geometric mean treatment ratios of C(max) [108.0% (90% CI, 100.4-116.3%)], AUC(last) [103.3% (90% CI, 99.5-107.4%)] were within the predefined range. The metoclopramide formulations were well tolerated at the administered doses and no significant adverse reactions were observed. Thus, these results confirm the good bioavailability of metoclopramide in the new formulation and rule out any impaired absorption when the drugs are formulated in combination. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Effect of slow and fast pranayama training on handgrip strength and endurance in healthy volunteers.

    Science.gov (United States)

    Thangavel, Dinesh; Gaur, Girwar Singh; Sharma, Vivek Kumar; Bhavanani, Ananda Balayogi; Rajajeyakumar, M; Syam, Sunder A

    2014-05-01

    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. 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. Present study was conducted in the Department of Physiology, JIPMER in 2011-12 (1.06.11 to 1.04.12). 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. 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. In SPG significant improvement occurred only in HGE parameter from 83.95±45.06 to 101.62±53.87 (seconds) (p0.05). Pranayama training decreases sympathetic activity, resulting in mental relaxation and decreased autonomic arousal thereby, decreasing force fluctuations during isometric contraction. This is reflected as improvement in HGS and HGE.

  7. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial.

    Science.gov (United States)

    Grubben, M J; Boers, G H; Blom, H J; Broekhuizen, R; de Jong, R; van Rijt, L; de Ruijter, E; Swinkels, D W; Nagengast, F M; Katan, M B

    2000-02-01

    An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. Sixty-four healthy volunteers (31 men and 33 women) with a mean (+/-SD) age of 43 +/- 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetière (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk. Consumption of 1 L unfiltered coffee/d for 2 wk significantly raised fasting plasma homocysteine concentrations by 10%, from 12.8 to 14.0 micromol/L. Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.

  8. Systemic and Local Effects of Warm Oxygen Exposure to the Lower Extremities in Healthy Volunteers.

    Science.gov (United States)

    Joshi, Vidya Sunil; Joshi, Sunil Subhash; Maruthy

    2017-04-01

    Warmth to the extremity is known to improve the cutaneous blood flow and tissue perfusion. Oxygen is essential for healing of chronic wounds. Topical oxygen therapy has become standard therapy in management of lower extremity wounds. A combination of local heat and oxygen is likely to be beneficial in many clinical scenarios of non-healing wounds without any systemic effects. To evaluate the local and systemic effects of the exposure of extremity to warm oxygen in healthy volunteers. Thirty one volunteers were included in the study. The index foot was exposed to oxygen 7l/min, 93%-95% concentration at temperature of 43(o)C for 90 minutes with the device. The following parameters such as basal and periprocedural blood pressure, body temperature, heart rate, 24 lead ECG, temperatures at foot and plethysmographic waveforms from the index foot were measured. A NRS-11 questionnaire was asked to the patient to rate his or her pain from 0 to 10 and documented by health care worker at the end of the session. The skin temperature of index foot reached to 34(o)C from 32.9(o)C, (p=0.011). The average pulse amplitude changed from 39.8 mV to 79.8 mV over the duration of the experiment (pwarm oxygen therapy. Further studies are required on patient population to prove benefits in clinical settings.

  9. Comparison of the visualisation of the subclavian and axillary veins: An ultrasound study in healthy volunteers.

    Science.gov (United States)

    Roger, Claire; Sadek, Meriem; Bastide, Sophie; Jeannes, Pascal; Muller, Laurent; Bobbia, Xavier; Lefrant, Jean-Yves

    2017-02-01

    To compare the area of the lumen of the axillary and subclavian veins using ultrasound (US) in 50 healthy volunteers. Using an ultrasound device, depth, area, short axis vein length and long axis vein, vein-artery and vein-pleura distances were measured for axillary and subclavian approaches. The mean cross-sectional area of the axillary vein was greater than the mean cross-sectional area of the subclavian vein (327±89 mm(2) versus 124±46 mm(2), Pvisualised in 3 and 45 volunteers, respectively (Pvisualisation of the axillary vein under US is greater than that for the subclavian vein, mainly due to a better alignment with the long axis of the axillary vein leading to a greater cross-sectional area of the axillary vein. NCT01647815. Copyright © 2016 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  10. Lower limb ischaemia and reperfusion injury in healthy volunteers measured by oxidative and inflammatory biomarkers

    DEFF Research Database (Denmark)

    Halladin, N. L.; Busch, Sarah Victoria Ekeløf; Alamili, M.

    2015-01-01

    exposed to 20 minutes of lower limb ischaemia. Muscle biopsies and blood samples were taken at baseline and 5, 15, 30, 60 and 90 minutes after tourniquet release and analysed for malondialdehyde (MDA), ascorbic acid, dehydroascorbic acid, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-1 receptor...... at any sampling time. CONCLUSION: Twenty minutes of lower limb ischaemia does not result in an ischaemia-reperfusion injury in healthy volunteers, measurable by oxidative and pro- and anti-inflammatory biomarkers in muscle biopsies and in the systemic circulation....... antagonist (IL-1Ra), IL-6, IL-10, TNF-receptor (TNF-R)I, TNF-RII and YKL-40. RESULTS: We found no significant increase in MDA in the muscle biopsies after reperfusion. Plasma levels of oxidative and pro- and anti-inflammatory parameters showed no significant differences between baseline and after reperfusion...

  11. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    Science.gov (United States)

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  12. An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers

    DEFF Research Database (Denmark)

    van der Schrier, R; Jonkman, K; van Velzen, M

    2017-01-01

    . We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg. Methods: Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized...... on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, P

  13. The dopamine augmenter L-DOPA does not affect positive mood in healthy human volunteers.

    Science.gov (United States)

    Liggins, John; Pihl, Robert O; Benkelfat, Chawki; Leyton, Marco

    2012-01-01

    Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans.

  14. Fractal analysis of EEG upon auditory stimulation during waking and hypnosis in healthy volunteers.

    Science.gov (United States)

    Lee, Jun-Seok; Koo, Bon-Hoon

    2012-01-01

    The authors tested fluctuation analyses (DFA) of EEGs upon auditory stimulation in waking and hypnotic states as related to topography and hypnotizability. They administered the Hypnotic Induction Profile (HIP), Dissociation Experience Scale, and Tellegen Absorption Scale to 10 healthy volunteers and measured subjects' EEGs while the subjects listened to sounds, either selecting or ignoring tones of different decibels, in waking and hypnotic states. DFA scaling exponents were closest to 0.5 when subjects reported the tones in the hypnotic state. Different DFA values at C3 showed significant positive correlations with the HIP eye-roll sign. Adding to the literature supporting the state theory of hypnosis, the DFA values at F3 and C3 showed significant differences between waking and hypnotic states. Application of auditory stimuli is useful for understanding neurophysiological characteristics of hypnosis using DFA.

  15. Cassava Flour Substitution Modulates Glycemic Responses and Glycemic Index of Wheat Breads in Apparent Healthy Volunteers.

    Science.gov (United States)

    Okafor, Ebelechukwu N; Erukainure, Ochuko L; Ozumba, Augusta U; Adewale, Chris O; Kayode, Funmi O; Asieba, Godfrey O; Adesegha, Olubukola I; Elemo, Gloria N

    2017-07-04

    Different carbohydrate foods produce different glycemic responses even with little or no difference in macronutrient composition. Cassava constitutes one of the major staples in Nigeria. Four blends of cassava-wheat bread samples with 0, 10, 15, and 20% cassava flour inclusion were fed individually to groups of healthy human volunteers. Subjects were studied on separate occasions in the morning after a 10-12-hr overnight fast. Blood glucose responses were measured at intervals of 30 min over a period of 2 hr. Glucose was used as a reference food. There were normal glucose responses to the bread samples studied. Increase in cassava incorporation led to less significant glycemic responses. The glycemic index values ranged from 91-94. Results from this study indicate that the inclusion of cassava flour in bread production might not pose a threat to blood glucose response of individuals.

  16. The comparative bioavailability of a generic and the innovator fluconazole preparations in healthy Thai volunteers.

    Science.gov (United States)

    Teekachunhatean, S; Rojanastein, N; Manorot, M; Sangdee, C; Apisariyakul, A; Ajayutphokin, U

    1998-10-01

    We studied the pharmacokinetics and compared the oral bioavailability of the "generic" (Biozole, Biolab Company, Thailand) and the "innovator" (Diflucan, Pfizer Incorporation, U.S.A.) fluconazole preparations in 12 healthy Thai volunteers. A 200 mg single oral dose of each preparation was given to the subjects in a randomized double-blind 2-period crossover design with 2 weeks washout period. Blood samples were collected just before and at 0.5, 1, 2, 2.5, 3, 4, 24, 48, 56 and 72 hours after drug administration. Serum fluconazole concentrations were determined by using high performance liquid chromatography. Individual concentration-time profiles and the pharmacokinetic parameters were analyzed by the noncompartmental pharmacokinetic method [TOPFIT, a pharmacokinetic data analysis program]. The pharmacokinetic parameters (Tmax, Cmax, Vd, Cl) of fluconazole in Thai healthy volunteers were comparable to those values observed in Caucasian subjects. The relative bioavailability of the generic Biozole was 102.38 +/- 9.79 per cent of Diflucan. The means and 90 per cent confidence intervals (90% CI) of the [Biozole/Diflucan] ratio of AUC0-72, AUC0-inf and Cmax were 1.02 (0.98-1.06), 0.99 (0.95-1.03) and 1.13 (1.03-1.25), respectively. These values were well within the acceptable bioequivalence ranges of 0.8-1.25 proposed by the US FDA. The means and 90 per cent CI of Tmax differences [Biozole-Diflucan] were -0.46 [(-1.03)-(0.12)]. This value was outside the stipulated bioequivalence range of +/- 0.41 h (+/- 20% of the Tmax of the reference formulation). Nevertheless, the Tmax difference was not expected to be related to the differences in safety and efficacy of the drug. Hence, Biozole and Diflucan were bioequivalent with respect to the extent of absorption (AUC), and the Cmax, and could be used interchangeably.

  17. Pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine at steady state in healthy volunteers.

    Science.gov (United States)

    Elger, Christian; Bialer, Meir; Falcão, Amílcar; Vaz-da-Silva, Manuel; Nunes, Teresa; Almeida, Luís; Soares-da-Silva, Patrício

    2013-08-01

    Investigate the pharmacokinetics of once-daily (QD; 900 mg) and twice-daily (BID; 450 mg) regimens of eslicarbazepine acetate (ESL) and BID (450 mg) regimen of oxcarbazepine (OXC) at steady state in healthy volunteers. Single-center, open-label, randomized, three-way (n = 12) crossover studies in healthy volunteers. Mean eslicarbazepine Cmax,ss (in μm) following ESL QD (87.3) was 33.3% higher (p eslicarbazepine plasma exposure (μmol h/L) to ESL daily-dose (μmol) was 0.381 (1156.3:3037.3), 0.368 (1117.6:3037.3), and 0.271 (968.4:3567.6) for ESL-QD, ESL-BID, and OXC-BID, respectively, which translates into a 40.6% increase in the ability of ESL-QD compared to OXC-BID to deliver into the plasma their major active entity eslicarbazepine. The extent of plasma exposure to ESL minor metabolites: (R)-licarbazepine and oxcarbazepine after ESL-QD was 71.5% and 61.1% lower, respectively, than after OXC-BID. Twenty, 24 and 38 treatment emergent adverse events were reported with ESL-QD, ESL-BID, and OXC-BID, respectively. ESL-QD resulted in 33.3% higher peak plasma concentration (Cmax,ss ) of eslicarbazepine and similar extent of plasma exposure (AUCss,0-τ ) when compared to ESL-BID, which may contribute to the efficacy profile reported with once-daily ESL. In comparison to OXC-BID, administration of ESL-QD resulted in 40.6% increase in the delivery of eslicarbazepine into the plasma as well as a significantly lower systemic exposure to (R)-licarbazepine and oxcarbazepine. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  18. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria.

    Science.gov (United States)

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

    2013-11-04

    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 reacidification 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 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 min, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 h. Betaine HCl significantly lowered gastric pH by 4.5 (± 0.5) units from 5.2 (± 0.5) to 0.6 (± 0.2) (P 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.

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

    Science.gov (United States)

    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 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 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

  20. Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers.

    Science.gov (United States)

    Levy, J H; Moore, K T; Neal, M D; Schneider, D; Marcsisin, V S; Ariyawansa, J; Weitz, J I

    2017-11-06

    Essentials Specific reversal agents for managing severe factor Xa inhibitor-associated bleeding are lacking. We assessed 4-factor-prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA). 4F-PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential. These agents may be viable options for reversal of therapeutic doses of rivaroxaban. Background Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four-factor prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F-PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated. Methods In this double-blind, parallel-group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F-PCC (50 IU kg-1 ), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F-PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP. Results As compared with saline, 4F-PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F-PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events. Conclusions Although 4F-PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F-PCC nor TXA influenced punch biopsy bleeding. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

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

    Science.gov (United States)

    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

  2. Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers.

    Science.gov (United States)

    Shah, Yasar; Iqbal, Zafar; Ahmad, Lateef; Khuda, Fazli; Khan, Abad; Khan, Abbas; Khan, Muhammad Imran; Ismail

    The current study aimed at the evaluation of, in vivo, the effect of omeprazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Omeprazole is an acid suppressant and CYP2C9, CYP3A4, and CYP2C19 substrate and inhibitor, as well as inhibitor of transporters (like P-gp). This was a randomized, open-label, 2-period, crossover study. Healthy male volunteers (N = 20), divided into 2 groups, were given single oral doses of rosuvastatin 40 mg either alone (treatment period I) or concomitantly with omeprazole 40-mg capsule (treatment period II). Plasma concentrations of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) were quantified by a validated liquid chromatography-tandem mass spectrometry method developed in our laboratory. An insignificant decrease (P > 0.05) has been observed in the values of maximum plasma concentrations, clearance, and half-life of rosuva, whereas an insignificant increase (P > 0.05) has been observed in the area under the plasma concentration-time curves from zero time to the last measurable concentration(Equation is included in full-text article.), that extrapolated to infinity (Equation is included in full-text article.), and mean residence time values after concomitant administration with omeprazole. Although omeprazole concomitant administration altered the pharmacokinetics of NDM-rosuva metabolite significantly, rosuva's very little metabolism (10%) suggests that these changes are of no clinical significance. Concomitant administration of omeprazole with rosuva did not alter the pharmacokinetics of rosuva in healthy volunteers. These data are consistent with other reported studies, indicating that rosuva is not a good candidate for metabolism-based drug-drug interactions. Therefore, rosuva can be administered safely along with omeprazole.

  3. Lack of circadian variation of pulse wave velocity measurements in healthy volunteers.

    Science.gov (United States)

    Drager, Luciano F; Diegues-Silva, Luzia; Diniz, Patrícia M; Lorenzi-Filho, Geraldo; Krieger, Eduardo M; Bortolotto, Luiz A

    2011-01-01

    Arterial stiffness is an independent marker of cardiovascular events. Pulse wave velocity (PWV) is a validated method to detect arterial stiffness that can be influenced by several factors including age and blood pressure. However, it is not clear whether PWV could be influenced by circadian variations. In the present study, the authors measured blood pressure and carotid-femoral PWV measurements in 15 young healthy volunteers in 4 distinct periods: 8 am, noon, 4 pm, and 8 pm. No significant variations of systolic (P=.92), mean (P=.77), and diastolic (P=.66) blood pressure among 8 am (113±15, 84±8, 69±6 mm Hg), noon (114±13, 83±8, 68±6 mm Hg), 4 pm (114±13, 85±8, 70±7 mm Hg), and 8 pm (113±7, 83±10, 68±7 mm Hg), respectively, were observed. Similarly, carotid-femoral PWV did not change among the periods (8 am: 7.6 ± 1.4 m/s, noon: 7.4±1.1 m/s, 4 pm: 7.6±1.0 m/s, 8 pm, 7.6±1.3 m/s; P=.85). Considering all measurements, mean blood pressure significantly correlated with PWV (r=.31; P=.016). In young healthy volunteers, there is no significant circadian variation of carotid-femoral PWV. These findings support the concept that it does not appear mandatory to perform PWV measurements at exactly the same period of the day. © 2010 Wiley Periodicals, Inc.

  4. Pain rather than induced emotions and ICU sound increases skin conductance variability in healthy volunteers.

    Science.gov (United States)

    Günther, A C; Schandl, A R; Berhardsson, J; Bjärtå, A; Wållgren, M; Sundin, Ö; Alvarsson, J; Bottai, M; Martling, C-R; Sackey, P V

    2016-09-01

    Assessing pain in critically ill patients is difficult. Skin conductance variability (SCV), induced by the sympathetic response to pain, has been suggested as a method to identify pain in poorly communicating patients. However, SCV, a derivate of conventional skin conductance, could potentially also be sensitive to emotional stress. The purpose of the study was to investigate if pain and emotional stress can be distinguished with SCV. In a series of twelve 1-min sessions with SCV recording, 18 healthy volunteers were exposed to standardized electric pain stimulation during blocks of positive, negative, or neutral emotion, induced with pictures from the International Affective Picture System (IAPS). Additionally, authentic intensive care unit (ICU) sound was included in half of the sessions. All possible combinations of pain and sound occurred in each block of emotion, and blocks were presented in randomized order. Pain stimulation resulted in increases in the number of skin conductance fluctuations (NSCF) in all but one participant. During pain-free baseline sessions, the median NSCF was 0.068 (interquartile range 0.013-0.089) and during pain stimulation median NSCF increased to 0.225 (interquartile range 0.146-0.3175). Only small increases in NSCF were found during negative emotions. Pain, assessed with the numeric rating scale, during the sessions with pain stimulation was not altered significantly by other ongoing sensory input. In healthy volunteers, NSCF appears to reflect ongoing autonomous reactions mainly to pain and to a lesser extent, reactions to emotion induced with IAPS pictures or ICU sound. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers.

    Science.gov (United States)

    Schmidt, Kristin; Cowen, Philip J; Harmer, Catherine J; Tzortzis, George; Errington, Steven; Burnet, Philip W J

    2015-05-01

    There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported. The present study explored the effects of two prebiotics on the secretion of the stress hormone, cortisol and emotional processing in healthy volunteers. Forty-five healthy volunteers received one of two prebiotics (fructooligosaccharides, FOS, or Bimuno®-galactooligosaccharides, B-GOS) or a placebo (maltodextrin) daily for 3 weeks. The salivary cortisol awakening response was sampled before and after prebiotic/placebo administration. On the final day of treatment, participants completed a computerised task battery assessing the processing of emotionally salient information. The salivary cortisol awakening response was significantly lower after B-GOS intake compared with placebo. Participants also showed decreased attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to placebo intake. No effects were found after the administration of FOS. The suppression of the neuroendocrine stress response and the increase in the processing of positive versus negative attentional vigilance in subjects supplemented with B-GOS are consistent with previous findings of endocrine and anxiolytic effects of microbiota proliferation. Further studies are therefore needed to test the utility of B-GOS supplementation in the treatment of stress-related disorders.

  6. Doppler Ultrasound Triggering for Cardiovascular MRI at 3T in a Healthy Volunteer Study.

    Science.gov (United States)

    Kording, Fabian; Yamamura, Jin; Lund, Gunnar; Ueberle, Friedrich; Jung, Caroline; Adam, Gerhard; Schoennagel, Bjoern Philip

    2017-04-10

    Electrocardiogram (ECG) triggering for cardiac magnetic resonance (CMR) may be influenced by electromagnetic interferences with increasing magnetic field strength. The aim of this study was to evaluate the performance of Doppler ultrasound (DUS) as an alternative trigger technique for CMR in comparison to ECG and pulse oximetry (POX) at 3T and using different sequence types. Balanced turbo field echo two-dimensional (2D) short axis cine CMR and 2D phase-contrast angiography of the ascending aorta was performed in 11 healthy volunteers at 3T using ECG, DUS, and POX for cardiac triggering. DUS and POX triggering were compared to the reference standard of ECG in terms of trigger quality (trigger detection and temporal variability), image quality [endocardial blurring (EB)], and functional measurements [left ventricular (LV) volumetry and aortic blood flow velocimetry]. Trigger signal detection and temporal variability did not differ significantly between ECG/DUS (I = 0.6) and ECG/POX (P = 0.4). Averaged EB was similar for ECG, DUS, and POX (pECG/DUS = 0.4, pECG/POX = 0.9). Diastolic EB was significantly decreased for DUS in comparison to ECG (P = 0.02) and POX (P = 0.04). The LV function assessment and aortic blood flow were not significantly different. This study demonstrated the feasibility of DUS for gating human CMR at 3T. The magnetohydrodynamic effect did not significantly disturb ECG triggering in this small healthy volunteer study. DUS showed a significant improvement in diastolic EB but could not be identified as a superior trigger method. The potential benefit of DUS has to be evaluated in a larger clinical patient population.

  7. Comparative pharmacokinetic and pharmacodynamic evaluation of branded and generic formulations of meloxicam in healthy male volunteers

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    Del Tacca M

    2013-07-01

    Full Text Available Mario Del Tacca,1,2 Giuseppe Pasqualetti,3 Giovanni Gori,1 Pasquale Pepe,1 Antonello Di Paolo,2 Marianna Lastella,2 Ferdinando De Negri,1 Corrado Blandizzi2 1Clinical Pharmacology Centre for Drug Experimentation, Pisa University Hospital, 2Department of Clinical and Experimental Medicine, 3Geriatrics Unit, University of Pisa, Pisa, Italy Purpose: The primary aim of the present study was to assess the pharmacokinetic bioequivalence between a generic formulation of meloxicam 15 mg tablets (Meloxicam Hexal and its respective brand product (Mobic, in order to verify whether the generic product conforms to the regulatory standards of bioequivalence in the postmarketing setting. As a secondary exploratory aim, the pharmacodynamic effects of the two formulations were also evaluated by means of rating scales following hyperalgesia induced by cutaneous freeze injury. Subjects and methods: A single 15 mg dose of generic or branded meloxicam tablets was administered to 24 healthy male volunteers in a crossover fashion. Plasma samples, collected for 24 hours after dosing, were assayed for meloxicam concentration by a validated high-performance liquid chromatography method. Results: The analysis of pharmacokinetic parameters did not show any significant difference between the two meloxicam formulations: the 90% confidence intervals fell within the acceptance range of 80%–125% (0.84–1.16 for area under the curve [0–24], and 0.89–1.23 for peak concentration. No difference in the pharmacodynamic end point was observed between the two groups. Conclusion: The pharmacokinetic profiles of the two meloxicam formulations confirm the regulatory criteria for bioequivalence; pharmacodynamic data indicate a similar antihyperalgesic effect. The two formulations can be used interchangeably in the clinical setting. Keywords: meloxicam, pharmacokinetics, healthy volunteers, generic drug, bioequivalence, postmarketing

  8. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers.

    Science.gov (United States)

    Bin Sayeed, Muhammad Shahdaat; Asaduzzaman, Md; Morshed, Helal; Hossain, Md Monir; Kadir, Mohammad Fahim; Rahman, Md Rezowanur

    2013-07-30

    Experimental evidences have demonstrated that Nigella sativa Linn. seed (NS) has positive modulation effects on aged rats with memory impairments, prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats. NS has neuroprotective, nephroprotective, lung protective, cardioprotective, hepatoprotective activities as established by previous studies on animals. Several clinical trials with NS on human have also demonstrated beneficial effect. The present study was designed to investigate the effects of NS on memory, attention and cognition in healthy elderly volunteers. Furthermore, safety profile of NS was assessed during the nine-week study period. Forty elderly volunteers were recruited and divided randomly into group A and group B--each consisting of 20 volunteers. The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner. All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks. The neuropsychological tests were logical memory test, digit span test, Rey-Osterrieth complex figure test, letter cancellation test, trail making test and stroop test. Safety profile was assessed by measuring biochemical markers of Cardiac (total cholesterol, triglycerides and high density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein cholesterol, creatine kinase-MB); Liver (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin) and Kidney (creatinine and blood urea nitrogen) through using commercial kits. There was significant difference (pmemory test-I and II, total score of digit span, 30 min delayed-recall, percent score in Rey-Osterrieth complex figure test, time taken to complete letter cancellation test, time taken in trail making test-A and test

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

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    Wu GL

    2015-10-01

    Full Text Available Guolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China 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

  10. Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers.

    Science.gov (United States)

    Ambarki, K; Wåhlin, A; Zarrinkoob, L; Wirestam, R; Petr, J; Malm, J; Eklund, A

    2015-10-01

    The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g. pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P volunteers. The systematic differences (mean ± 2 standard deviations) were -4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001). The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging. © 2015 by American Journal of Neuroradiology.

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

    Directory of Open Access Journals (Sweden)

    Tarning Joel

    2010-10-01

    Full Text Available Abstract 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.

  12. A pharmacokinetic drug interaction study between nebivolol and paroxetine in healthy volunteers.

    Science.gov (United States)

    Briciu, C; Neag, M; Muntean, D; Vlase, L; Bocsan, C; Buzoianu, A; Gheldiu, A-M; Achim, M; Popa, A

    2014-10-01

    Nebivolol is a highly selective beta-blocker with additional vasodilator properties, widely used in the clinical practice for the treatment of hypertension and heart failure. Paroxetine is a second-generation antidepressant and a potent inhibitor of CYP2D6, the same isoenzyme involved in the metabolism of nebivolol. The objective of this study was to investigate the effect of multiple-dose paroxetine intake on the pharmacokinetics of nebivolol in healthy volunteers and its potential consequences upon nebivolol pharmacodynamics. The study included 23 healthy subjects and was designed as an open-label, single-centre, non-randomized, two-period clinical trial. During period 1 (reference), each volunteer received a single dose of 5 mg nebivolol, whereas during period 2 (test), each volunteer received a single dose of 5 mg nebivolol and 20 mg paroxetine, after a pretreatment regimen with paroxetine (20-40 mg/day for 6 days). The pharmacokinetic parameters of nebivolol and its active metabolite were analysed by non-compartmental modelling. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest, after each nebivolol intake. Pretreatment with paroxetine increased the mean peak plasma concentrations (Cmax ) for unchanged nebivolol (1·78 ± 1·17 vs. 4·24 ± 1·67 ng/mL) and for its active metabolite (0·58 ± 0·21 vs. 0·79 ± 0·24 ng/mL) compared to nebivolol alone. The time (tmax ) to reach Cmax was 1·37 ± 0·88 (h) and 3·11 ± 1·76 (h) for the parent compound and its active metabolite after nebivolol administered alone and 3·96 ± 1·76 (h), respectively, 7·33 ± 7·84 (h) after pretreatment with paroxetine. Also, the total areas under the curve (AUC0-∞ ) were significantly increased from 17·26 ± 43·06 to 106·20 ± 65·56 h ng/mL for nebivolol unchanged and 13·03 ± 11·29 to 74·56 ± 88·77 h ng/mL for its hydroxylated metabolite, before and after paroxetine intake. All the

  13. Hemodynamic changes caused by acupuncture in healthy volunteers: a prospective, single-arm exploratory clinical study.

    Science.gov (United States)

    Kim, Tae-Hun; Ku, Boncho; Bae, Jang-Han; Shin, Jae-Young; Jun, Min-Ho; Kang, Jung Won; Kim, Junghwan; Lee, Jun-Hwan; Kim, Jaeuk U

    2017-05-22

    Radial pressure pulse wave (RPPW) examination has been a key diagnostic component of traditional Chinese medicine. The objective of this study was to investigate the changes in RPPW along with various hemodynamic variables after acupuncture stimulation and to examine the validity of pulse diagnosis as a modern diagnostic tool. We conducted acupuncture stimulation at both ST36 acupuncture points in 25 healthy volunteers. We simultaneously assessed the RPPW by pulse tonometry; heart rate variability (HRV) by electrocardiogram; photoplethysmogram (PPG) signals, respiration rate, peripheral blood flow velocity and arterial depth by ultrasonography; and cardiac output by impedance cardiography, before, during and after a session of acupuncture stimulation. We observed consistent patterns of increased spectral energy at low frequency (pulse power using RPPW examination and in the amplitude and systolic area of the PPG signal during the entire acupuncture session. The low- and high-frequency domains of HRV increased and decreased, respectively, during the acupuncture session. The peripheral blood velocity rose shortly after needle insertion, reached a maximum in the middle of the session and decreased afterwards. The augmentation index (AIX) and pulse transit time (PTT) obtained from RPPW did not change significantly. Acupuncture stimulation at ST36 in healthy subjects increased the peripheral pulse amplitudes (pressure pulse wave (PPW) and PPG), blood flow velocity (ultrasonography) and sympathetic nerve activity (HRV). The lack of changes in the AIX and PTT suggests that the increased pulse amplitudes and blood flow velocity may result from increased cardiac output. Clinical Research Information Service ( KCT0001663 ).

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

    Science.gov (United States)

    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 Prisperidone 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

  15. A bioequivalence study of two omeprazole formulations in healthy male volunteers.

    Science.gov (United States)

    Kim, Yu Kyong; Yoon, Seonghae; Yu, Kyung-Sang; Kim, Bo-Hyung; Yim, Sung-Vin

    2016-11-01

    This study had a single-dose, randomized, open-label, 2-period, and 2-sequence crossover design to evaluate pharmacokinetic (PK) bioequivalence between the test and reference formulations. Of the 34 healthy male volunteers enrolled, 4 were excluded owing to consent withdrawal before drug administration and the remaining 30 subjects were administered 20 mg each of the test and reference formulations of omeprazole. The blood samples for PK analysis were collected at the scheduled time-points, prior to dosing to 10 hours after dosing. Plasma concentrations of omeprazole were quantified by a liquid chromatography-tandem mass spectrometry method. Bioequivalence was assessed according to current guidelines issued by regulatory authorities. The plasma concentration-time profiles of omeprazole were similar between the reference and test drugs. The geometric mean ratios (90% confidence interval: CI) of test to reference were 0.9104 (0.8538 - 0.9708) for peak plasma concentration (Cmax) and 0.9304 (0.8836 - 0.9796) for area under the plasma concentration-time curve from time zero to time of last measureable concentration (AUC0-t). The results from the PK analysis suggested that the reference and test formulations of 20 mg omeprazole capsules were bioequivalent in healthy male subjects.

  16. Parallel role for the dopamine D1 receptor in gambling and amphetamine reinforcement in healthy volunteers.

    Science.gov (United States)

    Zack, Martin H; Lobo, Daniela S; Biback, Candice; Fang, Tim; Smart, Kelly; Tatone, Daniel; Kalia, Aditi; Digiacomo, Daniel; Kennedy, James L

    2017-01-01

    This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers ( n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II). HAL decreased and FLU increased the post-game desire to gamble and post-AMPH desire to take AMPH again, as well as amphetamine scale ratings on the Addiction Research Center Inventory after gambling and AMPH. The effects of the antagonists on desire to gamble and to take AMPH again were significantly intercorrelated. HAL increased and FLU decreased the salience of negative affective words on a rapid reading task after both reinforcers. HAL also decreased the salience of gambling words after AMPH. Both reinforcers increased diastolic blood pressure equally under antagonists and placebo. Results indicate that D1R plays a parallel role in the psychostimulant-like, incentive-motivational, and salience-enhancing effects of gambling and AMPH. Moderate D1R activation appears to optimize these effects in healthy subjects.

  17. The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers.

    Science.gov (United States)

    Murphy, F C; Smith, K A; Cowen, P J; Robbins, T W; Sahakian, B J

    2002-08-01

    Cognitive impairment is a common feature of depressive illness. While accumulating evidence suggests that brain serotonin (5-HT) pathways play an important role in the neurobiology of depression, the extent to which altered 5-HT function is responsible for the associated changes in cognition and emotion remains unclear. The present study examined the effects of acute dietary depletion of tryptophan (TRP) on cognitive and affective processing in healthy volunteers and explored the putative role of 5-HT in the neuropsychology of depression. We administered computerised cognitive tests to healthy control participants following ingestion of TRP-free and nutritionally balanced amino acid drinks in a double-blind, placebo-controlled, crossover design. The TRP-free amino acid mixture significantly lowered plasma total and free TRP concentrations relative to baseline values and produced selective deficits similar to those observed previously in cases of clinical depression. In particular, TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and slowed responding in a visual discrimination and reversal learning task. These deficits were not due to a global sedative effect, as planning ability was unimpaired. The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function, such as planning ability. These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry.

  18. The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population

    Directory of Open Access Journals (Sweden)

    Kim Hack-Lyoung

    2013-01-01

    Full Text Available Abstract Background The aim of this study is to investigate the association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population. Methods A total of 115 healthy subjects without known cardiovascular risk factors or overt heart disease who underwent both transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV measurement at the same day during their routine check-ups were analyzed. Results The mean age of study subjects was 52.8 ± 8.4 years, and 78 (67.8% were men. The mean baPWV value was 1,325 ± 185 cm/s. Study subjects were divided into 3 groups according to E/E’ value: subjects with E/E’ p β = 0.371, p after controlling confounders including age, sex and body mass index. In receiver-operating characteristic (ROC curve analysis, the sensitivity and specificity for detection of E/E’ ≥ 10 were 78.6% and 59.8%, respectively with mean baPWV of 1,282 cm/s as the cut off value. The discriminatory capacity for predicting E/E’ ≥ 10 was improved from an area under the ROC curve of 0.646 with age alone to 0.734 when baPWV was added (p Conclusions There is a significant association between baPWV and E/E’ in an apparently healthy Korean population. BaPWV is useful as a simple and non-invasive method for early detection of increased LV filling pressure among these people.

  19. Genetic influence on bone mineral density in Korean twins and families: the healthy twin study.

    Science.gov (United States)

    Park, J-H; Song, Y-M; Sung, J; Lee, K; Kim, Y S; Park, Y S

    2012-04-01

    Bone mineral density (BMD), a representative marker of osteoporosis risk, is found to be highly heritable in this Korean study, which is very consistent with the findings in Western populations. This finding strongly supports that genetic factors are significant determinants of osteoporosis risk along with individual biological and behavioral factors. Although genetic factors are known to contribute significantly to variations in BMD in Western populations, such an association has not been fully evaluated in an Asian population. This study was conducted to determine the role of genetic factors on BMD in Korean population. The study participants were 2,728 men and women consisting of 497 monozygotic (MZ) twin pairs, 119 dizygotic (DZ) twin pairs, and 1,496 first-degree relatives from the Healthy Twin Study. BMD was measured using dual-energy X-ray absorptiometry. Quantitative genetic analysis based on a variance decomposition model was performed. Age and the measured covariates accounted for 17~61% of the variation in BMD, depending on the sites of measurement. After accounting for the covariate effects, the heritability of BMD at the whole body, thoracic and lumbar spine, whole ribs, whole pelvis, whole arms, and whole legs were 0.76, 0.72, 0.73, 0.71, 0.51, and 0.75, respectively. The pair-wise correlation of BMD was the highest within MZ twin pairs, followed by DZ twin pairs, sibling pairs, and parents-child pairs. Cross-trait correlation analysis revealed a positive genetic correlation between BMDs at different sites, ranging from 0.80 (arm and leg BMD) to 0.50 (pelvis and arm BMD). The high heritability of BMD in this Korean population similar to those found in Western populations and the significant common genetic basis between BMDs at different sites strongly supports a significant role of genetic determinants on the risk of osteoporosis.

  20. Relationships between Dietary Intake and Cognitive Function in Healthy Korean Children and Adolescents.

    Science.gov (United States)

    Kim, Jin Young; Kang, Seung Wan

    2017-01-01

    It has long been theorized that a relatively robust dietary intake impacts cognitive function. The aim of the study was to explore dietary intake and cognitive function in healthy Korean children and adolescents. Three hundred and seventeen healthy children with no previous diagnosis of neurologic or psychiatric disorders were evaluated (167 girls and 150 boys with a mean age of 11.8 ± 3.3 years). Analysis indicators including food frequency questionnaires (FFQs) consisting of 76 items and neurocognitive tests including symbol digit modalities (SDMT), verbal memory, visual memory, shift attention, reasoning, and digit span (forward and backward) tests were observed and recorded. The standard deviation in reaction time was significantly shorter in girls than in boys (p consumption of noodles showed negative correlation with verbal memory, SDMT, shift attention, and reasoning test results (p consumption of fast food showed negative correlation with SDMT and reasoning test results (p consumption of Coca-Cola showed negative correlation with the results of verbal memory tests (p consumption of mushrooms showed positive correlation with visual memory and reasoning test results (p consumption of nuts showed positive correlation with SDMT results (p consumption of rice and ramyeon (p consumption of snacks (p consumption of rice (p consumption of rice with mixed grains (p function is generally better observed in girls than in boys. The consumption of healthy foods is correlated with good cognitive function. These results suggest that diet is closely related to cognitive function, even in healthy children and adolescents.

  1. Increase in intracranial pressure by application of a rigid cervical collar: a pilot study in healthy volunteers.

    Science.gov (United States)

    Maissan, Iscander M; Ketelaars, Rein; Vlottes, Boris; Hoeks, Sanne E; den Hartog, Dennis; Stolker, Robert J

    2017-07-19

    Rigid cervical collars are known to increase intracranial pressure (ICP) in severe traumatic brain injury (TBI). Cerebral blood flow might decrease according to the Kellie Monroe doctrine. For this reason, the use of the collar in patients with severe TBI has been abandoned from several trauma protocols in the Netherlands. There is no evidence on the effect of a rigid collar on ICP in patients with mild or moderate TBI or indeed patients with no TBI. As a first step we tested the effect in healthy volunteers with normal ICPs and intact autoregulation of the brain. In this prospective blinded cross-over study, we evaluated the effect of application of a rigid cervical collar in 45 healthy volunteers by measuring their optical nerve sheath diameter (ONSD) by transocular sonography. Sonographic measurement of the ONSD behind the eye is an indirect noninvasive method to estimate ICP and pressure changes. We included 22 male and 23 female volunteers. In total 360 ONSD measurements were performed in these 45 volunteers. Application of a collar resulted in a significant increase in ONSD in both the left (β=0.06, 95% confidence interval: 0.05-0.07, Pvolunteers with intact cerebral autoregulation. This suggests that ICP may increase after application of a collar. In healthy volunteers, this seems to be of minor importance. On the basis of our findings the effect of a collar on ONSD and ICP in patients with mild and moderate TBI needs to be determined.

  2. Centella asiatica Improves Physical Performance and Health-Related Quality of Life in Healthy Elderly Volunteer

    Directory of Open Access Journals (Sweden)

    Lugkana Mato

    2011-01-01

    Full Text Available Recently, oxidative stress has been reported to contribute an important role in the decline of physical function as age advances. Numerous antioxidants can improve both physical and psychological performances resulting in the increase of health-related quality of life (HQOL. Therefore, we hypothesized that Centella asiatica, a medicinal plant reputed for nerve tonic, strength improvement and antioxidant activity, could improve the physical performance and HQOL especially in the physical satisfaction aspect, of the healthy elderly volunteer. To test this hypothesis, a double-blind, placebo-controlled, randomized trial was performed. Eighty healthy elderly were randomly assigned to receive placebo or standardized extract of C. asiatica at doses of 250, 500 and 750 mg once daily for 90 days. The subjects were evaluated to establish baseline data of physical performance using 30-s chair stand test, hand grip test and 6-min walk test. The health-related quality of life was assessed using SF-36. These assessments were repeated every month throughout the 3-month experimental period using the aforementioned parameters. Moreover, 1 month after the cessation of C. asiatica treatment, all subjects were also evaluated using these parameters again. The results showed that after 2 months of treatment, C. asiatica at doses of 500 and 750 mg per day increased lower extremity strength assessed via the 30-s chair stand test. In addition, the higher doses of C. asiatica could improve the life satisfaction subscale within the physical function subscale. Therefore, the results from this study appear to support the traditional reputation of C. asiatica on strength improvement, especially in the lower extremities of the elderly. C. asiatica also possesses the potential to be a natural resource for vigor and strength increase, in healthy elderly persons. However, further research is essential.

  3. Centella asiatica Improves Physical Performance and Health-Related Quality of Life in Healthy Elderly Volunteer

    Science.gov (United States)

    Mato, Lugkana; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Tongun, Terdthai; Piyawatkul, Nawanant; Yimtae, Kwanchanok; Thanawirattananit, Panida; Sripanidkulchai, Bungorn

    2011-01-01

    Recently, oxidative stress has been reported to contribute an important role in the decline of physical function as age advances. Numerous antioxidants can improve both physical and psychological performances resulting in the increase of health-related quality of life (HQOL). Therefore, we hypothesized that Centella asiatica, a medicinal plant reputed for nerve tonic, strength improvement and antioxidant activity, could improve the physical performance and HQOL especially in the physical satisfaction aspect, of the healthy elderly volunteer. To test this hypothesis, a double-blind, placebo-controlled, randomized trial was performed. Eighty healthy elderly were randomly assigned to receive placebo or standardized extract of C. asiatica at doses of 250, 500 and 750 mg once daily for 90 days. The subjects were evaluated to establish baseline data of physical performance using 30-s chair stand test, hand grip test and 6-min walk test. The health-related quality of life was assessed using SF-36. These assessments were repeated every month throughout the 3-month experimental period using the aforementioned parameters. Moreover, 1 month after the cessation of C. asiatica treatment, all subjects were also evaluated using these parameters again. The results showed that after 2 months of treatment, C. asiatica at doses of 500 and 750 mg per day increased lower extremity strength assessed via the 30-s chair stand test. In addition, the higher doses of C. asiatica could improve the life satisfaction subscale within the physical function subscale. Therefore, the results from this study appear to support the traditional reputation of C. asiatica on strength improvement, especially in the lower extremities of the elderly. C. asiatica also possesses the potential to be a natural resource for vigor and strength increase, in healthy elderly persons. However, further research is essential. PMID:19880441

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Structural and biomechanical corneal differences between patients suffering from primary congenital glaucoma and healthy volunteers.

    Science.gov (United States)

    Perucho-González, Lucía; Sáenz-Francés, Federico; Morales-Fernández, Laura; Martínez-de-la-Casa, José María; Méndez-Hernández, Carmen D; Santos-Bueso, Enrique; Brookes, John L; García-Feijoó, Julián

    2017-03-01

    To determine whether a set of ocular morphometric and biomechanical variables are able to discriminate between healthy volunteers and patients suffering from primary congenital glaucoma (PCG). Case-control study in which 66 patients with PCG and 94 age-matched healthy subjects were evaluated using ocular response analyser (ORA) to record corneal biomechanical properties. Topographic corneal variables were obtained using the Pentacam in both groups. To determine the ability to discern between both groups, a multivariate binary logistic model was constructed. The outcome was the diagnosis of PCG and the predictors; the corneal variables analysed along with their first-term interactions. Sensitivity and specificity of this model along with the area under the receiver characteristic operating curve (AUC of ROC) were determined. The best model to discriminate between both groups included the following predictors: corneal hysteresis (CH), corneal resistance factor (CRF), posterior maximum elevation (PME), anterior maximum elevation (AME) and central corneal thickness (CCT). This model, for a cut-point of 50%, presents a sensitivity of 86.67%, a specificity of 86.89% and an AUC of the ROC curve of 93.16% [95% confidence interval (CI): 88.97-97.35]. The adjusted odds ratios of those predictors which showed a significant discriminating capacity were as follows: for CH, 0.27 (95% confidence interval: 0.15-0.46); for CRF, 2.13 (95% CI: 1.33-3.40); for PME, 1.06 (95% CI: 1.01-1.12); and for AME, 1.35 (95% CI: 1.10-1.66). Corneal hysteresis (CH), CRF, PME and AME are able to discern between patients with PCG and healthy controls. This fact suggests that there are structural and biomechanical differences between these groups. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Physiological {sup 18}F-FDG uptake in the ovaries and uterus of healthy female volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Nishizawa, Sadahiko; Inubushi, Masayuki; Okada, Hiroyuki [Hamamatsu Medical Photonics Foundation, Hamamatsu Medical Imaging Center, Hamakita, Shizuoka (Japan)

    2005-04-01

    Good knowledge of physiological {sup 18}F-fluorodeoxglucose ({sup 18}F-FDG) uptake in the healthy population is of great importance for the correct interpretation of {sup 18}F-FDG positron emission tomography (PET) images of pathological processes. The purpose of this study was to investigate the physiological {sup 18}F-FDG uptake in the ovaries and uterus of healthy female volunteers. One hundred and 33 healthy females, 78 of whom were premenopausal (age 37.2{+-}6.9 years) and 55 postmenopausal (age 55.0{+-}2.7 years), were examined using whole-body {sup 18}F-FDG PET and pelvic magnetic resonance (MR) imaging. Focal {sup 18}F-FDG uptake in the ovaries and uterus was evaluated visually and using standardised uptake value (SUVs). Anatomical and morphological information was obtained from MR images. Distinct ovarian {sup 18}F-FDG uptake with an SUV of 3.9{+-}0.7 was observed in 26 premenopausal women out of 32 examined during the late follicular to early luteal phase of the menstrual cycle. Eighteen of the 32 women also showed focal {sup 18}F-FDG uptake in the endometrium, with an SUV of 3.3{+-}0.3. On the other hand, all nine women in the first 3 days of the menstrual cycle demonstrated intense {sup 18}F-FDG uptake in the endometrium, with an SUV of 4.6{+-}1.0. No physiological {sup 18}F-FDG uptake was observed in the ovaries or uterus of any postmenopausal women. In women of reproductive age, {sup 18}F-FDG imaging should preferably be done within a week before or a few days after the menstrual flow phase to avoid any misinterpretation of pelvic {sup 18}F-FDG PET images. (orig.)

  7. The effect of ticagrelor on the metabolism of midazolam in healthy volunteers.

    Science.gov (United States)

    Teng, Renli; Butler, Kathleen

    2013-07-01

    In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur. The goal of this article was to report study results on the effect of ticagrelor on the pharmacokinetics of oral midazolam (oral midazolam study) and oral versus intravenous (IV) midazolam (oral/IV midazolam study). Secondary objectives included assessing the effect of midazolam on ticagrelor pharmacokinetic parameters, and the safety and tolerability of ticagrelor/midazolam coadministration. Two randomized crossover studies were conducted in healthy volunteers (n = 28 in each) with ticagrelor and midazolam. In the first study, volunteers received oral ticagrelor (400 mg daily) or placebo for 6 days, then oral midazolam (7.5 mg). The second study regimen was a single dose of ticagrelor 270 mg, then ticagrelor 180 mg BID for 6 days with a single oral (7.5 mg) or IV (2.5 mg) dose of midazolam. After oral midazolam administration, ticagrelor significantly reduced the AUC(0-∞) of midazolam (30%-32%) and 4-hydroxymidazolam (42%-47%) but not 1-hydroxymidazolam. After administration of IV midazolam, ticagrelor reduced the AUC(0-∞) of midazolam (12%) and 4-hydroxymidazolam (23%) but not 1-hydroxymidazolam. These results indicate that ticagrelor can weakly activate the metabolism of midazolam to its major 1'-hydroxy metabolite, and at the same time, seems to weakly inhibit midazolam 4'-hydroxylation. Furthermore, ticagrelor affects both hepatic and intestinal CYP3A activity. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  8. The effect of desmopressin on bleeding time and platelet aggregation in healthy volunteers administered ticagrelor.

    Science.gov (United States)

    Teng, R; Mitchell, P D; Butler, K

    2014-04-01

    Ticagrelor is a reversibly binding and selective P2Y12 -receptor antagonist approved for the prevention of atherothrombotic events in patients with acute coronary syndromes. As bleeding events remain a hazard with antiplatelet therapy, this study investigated the effect of the vasopressin agonist, desmopressin, on ticagrelor-induced bleeding time prolongation. Desmopressin has previously been shown to improve primary haemostasis and is widely used as first-line therapy for individuals with bleeding disorders. In a randomized, double-blind, 2-period crossover study, healthy volunteers received ticagrelor (270 mg loading dose; 180 mg bid) for 5 days. On Day 5, desmopressin (0·3 μg/kg) or saline intravenous infusions were administered. The impact of desmopressin on bleeding time, inhibition of platelet aggregation (IPA), platelet function and ticagrelor pharmacokinetic parameters was investigated. Twenty-one volunteers (81% male) were enrolled. Median [range] bleeding times were slightly reduced with ticagrelor plus desmopressin compared with ticagrelor alone (7·50 [3-17] vs. 10·50 [3-25] min at 2·5 h). Median reductions in bleeding time from baseline were generally similar between ticagrelor plus desmopressin compared with ticagrelor alone at all time points. Co-administration of desmopressin had no impact on IPA, although platelet reactivity was significantly increased (von Willebrand Factor antigen: GLS mean AUEC was 4667%.h for ticagrelor plus desmopressin compared with 2750%.h for ticagrelor alone). Desmopressin did not influence the pharmacokinetics of ticagrelor. Desmopressin had no significant effect on bleeding time or inhibition of platelet aggregation by ticagrelor, although primary haemostatic activity was significantly increased. Ticagrelor pharmacokinetic parameters were not affected by co-administration with desmopressin. Therefore, desmopressin is unlikely to be an effective therapeutic agent for control of the potential bleeding events

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

    Science.gov (United States)

    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. © The Author(s) 2014.

  10. In vivo evaluation of limonene-based transdermal therapeutic system of nicorandil in healthy human volunteers.

    Science.gov (United States)

    Krishnaiah, Y S R; Chandrasekhar, D V; Rama, B; Jayaram, B; Satyanarayana, V; Al-Saidan, S M

    2005-01-01

    Hydroxypropyl methylcellulose (HPMC) gel drug reservoir system prepared with 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene was effective in promoting the in vitro transdermal delivery of nicorandil. The objective of the present study was to fabricate and evaluate a limonene-based transdermal therapeutic system (TTS) for its ability to provide the desired steady-state plasma concentration of nicorandil in human volunteers. The in vitro permeation of nicorandil from a limonene-based HPMC gel drug reservoir was studied across excised rat skin (control), EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite to account for their effect on the desired flux of nicorandil. The flux of nicorandil from the limonene-based HMPC drug reservoir across EVA2825 membrane decreased to 215.8 +/- 9.7 microg/cm(2).h when compared to that obtained from control, indicating that EVA2825 was effective as a rate-controlling membrane. The further decrease in nicorandil flux across adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite showed that the adhesive coat and skin also controlled the in vitro transdermal delivery. The limonene-based drug reservoir was sandwiched between adhesive-coated EVA2825-release liner composite and a backing membrane. The resultant sandwich was heat-sealed as circle-shaped patch (20 cm(2)), trimmed and subjected to in vivo evaluation in human volunteers against immediate-release tablets of nicorandil (reference formulation). The fabricated limonene-based TTS of nicorandil provided a steady-state plasma concentration of 21.3 ng/ml up to 24 h in healthy human volunteers. It was concluded that the limonene-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations and improved bioavailability. Copyright 2005 S. Karger AG, Basel

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

    Directory of Open Access Journals (Sweden)

    Zhang YF

    2016-01-01

    Full Text Available Yi-fan Zhang,1 Xiao-jian Dai,1 Yong Yang,1 Xiao-yan Chen,1 Ting Wang,2 Yun-biao Tang,3 Cheng-yuan Tsai,4 Li-wen Chang,4 Yu-ting Chang,4 Da-fang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The First Hospital Affiliated to Lanzhou University, Lanzhou, 3Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China; 4TaiGen Biotechnology Co., Ltd., Taipei, Taiwan 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

  12. The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults.

    Science.gov (United States)

    Ju, Deok Yun; Choe, Young Gil; Cho, Yong Kyun; Shin, Dong Suk; Yoo, Su Hyeon; Yim, Seo Hyoung; Lee, Ji Yong; Park, Jung Ho; Kim, Hong Joo; Park, Dong Il; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

    2013-06-01

    Waist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults. The volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC. NAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (PKorean adults, and thus may be an important factor in the development of IR and NAFLD.

  13. Associations between socio-demographic characteristics and healthy lifestyles in Korean Adults: the result of the 2010 Community Health Survey.

    Science.gov (United States)

    Ryu, So Yeon; Park, Jong; Choi, Seong Woo; Han, Mi Ah

    2014-03-01

    Several previous studies have found that healthy behaviors substantially reduce non-communicable disease incidence and mortality. The present study was performed to estimate the prevalence of four modifiable healthy behaviors and a healthy lifestyle among Korean adults according to socio-demographic and regional factors. We analyzed data from 199 400 Korean adults aged 19 years and older who participated in the 2010 Korean Community Health Survey. We defined a healthy lifestyle as a combination of four modifiable healthy behaviors: non-smoking, moderate alcohol consumption, regular walking, and a healthy weight. We calculated the prevalence rates and odds ratios of each healthy behavior and healthy lifestyle according to socio-demographic and regional characteristics. The prevalence rates were as follows: non-smoking, 75.0% (53.7% in men, 96.6% in women); moderate alcohol consumption, 88.2% (79.7% in men, 96.9% in women); regular walking, 45.0% (46.2% in men, 43.8% in women); healthy weight, 77.4% (71.3% in men, 73.6% in women); and a healthy lifestyle, 25.5% (16.4% in men, 34.6% in women). The characteristics associated with a low prevalence of healthy lifestyle were male gender, younger age (19 to 44 years of age), low educational attainment, married, living in a rural area, living in the Chungcheong, Youngnam, or Gwangwon-Jeju region, and poorer self-rated health. Further research should be implemented to explore the explainable factors of disparities for socio-demographic and regional characteristics to engage in the healthy lifestyle among adults.

  14. Associations Between Socio-demographic Characteristics and Healthy Lifestyles in Korean Adults: The Result of the 2010 Community Health Survey

    Directory of Open Access Journals (Sweden)

    So Yeon Ryu

    2014-03-01

    Full Text Available ObjectivesSeveral previous studies have found that healthy behaviors substantially reduce non-communicable disease incidence and mortality. The present study was performed to estimate the prevalence of four modifiable healthy behaviors and a healthy lifestyle among Korean adults according to socio-demographic and regional factors.MethodsWe analyzed data from 199 400 Korean adults aged 19 years and older who participated in the 2010 Korean Community Health Survey. We defined a healthy lifestyle as a combination of four modifiable healthy behaviors: non-smoking, moderate alcohol consumption, regular walking, and a healthy weight. We calculated the prevalence rates and odds ratios of each healthy behavior and healthy lifestyle according to socio-demographic and regional characteristics.ResultsThe prevalence rates were as follows: non-smoking, 75.0% (53.7% in men, 96.6% in women; moderate alcohol consumption, 88.2% (79.7% in men, 96.9% in women; regular walking, 45.0% (46.2% in men, 43.8% in women; healthy weight, 77.4% (71.3% in men, 73.6% in women; and a healthy lifestyle, 25.5% (16.4% in men, 34.6% in women. The characteristics associated with a low prevalence of healthy lifestyle were male gender, younger age (19 to 44 years of age, low educational attainment, married, living in a rural area, living in the Chungcheong, Youngnam, or Gwangwon-Jeju region, and poorer self-rated health.ConclusionsFurther research should be implemented to explore the explainable factors of disparities for socio-demographic and regional characteristics to engage in the healthy lifestyle among adults.

  15. Comparison of upper limb volume measurement techniques and arm symptoms between healthy volunteers and individuals with known lymphedema.

    Science.gov (United States)

    Ridner, S H; Montgomery, L D; Hepworth, J T; Stewart, B R; Armer, J M

    2007-03-01

    Lymphedema is a problem for breast cancer survivors. The proliferation of limb measurement techniques makes it difficult to know how best to measure an at-risk limb. Using a sample of healthy volunteers and individuals with lymphedema, this study: 1) examined the relationship between more commonly used circumferential limb measurement methods and newer measurement methods of infrared laser perometry and bioelectrical impedance; 2) compared self-reported arm symptoms in healthy volunteers and breast cancer survivors with known lymphedema; and 3) explored the relationships among self-reported arm symptoms and circumferential tape measurement, infrared laser (perometry), and single and multi-frequency bioelectrical impedance. Lymphedema index ratios were calculated to allow comparison among measurement methods. Measurement methods correlated strongly with each other. Fourteen symptoms were reported by one or more participants in the lymphedema group while participants in the healthy volunteer group reported only eight symptoms over the same time frames. Using p < 0.001, all measurement methods correlated with self-reported arm swelling in the past year, while only circumferential and impedance measurements correlated with firmness. Future research needs to include serial arm measurements to explore arm volume variation in healthy and lymphedema volunteers and to further investigate possible lymphedema index ratios cut points as lymphedema diagnostic criteria.

  16. Levodropropizine does not affect P0.1 and breathing pattern in healthy volunteers and patients with chronic respiratory impairment.

    Science.gov (United States)

    Bruschi, C; Crotti, P; Dacosto, E; Fanfulla, F; Daffonchio, L; Novellini, R

    2003-01-01

    To evaluate whether the peripherally acting antitussive levodropropizine could affect the respiratory drive and the breathing pattern, we performed a double-blind, randomised, cross-over trial in 12 healthy volunteers and 12 patients with chronic respiratory impairment associated with chronic obstructive pulmonary disease. Levodropropizine 6% drops (at the recommended dose for adults) or placebo were administered orally t.i.d. for 10 consecutive administrations. Mouth occlusion pressure (P0.1), minute ventilation (V(e)), tidal volume (V(t)), respiratory rate (RR), mean inspiratory flow (V(t)/T(i)), end-tidal CO(2) (EtCO(2)), oxygen saturation (SaO(2)), forced expiratory volume in 1 s (FEV(1)), and the response to a hypercapnic stimulus were measured before and 1 h after the first and the last drug administration. Levodropropizine did not modify P0.1 in basal conditions and after a hypercapnic stimulus, either in healthy volunteers or in patients. In parallel, levodropropizine did not significantly affect V(t), RR, V(e), V(t)/T(i) and EtCO(2) in both the populations. Minor changes were induced by levodropropizine on SaO(2) in healthy volunteers, which despite a statistical difference, were too low to gain a clinical significance. These results confirmed the respiratory safety of levodropropizine 6% drops administered at the recommended dosage either in healthy volunteers or patients with chronic respiratory impairment.

  17. The effects of paroxetine and maprotiline on mood, perceptual motor skills, and eye movements in healthy volunteers

    NARCIS (Netherlands)

    Deijen, J.B.; Loriaux, S.M.; Orlebeke, J.F.; de Vries, J.

    1989-01-01

    Sixteen healthy young volunteers (seven females, nine males) received repeated doses of either 30 mg paroxetine, 100 mg maprotiline or placebo in a double-blind crossover study. Each of the three treatments lasted 1 week separated by 2 weeks of no treatment. Treatment order was counterbalanced.

  18. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers

    DEFF Research Database (Denmark)

    Kruuse, C; Iversen, Helle Klingenberg; Jansen-Olesen, I

    2010-01-01

    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...

  19. Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers.

    Science.gov (United States)

    Bedada, Satish Kumar; Boga, Praveen Kumar

    2017-12-01

    1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers. 2. An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20 mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC. 3. Treatment with PIP significantly enhanced maximum plasma concentration (Cmax) (3.14-4.96 μg/mL), area under the curve (AUC) (10.46-17.78 μg h/mL), half life (T1/2) (1.26-1.82 h) and significantly decreased elimination rate constant (Kel) (0.57-0.41 h (-) (1)), apparent oral clearance (CL/F) (24.76-13.65 L/h) of CHZ when compared to control. In addition, treatment with PIP significantly decreased Cmax (0.22-0.15 μg/mL), AUC (0.94-0.68 μg h/mL), T1/2 (2.54-1.68 h) and significantly increased Kel (0.32-0.43 h (-) (1)) of 6-hydroxychlorzoxazone (6-OHCHZ) as compared to control. Furthermore, treatment with PIP significantly decreased metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC, T1/2 and significantly increased Kel ratio of 6-OHCHZ/CHZ, which indicate the decreased formation of CHZ to 6-OHCHZ. 4. The results suggest that altered pharmacokinetics of CHZ might be attributed to PIP mediated inhibition of CYP2E1 enzyme, which indicate significant pharmacokinetic interaction present between PIP and CHZ. The inhibition of CYP2E1 by PIP may represent a novel therapeutic benefit for minimizing ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol.

  20. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

    Science.gov (United States)

    Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

    2016-02-01

    Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

  1. Bioequivalence Study of a New Fixed-dose Combination Tablet Containing S-Amlodipine Nicotinate and Olmesartan Medoxomil in Healthy Korean Male Subjects.

    Science.gov (United States)

    Oh, Mi Jin; Hwang, Hyun Hwan; Kim, Hyun Gyu; Lee, Geun Hyeog; Cho, Yun-Seok; Lee, Sun Young; Kang, Soo Yeon; Cho, Kyung Hee; Lee, Yun Young; Lee, Yun Jeong; Jang, Choon-Gon; Lee, Seok-Yong

    2017-07-01

    A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the Cmax and the area under the curve from time 0 to the last measurable concentration (AUC0-last) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using Cmax and AUC0-last converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of Cmax and AUC0-last were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1

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

    Science.gov (United States)

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

    2015-07-09

    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). 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. 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). 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.

  3. fMRI and MEG analysis of visceral pain in healthy volunteers.

    Science.gov (United States)

    Smith, J K; Humes, D J; Head, K E; Bush, D; White, T P; Stevenson, C M; Brookes, M J; Marciani, L; Spiller, R C; Gowland, P A; Francis, S T

    2011-07-01

    Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis. Liminal and painful rectal barostat balloon inflation thresholds were assessed in 14 female healthy volunteers. Subliminal, liminal and painful 40s periods of distension were applied in a pseudo-randomized paradigm during fMRI and MEG neuroimaging. Functional MRI data analysis was performed comparing standard box-car models of the full 40s of stimulus (Block) with models of the inflation (Ramp-On) and deflation (Ramp-Off) of the barostat. Similar models were used in MEG analysis of oscillatory activity. Modeling the data using a standard Block analysis failed to detect areas of interest found to be active using Ramp-On and Ramp-Off models. Ramp-On generated activity in anterior insula and cingulate regions and other pain-matrix associated areas. Ramp-Off demonstrated activity of a network of posterior insula, SII and posterior cingulate. Active areas were consistent with those identified from MEG data. In studies of visceral pain, fMRI model design strongly influences the detected activity and must be accounted for to effectively explore the fMRI data in healthy subjects and within patient groups. In particular a strong cortical response is detected to inflation and deflation of the barostat, rather than to its absolute volume. © 2011 Blackwell Publishing Ltd.

  4. Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers.

    Science.gov (United States)

    Antoniewicz, Lukasz; Bosson, Jenny A; Kuhl, Jeanette; Abdel-Halim, Samy M; Kiessling, Anna; Mobarrez, Fariborz; Lundbäck, Magnus

    2016-12-01

    The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes. Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h. EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. The relation of diet with PAF and its metabolic enzymes in healthy volunteers.

    Science.gov (United States)

    Detopoulou, P; Fragopoulou, E; Nomikos, T; Yannakoulia, M; Stamatakis, G; Panagiotakos, D B; Antonopoulou, S

    2015-02-01

    Platelet-activating factor (PAF), a potent inflammatory mediator, is implicated in atherosclerosis. Its key biosynthetic enzymes are lyso-PAF acetyltransferases (lyso-PAF-AT), responsible for PAF synthesis through the remodeling route and a specific CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), responsible for its de novo biosynthesis. PAF acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase A₂ catabolize PAF. The impact of diet on PAF metabolism is ill-defined. The aim was to investigate associations between PAF, its enzymes and dietary factors. One-hundred and six (n = 106) healthy volunteers were recruited. Food-frequency questionnaires, dietary recalls, lifestyle and biochemical variables were collected. Food groups, macronutrient intake, a priori (MedDietScore) and a posteriori defined food patterns with PCA analysis, dietary antioxidant capacity (DAC), glycemic index (GI) and glycemic load were assessed. PAF was inversely correlated with antioxidant-rich foods (herbal drinks and coffee), the DAC as well as a dietary pattern characterized by legumes, vegetables, poultry and fish (all Ps PAF was positively correlated to % fat intake. Lyso-PAF-AT was also negatively associated with healthy patterns (fruits, nuts and herbal drinks, and a pattern rich in olive oil and whole-wheat products), as well as the DAC and % monounsaturated fatty acids. PAF-CPT was negatively associated with GI and coffee intake and positively with dietary cholesterol. PAF-AH was negatively associated with coffee and positively associated with alcohol consumption (all Ps PAF or its biosynthetic enzymes, suggesting potential new mechanisms of the diet-disease associations.

  6. The hemodynamic and respiratory effects of cuirass ventilation in healthy volunteers: Part 1.

    Science.gov (United States)

    McBride, William T; Ranaldi, Giulia; Dougherty, Mark J; Siciliano, Tommaso; Trethowan, Brian; Elliott, Peter; Rice, Claire; Scolletta, Sabino; Giomarelli, Pierpaolo; Romano, Salvatore Mario; Linton, David M

    2012-10-01

    Negative-pressure ventilation (NPV) by external cuirass (RTX; Deminax Medical Instruments Limited, London, UK) in intubated patients after cardiac surgery improves hemodynamics measured by pulmonary artery catheter (PAC)-based methods, with an increased cardiac output (CO) and stroke volume (SV), without changing the heart rate (HR). The less-invasive pressure recording analytical method (PRAM) (Mostcare; Vytech Health srl, Padova, Italy) allows radial artery-based monitoring of the CO, SV, SV variation, and cardiac cycle efficiency (CCE). The authors investigated the hypothesis that NPV improves PRAM-based hemodynamics and arterial blood gas analysis in spontaneously breathing subjects. A clinical investigation. A teaching hospital. Ten healthy volunteers. Subjects underwent 5 consecutive experimental ventilation modalities lasting 5 minutes: (1) baseline (no cuirass ventilation), (2) mode 1: cuirass ventilation with a continuous negative pressure of -20 cmH(2)O, (3) first rest period (no cuirass ventilation), (4) mode 2: cuirass ventilation in control mode of 12 breaths/min at -20 cmH(2)O, and (5) second rest period. PRAM parameters were analyzed throughout the final minute of each experimental modality, which concluded with arterial blood gas sampling. Both NPV modes significantly reduced HR without changing CO or systemic vascular resistance. Mode 1 significantly increased CCE and decreased SVV. PO(2) decreased in both rest modes compared with baseline. This was prevented by NPV. In 5 smokers, PO(2) significantly increased in the control mode compared with first rest period. The control mode NPV improved oxygenation with a reduced PCO(2) and reciprocally increased pH. Five minutes of NPV improves hemodynamics and oxygenation in healthy subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study.

    Science.gov (United States)

    Nawata, Shuichi; Kohyama, Noriko; Uchida, Naoki; Numazawa, Satoshi; Ohbayashi, Masayuki; Kobayashi, Yasuna; Iwata, Masanori; Nakajima, Takanori; Saito, Hiroshi; Izuka, Akira; Yamamoto, Toshinori

    2016-01-01

    We formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers. Mianserin suppositories were prepared by a melting technique using Tetramide® tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma mianserin levels were determined using gas chromatography-mass spectrometry. In dogs, the maximum plasma mianserin concentration (Cmax) was 1.3 ± 0.4 ng/mL, the time to Cmax (tmax) was 5.5 ± 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 ± 1.9 h・ng/mL. In humans, the Cmax was 14.6 ± 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 ± 103 h・ng/mL. The current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma mianserin concentration for effective and safe clinical use. UMIN000013853.

  8. Differences in glenohumeral joint morphology between patients with anterior shoulder instability and healthy, uninjured volunteers.

    Science.gov (United States)

    Peltz, Cathryn D; Zauel, Roger; Ramo, Nicole; Mehran, Nima; Moutzouros, Vasilios; Bey, Michael J

    2015-07-01

    Traumatic glenohumeral joint (GHJ) dislocations are common, resulting in significant shoulder disability and pain. Previous research indicates that bony morphology is associated with an increased risk of injury in other joints (eg, the knee), but the extent to which bony morphology is associated with traumatic GHJ dislocation is unknown. This study assessed GHJ morphology in patients with anterior GHJ instability and in a control population of healthy volunteers. Bilateral computed tomography scans were used to measure GHJ morphology in both shoulders of 11 patients with instability and 11 control subjects. Specific outcome measures included the glenoid radius of curvature (ROC) in the anterior/posterior (A/P) and superior/inferior (S/I) directions, humeral head ROC, A/P and S/I conformity index, and A/P and S/I stability angle. Compared with the control subjects, the glenoid of the instability the injured shoulder in patients with instability was flatter (ie, higher ROC) in the A/P (P = .001) and S/I (P = .01) directions and this finding was also true for uninjured, contralateral shoulder (A/P: P = .01, S/I: P = .03). No differences in GHJ morphology were detected between the instability patients' injured and contralateral shoulders (P > .07). Similarly, no differences in GHJ morphology were detected between the control subjects' dominant and nondominant shoulders (P > .51). There are significant differences in GHJ morphology between healthy control subjects and both shoulders (injured and uninjured, contralateral) of patients diagnosed with anterior instability after GHJ dislocation. These findings are important clinically because they suggest that glenoid morphology may influence the risk of GHJ dislocation. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  9. Various Oscillation Patterns of Serum Fibroblast Growth Factor 21 Concentrations in Healthy Volunteers

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    Sang Ah Lee

    2012-02-01

    Full Text Available BackgroundFibroblast growth factor 21 (FGF21 was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers.MethodsBlood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m2 and five obese (BMI ≥25 kg/m2 healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured.ResultsThe serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours. The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P<0.001. There was no difference in the total frequency or duration of oscillations between non-obese and obese subjects, but obese individuals had increased numbers of larger oscillations (amplitude ≥0.19 ng/mL.ConclusionVarious oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.

  10. Esomeprazole inhibits the pentagastrin-stimulated secretion of gastric acid in healthy Japanese volunteers.

    Science.gov (United States)

    Maejima, Ryuhei; Koike, Tomoyuki; Nakagawa, Kenichiro; Iijima, Katsunori; Shimosegawa, Tooru

    2015-03-01

    Gastroesophageal reflux disease (GERD) is a common disease, in which the reflux of gastric acid causes mucosal damage of the esophagus and/or troublesome symptoms. Esomeprazole, a proton pump inhibitor, has been used for treatment of GERD in Japan since 2011; namely, only little is known about its effect on gastric acid secretion in Japanese. We, therefore, assessed the relationship between dose and timing of esomeprazole administration and gastric acid inhibition in 11 healthy male Japanese volunteers by directly examining gastric acid secretion capacity. In this randomized, open-label, three-way crossover study, the subjects were dosed with esomeprazole 10 mg or 20 mg once a day (q.d.), or 20 mg twice a day (b.i.d.) for 14 days, and pentagastrin-stimulated gastric acid secretion was measured by endoscopic gastrin test. At steady states, gastric acid inhibition rates were significantly higher in esomeprazole 20 mg b.i.d. (median 100.0%, interquartile range [IQR] 99.4-100%, P = 0.027) or 20 mg q.d. (100.0%, IQR 99.7-100%, P = 0.016), compared with 10 mg q.d. (98.4%, IQR 84.4-100%). At trough states, esomeprazole 20 mg b.i.d. showed significantly higher gastric acid inhibition (99.6%, IQR 99.0-100%) than did 20 mg q.d. (84.2%, IQR 76.4-88.8%, P = 0.002) or 10 mg q.d. (64.9%, IQR 59.1-76.7%, P = 0.001). Thus, esomeprazole 20 mg b.i.d. was sufficient to inhibit > 99% gastric acid secretion in healthy subjects. We propose that esomeprazole 20 mg b.i.d. is effective for treating Japanese patients with refractory GERD who require long-lasting gastric acid inhibition.

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

    Science.gov (United States)

    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. © 2016, The American College of Clinical Pharmacology.

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

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    Metta S.S. Wiria

    2007-09-01

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

  13. Pharmacokinetics and bioequivalence testing of generic fluconazole preparations in healthy thai volunteers.

    Science.gov (United States)

    Manorot, M; Rojanasthien, N; Kumsorn, B; Teekachunhatean, S

    2000-07-01

    To determine the bioequivalence of two oral formulations of generic fluconazole in twelve healthy Thai volunteers. The test preparation was Flucozole (Siam Bheasach, Thailand) and the reference was Diflucan (Pfizer Inc.). The two products were administered as 200 mg single oral doses in a two-period crossover design with a two-week washout period. After drug administration, serial blood samples were collected over a period of 72 hours. Serum fluconazole concentrations were determined by HPLC, and the pharmacokinetic parameters were analyzed by non-compartmental analysis. The time to reach the maximal concentration (Tmax, hour) of Flucozole (1.18 +/- 0.56) was statistically faster than that of Diflulan (1.59 +/- 0.54). The 90% confidence intervals of the AUC(0 - infinity) ratio and the Cmax, ratio muT/muR for Flucozole/Diflucan were 0.97 - 1.20 and 1.01 - 1.26, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25 and 0.7 - 1.43 for the ratio of the average AUC(0 - infinity) and Cmax, respectively. Thus, our study demonstrated the bioequivalence of Flucozole and Diflucan with respect to the rate (Cmax) and extent of absorption (AUC(0 - infinity).

  14. Assessment of a Potential Pharmacokinetic Interaction between Nebivolol and Bupropion in Healthy Volunteers.

    Science.gov (United States)

    Gheldiu, Ana-Maria; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Tomuta, Ioan; Briciu, Corina

    2016-01-01

    The study aimed at investigating the effects of multiple-dose bupropion (potent inhibitor of CYP2D6) on the pharmacokinetics (PKs) of single-dose nebivolol (CYP2D6 substrate) and to evaluate the clinical relevance of this potential drug interaction. This open-label, nonrandomized clinical study had a 2-period design: during period 1 (reference), a single dose of 5 mg nebivolol was administered, while during period 2 (test), 5 mg nebivolol + 300 mg bupropion were ingested concomitantly, after a pretreatment regimen with bupropion (7 days). The PK parameters of nebivolol and its active metabolite were analyzed by noncompartmental modeling, while the pharmacodynamic (PD) parameters (blood pressure and heart rate) were assessed at rest. Bupropion plus nebivolol increased the mean peak plasma concentrations (Cmax) of nebivolol (1.67 ± 0.69 vs. 3.80 ± 1.70 ng/ml) and its active metabolite (0.68 ± 0.22 vs. 1.13 ± 0.38 ng/ml) compared to nebivolol alone. After bupropion pretreatment, the exposure to nebivolol was increased by 7.2-fold for the parent drug and 4-fold for the hydroxylated active metabolite. The difference between the PD parameters measured during the 2 periods was not significant. The study concluded that bupropion influenced the PKs of nebivolol in healthy volunteers, but a clinical relevance was not established. However, this latter aspect requires further investigation. © 2016 S. Karger AG, Basel.

  15. Characterizing functional connectivity during rest in multiple sclerosis patients versus healthy volunteers using independent component analysis

    Energy Technology Data Exchange (ETDEWEB)

    Palacio Garcia, L.; Andrzejak, R.; Prchkovska, V.; Rodrigues, P.

    2016-07-01

    It is commonly thought that our brain is not active when it does not receive any external input. However, during rest, there are still certain distant regions of the brain that are functionally correlated between them: the so-called resting-state networks. This functional connectivity of the brain is disrupted in many neurological diseases. In particular, it has been shown that one of the most studied resting-state networks (the default-mode network) is affected in multiple sclerosis, which is the most common disabling neurological condition affecting the central nervous system of young adults. In this work, I focus on the study of the differences in the resting-state networks between multiple sclerosis patients and healthy volunteers. In order to study the effects of multiple sclerosis on the functional connectivity of the brain, a numerical method known as independent component analysis (ICA) is applied. This technique divides the resting-state fMRI data into independent components. Nonetheless, noise, which could be due to head motion or physiological artifacts, may corrupt the data by indicating a false activation. Therefore, I create a web user interface that allows the user to manually classify all the independent components for a given subject. Eventually, the components classified as noise should be removed from the functional data in order to prevent them from taking part in any further analysis. (Author)

  16. Effect of food on the bioavailability of pidotimod in healthy volunteers.

    Science.gov (United States)

    D'Angelo, L; De Ponti, F; Crema, F; Caravaggi, M; Crema, A

    1994-12-01

    Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) is a dipeptide-like molecule with immunostimulating activity in animals and in men. According to a cross-over randomized study design, 12 healthy volunteers received pidotimod both as 800 mg sachets and 800 mg ampoules after fasting and after a standard meal. The intake of a standard meal before pidotimod administration, either as sachet or as ampoule, reduced the bioavailability of the drug, probably due to an interference at the absorption level. After eating, the time of maximum plasma level was significantly longer than that observed after fasting, while AUC values and the maximum concentration were reduced by 50%. On the contrary, the pharmacokinetics after absorption phase were not influenced by food: as a matter of fact, half-life and MRT did not differ significantly when the drug was taken after fasting or after a standard meal. Finally, the two formulations used in this study resulted bioequivalent.

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

    Directory of Open Access Journals (Sweden)

    Xin-Yan Gao

    2012-01-01

    Full Text Available 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 (≤0.001 and a significant increase in HRV total (=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.

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

    Science.gov (United States)

    Fischer, Andreas; Jönsson, Martin; Hjelmström, Peter

    2015-01-01

    Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. 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). 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. A sublingual tablet formulation with an improved acceptability has been successfully developed.

  19. Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers.

    Science.gov (United States)

    Walker, D J; Zacny, J P

    1998-11-01

    The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included to test this assumption. Codeine and morphine increased ratings of "feel drug effect" but had little effect on other subjective measures, including the Addiction Research Center Inventory, visual analog scales, and adjective checklists. The few subjective effects that were observed were modest and were dose-related for morphine but not for codeine. The drugs did not affect performance on Maddox-Wing, digit-symbol substitution, coordination, auditory reaction, reasoning, and memory tests. Dose-related decreases in pupil size (miosis) were observed following codeine and morphine. Ratings of pain intensity decreased in a dose-related manner for morphine but not for codeine. Plasma codeine and morphine levels varied as an orderly function of dose. These results suggest that oral codeine and morphine are appropriate drugs for outpatient pain relief because they are effective analgesics at doses that have only modest effects on mood, produce few side effects, and do not impair performance. The results also suggest a possible ceiling effect of codeine on analgesia and subjective effects.

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

    Directory of Open Access Journals (Sweden)

    Naoko Ikuta

    2016-06-01

    Full Text Available 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.

  1. Comparative bioavailability study with two gemfibrozil tablet formulations in healthy volunteers.

    Science.gov (United States)

    Borges, Ney Carter do C; Mendes, Gustavo Duarte; Barrientos-Astigarraga, Rafael E; Zappi, Eduardo; Mendes, Fabiana Duarte; De Nucci, Gilberto

    2005-01-01

    To assess the bioequivalence of gemfibrozil (CAS 25812-30-0) 900 mg tablet formulation from EMS Farmaceutica as test formulation versus a 900 mg tablet formulation as reference in 36 healthy volunteers of both sexes. The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained over a 24-h period. Plasma gemfibrozil concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). From the gemfibrozil plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC(0-inf) and Cmax. The limit of quantification was 0.05 microg/mL for plasma gemfibrozil analysis. The geometric mean and respective 90% confidence interval (CI) of Test/Reference percent ratios were 90.29 (81.39-100.17) for Cmax, 96.26 (90.33-102.59) for AUClast, 96.04 (90.21-102.23) for AUC(0-24 h) and 96.62 (90.82-102.78) for AUC(0-infinity). Since the 90% CI for AUClast, AUC(0-inf) and Cmax, ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that gemfibrozil 900 mg tablet (test formulation) was bioequivalent to the 900 mg tablet reference formulation for both rate and extent of absorption.

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

    Science.gov (United States)

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

    2014-05-15

    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 4,790 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). Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Brain-modulated effects of auricular acupressure on the regulation of autonomic function in healthy volunteers.

    Science.gov (United States)

    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.

  4. Effects of acute hypoventilation and hyperventilation on exhaled carbon monoxide measurement in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Di Donato Michele

    2009-12-01

    Full Text Available Abstract Background High levels of exhaled carbon monoxide (eCO are a marker of airway or lung inflammation. We investigated whether hypo- or hyperventilation can affect measured values. Methods Ten healthy volunteers were trained to achieve sustained end-tidal CO2 (etCO2 concentrations of 30 (hyperventilation, 40 (normoventilation, and 50 mmHg (hypoventilation. As soon as target etCO2 values were achieved for 120 sec, exhaled breath was analyzed for eCO with a photoacoustic spectrometer. At etCO2 values of 30 and 40 mmHg exhaled breath was sampled both after a deep inspiration and after a normal one. All measurements were performed in two different environmental conditions: A ambient CO concentration = 0.8 ppm and B ambient CO concentration = 1.7 ppm. Results During normoventilation, eCO mean (standard deviation was 11.5 (0.8 ppm; it decreased to 10.3 (0.8 ppm during hyperventilation (p 2 changes (hyperventilation: 10% Vs 25% decrease; hypoventilation 3% Vs 25% increase. Taking a deep inspiration before breath sampling was associated with lower eCO values (p Conclusions eCO measurements should not be performed during marked acute hyperventilation, like that induced in this study, but the influence of less pronounced hyperventilation or of hypoventilation is probably negligible in clinical practice

  5. Effect of tipranavir/ritonavir combination on the pharmacokinetics of tadalafil in healthy volunteers.

    Science.gov (United States)

    Garraffo, R; Lavrut, T; Ferrando, S; Durant, J; Rouyrre, N; MacGregor, T R; Sabo, J P; Dellamonica, P

    2011-07-01

    This study evaluated the effects of single-dose administration and steady-state concentrations of tipranavir 500 mg and ritonavir 200 mg (TPV/r) combination on the pharmacokinetics of tadalafil 10 mg (TAD) in an open-label study. Seventeen healthy male volunteers received sequential dosing of the studied product: TAD (day 1) alone in a single dose for 7 days followed by TAD (day 8) in a single dose with TPV/r (500/200 mg twice daily, days 8-18). Pharmacokinetic parameters were determined in a noncompartmental analysis. The geometric mean ratio and 90% confidence interval were used to evaluate drug interactions. The effect of a single dose of TAD on the pharmacokinetics of TPV/r resulted in a small decrease in exposure after either first-dose or steady-state TPV/r (geometric mean ratios [90% confidence interval]: area under the concentration-time curve, 0.85 [0.74-0.97]). In contrast, coadministration of TAD exposure was increased significantly (2.33 [2.02-2.69]) when administered with the first dose of TPV/r but not when TPV/r steady state was reached (1.01 [0.83-1.21]). Antiretroviral activity may not be reduced, but the dose of TAD should be reduced at the start of TPV/r therapy and then a full dose can be resumed after steady state is reached.

  6. Comparative pharmacokinetics of oral ceftibuten, cefixime, cefaclor, and cefuroxime axetil in healthy volunteers.

    Science.gov (United States)

    Nix, D E; Symonds, W T; Hyatt, J M; Wilton, J H; Teal, M A; Reidenberg, P; Affrime, M B

    1997-01-01

    To compare the pharmacokinetics of ceftibuten, cefixime, ceturoxime axetil, and cefaclor after oral administration. Randomized, four-period, crossover study. Hospital-based clinical research center. Healthy adult men and women volunteers. Single 400-mg doses of cefixime and ceftibuten, and 500-mg doses of cefuroxime axetil and cefaclor. Serum concentrations were determined by high-performance liquid chromatography methods. The mean oral clearances of cefixime, cefuroxime axetil, and cefaclor were similar, ranging from 20.4-27.0 L/hour; clearance of ceftibuten was approximately 4-fold less, 5.45 L/hour. The serum half-lives of ceftibuten (2.35 hrs) and cefixime (2.38 hrs) were prolonged compared with those of cefuroxime axetil (1.30 hrs) and cefaclor (0.693 hr). These agents also differed in terms of time to maximum concentration, time to peak plasma level, area under the curve, and apparent volume of distribution, the last reflecting differences in biovailability. Ceftibuten had a relatively high time to maximum concentration and long half-life, resulting in a 3.5-fold higher area under the curve than cefixime, cefuroxime axetil, and cefaclor. These pharmacokinetic data can be used as a basis to compare the four oral cephalosporins; however, comparative susceptibility data must also be considered.

  7. Assessment of trigeminal nerve functions by quantitative sensory testing in patients and healthy volunteers.

    Science.gov (United States)

    Yekta, Sareh Said; Smeets, Ralf; Stein, Jamal M; Ellrich, Jens

    2010-10-01

    Orofacial sensory dysfunction plays an important role in oral and maxillofacial surgery. Quantitative sensory testing (QST) is a psychophysical approach to evaluate thermal and mechanical somatosensation. The present human study 1) collected normative QST data in extraoral and intraoral regions, 2) analyzed effects of age, gender, and anatomical sites on QST, and 3) applied QST in 11 patients with iatrogenic inferior alveolar nerve lesions. Sixty (30 male and 30 female) healthy volunteers were tested bilaterally in the innervation areas of infraorbital, mental, and lingual nerves. Ten patients with sensory disturbances in innervation areas of the mental nerve were investigated at 1, 4, and 8 weeks after surgery. Another patient with a complete sensory loss after surgery was repetitively tested within 453 days after primary surgery (dental implant) and subsequent surgical reconstruction of the inferior alveolar nerve by autologous graft. Older subjects were significantly less sensitive than younger subjects for thermal parameters. Thermal detection thresholds in infraorbital and mental regions showed higher sensitivity in women. Sensitivity to thermal stimulation was higher in the infraorbital region than in the mental and lingual regions. QST monitored somatosensory deficits and recovery of inferior alveolar nerve functions in all patients. Age, gender, and anatomic region affect various QST parameters. QST might be useful in the diagnosis of inferior alveolar nerve disorders in patients. In dentistry, the monitoring of afferent nerve fiber functions by QST might support decisions on further interventions. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Impact of endoscopy-based research on quality of life in healthy volunteers

    Science.gov (United States)

    Link, Alexander; Treiber, Gerhard; Peters, Brigitte; Wex, Thomas; Malfertheiner, Peter

    2010-01-01

    AIM: To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers (HV). METHODS: Ten HV were included into a long-term prospective endoscopy-based placebo-controlled trial with 15 endoscopic examinations per person in 5 different drug phases. Participants completed short form-36 (SF-36) and visual analog scale-based questionnaires (VAS) for different abdominal symptoms at days 0, 7 and 14 of each drug phase. Analyses were performed according to short- and long-term changes and compared to the control group. RESULTS: All HV completed the study with duration of more than 6 mo. Initial quality of life score was comparable to a general population. Analyses of the SF-36 questionnaires showed no significant changes in physical, mental and total scores, either in a short-term perspective due to different medications, or to potentially endoscopic procedure-associated long-term cumulative changes. Analogous to SF-36, VAS revealed no significant changes in total scores for pathological abdominal symptoms and remained unchanged over the time course and when compared to the control population. CONCLUSION: This study demonstrates that quality of life in HV is not significantly affected by a long-term endoscopy-based study with multiple endoscopic procedures. PMID:20101773

  9. Antimicrobial resistance pattern and genetic correlation in Enterococcus faecium isolated from healthy volunteers.

    Science.gov (United States)

    Asadian, M; Sadeghi, J; Rastegar Lari, A; Razavi, Sh; Hasannejad Bibalan, M; Talebi, M

    2016-03-01

    Enterococci are known as a cause of nosocomial infections and this aptitude is intensified by the growth of antibiotic resistance. In the present study, Enterococcus faecium isolates from healthy volunteers were considered to determine the antibiotic resistance profiles and genetic correlation. A total 91 normal flora isolates of enterococci were included in this study. Identification of Enterococcus genus and species were done by biochemical and PCR methods, respectively. Sensitivity for 10 antibiotics was determined and genetic relatedness of all isolates was assessed using Repetitive Element Palindromic PCR (REP-PCR) followed by Pulse Field Gel Electrophoresis (PFGE) on the representative patterns. None of the isolates were resistant to teicoplanin, vancomycin, quinupristin-dalfopristin, linezolid, chloramphenicol, ampicillin and high-level gentamicin. On the other hand, the resistance rate was detected in 30.7%, 23%, and 3.29% of isolates for erythromycin, tetracycline and ciprofloxacin, respectively. The results of PFGE showed 19 (61.5% of our isolates) common types (CT) and 35 (38.5%) single types (ST) amongst the isolates. This is the first study to describe antibiotic resistance pattern and genetic relationship among normal flora enterococci in Iran. This study showed no prevalence of Vancomycin Resistant Enterococci (VRE) and high degrees of diversity among normal flora isolates by genotyping using PFGE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Immediate physiological responses of healthy volunteers to different types of music: cardiovascular, hormonal and mental changes.

    Science.gov (United States)

    Möckel, M; Röcker, L; Störk, T; Vollert, J; Danne, O; Eichstädt, H; Müller, R; Hochrein, H

    1994-01-01

    A group of 20 healthy volunteers [10 women, 10 men; median age 25 (20-33) years] were examined by means of pulsed wave Doppler echocardiography, blood sample analysis and psychological testing before and after listening to three different examples of music: a waltz by J. Strauss, a modern classic by H. W. Henze, and meditative music by R. Shankar. To assess small haemodynamic changes, mitral flow, which reflects left ventricular diastolic behaviour, was measured by Doppler ultrasound. Heart rate, arterial blood pressure and plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin, adrenaline, noradrenaline, atrial natriuretic peptide (ANP) and tissue plasminogen activator (t-PA) were determined simultaneously. Transmitral flow profile is characterized by early E-wave and late atrial induced A-wave. Velocity-time integrals were measured and the atrial filling fraction was calculated. The mental state was measured by using a psychological score (Zerssen) with low values (minimum 0) for enthusiastic and high values (maximum 56) for depressive patterns. Music by J. Strauss resulted in an increase of atrial filling fraction (AFF; 29% vs 26%; P music of H. W. Henze prolactin values were lowered (7.7 ng.ml-1 vs 9.1 ng.ml-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; Robertson, Philmore; Hellriegel, Edward; Jiang, John G

    2007-01-01

    This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.

  12. A single high dose of escitalopram disrupts sensory gating and habituation, but not sensorimotor gating in healthy volunteers

    DEFF Research Database (Denmark)

    Oranje, Bob; Wienberg, Malene; Glenthøj, Birte Yding

    2011-01-01

    Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers. In the ......Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers....... In the current study a higher dose of 15mg was used. The hypothesis was that this higher dose of escitalopram would not only disrupt habituation, but also sensory and sensorimotor gating. Twenty healthy male volunteers received either placebo or 15mg escitalopram, after which they were tested in a P50...... suppression, and a habituation and prepulse inhibition (PPI) of the startle reflex paradigm. Escitalopram significantly decreased P50 suppression and habituation, but had no effect on PPI. The results indicate that habituation and sensory gating are disrupted by increased serotonergic activity, while...

  13. P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR*28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects.

    Science.gov (United States)

    Hatta, Fazleen H M; Aklillu, Eleni

    2015-12-01

    CYP2C9 enzyme contributes to the metabolism of several pharmaceuticals and xenobiotics and yet displays large person-to-person and interethnic variation. Understanding the mechanisms of CYP2C9 variation is thus of immense importance for personalized medicine and rational therapeutics. A genetic variant of P450 (cytochrome) oxidoreductase (POR), a CYP450 redox partner, is reported to influence CYP2C9 metabolic activity in vitro. We investigated the impact of a common variant, POR*28, on CYP2C9 metabolic activity in humans. 148 healthy Swedish and 146 healthy Korean volunteers were genotyped for known CYP2C9 defective variant alleles (CYP2C9*2, *3). The CYP2C9 phenotype was determined using a single oral dose of 50 mg losartan. Excluding oral contraceptive (OC) users and carriers of 2C9*2 and *3 alleles, 117 Korean and 65 Swedish were genotyped for POR*5, *13 and *28 using Taqman assays. The urinary losartan to its metabolite E-3174 metabolic ratio (MR) was used as an index of CYP2C9 metabolic activity. The allele frequency of the POR*28 variant allele in Swedes and Koreans was 29% and 44%, respectively. POR*5 and *13 were absent in both study populations. Considering the CYP2C9*1/*1 genotypes only, the CYP2C9 metabolic activity was 1.40-fold higher in carriers of POR*28 allele than non-carriers among Swedes (p = 0.02). By contrast, no influence of the POR*28 on CYP2C9 activity was found in Koreans (p = 0.68). The multivariate analysis showed that ethnicity, POR genotype, and smoking were strong predictors of CYP2C9 MR (p < 0.05). This is the first report to implicate the importance of POR*28 genetic variation for CYP2C9 metabolic activity in humans. These findings contribute to current efforts for global personalized medicine and using medicines by taking into account pharmacogenetic and phenotypic variations.

  14. Effect of ticagrelor on the pharmacokinetics of ethinyl oestradiol and levonorgestrel in healthy volunteers.

    Science.gov (United States)

    Butler, Kathleen; Teng, Renli

    2011-08-01

    Cytochrome P450 3 A is involved in ticagrelor and ethinyl oestradiol/levonorgestrel metabolism; so a potential drug-drug interaction may occur. To assess: ticagrelor effects on ethinyl oestradiol/levonorgestrel pharmacokinetics, endogenous sex hormone levels; ethinyl oestradiol/levonorgestrel effects on ticagrelor pharmacokinetics; tolerability of ticagrelor + ethinyl oestradiol/levonorgestrel. This trial was a randomized, double-blind, two-way crossover, single-center study. Twenty-two healthy female volunteers (on stable ethinyl oestradiol/levonorgestrel) received 90 mg ticagrelor or placebo twice daily with ethinyl oestradiol/levonorgestrel (0.03 mg/0.15 mg; Nordette) on cycle days 1-21. Volunteers crossed over treatment on day 1/cycle 2. Pharmacokinetic parameters were evaluated on cycle day 21, and endogenous hormones assayed on cycle days 1, 7, 14 and 21. NCT006895906. Ethinyl oestradiol absorption was rapid (median t(max) approximately 1 hour), and was not affected by ticagrelor. Ticagrelor co-administration (90% confidence interval [CI]) increased AUC(0-τ), C(min), and C(max) of ethinyl oestradiol by 20% (1.03-1.40), 20% (0.96-1.50) and 31% (1.18-1.44), respectively. Ticagrelor had no effect on levonorgestrel pharmacokinetic parameters versus placebo (90% CI: AUC(0-τ) 0.97-1.10; C(min) 0.94-1.10; C(max) 1.02-1.16). Steady-state ticagrelor, and AR-C124910XX (major and equally pharmacologically active metabolite), AUC(0-τ), C(max), and t(max) were comparable with published findings. Pre-dose ticagrelor and AR-C124910XX plasma concentrations were higher on cycle day 21 versus days 7 and 14. Endogenous sex hormone plasma levels were unaffected by ticagrelor. Co-administration of ticagrelor with ethinyl oestradiol/levonorgestrel was well tolerated. Study limitations included: no ticagrelor-only arm; only one type of oral contraceptive; short study duration; using oestradiol/levonorgestrel pharmacokinetic parameters as surrogate marker for

  15. Pharmacodynamic equivalence study of two preparations of eye drops containing dorzolamide and timolol in healthy volunteers.

    Science.gov (United States)

    Gatchev, Emil; Petrov, Andrey; Kolev, Emil; Hristova, Russka; Demircheva, Irena; Koytchev, Rossen; Richter, Wolfram; Tegel, Friedrich; Thyroff-Friesinger, Ursula

    2011-01-01

    The aim of the present study was to assess the pharmacodynamic equivalence (lowering of intraocular pressure) of two preparations of eye drops containing 20 mg dorzolamide (CAS 120279-96-1) and 5 mg timolol (CAS 26839-75-8). The study was conducted as a monocentric, observer-blinded, randomized, single-dose, two-period crossover study in 38 healthy volunteers. Each volunteer received on day 1 in each period in a random way a single dose of 1 drop of the test or the reference formulation in the conjunctival sac of the right eye separated by a wash-out period of 7 days. Measurement of intraocular pressure (IOP) of the right eye (by a blinded observer) was performed on day 1 of each study period pre-dose and 2 h post dosing by means of Goldmann applanation tonometry. In order to investigate the pharmacodynamic equivalence of both products, the two-sided 95% confidence interval was calculated for the difference of the primary target parameter (absolute decrease in IOP 2 h post dose), by means of a parametric (ANOVA) statistical method. The results of the statistical evaluation of the primary target parameter "absolute decrease in IOP 2 h post dose" demonstrated a decrease in the IOP of 4.72 mmHg for the eye treated with the test formulation (dorzolamide 20 mg/ml + timolol 5 mg/ml eye drops) and 4.61 mmHg for the treated with the reference formulation. The mean difference was 0.11 mmHg. The 95% confidence interval was between -0.33 and 0.55 mmHg and thus entirely within the pre-defined equivalence range (+/- 1.5 mmHg). The results of the statistical evaluation of the secondary target parameter relative (as % of baseline) decrease in IOP 2 h post dose demonstrated essentially similar effectiveness in lowering the IOP by 27.63% (test formulation) and 27.12% (reference formulation), respectively. Both drug products were well tolerated. Both formulations showed comparable results obtained at a time probably equal to the maximum effect concerning the primary target parameter

  16. Optimal Fasting Time before Measurement of Serum Triglyceride Levels in Healthy Volunteers.

    Science.gov (United States)

    Pongsuthana, Surapun; Tivatunsakul, Naris

    2016-02-01

    Coronary heart disease is a major public health problem. Elevated triglyceride levels are a risk factor for atherosclerosis and coronary heart disease. Food intake interferes with the measurement of serum triglyceride levels, and in previous studies, fasting for 12 hours was recommended before blood sampling. In real-world practice, long fasting times cause patient discomfort and poor compliance, and the present study was, therefore, designed to determine the appropriate fasting time prior to measuring serum triglyceride levels. To determine the appropriate fasting time before measuring serum triglyceride levels. This was a pilot study performed using healthy volunteers aged between 20 and 30 years old from November 2013 to December 2013 at Rajavithi Hospital. The first blood sample was measured in the morning after fasting over 12 hours. The subjects then took their regular breakfast, after which they fasted for 8 hours. Blood samples were taken 6 and 8 hours later and sent to the laboratory for measurement of serum triglyceride levels. 40 volunteers, of whom 25 were female, were enrolled. Their mean age was 25.9 ± 2.81 years old, and their mean weight, height, and body mass index were 61.5 ± 12.5 kg, 167.2 ± 8.3 cm and 21.84 ± 3.1 kg/m2, respectively. Mean fasting serum triglyceride level at 12 hours was 80.23 ± 36.33 mg/dl, at 6 hours it was 110.65 ± 73.45 mg/dl, and at 8 hours it was 75.62 ± 46.81 mg/dl. The group fasting for 12 hours had significantly lower serum triglyceride levels than the group fasting for 6 hours (p-value = 0.003), but no significant difference was found between the group fasting for 12 hours and the one fasting for 8 hours (p-value = 0.493). The present study showed no significant difference in triglyceride levels in patients who had fasted or 8 hours and those who had done so for 12 hours. Fasting for only 8 hours before measurement of serum triglyceride may be sufficient.

  17. The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

    Science.gov (United States)

    Trabado, Séverine; Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

    2017-01-01

    Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.

  18. Electrometric measurement of plasma, erythrocyte, and whole blood cholinesterase activities in healthy human volunteers.

    Science.gov (United States)

    Mohammad, F K; Alias, A S; Ahmed, O A H

    2007-03-01

    The measurement of blood cholinesterase activity is a useful tool for monitoring exposure to organophosphate and carbamate insecticides. Blood cholinesterase activity is measured colorimetrically or electrometrically. Recently, a simple and practical electrometric method has been described and validated for measuring blood cholinesterase activity in people and animals. The purpose of the present report was to use the modified electrometric technique for measuring blood (plasma, erythrocyte and whole blood) cholinesterase activities in apparently healthy human volunteers in Mosul, Iraq. Cholinesterase activities in the plasma, erythrocytes, and whole blood of healthy male (n = 72) and female (n = 31) volunteers were measured by an electrometric method; the method involved the addition of 0.2 ml of blood sample to 3 ml of distilled water followed by 3 ml of barbital-phosphate buffer solution (pH 8.1). The pH (pH1) of the mixture was measured, and then 0.1 ml of 7.5% of acetylcholine iodide, as a substrate, was added. The reaction mixture was incubated at 37 degrees C for 20 minutes. The pH (pH2) of the reaction mixture was measured after the end of the incubation period. Enzyme activity was expressed as DeltapH/20 min = pH1- pH2 - (DeltapH of the blank). The blank was without the blood sample. Following in vitro inhibition of pseudo cholinesterase by quinidine sulfate, true cholinesterase activity was estimated in the plasma of the subjects. After in vitro addition of the organophosphate (chlorpyrifos and methidathion, 0.5 and 1 microM) and carbamate (carbaryl, 5 and 10 microM) insecticides to the reaction mixtures, inhibitions of blood cholinesterases were measured. Mean reference cholinesterase activities (DeltapH/20 min) in the plasma, erythrocytes, and whole blood of male subjects were 0.98, 1.39, and 1.41, respectively. Females were 0.85, 1.22, and 1.23, respectively. Ten minutes after in vitro addition of quinidine sulfate to inhibit pseudo cholinesterase

  19. Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers.

    Science.gov (United States)

    Luo, Zhu; Shen, Yali; Liang, Maozhi; Miao, Jia; Mei, Yajun; Wang, Ying; Qin, Yongping

    2015-11-15

    Few pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China. 1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions. This open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests. Totally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94±6.59 and 9.47±5.47h, Cmax 435.74±348.10 and 346.54±155.66ng·mL(-1), AUC0-t 8600.52±5264.77 and 9315.10±6820.03ng·mL(-1)·h, AUC0-∞ 8845.38±5838.18 and 9669.24±7326.53ng·mL(-1)·h, t1/2 10.06±8.83 and 9.87±10.35h; single dosing under fasting conditions, Tmax 7.29±4.87 and 6.57±1.85h, Cmax 247.85±110.05 and 244.64±132.43ng·mL(-1), AUC0-t 3385.41±1418.92 and 3496.24±1767.29ng·mL(-1)·h, AUC0-∞ 3781.53±1556.96 and 3829.56±1981.25ng·mL(-1)·h, t1/2 13.07±17.24 and 10.26±7.78h; single dosing under fed conditions, Tmax 17.72±9.42 and 19.50±9.84h, Cmax 183.90±74.52 and 168.14±60.67ng·mL(-1), AUC0-t 3181.71±1368.24 and 3575.11±1416.39ng·mL(-1)·h, AUC0-∞3442.39±2002.53 and 3624

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

    Directory of Open Access Journals (Sweden)

    Xingze Wang

    2015-01-01

    Full Text Available 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.

  1. Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers.

    Science.gov (United States)

    Pithavala, Yazdi K; Chen, Ying; Toh, Melvin; Selaru, Paulina; LaBadie, Robert R; Garrett, May; Hee, Brian; Mount, Janessa; Ni, Grace; Klamerus, Karen J; Tortorici, Michael A

    2012-07-01

    To evaluate the effect of food on axitinib pharmacokinetics in healthy volunteers with two different crystal polymorphs. Two separate open-label, randomized, single-dose, three-period, crossover trials were conducted. Study I, conducted first using 5-mg axitinib Form IV film-coated immediate-release (FCIR) tablets, enrolled 18 subjects to compare fed versus fasted states and 24 subjects to evaluate the effect of timing of food consumption on axitinib pharmacokinetics. Study II enrolled 30 subjects to assess the effect of food using 5-mg axitinib Form XLI FCIR tablets. Subjects received axitinib after overnight fasting, with limited fasting or, depending on the study design, after consuming high-fat, high-calorie or moderate-fat, standard-calorie meals. For Form IV FCIR, compared with overnight fasting, axitinib plasma exposure [area under the concentration curve (AUC)] was decreased 23 % when administered with food. For Form XLI FCIR, mean axitinib plasma AUC and maximum plasma concentration (C(max)) were 19 and 11 % higher, respectively, with a high-fat, high-calorie meal compared with overnight fasting. When Form XLI FCIR was administered with moderate-fat, standard-calorie meal, AUC and C(max) were 10 and 16 % lower compared with overnight fasting. Both formulations were well tolerated. Adverse events, mostly gastrointestinal (7 % with Form IV FCIR and 13 % with Form XLI FCIR), were mild to moderate in both studies. While axitinib Form IV FCIR was associated with higher plasma exposure after overnight fasting, axitinib Form XLI FCIR can be administered with or without food as differences in axitinib pharmacokinetics under the two conditions were not clinically meaningful.

  2. Comparative bioavailability of two oral formulations of levofloxacin in healthy Mexican volunteers.

    Science.gov (United States)

    M; Flores-Murrieta, F J

    2009-04-01

    To assess the bioequivalence of two levofloxacin 500 mg tablets marketed in Mexico. The clinical investigation was designed as a randomized, open-labeled, two-part, two-treatment, two-period crossover study, in 27 healthy male volunteers. 1 tablet of each formulation was administered with 200 ml of water after 10 h overnight fast. After dosing, serial blood samples were collected for a period of 24 h. Plasma concentrations were determined by a validated high-performance liquid chromatographic method and pharmacokinetic parameters were obtained by non-compartmental approach. Analysis of variance (ANOVA) was carried out using log-transformed AUClast, AUC yen and Cmax and untransformed tmax, and 90% confidence intervals for AUClast, AUC yen and Cmax were calculated. If the 90% confidence intervals (CI) for AUClast, AUC yen and Cmax fell fully within the interval 80 - 125%, the bioequivalence of the two formulations was established. The means (test and reference) for AUClast were 58.869 and 56.297 microg x h/ml, for AUC yen were 63.456 and 60.748 microg x h/ml and for Cmax were 8.691 and 8.445 microg/ml. The geometric mean ratios of the test formulation to reference formulation for AUClast, AUC yen and Cmax (CI) were 104.53% (102.73 - 106.36%), 104.37% (102.04 - 106.75%) and 103.45% (95.57 - 111.97%), respectively. All 90% CI for AUClast, AUC yen and Cmax fell within the Mexican Federal Commission for Prevention of Sanitary Risks (COFEPRIS) accepted bioequivalence range of 80 - 125%. Based on the results, the formulations tested are bioequivalent.

  3. Release and Decay Kinetics of Copeptin versus AVP in Response to Osmotic Alterations in Healthy Volunteers.

    Science.gov (United States)

    Fenske, Wiebke K; Schnyder, Ingeborg; Koch, Gilbert; Walti, Carla; Pfister, Marc; Kopp, Peter; Fassnacht, Martin; Strauss, Konrad; Christ-Crain, Mirjam

    2017-12-15

    Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. To characterize the physiology of osmotically-regulated copeptin release and its half-life in direct comparison to plasma AVP. Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (i) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (ii) oral water load and (iii) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium and osmolality levels were measured in regular intervals. In phase 1 an increase in median osmotic pressure (289 [286; 291] to 311 [309; 314] mOsm/kgH2O) caused similar release kinetics of plasma copeptin (4 [3.1; 6] to 29.3 [18.6; 48.2] pmol/L) and AVP (1 [0.7; 1.6] to 10.3 [6.8; 18.8] pg/mL). Subsequent osmotic suppression to 298 [295; 301] mOsm/kg at the end of phase 3, revealed markedly different decay kinetics between both peptides - an estimated initial half-life of copeptin being approximately 2-times longer than that of AVP (26 min vs 12 min). Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe first time the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison to AVP.

  4. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers

    Science.gov (United States)

    Butler, Kathleen; Teng, Renli

    2010-01-01

    AIM To determine the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple oral doses of ticagrelor, a P2Y12 receptor antagonist, in healthy volunteers. METHODS This was a randomized, single-blind, placebo-controlled, ascending dose study. Thirty-two subjects received ticagrelor 50–600 mg once daily or 50–300 mg twice daily or placebo for 5 days at three dose levels in two parallel groups. Another group of 16 subjects received a clopidogrel 300 mg loading dose then 75 mg day−1, or placebo for 14 days. RESULTS Ticagrelor was absorbed with median tmax 1.5–3 h, exhibiting predictable pharmacokinetics over the 50–600 mg dose range. Mean Cmax and AUC for ticagrelor and its main metabolite, AR-C124910XX, increased approximately dose-proportionately (approximately 2.2- to 2.4-fold with a twofold dose increase) over the dose range. Inhibition of platelet aggregation (IPA) with ticagrelor was greater and better sustained at high levels with ticagrelor twice daily vs. once daily regimens. Throughout dosing, more consistent IPA was observed at doses ≥300 mg once daily and ≥100 mg twice daily compared with clopidogrel. Mean IPA with ticagrelor ≥100 mg twice daily was greater and less variable (93–100%, range 65–100%) than with clopidogrel (77%, range 11–100%) at trough concentrations. No safety or tolerability issues were identified. CONCLUSIONS Multiple dosing provided predictable pharmacokinetics of ticagrelor and its metabolite over the dose range of 50–600 mg once daily and 50–300 mg twice daily with Cmax and AUC(0,t) increasing approximately dose-proportionally. Greater and more consistent IPA with ticagrelor at doses ≥100 mg twice daily and ≥300 mg once daily were observed than with clopidogrel. Ticagrelor at doses up to 600 mg day−1 was well tolerated. PMID:20642549

  5. A pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers.

    Science.gov (United States)

    Teng, Renli; Butler, Kathleen

    2013-10-01

    Ticagrelor is a reversibly binding P2Y12 receptor antagonist for the prevention of atherothrombotic events in patients with acute coronary syndrome. Previous in vitro studies showed that ticagrelor is a substrate and inhibitor of P-glycoprotein (ABCB1). Therefore, we examined the potential interaction between digoxin, a P-glycoprotein substrate, and ticagrelor by evaluating the pharmacokinetics, safety, and tolerability. This was a randomized, double-blind, two-period crossover study in healthy volunteers (n = 20). Pharmacokinetic parameters of digoxin and ticagrelor were evaluated following co-administration of ticagrelor 400 mg qd or placebo on days 1-16, and digoxin (0.25 mg bid on day 6 and 0.25 mg qd on days 7-14). Co-administration of ticagrelor increased the digoxin maximum plasma concentration by 75 %, from 1.8 ng/ml to 3.0 ng/ml (Gmean ratio [GMR] 1.75 [95 % CI, 1.52-2.01]); minimum plasma concentration by 31 %, from 0.5 ng/ml to 0.7 ng/ml (GMR 1.31, 1.13-1.52); and mean area under the curve by 28 %, from 16.8 ng · h/ml to 21.0 ng · h/ml (GMR 1.28, 1.12-1.46), compared with placebo. Renal clearance of digoxin was unaffected by the presence of ticagrelor. Digoxin had no effect on the pharmacokinetics of ticagrelor or its active metabolite, AR-C124910XX. Co-administration of ticagrelor and digoxin was well tolerated. Collectively, these results indicate that ticagrelor is a weak inhibitor of the P-glycoprotein transporter. Based on these findings, it is recommended that serum concentrations of drugs like digoxin (P-glycoprotein transporter substrates with a narrow therapeutic range) are monitored when initiating or changing ticagrelor therapy.

  6. Effects of tipranavir, darunavir, and ritonavir on platelet function, coagulation, and fibrinolysis in healthy volunteers.

    Science.gov (United States)

    Kort, Jens J; Aslanyan, Stella; Scherer, Joseph; Sabo, John P; Kohlbrenner, Veronika; Robinson, Patrick

    2011-06-01

    The use of HIV protease inhibitors (PIs) as part of antiretroviral therapy in the treatment of HIV-1 infection may be associated with an increased risk of bleeding. This prospective, randomized, open-label trial in healthy volunteers compared the effects of tipranavir/ritonavir (TPV/r), darunavir/ ritonavir (DRV/r), and ritonavir (RTV) alone on platelet aggregation after a single dose and at steady-state concentrations. Subjects were selected on the basis of normal platelet aggregation and arachidonic acid (AA)-induced platelet aggregation inhibition after administration of a single 325-mg dose of aspirin. All 3 PI therapies were administered twice daily for 10 days. In some but not all subjects, TPV/r inhibited AA-induced platelet aggregation and prolonged PFA-100® closure time with collagen-epinephrine cartridge, which was of lesser magnitude and consistency compared with aspirin, but greater when compared to DRV/r and RTV. At least 2 subjects in each treatment arm showed complete inhibition of AA-induced platelet aggregation on treatment, and the magnitude of change in all platelet-function tests did not correlate with PI plasma concentrations. Effects of TPV/r on platelet aggregation were reversed 24 hours after the last TPV/r dose. None of the PI treatments tested were associated with increases in bleeding time, decreases in plasma coagulation factors, or increase in fibrinolysis. There was large inter-patient variability in antiplatelet effect for all PI treatments, ranging from no effect to complete inhibition of AA-induced platelet aggregation.

  7. Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers.

    Science.gov (United States)

    Vlisides, Phillip E; Bel-Bahar, Tarik; Lee, UnCheol; Li, Duan; Kim, Hyoungkyu; Janke, Ellen; Tarnal, Vijay; Pichurko, Adrian B; McKinney, Amy M; Kunkler, Bryan S; Picton, Paul; Mashour, George A

    2017-07-01

    Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

  8. Emotional traits predict individual differences in amphetamine-induced positive mood in healthy volunteers.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Goldenson, Nicholas I; Kapadia, Nahel; Kahler, Christopher W; de Wit, Harriet; Swift, Robert M; McGeary, John E; Sussman, Steve; Leventhal, Adam M

    2016-01-01

    Previous research on emotional correlates of individual differences in subjective responses to D-amphetamine has focused on relatively broad personality traits. Yet, emotional functioning is best characterized by several narrow subcomponents, each of which may contribute uniquely to amphetamine response. Here, we examine several specific subdomains of emotional functioning in relation to acute amphetamine response. At a baseline session, healthy stimulant-naive volunteers (N = 97) completed measures of several subdomains of baseline trait emotional functioning and then completed two counterbalanced experimental sessions during which they received a single oral dose of 20 mg D-amphetamine or placebo. Acute subjective drug response measures were completed at repeated intervals before and after drug administration. Data from subjective measures that were significantly modulated by amphetamine were reduced using principal component analysis (amphetamine or placebo) into three higher-order factors of "positive mood," "arousal," and "drug high." Amphetamine did not significantly alter any "negative" subjective states. Separate multiple regression analyses were conducted regressing these three drug factors on baseline trait emotional functioning scales. The combined set of trait emotional functioning indicators accounted for approximately 22 % of the variance in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure and greater anxious distress each uniquely predicted greater amphetamine-induced positive mood. Trait emotional functioning did not significantly predict amphetamine-induced changes in arousal or drug high. Emotional traits appear to moderate drug-induced positive mood but not other dimensions of amphetamine effects. Different facets of emotional functioning may differentially modulate amphetamine's subjective effect profile.

  9. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers.

    Science.gov (United States)

    Deloose, Eveline; Janssen, Pieter; Corsetti, Maura; Biesiekierski, Jessica; Masuy, Imke; Rotondo, Alessandra; Van Oudenhove, Lukas; Depoortere, Inge; Tack, Jan

    2017-03-01

    Background: Denatonium benzoate (DB) has been shown to influence ongoing ingestive behavior and gut peptide secretion.Objective: We studied how the intragastric administration of DB affects interdigestive motility, motilin and ghrelin plasma concentrations, hunger and satiety ratings, and food intake in healthy volunteers.Design: Lingual bitter taste sensitivity was tested with the use of 6 concentrations of DB in 65 subjects. A placebo or 1 μmol DB/kg was given intragastrically to assess its effect on fasting gastrointestinal motility and hunger ratings, motilin and ghrelin plasma concentrations, satiety, and caloric intake.Results: Women (n = 39) were more sensitive toward a lingual bitter stimulus (P = 0.005) than men (n = 26). In women (n = 10), intragastric DB switched the origin of phase III contractions from the stomach to the duodenum (P = 0.001) and decreased hunger ratings (P = 0.04). These effects were not observed in men (n = 10). In women (n = 12), motilin (P = 0.04) plasma concentrations decreased after intragastric DB administration, whereas total and octanoylated ghrelin were not affected. The intragastric administration of DB decreased hunger (P = 0.008) and increased satiety ratings (P = 0.01) after a meal (500 kcal) in 13 women without affecting gastric emptying in 6 women. Caloric intake tended to decrease after DB administration compared with the placebo (mean ± SEM: 720 ± 58 compared with 796 ± 45 kcal; P = 0.08) in 20 women.Conclusions: Intragastric DB administration decreases both antral motility and hunger ratings during the fasting state, possibly because of a decrease in motilin release. Moreover, DB decreases hunger and increases satiety ratings after a meal and shows potential for decreasing caloric intake. This trial was registered at clinicaltrials.gov as NCT02759926. © 2017 American Society for Nutrition.

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

    Science.gov (United States)

    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

  11. Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies.

    Science.gov (United States)

    Pollock, Sean; Keall, Robyn; Keall, Paul

    2015-09-01

    The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. From August 1-14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the clinical impact of breathing guidance

  12. An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers.

    Science.gov (United States)

    van der Schrier, R; Jonkman, K; van Velzen, M; Olofsen, E; Drewes, A M; Dahan, A; Niesters, M

    2017-10-04

    There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg. Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake. All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, Ptapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05). In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

  13. Meta-analysis for cardiovascular effects of NRL001 after rectal application in healthy volunteers.

    Science.gov (United States)

    Gruss, H J; Pediconi, C; Jacobs, A

    2014-03-01

    NRL001 is a highly specific α1 -adrenoceptor agonist currently under evaluation for the treatment of faecal incontinence caused by a weak internal anal sphincter. The aim of this meta-analysis was to quantify the effect of NRL001 on cardiovascular parameters including heart rate, blood pressure and QT interval. Data from the four Phase I healthy volunteer studies SUM (NCT00857467), SURD (NCT01099670), SUSD (NCT00850590) and SAGE (NCT01099683) were pooled and analyses were performed on individual subject data. Mixed effects regression analysis was used to determine the effect of NRL001 on heart rate, blood pressure and QT intervals. A multivariate statistical model was used to determine the effect of covariates on heart rate. Subjects given NRL001 experienced a dose related decrease in heart rate of up to 9.48 bpm compared with subjects in the placebo arms. No statistically significant evidence for a threshold effect was found. There was no clear evidence of dose effect of NRL001 on blood pressure. QT interval increased in all NRL001 subject as expected; QTC F also showed a statistically significant increase. However, QTC B was shortened with no significant treatment effect. NRL001 was found to have a dose-dependent effect on heart rate; however clinically-relevant bradycardia was not reported, indicating the decrease in heart rate was not of clinical significance. Furthermore, no clinically-significant drug effect on blood pressure or mean arterial pressure was observed. QT intervals were affected by changes in heart rate. However, trends were dependant on the correction factor used. No consistent QT effect was observed, but a thorough QTC study will be required to confirm the effects of rectally applied NRL001. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  14. Temperature cycling during platelet cold storage improves in vivo recovery and survival in healthy volunteers.

    Science.gov (United States)

    Vostal, Jaroslav G; Gelderman, Monique P; Skripchenko, Andrey; Xu, Fei; Li, Ying; Ryan, Johannah; Cheng, Chunrong; Whitley, Pam; Wellington, Michael; Sawyer, Sherrie; Hanley, Shalene; Wagner, Stephen J

    2018-01-01

    Room temperature (RT) storage of platelets (PLTs) can support bacterial proliferation in contaminated units, which can lead to transfusion-transmitted septic reactions. Cold temperature storage of PLTs could reduce bacterial proliferation but cold exposure produces activation-like changes in PLTs and leads to their rapid clearance from circulation. Cold-induced changes are reversible by warming and periodic rewarming during cold storage (temperature cycling [TC]) has been proposed to alleviate cold-induced reduction in PLT circulation. A clinical trial in healthy human volunteers was designed to compare in vivo recovery, survival, and area under the curve (AUC) of radiolabeled autologous apheresis PLTs stored for 7 days at RT or under TC or cold conditions. Paired comparisons of RT versus TC and TC versus cold PLTs were conducted. Room temperature PLTs had in vivo recovery of 55.7 ± 13.9%, survival of 161.3 ± 28.8 hours, and AUC of 5031.2 ± 1643.3. TC PLTs had recovery of 42.6 ± 16.4%, survival of 48.1 ± 14.4% hours, and AUC of 1331.3 ± 910.2 (n = 12, p cold PLTs had recovery of 23.1 ± 8.8%, survival of 33.7 ± 14.7 hours, and AUC of 540.2 ± 229.6 while TC PLTs had recovery of 36.5 ± 12.9%, survival of 49.0 ± 17.3 hours, and AUC of 1164.3 ± 622.2 (n = 4, AUC had p cold storage but is not equivalent to RT storage. © 2017 AABB.

  15. Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers.

    Science.gov (United States)

    Barbanoj, Manel J; Riba, Jordi; Clos, S; Giménez, S; Grasa, E; Romero, S

    2008-02-01

    Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT(1A) and 5-HT(2A/2C) receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters. Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg(-1) body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of 'light' vs 'deep' sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to d-amphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band. Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an

  16. Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies

    Energy Technology Data Exchange (ETDEWEB)

    Pollock, Sean, E-mail: sean.pollock@sydney.edu.au; Keall, Paul [Radiation Physics Laboratory, University of Sydney, Sydney 2050 (Australia); Keall, Robyn [Central School of Medicine, University of Sydney, Sydney 2050, Australia and Hammond Care, Palliative Care and Supportive Care Service, Greenwich 2065 (Australia)

    2015-09-15

    Purpose: The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. Methods: From August 1–14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. Results: The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. Conclusions: There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the

  17. Effect of ginkgo biloba on the pharmacokinetics of raltegravir in healthy volunteers.

    Science.gov (United States)

    Blonk, Maren; Colbers, Angela; Poirters, Anne; Schouwenberg, Bas; Burger, David

    2012-10-01

    Medicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an open-label, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC(0-∞)) and the maximum plasma concentration (C(max)) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the C(max) of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.

  18. PAF and its metabolic enzymes in healthy volunteers: interrelations and correlations with basic characteristics.

    Science.gov (United States)

    Detopoulou, Paraskevi; Nomikos, Tzortzis; Fragopoulou, Elizabeth; Stamatakis, George; Panagiotakos, Demosthenes B; Antonopoulou, Smaragdi

    2012-01-01

    PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent inflammatory mediator, is synthesized via the remodeling and the de novo route, key enzymes of which are acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), respectively. PAF-acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase-A(2) (Lp-PLA(2)) catabolize PAF. This study evaluated PAF levels together with leukocyte PAF-CPT, lyso-PAF-AT, PAF-AH and Lp-PLA(2) activities in 106 healthy volunteers. Men had lower PAF levels and higher activity of both catabolic enzymes and lyso-PAF-AT than women (P-values PAF levels in men (r=-0.279, P=0.06) and lyso-PAF-AT in women (r=-0.280, P=0.05). In contrast, Lp-PLA(2) was positively correlated with age (r=0.201, P=0.04). Moreover, PAF-CPT was positively correlated with glucose (r=0.430, P=0.002) in women. In addition, Principal Component Analysis revealed three PAF metabolic patterns: (i) increased activities of PAF-CPT and PAF-AH, (ii) increased activities of PAF-CPT and lyso-PAF-AT and (iii) increased activity of Lp-PLA(2). The present study underlines the complexity of PAF's metabolism determinants. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Immediate effect of suryanadi pranayama on pulmonary function (ventilatory volumes and capacities in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Shravya Keerthi G, Hari Krishna Bandi, Suresh M, Mallikarjuna Reddy N

    2013-10-01

    Full Text Available Objectives: we found only effects of at least a short term practice extended over a period of a few days to weeks of pranayama (alternate nostril breathing rather than acute effects of unilateral right nostril breathing (suryanadi pranayama. Keeping this in mind the present study was designed to test the hypothesis that 10 min. of right nostril breathing have any immediate effect on ventilatory volumes and capacities in healthy volunteers. Methodology: Forced vital capacity (FVC, Forced expiratory volume in the first second (FEV1, Forced expiratory volume percent (FEV1/FVC%, Peak expiratory flow rate (PEFR, Forced expiratory flow25-75% (FEF25-75%, Maximum voluntary ventilation (MVV, Slow vital capacity (SVC, Expiratory reserve volume (ERV, Inspiratory reserve volume (IRV and Tidal volume (TV were recorded before and after Surya Nadi Pranayama. Results & Conclusion: There was a significant increase in FVC (p<0.0001, FEV1 (p<0.0007, PEFR (p<0.0001, FEF25-75% (p<0.0001, MVV (p<0.0001, SVC (p<0.0001, ERV (0.0006, IRV (p<0.0001 and TV (0.0055 after suryanadi pranayama. The immediate effect of suryanadi pranayama practice showed alleviation of ventilatory capacities and volumes. Any practice that increases PEFR and FEF25–75% is expected to retard the development of COPD’s. The increase in PEFR, vital capacities and flow rates by suryanadi pranayama practice obviously offers an increment in respiratory efficiency and it can be advocated to the patients of early bronchitis and as a preventive measure for COPD.

  20. Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers

    Science.gov (United States)

    Brealey, Noushin; Gupta, Ashutosh; Renaux, Jessica; Mehta, Rashmi; Allen, Ann; Henderson, Alex

    2015-01-01

    Objective: Two single-center, four-way, single-dose, crossover studies assessed the systemic exposure, systemic pharmacodynamics (PD), and safety profile of the closed triple fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) therapy compared with dual therapies. These are the first studies where pharmacokinetic (PK) profile assessment was possible for this inhaled triple fixed-dose combination product. Methods: Healthy volunteers were randomized to receive 4 consecutive inhalations (each administered as a single dose) via a single ELLIPTA® dry powder inhaler: in study 1 (CTT116415/NCT01691547), FF/UMEC/VI at total doses of 400/500/100 μg, FF/UMEC 400/500 μg, UMEC/VI 500/100 μg, or FF/VI 400/100 μg; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 μg or 400/250/100 μg, FF/VI 400/100 μg, or UMEC/VI 250/100 μg. PK and PD parameters and safety were assessed. Results: Of 88 subjects, 95% completed both studies and received all planned treatments. Total systemic exposure was similar for FF, UMEC, and VI when administered as a triple therapy compared with FF/VI and UMEC/VI. No clinically significant systemic PD findings were detected. The incidence of adverse events was low and similar across treatment arms. Conclusions: Systemic exposure to all three components of the closed triple therapy, following single-dose delivery, was similar to that seen with the dual therapies FF/VI and UMEC/VI. The delivered lung dose and safety profile of all three agents, delivered via a single inhaler, are expected to be similar to those of the dual therapies. PMID:26227101

  1. Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers.

    Science.gov (United States)

    Brealey, Noushin; Gupta, Ashutosh; Renaux, Jessica; Mehta, Rashmi; Allen, Ann; Henderson, Alex

    2015-09-01

    Two single-center, four-way, single-dose, crossover studies assessed the systemic exposure, systemic pharmacodynamics (PD), and safety profile of the closed triple fluticasone furoate/ umeclidinium/vilanterol (FF/UMEC/VI) therapy compared with dual therapies. These are the first studies where pharmacokinetic (PK) profile assessment was possible for this inhaled triple fixed-dose combination product. Healthy volunteers were randomized to receive 4 consecutive inhalations (each administered as a single dose) via a single ELLIPT® dry powder inhaler: in study 1 (CTT116415/NCT01691547), FF/UMEC/VI at total doses of 400/500/100 μg, FF/UMEC 400/500 μg, UMEC/VI 500/100 μg, or FF/VI 400/100 μg; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 μg or 400/250/100 μg, FF/VI 400/100 μg, or UMEC/VI 250/100 μg. PK and PD parameters and safety were assessed. Of 88 subjects, 95% completed both studies and received all planned treatments. Total systemic exposure was similar for FF, UMEC, and VI when administered as a triple therapy compared with FF/VI and UMEC/VI. No clinically significant systemic PD findings were detected. The incidence of adverse events was low and similar across treatment arms. Systemic exposure to all three components of the closed triple therapy, following single-dose delivery, was similar to that seen with the dual therapies FF/VI and UMEC/VI. The delivered lung dose and safety profile of all three agents, delivered via a single inhaler, are expected to be similar to those of the dual therapies.

  2. Absorption of effervescent paracetamol tablets relative to ordinary paracetamol tablets in healthy volunteers.

    Science.gov (United States)

    Rygnestad, T; Zahlsen, K; Samdal, F A

    2000-05-01

    The aim of this study was to compare the rate of absorption between ordinary paracetamol tablets and effervescent paracetamol tablets. Twenty healthy volunteers participated in an open randomised crossover study and were given a 1000-mg dose of either ordinary paracetamol tablets (2 x 500 mg Panodil tablets, SmithKline Beecham) or effervescent paracetamol tablets (2 x 500 mg Pinex Brusetablett, Alpharma AS) with a 3-week washout period in between. Blood samples were collected for 3 h. Maximum serum concentration (Cmax) and the time to maximum serum concentration (tmax) were recorded and the area under the concentration versus time curve (AUC) was calculated. The mean tmax was significantly shorter when paracetamol effervescent tablets were taken (27 min) rather than ordinary paracetamol tablets (45 min) (P = 0.004). There was no significant difference between the mean Cmax of 143 micromol/l with effervescent tablets and that of 131 micromol/l with ordinary tablets. The mean AUC(0-3 h) was significantly higher with paracetamol effervescent tablets (223.8 micromol x h x l(-1)) than with ordinary tablets (198.2 micromol x h x l(-1); P = 0.003). After 15 min, 17 (85%) subjects in the effervescent group had a serum concentration of 70 micromol/l (lower therapeutic serum concentration) or higher relative to only 2 (10%) subjects in the ordinary tablet group (P = 0.001). Paracetamol effervescent tablets are absorbed significantly faster than ordinary paracetamol. Thus, effervescent tablets might offer significantly faster pain relief when paracetamol is used.

  3. Comparing the effectiveness and wash-off resistance of skin barrier creams: a healthy volunteer study.

    Science.gov (United States)

    Dykes, P; Bradbury, S

    2017-09-02

    Preventing moisture damage and breakdown of the skin can be a particular challenge for patients with incontinence. The level of protection offered by various skin protectant products can vary according to the chemical nature of the formulation and can decrease following wash procedures. The aim of this study was to compare five silicone-containing skin barrier creams indicated for use on incontinence-associated dermatitis (IAD) in terms of their resistance to a standardised wash cycle in healthy volunteer subjects. A skin surface hygrometer (Skicon 200EX) evaluated skin surface conduction non-invasively on 36 non-patient subjects using a high-frequency (3.5MHz) electric current. This provided an index of the degree of protection given by barrier products after a single application and also any reduction in barrier properties after a repeated wash procedure. Medi Derma-S barrier cream (MDS), Cavilon barrier cream (CBC) and LBF barrier cream (LBF) all demonstrated statistically significant differences (pcream (RBC) and the untreated control. All other comparisons were not significant (p>0.05). Statistical analysis following four moisture challenges reflected the results following the first, whereby Skicon values following treatment with MDS, CBC and LBF was significantly different compared with MH, RBC and the untreated control. Again, all other comparisons were not significant (p>0.05). When expressed as percentage barrier effectiveness, the results show a similar pattern to the absolute Skicon values. The results of this study show that there were differences between the barrier creams in terms of the initial moisture challenge and the resistance to wash-off following a repeated standardised wash procedure. It was concluded that MDS, CBC and LBF barrier cream all showed significant and equally effective moisture barrier protection and wash-off resistance.

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

    Science.gov (United States)

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

    2010-06-01

    Hydrogen sulphide (H(2)S) 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 H(2)S to the tissues. In the current study, we have measured H(2)S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. 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 H(2)S concentrations using a custom-made device based on a sulphide gas detector (Interscan). Administration of IK-1001, a parenteral formulation of Na(2)S (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 H(2)S was observed to be higher than the ambient concentration of H(2)S gas in room air, indicative of on-going endogenous H(2)S production in human subjects. Upon intravenous administration of Na(2)S, a rapid elevation of exhaled H(2)S concentrations was observed. The amount of exhaled H(2)S rapidly decreased after discontinuation of the infusion of Na(2)S. Exhaled H(2)S represents a detectable route of elimination after parenteral administration of Na(2)S.

  5. Mass balance and metabolism of Z-215, a novel proton pump inhibitor, in healthy volunteers.

    Science.gov (United States)

    Toda, Ryoko; Miyagawa, Tomoharu; Masuda, Yuka; Hoshino, Yusuke; Yoshii, Kazuyoshi; Hirayama, Masamichi; Shibuya, Minaka; Kawabata, Yoshihiro

    2017-11-02

    The human mass balance of [(14 )C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [(14 )C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [(14 )C]Z-215 was rapidly absorbed, with a Cmax of 434 ng/mL at 0.38 h for Z-215 and 732 ng eq./mL at 0.5 h for total radioactivity. Means of 59.61% and 31.36% of the administered radioactive dose were excreted in urine and faeces, respectively, within 168 h post-dose. The majority of the dose was recovered within 24 h in urine and 96 h in faeces. Unchanged Z-215 was excreted in urine at trace levels but was not detected in faeces. The main components in plasma were Z-215 and Z-215 sulphone, accounting for 29.8% and 13.3% of the total circulating radioactivity, respectively. Additionally, Z-215 was metabolised through oxidation, reduction and conjugation. Our in vitro Z-215 metabolism study showed that the major isozyme contributing to the oxidation of Z-215, including the formation of Z-215 sulphone, was CYP3A4. In conclusion, Z-215 is well absorbed in humans and primarily eliminated via metabolism, where CYP3A4 plays an important role.

  6. Methylnaltrexone: Its Pharmacological Effects Alone and Effects on Morphine in Healthy Volunteers

    Science.gov (United States)

    Zacny, James P.; Wroblewski, Kristen; Coalson, Dennis W.

    2014-01-01

    Rationale Methylnaltrexone bromide (MTNX) is a peripherally acting mu-opioid receptor antagonist, prescribed for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care. Studies have used this drug to determine if other opioid-induced effects besides constipation are altered by MTNX in humans, and have suggested based on their results that these other effects are altered by peripheral opioid actions. Objective The primary objective of this report is to present results that provide indirect evidence that MTNX has centrally-mediated effects, albeit slight, and secondarily to describe the effects of MTNX on psychopharmacological effects of morphine. Methods In a crossover, randomized, placebo-controlled, double-blind study, 29 healthy volunteers received 0.45 mg/kg MTNX or saline subcutaneously, followed by saline intravenously. In three other conditions 0.143 mg/kg of morphine sulfate administered intravenously was preceded by subcutaneous administration of 0, 0.225, or 0.45 mg/kg MTNX. Before and after drug administration, subjective and physiological measures, including pupil diameter, were assessed. Results Two separate analyses confirmed that 0.45 mg/kg MTNX alone induced a slight degree of miosis, a centrally mediated opioid agonist effect. This dose had minimal subjective effects. MTNX at either or both the 0.225 and 0.45 mg/kg dose reduced some subjective effects of morphine without altering miosis. Conclusions We present indirect evidence that MTNX crosses the blood-brain barrier in humans. Therefore, whether the reductions in subjective effects of morphine by MTNX that were observed in past studies and in this study can be attributed to peripheral mechanisms is open to question. PMID:24871705

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  9. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Ryszard M Pluta

    Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

  10. Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects

    Directory of Open Access Journals (Sweden)

    Woo HI

    2017-04-01

    Full Text Available Hye In Woo,1 Suk Ran Kim,2 Wooseong Huh,3,4 Jae-Wook Ko,4 Soo-Youn Lee4,5 1Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea; 2Clinical Research and Development, Hanmi Pharm. Co., Ltd., Seoul, Korea; 3Department of Medicine, 4Department of Clinical Pharmacology and Therapeutics, 5Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Background: Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals.Methods: Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array.Results: The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1, SLCO1B3, and ABCC2 genes were associated with either the maximum concentration (Cmax of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C. Minor homozygotes (76.5 ng/mL of SLCO1B1 c.-910G>A showed higher Cmax than heterozygotes (34.0 ng/mL and major homozygotes (33.5 ng/mL, false discovery rate P=0.040. Cmax and the area under the plasma concentration curve from hour 0 to infinity (AUC∞ were higher in carriers of the SLCO1B1*17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for Cmax; 221.5 vs 154.2 ng/mL for AUC∞. SLCO1B3 c.334G>T homozygotes (63.0 ng/mL also showed higher Cmax than

  11. Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Tempero, Kenneth; Kirby, Mary; Thompson, Jeffrey

    2005-01-01

    Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. This study was undertaken to characterise the pharmacokinetics and assess the dose proportionality of FEBT in healthy volunteers within the potential therapeutic dose range. Twenty-five healthy adults (mean age 33 years) completed a single-dose, randomised, open-label, four-dose, four-period, crossover study of FEBT. They were administered FEBT 200, 500, 810 or 1080microg. The subjects in this study were not opioid tolerant; therefore, naltrexone was administered to block any opioid receptor-mediated effects of fentanyl. Venous blood samples for measurement of serum fentanyl concentrations were obtained over 36 hours following dosing. Adverse events were recorded throughout the study. The pharmacokinetics of FEBT were characterised by an absorption phase with a median time to reach maximum serum concentration (tmax) of 0.75-0.99 hours that was consistent irrespective of dose. Mean serum fentanyl concentrations exhibited a biexponential decline from peak after FEBT 200 and 500microg doses and a triexponential decline after FEBT 810 and 1080microg doses. The maximum serum concentration (Cmax) of fentanyl was proportional up to and including the 810microg dose. The increase in Cmax was 20% less than proportional at the 1080microg dose. Systemic exposure to fentanyl, as measured by the area under the serum concentration-time curve from time zero to infinity (AUCinfinity), increased proportionally with increasing doses of FEBT (200-1080microg). No serious adverse events were reported during the study. The pharmacokinetics of FEBT were characterised by a high early fentanyl concentration as a result of absorption across the buccal mucosa of the oral cavity, which results in bypassing first-pass metabolism. This high early tmax contributed to enhanced early systemic fentanyl exposure. Maximum concentration and AUCinfinity of FEBT

  12. Myocardial extracellular volume fraction from T1 measurements in healthy volunteers and mice: relationship to aging and cardiac dimensions.

    Science.gov (United States)

    Neilan, Tomas G; Coelho-Filho, Otavio R; Shah, Ravi V; Abbasi, Siddique A; Heydari, Bobak; Watanabe, Eri; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond Y; Jerosch-Herold, Michael

    2013-06-01

    This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. In healthy volunteers (N = 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r = 0.74, p volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Photoreceptor outer segment layer thickness measured manually on images from spectral domain optical coherence tomography in healthy volunteers.

    Science.gov (United States)

    Özkaya, A; Alkin, Z; Karatas, G; Karakucuk, Y; Perente, I; Taylan Yazici, A; Demirok, A

    2014-06-01

    To investigate photoreceptor outer segment layer thickness measured with a manual technique on images from spectral domain optical coherence tomography (OCT) in healthy volunteers. In 60 eyes of 30 healthy volunteers, a spectral domain OCT device (Spectralis, Heidelberg Engineering) was used to obtain cross-sectional images of the retina. For each volunteer, two images of each eye were obtained in one sitting. Images were digitally enlarged and the manual calipers feature of the device's software was used to measure, at the lowest point in the fovea, the thickness of the photoreceptor outer segment layer. All measurements were performed by the same investigator. Repeatability was evaluated with the Bland-Altman repeatability coefficient, and intersubject variability with Pearson's coefficient of variation. The mean values of measurements across all the volunteers were as follows: right eye first image 38.1 micrometers, right eye second image 37.9 micrometers, left eye first image 37.9 micrometers, left eye second image 37.9 micrometers. The repeatability coefficient, i.e. the difference between repeated measurements which would be exceeded in only 5% of cases, was 1.6 micrometers. Coefficients of variation for the right eye were 3.4% for the first images and 3.4% for the second images, and for the left eye they were 3.2 and 4.0% respectively. With a manual method based on spectral domain OCT, the thickness of the photoreceptor outer segment layer at the central fovea can be measured within a useful range of repeatability and appears to be relatively constant across healthy volunteers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. A phase I, dose-escalation trial evaluating the safety and efficacy of emulsified isoflurane in healthy human volunteers.

    Science.gov (United States)

    Huang, Han; Li, Rui; Liu, Jin; Zhang, Wensheng; Liao, Tianzhi; Yi, Xiaoqian

    2014-03-01

    This first-in-human volunteer phase I clinical trial aimed to evaluate the safety, tolerability, and anesthesia efficacy of emulsified isoflurane (EI), an intravenously injectable formulation of isoflurane. Seventy-eight healthy volunteers were recruited in this open-label, single-bolus, dose-escalation, phase I trial and were allocated into 16 cohorts. Each volunteer received a single bolus injection of EI. The dose started with 0.3 mg/kg (for isoflurane) and was planned to end with 64.6 mg/kg. Postdose vital signs, physical examination, laboratory tests, chest radiograph, 12-lead electrocardiogram, and development of any adverse event were closely monitored as safety measurements. Effectiveness in producing sedation/anesthesia was assessed by Modified Observer's Assessment of Alertness/Sedation and Bispectral Index. The dose escalation ended as planned. The most common adverse events associated with EI were injection pain (77 of 78, 98.7%) and transient tachycardia (22 of 78, 25.6%). Only at high doses (≥38.3 mg/kg) did EI cause transient hypotension (5 of 78, 6.4%) or apnea (11 of 78, 14.1%), but all the affected volunteers recovered uneventfully. Fast onset of unconsciousness (typically 40 s after injection) was developed in all volunteers receiving doses of 22.6 mg/kg or greater. Waking-up time and depression in Modified Observer's Assessment of Alertness/Sedation correlated well with EI dose. None of the postdose tests revealed any abnormal result. EI is safe for intravenous injection in human volunteers in the dose range of 0.3 to 64.6 mg/kg. At doses of 22.6 mg/kg or higher, EI produced rapid onset of unconsciousness in all volunteers followed by fast, predictable, and complete recovery.

  15. Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Petersen, Jesper; Wienecke, Troels

    2009-01-01

    sumatriptan modulate the baseline CGRP levels in vivo, under conditions without trigeminovascular system activation. We sampled blood from the internal and external jugular, the cubital veins, and the radial artery before and after administration of subcutaneous sumatriptan in 16 healthy volunteers. Repeated-measure...... not differ between the four vascular compartments (P=0.49). It was found that Sumatriptan did not change the levels of circulating CGRP in the intra or extracerebral circulation in healthy volunteers. This speaks against a direct CGRP-reducing effect of sumatriptan in vivo in humans when the trigemino......Triptans are effective and well tolerated in acute migraine management but their exact mechanism of action is still debated. Triptans might exert their antimigraine effect by reducing the levels of circulating calcitonin gene-related peptide (CGRP). To examine this question, we examined whether...

  16. Comparison of Quantitative Cartilage T2 Measurements and Qualitative MR Imaging between Professional Ballet Dancers and Healthy Volunteers.

    Science.gov (United States)

    Cha, Jang Gyu; Yi, Ji Sook; Han, Jong Kyu; Lee, Young Koo

    2015-07-01

    To compare qualitative magnetic resonance (MR) images and quantitative T2 measurements of the tibiotalar cartilage between ballerinas and healthy volunteers. Institutional review board approval for this study and informed consent (from all participants) were obtained. MR examinations were performed by using a 3-T MR imaging system with 21 professional female ballet dancers and 20 healthy female volunteers. Two musculoskeletal radiologists qualitatively measured tibiotalar cartilage T2 values in the anterior zones, middle zones, and posterior zones of cartilage. MR findings were also qualitatively analyzed in both groups. The tibial cartilage T2 values measured in the anterior and posterior zones and the talar cartilage T2 values measured in all three zones were significantly higher in the ballerina group than in the control group (P measurement may potentially be used as a noninvasive imaging tool for early detection of cartilage lesions in the tibiotalar joint.

  17. Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers.

    Science.gov (United States)

    Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen

    2014-12-01

    The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

  18. Disassociation of Static and Dynamic Cerebral Autoregulatory Performance in Healthy Volunteers After Lipopolysaccharide Infusion and in Patients with Sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan Martin Griffin; Plovsing, Ronni R.; Ronit, Andreas

    2012-01-01

    -experimental model of the systemic inflammatory response during early sepsis, and (ii) in patients with advanced clinical sepsis. Cerebral autoregulation was tested using transcranial Doppler ultrasonography (i) before and after lipopolysaccharide (LPS) infusion in healthy volunteers (n=9), and (ii) in patients...... with sepsis (n=16). Static autoregulation was tested by norepinephrine infusion and dynamic autoregulation by transfer function analysis (TFA) of spontaneous oscillations between mean arterial blood pressure and middle cerebral artery blood flow velocity in the low frequency range (0.07-0.20 Hz). Static...... autoregulatory performance after LPS infusion and in patients with sepsis was similar to values in healthy volunteers at baseline. In contrast, TFA showed decreased gain and an increased phase difference between blood pressure and cerebral artery blood flow velocity after LPS (both p

  19. Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

    Science.gov (United States)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

  20. An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers

    OpenAIRE

    Teng, Renli; Carlson, Glenn; Hsia, Judith

    2014-01-01

    Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric t...

  1. Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers

    OpenAIRE

    Berteau, Cecile; Schwarzenbach, Florence; Donazzolo, Yves; Latreille, Mathilde; Berube, Julie; Abry, Herve; Cotten, Jo?l; Feger, Celine; Laurent, Philippe E

    2010-01-01

    Objective: A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. Methods: This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered ...

  2. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants

    OpenAIRE

    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

    2013-01-01

    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 an...

  3. Scarce Evidence of Yogurt Lactic Acid Bacteria in Human Feces after Daily Yogurt Consumption by Healthy Volunteers

    OpenAIRE

    del Campo, Rosa; Bravo, Daniel; Cantón, Rafael; Ruiz-Garbajosa, Patricia; García-Albiach, Raimundo; Montesi-Libois, Alejandra; Yuste, Francisco-Javier; Abraira, Victor; Baquero, Fernando

    2005-01-01

    In a double-blind prospective study including 114 healthy young volunteers, the presence in human feces of the yogurt organisms Lactobacillus delbrueckii and Streptococcus thermophilus after repeated yogurt consumption (15 days) was analyzed by culture, specific PCR, and DNA hybridization of total fecal DNA. Detection of yogurt lactic acid bacteria in total fecal DNA by bacterial culture and PCR assay was consistently negative. DNA compatible with yogurt bacteria was found by hybridization ex...

  4. Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

    Science.gov (United States)

    Lees, J; Michalopoulou, P G; Lewis, S W; Preston, S; Bamford, C; Collier, T; Kalpakidou, A; Wykes, T; Emsley, R; Pandina, G; Kapur, S; Drake, R J

    2017-10-01

    Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

  5. Shear-wave sonoelastography for assessing masseter muscle hardness in comparison with strain sonoelastography: study with phantoms and healthy volunteers.

    Science.gov (United States)

    Ariji, Yoshiko; Nakayama, Miwa; Nishiyama, Wataru; Nozawa, Michihito; Ariji, Eiichiro

    2016-01-01

    Objectives Shear-wave sonoelastography is expected to facilitate low operator dependency, high reproducibility and quantitative evaluation, whereas there are few reports on available normative values of in vivo tissue in head and neck fields. The purpose of this study was to examine the reliabilities on measuring hardness using shear-wave sonoelastography and to clarify normal values of masseter muscle hardness in healthy volunteers. Methods Phantoms with known hardness ranging from 20 to 140 kPa were scanned with shear-wave sonoelastography, and inter- and intraoperator reliabilities were examined compared with strain sonoelastography. The relationships between the actual and measured hardness were analyzed. The masseter muscle hardness in 30 healthy volunteers was measured using shear-wave sonoelastography. The inter- and intraoperator intraclass correlation coefficients were almost perfect. Strong correlations were seen between the actual and measured hardness. The mean hardness of the masseter muscles in healthy volunteers was 42.82 ± 5.56 kPa at rest and 53.36 ± 8.46 kPa during jaw clenching. The hardness measured with shear-wave sonoelastography showed high-level reliability. Shear-wave sonoelastography may be suitable for evaluation of the masseter muscles.

  6. Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers.

    Science.gov (United States)

    Mondal, Shankar; Varma, Saurabh; Bamola, Vishwa Deepak; Naik, Satya Narayan; Mirdha, Bijay Ranjan; Padhi, Madan Mohan; Mehta, Nalin; Mahapatra, Sushil Chandra

    2011-07-14

    Tulsi (Ocimum sanctum Linn.) is considered as a sacred herb and traditionally it is believed that consumption of Tulsi leaf on empty stomach increases immunity. Experimental studies have shown that alcoholic extract of Tulsi modulates immunity. The present study was designed to evaluate the immunomodulatory effects of ethanolic extract of Tulsi leaves through a double-blinded randomized controlled cross-over trial on healthy volunteers. Three hundred milligrams capsules of ethanolic extracts of leaves of Tulsi or placebo were administered to 24 healthy volunteers on empty stomach and the results of 22 subjects who completed the study were analyzed. The primary objective was to study the levels of Th1 and Th2 cytokines (interferon-γ and interleukin-4) during both pre and post intervention period in blood culture supernatants following stimulation with lipopolysaccharide and phytohaemagglutinin. Other immunological parameters such as T-helper and T-cytotoxic cells, B-cells and NK-cells also were analyzed using Flowcytometry. Statistically significant increase in the levels of IFN-γ (p=0.039), IL-4 (p=0.001) and percentages of T-helper cells (p=0.001) and NK-cells (p=0.017) were observed after 4 weeks in the Tulsi extract intervention group in contrast to the placebo group. These observations clearly ascertain the immunomodulatory role of Tulsi leaves extract on healthy volunteers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple-dose administration in healthy volunteers

    Science.gov (United States)

    Tiseo, P J; Foley, K; Friedhoff, L T

    1998-01-01

    Aim The aim of the study was to evaluate the pharmacokinetics of theophylline administered alone, and in combination with donepezil HCl, following multiple-dose administration of both drugs in healthy volunteers. Methods This was an open-label, randomized, two-period crossover study in healthy male volunteers (n = 12). During each treatment period, subjects received either titrated-dose theophylline alone, or in combination with donepezil (5 mg, once daily) for 10 consecutive days. On day 10 of each treatment period, serial blood samples for the determination of theophylline concentrations in plasma were measured up to 24 h. Treatment periods were separated by a 3-week, drug-free washout. Plasma concentrations of theophylline were determined by HPLC with UV detection. Results No statistically significant differences in theophylline pharmacokinetics (Cmax, AUC or tmax) were observed between theophylline administered alone and in combination with donepezil. No clinically significant changes in vital signs, ECG parameters or clinical laboratory tests were observed in any subject during any treatment period. Conclusions Concurrent administration of donepezil HCl does not alter the pharmacokinetic profile of theophylline following multiple-dose administration of both drugs in healthy volunteers. These findings suggest that donepezil may be safely co-administered with theophylline without a need for dose modification or additional monitoring procedures. PMID:9839764

  8. Development and Evaluation of Korean Version of Quality of Sexual Function (QSF-K) in Healthy Korean Women

    OpenAIRE

    Lee, Yumi; Lim, Myong Cheol; Son, Yedong; Joo, Jungnam; Park, KiByung; Kim, Jung-Sup; Lee, Dong Ock; Park, Sang-Yoon

    2014-01-01

    This study was done to develop a Korean version of the Quality of Sexual Function (QSF-K) and evaluate the validity and reliability of the QSF-K. The participants were 220 women who visited the Center for Uterine Cancer at the National Cancer Center in Korea. Participants completed the scale once and then again at a two to four week interval. The QSF-K, Female Sexual Function Index (FSFI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EOR...

  9. Modafinil increases the latency of response in the Hayling Sentence Completion Test in healthy volunteers: a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Ahmed Dahir Mohamed

    Full Text Available 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.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.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.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 accuracy of performance. This finding may

  10. Modafinil increases the latency of response in the Hayling Sentence Completion Test in healthy volunteers: a randomised controlled trial.

    Science.gov (United States)

    Mohamed, Ahmed Dahir; Lewis, Chris Roberts

    2014-01-01

    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). 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. 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. 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 accuracy of performance. This finding may provide

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

    Directory of Open Access Journals (Sweden)

    Pickering G

    2015-07-01

    Full Text Available Gisèle Pickering,1–3 Adrian Kastler,4 Nicolas Macian,1,2 Bruno Pereira,5 Romain Valabrègue,6 Stéphane Lehericy,6 Louis Boyer,4,7 Claude Dubray,1–3 Betty Jean4 1CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, 2Centre d’Investigation Clinique – Inserm 1405, 3Clermont Université, Laboratoire de Pharmacologie, Faculté de médecine, 4CHU Gabriel Montpied, Clermont-Ferrand, Service d’Imagerie Ostéo-articulaire thoracique et neurologique, 5CHU Clermont-Ferrand, Délégation Recherche Clinique et à l’Innovation, Clermont-Ferrand, France; 6Institut du Cerveau et de la Moelle epiniere – ICM, Centre de NeuroImagerie de Recherche CENIR, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris, Paris, France, Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 7UMR CNRS UdA 6284, Clemont-Ferrand, France 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

  12. Lack of significant food effect on the pharmacokinetics of ticagrelor in healthy volunteers.

    Science.gov (United States)

    Teng, R; Mitchell, P D; Butler, K

    2012-08-01

    Ticagrelor is the first reversibly binding oral P2Y(12) receptor antagonist and has been approved in the European Union and the USA for the reduction of clinical thrombotic events in patients with acute coronary syndromes. This study aimed to assess the effect of food on ticagrelor pharmacokinetics. The study was an open-label, randomized, 2-period crossover single-centre trial; 26 healthy volunteers received a single 270 mg (3×90 mg tablets) ticagrelor dose orally following: (i) a 10-h overnight fast; and (ii) after a standard high-fat, high-calorie breakfast. Ticagrelor and AR-C124910XX (a major pharmacologically active metabolite) plasma concentrations were quantified for pharmacokinetic analysis. Ticagrelor median time to maximum concentration (t(max); 2·5 h vs. 1·5 h) was slightly delayed in the fed vs. fasting state. Maximum concentration of ticagrelor (C(max)) was comparable between the two states with 95% confidence intervals (CI) of the geometric least-squares (GLS) mean ratio (0·85-1·03) being within no-effect limits (0·80-1·25). Ticagrelor exposure was slightly higher with food intake; area under the plasma concentration-time curve from zero to infinity (AUC) was 21% higher compared with fasting state (95% CI of GLS mean ratio=1·13-1·30). For AR-C124910XX, AUC (95% CI of GLS mean ratio=0·93-1·07) was unaffected by food consumption. Median t(max) of the metabolite was slightly longer in the fed than fasting state (3·5 h vs. 1·5 h). Mean C(max) for AR-C124910XX was slightly lower (22%) with food intake vs. fasting (95% CI of GLS mean ratio 0·69-0·88). Food effects on ticagrelor AUC and AR-C124910XX C(max) were small and are considered to be of minimal clinical significance. Thus, ticagrelor can be administered with or without food. © 2011 Blackwell Publishing Ltd.

  13. Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

    Directory of Open Access Journals (Sweden)

    Werawath Mahatthanatrakul

    2008-05-01

    Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

  14. ISOPROTERNENOL INCREASES EFFICIENCY AND EFFECTIVENESS OF A LARGE FLUID BOLUS IN HEALTHY VOLUNTEERS

    Science.gov (United States)

    Asmussen, Sven; Salter, Michael; Prough, Donald S.; Kramer, George C.; Svensen, Christer; Sheffield-Moore, Melinda; Kinsky, Michael P.

    2014-01-01

    Background The primary goal of fluid therapy is to maintain fluid homeostasis. Commonly used isotonic crystalloids are only marginally effective and contribute to fluid excess syndrome. In patients with decreased cardiovascular reserve, fluid therapy alone is not sufficient to maintain end-organ perfusion. Therefore, inotropes or vasoactive drugs are used to supplement fluid infusion. Recent animal data suggests that co-infusion of adrenergic agents modulate the distribution of fluid between the vascular and extravascular/interstitial compartments after a fluid bolus. We sought to determine if this effect would translate in humans by co-administering a beta (β)-adrenergic agonist with fluid. Methods Nine healthy volunteers (age 21–50 yrs) were randomly paired and received either a continuous isoproterenol infusion (ISO:0.05μg/kg/min) or 0.9% saline (control(CON)) 30min prior to a 25mL/kg 0.9% NaCl fluid bolus. Hemodynamics, ventricular volume and function and microcirculatory determinants (capillary filtration coefficient (CFC) and oncotic pressure) were measured. Vascular and extra-vascular volume (EVV) and fluid balance were determined. Results Compared to CON, ISO significantly increased heart rate (CON:64.2 ±4.1 bpm vs. ISO:97.4±5.7 bpm) and cardiac output (CON 4.4±0.7L/min vs. ISO:10.2±0.9) before fluid bolus. ISO significantly increased urinary output (ISO: 10.86±1.95 vs Control: 6.53±1.45 mL/kg) and reduced EVV (7.98±2.0 vs 14.15±1.1mL/kg). ISO prevented an increase in CFC (1.74±0.4 vs 3.21±0.4 mL/min/mmHg•10−3). Conclusion Isoproterenol, a non-selective β-adrenergic agonist, augments vascular volume expansion and eliminates EVV via enhanced diuresis, which may in part be due to enhanced endothelial barrier function. PMID:25046539

  15. Relative Bioavailability of Two Enteric-Coated Formulations of Omeprazole following Repeated Doses in Healthy Volunteers.

    Science.gov (United States)

    Vaz-da-Silva, M; Hainzl, D; Almeida, L; Dolgner, A; Silveira, P; Maia, J; Soares-da-Silva, P

    2001-03-01

    This study aimed to investigate the relative bioavailability and bioequivalence of two omeprazole enteric-coated formulations following repeated doses (steady state) in healthy male and female adult volunteers. The study formulation (Ompranyt® 20mg capsules, Bial-Industrial Farmaceutica SA, Spain) was compared with an omeprazole reference formulation (Mopral® 20mg capsules, Laboratório Astra, Spain). 24 participants were randomised using a two-way, crossover design to receive either one capsule/day of Ompranyt® or one capsule/day of Mopral® during two sequential periods of five consecutive days each. The participants were administered the drugs in the fasting state. Omeprazole concentrations in plasma samples were quantified by a validated method using a reversed-phase high performance liquid chromatography with UV detection (HPLC-UV). The validation method is described. The study was conducted at the Human Pharmacology Unit, Department of Research & Development, Laboratorios Bial (S. Mamede do Coronado, Portugal). The arithmetic mean ± SD values of the area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) were 1474 ± 1417 μg/L·h for Ompranyt® and 1490 ± 1276 μg/L·h for Mopral®. The geometric means ratio (Ompranyt®/Mopral®) was 0.99, with 90% confidence intervals (CI) of 0.97-1.03. The estimated maximum plasma concentration (Cmax) was 630.1 ± 516.7 μg/L for Ompranyt® and 736.7 ± 443.3 μg/L for Mopral®, with a geometric means ratio (Ompranyt®/Mopral®) of 0.96 (90% CI: 0.94-0.99). Bioequivalence of these two formulations was accepted based on the two one-sided ANOVA for AUC0-∞ as well as for Cmax. In both cases, the 90% CI lies within the acceptance range of 0.80-1.25. Bioequivalence of Ompranyt® and Mopral® was demonstrated after repeated drug administration in fasting conditions, and both products were similarly well tolerated. Therefore, both formulations are expected to be equivalent in a clinical

  16. Clarithromycin bioequivalence study of two oral formulations in healthy human volunteers.

    Science.gov (United States)

    Lerner, F E; Caliendo, G; Santagada, V; Santana GSM; Moraes MEA; De Nucci, G

    2000-07-01

    To assess the bioequivalence of two tablet formulations of clarithromycin (Clamicin 500 mg from Medley Indlistria Farmaceutica, Brazil, as the test formulation, and Biaxin 500 mg from Abbott Industries, USA, as the reference formulation). A single 500 mg oral dose of each formulation was administrated in 24 healthy volunteers of both sexes (12 males and 12 females). The study was conducted open, randomized, two-period crossover design with a 7-day interval between doses. The plasma concentrations of clarithromycin were quantified by reversed phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM) method. 14-hydroxyclarithromycin concentration was estimated semiquantitatively as equivalent of clarithromycin/ml. The precision of the method was evaluated using calibration curves and plasma quality control samples. The pharmacokinetic parameters calculated for both compounds included: AUC(0 - 48h), AUC(0 - infinity), Cmax, Cmax/AUC(0 - 48h), Tmax, T1/2 and Ke. Standard curves of clarithromycin in plasma were linear in the range of 0.05 microg x ml(-1) to 10 microg x ml(-1) (r > 0.999). The limit of quantification was 5 ng/ml. Within- and between-run plasma quality control CV were 5.8% and 15.7%, respectively. Inaccuracy within- and between-runs were 14% and 17%, respectively. 90% CI for clarithromycin geometric mean AUC(0 - 48h), AUC(0 - infinity) and Cmax ratios (test/reference) were: 8.7% - 103.1%, 89.4% - 103.7% and 85.4% - 99.6%, respectively, and for hydroxyclarithomycin were 80.3% - 108.6%, 80.1% - 110.1% and 85.4% - 112.6%, respectively. The method described for the quantification of charithomycin and its main metabolite is accurate and sensitive. Clamicin was considered bio-equivalent to Biaxin based on the rate and extent of absorption. Since these were no significant differences in the bioequivalence determined using the pharmacokinetic parameters of either

  17. Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

    Science.gov (United States)

    Costa, Marisa Boff; Picon, Paulo Dornelles; Sander, Guilherme Becker; Cuni, Hugo Nodarse; Silva, Carmen Valenzuela; Meireles, Rolando Páez; Góes, Ana Carolina Magalhães Andrade; Batoreu, Nadia Maria; Maia, Maria de Lourdes de Sousa; Albuquerque, Elizabeth Maciel; Matos, Denise Cristina de Souza; Saura, Pedro Lopez

    2018-01-04

    Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (T max : 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t 1/2 : 192 vs. 108 h [p = 0.0218]). BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

  18. Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization

    Science.gov (United States)

    Cao, G; Zhang, J; Wu, X; Yu, J; Chen, Y; Ye, X; Zhu, D; Zhang, Y; Guo, B; Shi, Y

    2013-01-01

    What is known and objective The pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen. Methods The PK study included single-dose (750 mg/150 mL) and multiple-dose (750 mg/150 mL once daily for 7 days) phases. The concentration of levofloxacin in blood and urine was determined using HPLC method. Both non-compartmental and compartmental analyses were performed to estimate PK parameters. Taking fCmax/MIC ≥5 and fAUC24 h/MIC ≥30 as a target, the cumulative fraction of response (CFR) of levofloxacin 750 mg for treatment of community-acquired pneumonia (CAP) was calculated using Monte Carlo simulation. The probability of target attainment (PTA) of levofloxacin at various minimal inhibitory concentrations (MICs) was also evaluated. Results and discussion The results of PK study showed that the Cmax and AUC0–∞ of levofloxacin were 14·94 μg/mL and 80·14 μg h/mL following single-dose infusion of levofloxacin. The half-life and average cumulative urine excretion ratio within 72 h post-dosing were 7·75 h and 86·95%, respectively. The mean Css,max, Css,min and AUC0–τ of levofloxacin at steady state following multiple doses were 13·31 μg/mL, 0·031 μg/mL and 103·7 μg h/mL, respectively. The accumulation coefficient was 1·22. PK/PD analysis revealed that the CFR value of levofloxacin 750-mg regimen against Streptococcus pneumoniae was 96·2% and 95·4%, respectively, in terms of fCmax/MIC and fAUC/MIC targets. What is new and conclusion The regimen of 750-mg levofloxacin once daily provides a satisfactory PK/PD profile against the main pathogenic bacteria of CAP, which implies promising clinical and bacteriological efficacy for patients with CAP. A large-scale clinical study is warranted to confirm these results. PMID:23701411

  19. Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sisse R Ostrowski

    Full Text Available Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG.Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour, with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest were recorded. Mixed models with Tukey post hoc tests and correlations were applied.Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05. Platelet aggregation decreased (all tests, p<0.05, whereas TEG whole blood clot firmness increased (G, p = 0.05. Furthermore, during endotoxemia (4 h, whole blood fibrinolysis increased (clot lysis time (CLT, p<0.001 and Functional Fibrinogen clot strength decreased (p = 0.049. After endotoxemia (6 h, whole blood fibrinolysis was reduced (CLT, p<0.05. In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001.Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are

  20. Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Parikh N

    2016-10-01

    Full Text Available Neha Parikh,1 William G Kramer,2 Varun Khurana,1 Christina Cognata Smith,1 Santosh Vetticaden,1 1INSYS Therapeutics, Inc., Chandler, AZ, USA; 2Kramer Consulting LLC, North Potomac, MD, USA Background: Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation. Methods: In an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry. Results: Fifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0–t and AUC from time zero to infinity (AUC0–∞. Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in <25% of patients when receiving capsules. Conclusion: Single-dose dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsule 5 mg under fasted conditions. Dronabinol oral solution formulation may provide an easy-to-swallow administration option with lower intraindividual variability as well as

  1. Effect of body mass index on global DNA methylation in healthy Korean women.

    Science.gov (United States)

    Na, Yeon Kyung; Hong, Hae Sook; Lee, Duk Hee; Lee, Won Kee; Kim, Dong Sun

    2014-06-01

    Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and 30 kg/m(2). However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.

  2. Association between Frequency of Breakfast Consumption and Academic Performance in Healthy Korean Adolescents.

    Science.gov (United States)

    So, Wi-Young

    2013-01-01

    The purpose of this study was to examine whether the frequency of breakfast consumption was related to academic performance in healthy Korean adolescents. We analyzed data from the seventh Korea Youth Risk Behavior Web-based Survey conducted in 2011, in which 75,643 adolescents from school grades 7-12 participated. We assessed the association between the frequency of breakfast consumption (per week) and academic performance using multivariate logistic regression analysis after adjusting for covariates such as age, body mass index, frequency of smoking, frequency of drinking, parents' education level, family economic status, frequency of vigorous physical activity (PA), frequency of moderate PA, frequency of muscular strength exercises, and level of mental stress. For male adolescents, the odds ratios (ORs) for achieving average or higher academic performance according to the breakfast frequency per week were once per week, 1.004 (P=0.945); twice per week, 0.915 (P=0.153); 3 days per week, 0.928 (P=0.237); 4 days per week, 1.087 (P=0.176); 5 days per week, 1.258 (Pbreakfast per week. For female adolescents, the ORs for achieving average or higher academic performance according to the breakfast frequency were once per week, 1.068 (P=0.320); twice per week, 1.140 (P=0.031); 3 days per week, 1.179 (P=0.004); 4 days per week, 1.339 (Pbreakfast per week. The frequency of breakfast consumption is positively correlated with academic performance in both male and female healthy adolescents in Korea.

  3. Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers.

    Science.gov (United States)

    Wang, Liqing; Hu, Zheyi; Deng, Xun; Wang, Yong; Zhang, Zhongyi; Cheng, Ze-Neng

    2013-04-01

    This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. Four polymorphisms CYP1A2 1C (G-3860A), G-3113A, CYP1A2 1F (C-163A) and CYP1A2 1B (C-5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200-mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after administration of 100-mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high-performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the -3113 AA genotype compared with those with the -3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the -3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2 1F polymorphisms were associated with increased CYP1A2 activity in volunteers with -3860G/-3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  4. Impact of prandial status on the comparison of capillary glucose meter and venous plasma glucose measurements in healthy volunteers.

    Science.gov (United States)

    Swaminathan, Akhilesh; Lunt, Helen; Chang, Winston S J; Logan, Florence J; Frampton, Christopher M A; Florkowski, Christopher M

    2013-01-01

    There is a negative glucose gradient between the capillary and venous systems, produced by glucose uptake into peripheral tissues. This gradient is augmented by oral glucose ingestion in healthy volunteers; thus prandial status may impact on capillary glucose meter performance. Our primary aim was to investigate whether the (capillary-venous plasma) glucose difference changed in relation to prandial status, in healthy volunteers. Glucose was measured fasting and also one hour after an ad libitum breakfast, in 103 healthy volunteers. Duplicate capillary (finger stick) measurements were undertaken at both time points, using both the FreeStyle Lite and AccuChek Performa meters. Simultaneous venous (antecubital fossa) samples were centrifuged immediately after collection and plasma glucose was measured using the laboratory hexokinase method. Results were compared by Bland-Altman difference analysis. The mean (95% CI) pre- and postprandial (capillary-plasma) glucose differences (mmol/L) were calculated for each meter. For the Freestyle Lite, the preprandial difference was -0.51 (-0.58 to -0.45) and postprandial difference was 0.81 (0.69-0.94). Corresponding differences for the Performa were -0.13 (-0.20 to -0.06) and 1.19 (1.07-1.31), respectively. T-test comparison of participants' paired pre- and postprandial (capillary-plasma) glucose differences confirmed a significant meal-related change in glucose estimation for both meters (P volunteers, both glucose meters showed a systematic positive bias one hour after breakfast. The significance of this finding in diabetes remains to be determined.

  5. The Myocardial Extracellular Volume Fraction from T1 Measurements in Healthy Volunteers and Mice; Relationship to Aging and Cardiac Dimensions

    Science.gov (United States)

    Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Watanabe, Eri; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond; Jerosch-Herold, Michael

    2013-01-01

    Objectives We aimed to test the characteristics of the myocardial extracellular volume (ECV) fraction derived from pre and post-contrast T1 measurements among healthy volunteers. Background Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Methods Healthy volunteers underwent a standard CMR with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, inter-slice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol and cardiac sections were harvested for measurement of fibrosis. Results In healthy volunteers (n=32, 56% female; ages 21 to 72), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intra-class coefficients for the intra-observer, inter-observer, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval, 0.84 to 0.98), 0.93 (95% confidence interval, 0.80 to 0.98), and 0.95 (95% confidence interval, 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r=0.74, pvolunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, LA volume, and LV mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. PMID:23643283

  6. Development and evaluation of Korean version of Quality of Sexual Function (QSF-K) in healthy Korean women.

    Science.gov (United States)

    Lee, Yumi; Lim, Myong Cheol; Son, Yedong; Joo, Jungnam; Park, KiByung; Kim, Jung-Sup; Lee, Dong Ock; Park, Sang-Yoon

    2014-06-01

    This study was done to develop a Korean version of the Quality of Sexual Function (QSF-K) and evaluate the validity and reliability of the QSF-K. The participants were 220 women who visited the Center for Uterine Cancer at the National Cancer Center in Korea. Participants completed the scale once and then again at a two to four week interval. The QSF-K, Female Sexual Function Index (FSFI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) were used in this study. Receiver operating characteristics (ROC) curve, area under the ROC curve (AUC), intraclass correlation coefficients (ICC), and Cronbach's alpha were analyzed. In the analysis of the reliability, Cronbach's alpha was 0.83 and the ICC was 0.70. The validity measured with the AUC of the QSF-K comparing the FSFI and Global Health/QOL of the EORTC-QLQ-C30 was 0.717 and 0.728, respectively. Specifically, the AUC of the sexual activity level of the QSF-K was 0.838 in the FSFI comparison. The AUC of the psycho-somatic QOL of the QSF-K was 0.758 in the Global Health/QOL of the EORTC-QLQ-C30 comparison. Approximately half of the women (51.8%) had mild complaints/problems. The Korean version of the QSF was developed and validated.

  7. The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

    Science.gov (United States)

    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

  8. Bioelectrical impedance self-measurement protocol development and daily variation between healthy volunteers and breast cancer survivors with lymphedema.

    Science.gov (United States)

    Ridner, Sheila H; Bonner, Candace M; Doersam, Jennifer K; Rhoten, Bethany A; Schultze, Benjamin; Dietrich, Mary S

    2014-03-01

    A significant percentage of breast cancer survivors are at risk for lymphedema for which lifelong self-care is required. Previous studies suggest that less than 50% of breast cancer survivors with lymphedema (BCS-LE) perform prescribed self-care tasks and that even wearing a compression sleeve, the most commonly reported self-care activity, is done irregularly. Reasons for poor self-care adherence include perceived lack of results from self-care (no available arm volume data) and perceived inability to manage the condition. A two-part pilot study was conducted to: 1) develop and determine the feasibility of a self-measurement protocol using a single frequency bioelectrical impedance device; and 2) examine daily variation in extracellular volume in healthy and lymphedematous limbs. Healthy and BCS-LE volunteers were recruited to refine and test a self-measurement protocol. Volunteers were trained in the use of the device and measured for 5 consecutive days in a laboratory setting. They were then given the device to use at home for an additional 5 consecutive days of self-measurement. All volunteers completed each scheduled home measurement. Daily variability in both groups was noted. Home self-measurement using bioelectrical impedance is feasible, acceptable, and captures change. This has implications for both self-care support and for the possibility of incorporating self-measurement using bioelectrical impedance in future clinical trials examining effectiveness of lymphedema treatment.

  9. Effect of two-linked mutations of the FMO3 gene on itopride metabolism in Chinese healthy volunteers.

    Science.gov (United States)

    Zhou, Li-Ping; Tan, Zhi-Rong; Chen, Hao; Guo, Dong; Chen, Yao; Huang, Wei-Hua; Wang, Lian-Sheng; Zhang, Guo-Gang

    2014-11-01

    Itopride is an effective gastroprokinetic agent mainly used for the treatment of functional dyspepsia. Flavin-containing monooxygenase 3 (FMO3) has been confirmed to be the key enzyme involved in the main itopride metabolic pathway. We investigated whether the FMO3 genotypes can affect itopride metabolism in Chinese healthy volunteers. Twelve healthy volunteers who had been genotyped for FMO3 gene were selected to participate in our study. Volunteers were given 50 mg itopride orally and then blood samples were collected from 0 to 24 h. The plasma concentrations of itopride and itopride N-oxide were determined by HPLC-MS/MS method. Itopride and itopride N-oxide both exhibit FMO3 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of itopride increased by 127.82 ± 41.99 % (P itopride N-oxide decreased by 30.30 ± 25.70 % (P itopride and itopride N-oxide were observed between these two genotypes. The FMO3 allele can significantly affect the metabolism of itopride. The pharmacokinetic parameters of both itopride and itopride N-oxide were significantly different between these two genotypes.

  10. Effectiveness of Topical Chia Seed Oil on Pruritus of End-stage Renal Disease (ESRD) Patients and Healthy Volunteers.

    Science.gov (United States)

    Jeong, Se Kyoo; Park, Hyun Jung; Park, Byeong Deog; Kim, Il-Hwan

    2010-05-01

    Several studies have been performed to evaluate the efficacy of dietary n-3 fatty acid for patients with renal dysfunction. While about 40% to 80% of patients with end-stage renal disease (ESRD) complain about pruritus and xerosis, there are few reports on the effects of topical n-3 fatty acid on these symptoms. In order to investigate the possible beneficial effects of topical n-3 fatty acid, oils extracted from chia (Salvia hispanica) seed were formulated into topical products, the effects of which were measured. Five healthy volunteers having xerotic pruritus symptoms and 5 patients with pruritus caused by either ESRD or diabetes were involved in this study. A topical formulation containing 4% chia seed oils were applied for an 8-week duration. Subjective itching symptoms were assessed on a 6-point scale, as were other skin functions, namely transepidermal water loss and skin capacitance. After the 8 weeks of application, significant improvements in skin hydration, lichen simplex chronicus, and prurigo nodularis were observed in all patients. A similar improvement was also observed among healthy volunteers with xerotic pruritus. Improvement of epidermal permeability barrier function and skin hydration, represented by trans-epidermal water loss and skin capacitance, respectively, were also observed. No adverse effects were observed in all the tested patients and volunteers. Chia seed oil can be used as an adjuvant moisturizing agent for pruritic skin, including that of ESRD patients.

  11. Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial.

    Science.gov (United States)

    Chinwong, Surarong; Chinwong, Dujrudee; Mangklabruks, Ampica

    2017-01-01

    This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18-25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results . Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL ( p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion . Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.

  12. Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

    Directory of Open Access Journals (Sweden)

    Surarong Chinwong

    2017-01-01

    Full Text Available This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18–25. At entry, participants were randomly allocated to receive either (i 15 mL VCO or (ii 15 mL 2% carboxymethylcellulose (CMC solution (as control, twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results. Of 32 volunteers with complete follow-up (16 males and 16 females, daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL (p=0.001 compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion. Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.

  13. Association between blood lead levels and blood pressures in a non-smoking healthy Korean population.

    Science.gov (United States)

    Lee, Kyu Rae; Ko, Ki Dong; Hwang, In Cheol; Suh, Heuy Sun; Kim, Kyoung Kon

    2017-09-01

    in a healthy Korean population, irrespective of sociodemographic factors and metabolic derangements. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Reproducibility of shear wave velocity measurements by acoustic radiation force impulse imaging of the liver: a study in healthy volunteers.

    Science.gov (United States)

    Guzmán-Aroca, Florentina; Reus, Manuel; Berná-Serna, Juan D; Serrano, Laura; Serrano, Cristina; Gilabert, Amparo; Cepero, Angela

    2011-07-01

    The purposes of this study were to investigate interobserver reproducibility using acoustic radiation force impulse imaging and to develop an acoustic radiation force impulse scoring system. Fifty healthy volunteers with normal liver function test values were selected for the study. Shear wave velocity measurements, expressed in meters per second, were taken in a deep portion of liver segment 6. Two observers with different levels of experience performed the measurements independently and blindly. All of the measurements taken by the 2 observers were valid, even in volunteers with a body mass index of greater than 28 kg/m(2). The results point to very good interobserver reproducibility of shear wave velocity measurements, with an intraclass coefficient correlation of 0.86 (P measurements using the acoustic radiation force impulse technique and a standardized protocol are accurate and reproducible.

  15. Case-control study: Determination of potential risk factors for the colonization of healthy volunteers with Streptococcus gallolyticus subsp. gallolyticus.

    Directory of Open Access Journals (Sweden)

    Jessika Dumke

    Full Text Available Streptococcus gallolyticus subsp. gallolyticus was identified in humans and animals as commensal of the gut and can act as a causative agent of endocarditis and septicemia. A case-control study was performed to identify yet unknown risk factors for the transmission of this facultative pathogen. The prevalence in the gut of 99 healthy volunteers was determined using real-time polymerase chain reaction resulting in 62.5% S. gallolyticus subsp. gallolyticus positive excrements. Subsequent cultivation offered three isolates and epidemiological analysis based on MLST revealed sequence type (ST 3 and ST 7, previously detected from bovine and endocarditis patients. These results support the hypotheses of the zoonotic potential of this bacterium. Participant questionnaires were evaluated concerning personal characteristics, nutritional habits and animal contact. Specifically, closer contact between participants and animals influenced the colonization of the human gut significantly and was further affected if volunteers used excrement for the fertilization of plants.

  16. The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers

    DEFF Research Database (Denmark)

    Duthie, GG; Pedersen, M W; PC, Morrice

    1998-01-01

    OBJECTIVE: To assess whether consumption of 100 ml of whisky or red wine by healthy male subjects increasedplasma total phenol content and antioxidant capacity. DESIGN: A Latin square arrangement to eliminate ordering effectswhereby, after an overnight fast, nine volunteers consumed 100 ml of red...... wine, malt whisky or unmatured 'new make'spirit. Each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Bloodsamples were obtained from the anticubital vein at intervals up to 4h after consumption of the beverages when a urinesample was also obtained....... RESULTS: Within 30 min of consumption of the wine and whisky, there was a similar andsignificant increase in plasma total phenol content and antioxidant capacity as determined by the ferric reducing capacityof plasma (FRAP). No changes were observed following consumption of 'new make' spirit. CONCLUSIONS:Consumption...

  17. An anatomical study of the parasacral block using magnetic resonance imaging of healthy volunteers.

    LENUS (Irish Health Repository)

    O'Connor, Maeve

    2012-01-31

    BACKGROUND: The parasacral approach to sciatic blockade is reported to be easy to learn and perform, with a high success rate and few complications. METHODS: Using magnetic resonance imaging, we evaluated the accuracy of a simulated needle (perpendicular to skin) in contacting the sacral plexus with this approach in 10 volunteers. Intrapelvic structures encountered during the simulated parasacral blocks were also recorded. RESULTS: The sacral plexus was contacted by the simulated needle in 4 of the 10 volunteers, and the sciatic nerve itself in one volunteer. The plexus was accurately located adjacent to a variety of visceral structures, including small bowel, blood vessels, and ovary. In the remaining five volunteers (in whom the plexus was not contacted on first needle pass), small bowel, rectum, blood vessels, seminal vesicles, and bony structures were encountered. Historically, when plexus is not encountered, readjustment of the needle insertion point more caudally has been recommended. We found that such an adjustment resulted in simulated perforation of intrapelvic organs or the perianal fossa. CONCLUSIONS: These findings question the reliability of the anatomical landmarks of the parasacral block and raise the possibility of frequent visceral puncture using this technique.

  18. Mercury Exposure in Healthy Korean Weaning-Age Infants: Association with Growth, Feeding and Fish Intake.

    Science.gov (United States)

    Chang, Ju Young; Park, Jeong Su; Shin, Sue; Yang, Hye Ran; Moon, Jin Soo; Ko, Jae Sung

    2015-11-17

    Low-level mercury (Hg) exposure in infancy might be harmful to the physical growth as well as neurodevelopment of children. The aim of this study was to investigate postnatal Hg exposure and its relationship with anthropometry and dietary factors in late infancy. We recruited 252 healthy Korean infants between six and 24 months of age from an outpatient clinic during the 2009/2010 and 2013/2014 seasons. We measured the weight and height of the infants and collected dietary information using questionnaires. The Hg content of the hair and blood was assessed using inductively coupled plasma mass spectroscopy. The geometric mean Hg concentration in the hair and blood was 0.22 (95% confidence interval: 0.20-0.24) µg/g and 0.94 (n = 109, 95% confidence interval: 0.89-0.99) µg/L, respectively. The hair Hg concentration showed a good correlation with the blood Hg concentration (median hair-to-blood Hg ratio: 202.7, r = 0.462, p 1 µg/g in five infants. The hair Hg concentration showed significant correlations with weight gain after birth (Z-score of the weight for age-Z-score of the birthweight; r = -0.156, p = 0.015), the duration (months) of breastfeeding as the dominant method of feeding (r = 0.274, p exposure through breastfeeding and fish intake as a complementary food did not directly affect anthropometry in this population. If prolonged breastfeeding is expected, however, the Hg exposure through fish intake may need to be monitored for both mothers and infants.

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

    Science.gov (United States)

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

    2016-05-01

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

  20. The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

    Science.gov (United States)

    Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

    2016-04-01

    The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

  1. The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

    Science.gov (United States)

    Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

    2016-01-01

    Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

  2. Pharmacokinetics of an extended release formulation of alprazolam (Xanax XR) in healthy normal adolescent and adult volunteers.

    Science.gov (United States)

    Glue, Paul; Fang, Annie; Gandelman, Kuan; Klee, Brian

    2006-01-01

    The purpose of this study was to estimate pharmacokinetics, safety, and tolerability of single doses of an extended release formulation of alprazolam (Xanax XR) in adolescent and adult healthy volunteers. This was a randomized, open-label, single-dose, 2-period crossover study. Twelve adolescent healthy volunteers (13-17 years) and 12 adult healthy volunteers (20-45 years) received single doses of Xanax XR 1 mg or 3 mg tablets. Blood samples were obtained predose and for 48 hours postdose. Plasma samples were assayed for alprazolam and its two active metabolites alpha-hydroxy-alprazolam and 4-hydroxy-alprazolam using a validated LC-MS/MS method. Safety assessments included clinical laboratory tests, vital signs, and adverse event monitoring. At both dose levels, mean plasma concentration-time profiles of alprazolam, alpha-hydroxy-alprazolam, and 4-hydroxy-alprazolam were similar in adolescent and adult subjects. The ratios of estimated geometric means for AUC(0-infinity) and Cmax between adolescents and adults for both dose levels were 115% (95% CI: [93, 143]) and 111% (95% CI: [95, 129]), respectively. An assessment of dose proportionality between the 3 mg and 1 mg alprazolam doses within both age groups indicated that the AUC(0-infinity) and Cmax were both within 80-125% equivalence limits. Parent-metabolite ratios were similar in both age groups and were consistent with those previously reported. Alprazolam was well tolerated by both age groups. The most common adverse event was somnolence, which occurred in a dose-related manner. Based on the similar pharmacokinetic profiles, dosing of Xanax XR should be similar in adolescents and adults.

  3. Comparative study on skin temperature response to menstruation at acupuncture points in healthy volunteers and primary dysmenorrhea patients

    Institute of Scientific and Technical Information of China (English)

    She Yanfen; Song Jiashan; Ma Liangxiao; Zhu Jiang; Qi Conghui; Wang Yanxia; Tang Ling; Li Chunhua; Yuan Hongwen; Liu Yuqi

    2017-01-01

    OBJECTIVE:To assess skin temperature response to menstruation at acupuncture points in primary dysmenorrhea (PD) patients and healthy volunteers so as to explore acupuncture point specificity in reflecting diseases in the light of skin temperature.METHODS:Fifty-two PD patients and 49 healthy volunteers were recruited.Skin temperature measurements were performed with a skin temperature assessment device at 10 points.Absolute difference between skin temperature of the same point on the left and right side is used as main outcome measure.RESULTS:On the first day of menstruation,when menstrual pain attacking in PD patients,a significant increase in skin temperature difference was detected at Taixi (KI 3) compared with the healthy group (P < 0.01).A significant reduction in skin temperature difference was detected at Taixi (KI 3) in the first day of menstruation compared with those values in the third day after menstruation (P < 0.01)in the healthy group.On the third day after menstruation,a significant reduction in skin temperature difference was found at Zhongdu (LR 6) in PD group compared with the healthy group (P < 0.05).No significant differences of skin temperature were detected at other points (P > 0.05).CONCLUSION:The skin temperature difference at menstruation-relevant points in PD patients did not all change significantly more than those in women without PD.Significant difference was only found in Taixi (KI 3),the Yuan-source point of Kidney meridian.

  4. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    and luminal output of PGE2 into the stomach and the duodenum of nine healthy volunteers using a new technique permitting simultaneous measurements. In the stomach modified sham feeding increased bicarbonate secretion from 382 (62) mumol/h (mean (SEM)) to 959 (224) mumol/h (p ... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p ... stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p stomach, but not the duodenum, basal and vagally stimulated PGE2 output increased significantly (p

  5. A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers

    DEFF Research Database (Denmark)

    Wienberg, M; Glenthøj, Birte Yding; Jensen, K S

    2009-01-01

    Information processing deficits are commonly found in psychiatric illnesses, while at the biochemical level serotonin seems to play a role in nearly all psychiatric disorders. Processing negativity (PN), mismatch negativity (MMN) and P300 amplitude are electrophysiological measures of information...... processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally...

  6. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers

    DEFF Research Database (Denmark)

    Madsen, Jan L; Linnet, Jan; Rumessen, Jüri J

    2006-01-01

    transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...

  7. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy

    DEFF Research Database (Denmark)

    Reimer, Christina; Søndergaard, Bo; Hilsted, Linda

    2009-01-01

    -controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid...... regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. RESULTS: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .023...

  8. Calcitonin gene-related peptide modulates heat nociception in the human brain - An fMRI study in healthy volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B.W.

    2016-01-01

    blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we...... measured BOLD-signals after injection of sumatriptan (5-HT1B/1D antagonist). Results: Brain activation to noxious heat stimuli following CGRP infusion compared to baseline resulted in increased BOLD-signal in insula and brainstem, and decreased BOLD-signal in the caudate nuclei, thalamus and cingulate...

  9. Short echo time proton spectroscopy of the brain in healthy volunteers using an insert gradient head coil

    DEFF Research Database (Denmark)

    Gideon, P; Danielsen, E R; Schneider, M

    1995-01-01

    An insert gradient head coil with built-in X, Y, and Z gradients was used for localized proton spectroscopy in the brain of healthy volunteers, using short echo time stimulated echo acquisition mode (STEAM) sequences. Volume of interest size was 3.4 ml, repetition time was 6.0 s, and echo times w....../glutamate and myo-inositols. These compounds were more prominent within grey matter than within white matter. Rough estimations of metabolite concentrations using water as an internal standard were in good agreement with previous reports....

  10. Imaging and quantification of subbasal nerve plexus in healthy volunteers and diabetic patients with or without retinopathy.

    Directory of Open Access Journals (Sweden)

    Andrey Zhivov

    Full Text Available BACKGROUND: The alterations of subbasal nerve plexus (SBP innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen eyes of diabetic patients with peripheral diabetic neuropathy aged 68.8±8.8 years and twenty eyes of healthy volunteers aged 66.3±13.3 yrs. were investigated with in vivo confocal laser-scanning microscopy (CLSM. An adapted algorithm for image analysis was used to quantify the morphological and topological properties of SBP. These properties were correlated to incidence of diabetic retinopathy (DR and corneal sensation (Cochet-Bonnet esthesiometer. The developed algorithm allows a fully automated analysis of pre-segmented SBP structures. Altogether, 10 parameters were analysed, and all of them revealed significant differences between diabetic patients and healthy volunteers. The nerve fibre density, total fibre length and nerve branches were found to be significantly lower in patients with diabetes than those of control subjects (nerve fibre density 0.006±0.002 vs. 0.020±0.007 mm/mm(2; total fibre length 6223±2419 vs. 19961±6553 µm; nerve branches 25.3±28.6 vs. 141.9±85.7 in healthy volunteers. Also the corneal sensation was significantly lower in diabetic group when compared to controls (43±11 vs. 59±18 mm. There was found no difference in SBP morphology or corneal sensation in the subgroups with (DR or without (NDR diabetic retinopathy. CONCLUSIONS/SIGNIFICANCE: SBP parameters were significantly reduced in diabetic patients, compared to control group. Interestingly, the SBP impairment could be shown even in the diabetic patients without DR. Although automatic adapted image analysis simplifies the evaluation of in vivo CLSM data, image acquisition and quantitative analysis should be optimised for

  11. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

    2003-08-28

    Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75{+-}1.55 {mu}m versus after supplementation: 70.25{+-}1.31 {mu}m; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels.

  12. Photoplethysmographic signals and blood oxygen saturation values during artificial hypothermia in healthy volunteers.

    Science.gov (United States)

    Shafique, M; Kyriacou, P A

    2012-12-01

    Pulse oximetry utilizes the technique of photoplethysmography to estimate arterial oxygen saturation (SpO(2)) values. During hypothermia, the amplitude of the photoplethysmograph (PPG) is compromised which can lead to inaccurate estimation of SpO(2). A new mutlimode PPG/pulse oximeter sensor was developed to investigate the behaviour of PPGs during conditions of induced hypothermia (hand immersed in an ice bath). PPG measurements from 20 volunteers were conducted and SpO(2) values were estimated at all stages of the experiment. Good quality PPG signals were observed from the majority of the volunteers at almost all hand temperatures. At low temperature ranges, from 13 to 21 °C, the failure rate to estimate SpO(2) values from the multimode transreflectance PPG sensor was 2.4% as compared to the commercial pulse oximeter with a failure rate of 70%.

  13. Unconscious physiological response of healthy volunteers to dynamic respiration-synchronized couch motion

    OpenAIRE

    Jöhl, Alexander; Bogowicz, Marta; Ehrbar, Stefanie; Guckenberger, Matthias; Klöck, Stephan; Meboldt, Mirko; Riesterer, Oliver; Zeilinger, Melanie; Schmid Daners, Marianne; Tanadini-Lang, Stephanie

    2017-01-01

    Background Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient’s stress and respiration behavior decreasing the couch-tracking effectiveness. Methods In total, 100 volunteers were positioned supine on a robotic couch, which moved dyna...

  14. Unconscious physiological response of healthy volunteers to dynamic respiration-synchronized couch motion

    OpenAIRE

    Jöhl, Alexander; Bogowicz, Marta; Ehrbar, Stefanie; Guckenberger, Matthias; Klöck, Stephan; Meboldt, Mirko; Riesterer, Oliver; Zeilinger, Melanie; Schmid Daners, Marianne; Tanadini-Lang, Stephanie

    2017-01-01

    BACKGROUND Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient's stress and respiration behavior decreasing the couch-tracking effectiveness. METHODS In total, 100 volunteers were positioned supine on a robotic couch, which moved dy...

  15. Pharmacokinetic interaction studies of co-administration of ticagrelor and atorvastatin or simvastatin in healthy volunteers.

    Science.gov (United States)

    Teng, Renli; Mitchell, Patrick D; Butler, Kathleen A

    2013-03-01

    Interactions between ticagrelor and atorvastatin or simvastatin were investigated in two-way crossover studies. Both studies were open-label for statin; the atorvastatin study was placebo-controlled for ticagrelor. For atorvastatin, volunteers (n = 24) received ticagrelor (loading dose 270 mg; 90 mg twice daily, 7 days) or placebo, plus atorvastatin calcium (80 mg; day 5). For simvastatin, volunteers (n = 24) received simvastatin 80 mg, or ticagrelor (loading dose 270 mg; 180 mg twice daily, 7 days) plus simvastatin (80 mg; day 5). In each study, volunteers received the alternate treatment after washout (≥ 7 days). Ticagrelor increased mean atorvastatin maximum plasma concentration (C(max)) and area under the plasma concentration-time curve from zero to infinity (AUC) by 23 % and 36 %, respectively. Simvastatin C(max) and AUC were increased by 81 % and 56 % with ticagrelor. Ticagrelor also increased C(max) and AUC of analysed atorvastatin metabolites by 13-55 % and 32-67 %, respectively, and simvastatin acid by 64 % and 52 %, respectively. Co-administration of ticagrelor with each statin was well tolerated. Exposure to ticagrelor and its active metabolite, AR-C124910XX, was generally unchanged by a single dose of either statin, except for a minor increase in ticagrelor C(max) in the presence of simvastatin. Effects of ticagrelor on atorvastatin pharmacokinetics were modest and unlikely clinically relevant, while with simvastatin, changes were slightly larger, and simvastatin doses >40 mg with ticagrelor should be avoided.

  16. Unconscious physiological response of healthy volunteers to dynamic respiration-synchronized couch motion.

    Science.gov (United States)

    Jöhl, Alexander; Bogowicz, Marta; Ehrbar, Stefanie; Guckenberger, Matthias; Klöck, Stephan; Meboldt, Mirko; Riesterer, Oliver; Zeilinger, Melanie; Schmid Daners, Marianne; Tanadini-Lang, Stephanie

    2017-11-28

    Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient's stress and respiration behavior decreasing the couch-tracking effectiveness. In total, 100 volunteers were positioned supine on a robotic couch, which moved dynamically and respiration synchronized. During the measurement, the skin conductivity, the heartrate, and the gaze location were measured indicating the volunteer's stress. Volunteers rated the subjective motion sickness using a questionnaire. The measurement alternated between static and tracking segments (three cycles), each 1 min long. The respiration amplitude showed no significant difference between tracking and static segments, but decreased significantly from the first to the last tracking segment (p < 0.0001). The respiration frequency differed significantly between tracking and static segments (p < 0.0001), but not between the first and the last tracking segment. The physiological parameters and the questionnaire showed mild signals of stress and motion sickness. Generally, people tolerated the couch motions. The interaction between couch motion and the patient's breathing pattern should be considered for a clinical implementation. The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal ( SNCTP000001878 ) on June 20, 2016.

  17. TOPS: an internet-based system to prevent healthy subjects from over-volunteering for clinical trials.

    Science.gov (United States)

    Boyce, M; Walther, M; Nentwich, H; Kirk, J; Smith, S; Warrington, S

    2012-07-01

    Our aim was to set up a system to help UK clinical research units to prevent healthy volunteers from participating in more than one non-therapeutic trial simultaneously, or from starting a second trial too soon after the first. TOPS (The Over-volunteering Prevention System) is internet-based, simple and quick to use, free to users and a charity run by a Board of Trustees. Users enter only two or three pieces of information: (1) 'National Insurance number' (NINO) of UK citizens, or 'passport number' and country of origin of non-UK citizens, as their identifier, (2) 'date of last dose' of trial medicine or (3) 'never dosed'. Subjects must consent, but TOPS collects only non-personal data, so it does not require Ethics Committee approval and is not covered by the Data Protection Act. A total of 55 research units (29 clinical research organisations, 5 pharmaceutical companies, 13 universities and 8 hospitals) throughout the UK have registered to use TOPS, and have entered 124,906 volunteers since we launched it. All commercial and many non-commercial units now use TOPS. In our unit, no subject has to the best of our knowledge participated in two trials simultaneously. TOPS has reduced to research units to comply with UK clinical trial regulations.

  18. Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers.

    Science.gov (United States)

    Webb, J; Kamali, F

    1998-06-01

    The analgesic activity of a single dose of lamotrigine (300 mg p.o.) and phenytoin (300 mg p.o.) was evaluated in a randomised, double-blind, placebo-controlled study in 12 healthy volunteers. A computerised cold-pressor test (CPT) was used to measure analgesia. Dihydrocodeine (90 mg p.o.) was used to validate the effectiveness of the CPT in measuring analgesia in the volunteers. On each study day the volunteers performed the CPT before study medication and at 1.25, 2.75, 4.25 and 5.75 h post-dose. Psychomotor tests were carried out before each CPT to determine possible drug-induced sedation. These included digit symbol substitution, critical flicker fusion and choice reaction time. Subjective feelings of concentration, vigilance and relaxation were also measured using visual analogue scales. All three active drugs significantly reduced pain scores. Maximum pain relief was achieved at 1.25 h post-dose for both dihydrocodeine and lamotrigine, whereas for phenytoin it occurred at 4.25 h post-dose. There was a significant association between analgesia and plasma concentrations of lamotrigine (P = 0.013) and phenytoin (P = 0.028). There were no significant differences in the sedation produced by any of the active drugs, compared to placebo. The findings of this study suggest that lamotrigine and phenytoin could have a wider clinical use as analgesics.

  19. Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers

    DEFF Research Database (Denmark)

    Lehtinen, Emilia K; Ucar, Ebru; Glenthøj, Birte Y

    2014-01-01

    with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were......Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients...... indicate a relationship between alertness and PPI. Further research examining the effects of melatonin on these processes in patients with schizophrenia is warranted....

  20. Traditional measures of normal anal sphincter function using high-resolution anorectal manometry (HRAM) in 115 healthy volunteers.

    Science.gov (United States)

    Carrington, E V; Brokjaer, A; Craven, H; Zarate, N; Horrocks, E J; Palit, S; Jackson, W; Duthie, G S; Knowles, C H; Lunniss, P J; Scott, S M

    2014-05-01

    High-resolution anorectal manometry (HRAM) is a relatively new method for collection and interpretation of data relevant to sphincteric function, and for the first time allows a global appreciation of the anorectum as a functional unit. Historically, traditional anal manometry has been plagued by lack of standardization and healthy volunteer data of variable quality. The aims of this study were: (i) to obtain normative data sets for traditional measures of anorectal function using HRAM in healthy subjects and; (ii) to qualitatively describe novel physiological phenomena, which may be of future relevance when this method is applied to patients. 115 healthy subjects (96 female) underwent HRAM using a 10 channel, 12F solid-state catheter. Measurements were performed during rest, squeeze, cough, and simulated defecation (push). Data were displayed as color contour plots and analysed using a commercially available manometric system (Solar GI HRM v9.1, Medical Measurement Systems). Associations between age, gender and parity were subsequently explored. HRAM color contour plots provided clear delineation of the high-pressure zone within the anal canal and showed recruitment during maneuvers that altered intra-anal pressures. Automated analysis produced quantitative data, which have been presented on the basis of gender and parity due to the effect of these covariates on some sphincter functions. In line with traditional manometry, some age and gender differences were seen. Males had a greater functional anal canal length and anal pressures during the cough maneuver. Parity in females was associated with reduced squeeze increments. The study provides a large healthy volunteer dataset and parameters of traditional measures of anorectal function. A number of novel phenomena are appreciated, the significance of which will require further analysis and comparisons with patient populations. © 2014 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Liu YF

    2017-12-01

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

  2. Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation.

    Science.gov (United States)

    Colin, P J; Hannivoort, L N; Eleveld, D J; Reyntjens, K M E M; Absalom, A R; Vereecke, H E M; Struys, M M R F

    2017-08-01

    Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG. We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise. The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation. NCT01879865.

  3. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria.

    Science.gov (United States)

    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.

  4. Acute anti-hyperglycaemic effects of an unripe apple preparation containing phlorizin in healthy volunteers: a preliminary study.

    Science.gov (United States)

    Makarova, Elina; Górnaś, Paweł; Konrade, Ilze; Tirzite, Dace; Cirule, Helena; Gulbe, Anita; Pugajeva, Iveta; Seglina, Dalija; Dambrova, Maija

    2015-02-01

    The health-promoting properties of apples are directly related to the biologically active compounds that they contain, such as polyphenols. The objective of this study was to prepare a low-sugar, fibre- and phlorizin-enriched powder from unripe apples and to gain insight regarding its anti-hyperglycaemic activity in healthy volunteers. The unripe apples (Malus domestica Borkh.) were collected 30 days after the full bloom day; blanched and pressed to obtain apple pomace which was then processed with a food cutter, oven-dried and milled to prepare apple powder. The concentrations of total sugars, water-soluble pectin and phlorizin in the apple preparation were 153.44 ± 2.46, 27.73 ± 0.51 and 12.61 ± 0.15 g kg(-1), respectively. Acute ingestion of the apple preparation improved glucose metabolism in the oral glucose tolerance test (OGTT) in six healthy volunteers by reducing the postprandial glucose response at 15 to 30 min by approximately two-fold (P apples can be used as a health-promoting natural product for the reduction of postprandial glycaemia and to improve the health of patients with diabetes. © 2014 Society of Chemical Industry.

  5. Preliminary study of relationships between hypnotic susceptibility and personality disorder functioning styles in healthy volunteers and personality disorder patients

    Directory of Open Access Journals (Sweden)

    He Wei

    2011-07-01

    Full Text Available Abstract 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.

  6. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers.

    Science.gov (United States)

    Morrow, Jasper M; Sinclair, Christopher D J; Fischmann, Arne; Reilly, Mary M; Hanna, Michael G; Yousry, Tarek A; Thornton, John S

    2014-07-01

    Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies. Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T₁-relaxometry, T₂-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. Mean between-muscle fat fraction and T₂ differences were small, but significant (p measures in neuromuscular disease treatment trials. • Quantitative lower limb muscle MRI provides potential outcome measures in neuromuscular diseases • Bilateral thigh/calf coverage using sequences sensitive to acute and chronic pathology • Measurements have excellent scan-rescan and interobserver reliability • Measurements show small but significant inter-subject age and weight dependency • Readily implementable sequences suitable for further assessment in patient studies.

  7. Bioequivalence evaluation of glibenclamide 5-mg tablets: diabenil® and daonil® (in 24 healthy volunteers).

    Science.gov (United States)

    Ghozzi, Hanen; Hammami, Serria; Affes, Hanen; Ksouda, Kamilia; Sahnoun, Zouheir; Hakim, Ahmed; Abid, Mohamed

    2015-02-01

    Prescription of generic products is a way to reduce health expense. Bioequivalence is the most appropriate procedure to evaluate the quality and therapeutic efficacy of a generic product. Generic prescriptions are a strategic choice in Tunisia. We expose in this work, a bioequivalence study witch compare a generic (test) product: DIABENIL* manufactured by a Tunisian pharmaceutical industry Dar Essaidaly to the innovative (reference) product: DAONIL* of Aventis pharma laboratories. The bioequivalence of two glibenclamide 5-mg tablets was determined in healthy human, adult volunteers after a single dose in a randomized cross-over in double blind study. Test and reference were administered to twenty-four healthy volunteers of both sexes after overnight fasting. In total, 15 Blood samples were collected before and following the administration of the drug. Serum concentrations of glibenclamide were determined by validated HPLC method. The pharmacokinetic parameters AUC0t, AUC0 , Cmax and tmax were tested for bioequivalence. All parameters showed bioequivalence between both formulations as their confidence intervals were within the bioequivalence acceptable range of 0.80-1.25 limits. We conclude that the two formulations exhibited comparable pharmacokinetic profiles and that the two products can be considered interchangeable in medical practice.

  8. Experimental low-level jaw clenching inhibits temporal summation evoked by electrical stimulation in healthy human volunteers.

    Science.gov (United States)

    Tada, Hiroaki; Torisu, Tetsurou; Tanaka, Mihoko; Murata, Hiroshi; De Laat, Antoon; Svensson, Peter

    2015-05-01

    To examine the effect of low-level jaw clenching on temporal summation in healthy volunteers. In 18 healthy volunteers, the pain intensities evoked at the masseter muscle and the hand palm by the first and last stimuli in a train of repeated electrical stimuli (0.3 or 2.0 Hz) were rated using 0-100mm visual analogue scales (VAS), in order to evaluate temporal summation before and after three types of jaw-muscle tasks: low-level jaw clenching, repetitive gum chewing and mandibular rest position. A set of concentric surface electrodes with different diameters (small and large) was used for the electrical stimulation. The temporal summation evoked by the large diameter electrode with 2.0 Hz stimulation decreased significantly both on the masseter and the hand after low-level clenching (P ≤ 0.03), but did not show any significant change after the other tasks (P > 0.23). The VAS score of the first stimulation did not show any significant changes after low-level clenching (P > 0.57). Experimental low-level jaw clenching can inhibit pain sensitivity, especially temporal summation. Low-level jaw clenching can modify pain sensitivity, most likely through the central nervous system. The findings suggest that potential harmful low-level jaw clenching or tooth contacting could continue despite painful symptoms, e.g., temporomandibular disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Gender Differences in Cerebral Regional Homogeneity of Adult Healthy Volunteers: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Chunsheng Xu

    2015-01-01

    Full Text Available Objective. We sought to use the regional homogeneity (ReHo approach as an index in the resting-state functional MRI to investigate the gender differences of spontaneous brain activity within cerebral cortex and resting-state networks (RSNs in young adult healthy volunteers. Methods. One hundred and twelve healthy volunteers (56 males, 56 females participated in the resting-state fMRI scan. The ReHo mappings in the cerebral cortex and twelve RSNs of the male and female groups were compared. Results. We found statistically significant gender differences in the primary visual network (PVN (P<0.004, with Bonferroni correction and left attention network (LAtN, default mode network (DMN, sensorimotor network (SMN, executive network (EN, and dorsal medial prefrontal network (DMPFC as well (P<0.05, uncorrected. The male group showed higher ReHo in the left precuneus, while the female group showed higher ReHo in the right middle cingulate gyrus, fusiform gyrus, left inferior parietal lobule, precentral gyrus, supramarginal gyrus, and postcentral gyrus. Conclusions. Our results suggested that men and women had regional specific differences during the resting-state. The findings may improve our understanding of the gender differences in behavior and cognition from the perspective of resting-state brain function.

  10. Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.

    Science.gov (United States)

    Hellriegel, E T; Arora, S; Nelson, M; Robertson, P

    2001-08-01

    The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.

  11. [Analysis on relevance between regional acupoint skin temperature and indoor temperature and humidity in healthy female volunteers during menstruation].

    Science.gov (United States)

    She, Yan-Fen; Zhu, Jiang; Ma, Liang-Xiao; Xie, Jie-Ping; Li, Chun-Hua; Yuan, Hong-Wen

    2012-04-01

    To observe the relationship between the cutaneous temperature of the acupoint area and the environmental temperature and humidity in healthy female undergraduate student volunteers. Forty-nine healthy female undergraduate student volunteers experiencing menstruation were enrolled in the present study. The cutaneous temperature of the acupoint region was detected for 60 min by using a "dynamic skin temperature detector" and under room temperature of (22.15 +/- 1.47) degrees C and indoor relative humidity of (50.12 +/- 4.52)%. The detected acupoints were Xuehai (SP10), Diji (SP8), Zhongdu (LR 6), Sanyinjiao (SP 6), Taixi (KI 3), Taibai (SP 3), Taichong (LR 3) and Shuiquan (KI 5)which have been well documented in effectively regulating uterine activity, and Xuanzhong (GB 39) and non-meridian acupoint nearby GB 39. The skin temperature measurement was conducted on the first day of menstruation. The skin temperature levels of Xuehai (SP 10), Diji (SP 8), Zhongdu (LR 6), Xuanzhong (GB 39) and non-acupoint near GB 39 were apparently hig-her under higher temperature, showing a significant relevance between the acupoint skin temperature and room temperature (P 0.05), between the skin temperature difference of the bilateral isonym acupoints and the indoor temperature, and between the skin temperature difference and the indoor humidity (P > 0.05). The skin temperature of some acupoints is influenced by the environment temperature rather than the indoor humidity.

  12. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo.

    Science.gov (United States)

    Oei, Gezina T M L; Smit, Kirsten F; vd Vondervoort, Djai; Brevoord, Daniel; Hoogendijk, Arjan; Wieland, Catharina W; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2012-09-24

    Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific "conditioning" protocols. Before widespread use of this "conditioning" agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo. Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O(2)) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples. Incubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation. We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Dutch Trial Register: http://www.trialregister.nl/ NTR2152.

  13. Prevalence of Desloratadine Slow-metabolizer Phenotype and Food-dependent Pharmacokinetics of Desloratadine in Healthy Chinese Volunteers.

    Science.gov (United States)

    Wang, Ting; Zhang, Kun; Li, Tingting; He, Lin; Xie, Huiru; Jiang, Xuehua; Wang, Ling

    2015-12-01

    Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolizer (DSM) phenotype and the effects of food on the pharmacokinetics of desloratadine and its active metabolite 3-OH-desloratadine in healthy Chinese volunteers. A total of 46 healthy Chinese male volunteers were included in this investigation. All subjects received a single dose of a 5-mg desloratadine tablet under fasting or fed conditions and the plasma concentrations of desloratadine and 3-OH-desloratadine were measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. The individuals with a 3-OH-desloratadine-to-desloratadine exposure ratio lower than 10 % or a desloratadine half-life (t 1/2) of ≥50 h were supposed to be DSM. There was only one DSM among the 46 volunteers, with a prevalence of 2.2 %. Moreover, administration in a fed state resulted in 34.07 and 32.06 % decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity for desloratadine and 47.26 and 48.46 % for 3-OH-desloratadine compared with those values under fasting conditions. Taken together, these results indicated that the incidence of the DSM phenotype in the Chinese population was low and that food intake could significantly decrease the absorption rate and extent of desloratadine.

  14. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.

    NARCIS (Netherlands)

    Knoester, P.D.; Jonker, D.M.; Hoeven, R.T. van der; Vermeij, T.A.; Edelbroek, P.M.; Brekelmans, G.J.; Haan, G.J. de

    2002-01-01

    AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a

  15. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

    OpenAIRE

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2012-01-01

    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, d...

  16. Mercury Exposure in Healthy Korean Weaning-Age Infants: Association with Growth, Feeding and Fish Intake

    Directory of Open Access Journals (Sweden)

    Ju Young Chang

    2015-11-01

    Full Text Available Low-level mercury (Hg exposure in infancy might be harmful to the physical growth as well as neurodevelopment of children. The aim of this study was to investigate postnatal Hg exposure and its relationship with anthropometry and dietary factors in late infancy. We recruited 252 healthy Korean infants between six and 24 months of age from an outpatient clinic during the 2009/2010 and 2013/2014 seasons. We measured the weight and height of the infants and collected dietary information using questionnaires. The Hg content of the hair and blood was assessed using inductively coupled plasma mass spectroscopy. The geometric mean Hg concentration in the hair and blood was 0.22 (95% confidence interval: 0.20–0.24 µg/g and 0.94 (n = 109, 95% confidence interval: 0.89–0.99 µg/L, respectively. The hair Hg concentration showed a good correlation with the blood Hg concentration (median hair-to-blood Hg ratio: 202.7, r = 0.462, p < 0.001 and was >1 µg/g in five infants. The hair Hg concentration showed significant correlations with weight gain after birth (Z-score of the weight for age—Z-score of the birthweight; r = −0.156, p = 0.015, the duration (months of breastfeeding as the dominant method of feeding (r = 0.274, p < 0.001, and the duration of fish intake more than once per week (r = 0.138, p = 0.033. In an ordinal logistic regression analysis with categorical hair Hg content (quartiles, dietary factors, including breastfeeding as the dominant method of feeding in late infancy (cumulative odds ratio: 6.235, 95% confidence interval: 3.086–12.597, p < 0.001 and the monthly duration of fish intake more than once per week (cumulative odds ratio: 1.203, 95% confidence interval: 1.034–1.401; p = 0.017, were significantly associated with higher hair Hg content. Weight gain after birth was not, however, significantly associated with hair Hg content after adjustment for the duration of breastfeeding as the dominant method of feeding. Low-level Hg

  17. The Relationship between T1 Sagittal Angle and Sagittal Balance: A Retrospective Study of 119 Healthy Volunteers.

    Science.gov (United States)

    Yang, Mingyuan; Yang, Changwei; Ni, Haijian; Zhao, Yuechao; 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, Psagittal 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 thoroughly replaced for SVA. maxTK was the primary contributor to T1 sagittal angle. According to this equation, we could restore sagittal balance by surgically changing thoracic kyphosis and lumbar lordosis, which could serve as a guideline for osteotomy.

  18. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers.

    Science.gov (United States)

    Belgrado, Jean-Paul; Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-06-01

    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. 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. 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). 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.

  19. Evaluating automated dynamic contrast enhanced wrist 3T MRI in healthy volunteers

    DEFF Research Database (Denmark)

    Rastogi, Anshul; Kubassova, Olga; Krasnosselskaia, Lada V

    2013-01-01

    Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so...... as to differentiate changes induced by treatment from the inherent variability of perfusion measures. The objective of this study was to test a pixel-by-pixel parametric map based approach for analysis of DCE-MRI (Dynamika) and to investigate the variability in signal characteristics over time in healthy controls...

  20. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers

    DEFF Research Database (Denmark)

    Naert, A.L.; Kehlet, H.; Kupers, R.

    2008-01-01

    model that can be applied without excessive discomfort in the majority of subjects and offers a valuable addition to the armamentarium of experimental pain models. The model can be particularly suitable for brain imaging receptor binding studies which require long stimulation periods Udgivelsesdato......The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged...... tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6...

  1. Effect of n-3 polyunsaturated fatty acids on the lipidic profile of healthy Mexican volunteers

    Directory of Open Access Journals (Sweden)

    CARVAJAL OCTAVIO

    1997-01-01

    Full Text Available Objective. The effect of n-3 polyunsaturated fatty acids on the serum lipid profile in a Mexican population was evaluated. Material and methods. Three g of salmon oil was the daily intake during four weeks. Total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and erythrocyte fatty acid composition were analyzed. Results. The hypertriglyceridemic group showed a statistically significant (p< 0.05 reduction of triglycerides and significant (p< 0.01 elevation of high density lipoproteins. The hypercholesterolemic group reduced significantly the levels of cholesterol and triglycerides; high density lipoproteins were augmented by 11.6%. Conclusions. The hipolipidemic effect of n-3 polyunsaturated fatty acids was manifest in the Mexican volunteers under the conditions here evaluated.

  2. Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers.

    Science.gov (United States)

    Rost, K L; Wierich, W; Masayuki, F; Tuthill, C W; Horwitz, D L; Herrmann, W M

    1999-01-01

    Thymosin alpha1, an immunomodulatory endogenous peptide, has been shown to be effective in the treatment of chronic hepatitis B and C. In this study, single- and 5-day multiple-dose pharmacokinetics were characterized in nine Caucasian volunteers after subcutaneous administration of 900 microg/m2 thymosin alpha1. Using a randomized, 3-way crossover design three available drug formulations were compared: Zadaxin (SciClone), Timosina (Sclavo), and Thymosin alpha1 (Tal-HLR; Hoffmann La Roche). AUC, Cmax, t(max), t(1/2), Cl/f, and the volume of distribution, V(Z)/f, were derived by model-independent methods. Endogenous serum concentrations were below the limit of quantification (0.10 microg/l) of the enzyme-linked immunosorbent assay method in most subjects. Thymosin alpha1 was well absorbed with a mean t(max) between 1-2 hours from all galenic formulations. Cmax concentrations of 30 to 80 microg/l and AUC(0-infinity) from 95 to 267 microg x h/l did not differ between single- and multiple-dose administration of all drugs. This apparent lack of accumulation was supported by the short elimination half-life of less than 3 hours. As indicated by a V(Z)/f in the range of 30-40 l, thymosin alpha1 appears to distribute within the extracellular volume. AUC and Cmax were similar for Zadaxin and T alpha1-HLR, but higher after administration of Timosina. Thymosin alpha1 kinetics from this study are comparable to those previously obtained in Japanese volunteers or cancer patients, but may be influenced by the drug formulation used.

  3. Engaging Stakeholders From Volunteer-Led Out-of-School Time Programs in the Dissemination of Guiding Principles for Healthy Snacking and Physical Activity

    OpenAIRE

    Folta, Sara C.; Koomas, Alyssa; Metayer, Nesly; Fullerton, Karen J.; Hubbard, Kristie L.; Anzman-Frasca, Stephanie; Hofer, Teresa; Nelson, Miriam; Newman, Molly; Sacheck, Jennifer; Economos, Christina

    2015-01-01

    Background Little effort has focused on the role of volunteer-led out-of-school time (OST) programs (ie, enrichment and sports programs) as key environments for the promotion of healthy eating and physical activity habits among school-aged children. The Healthy Kids Out of School (HKOS) initiative developed evidence-based, practical guiding principles for healthy snacks, beverages, and physical activity. The goal of this case study was to describe the methods used to engage regional partners ...

  4. Metformin and daclatasvir: absence of a pharmacokinetic-pharmacodynamic drug interaction in healthy volunteers

    NARCIS (Netherlands)

    Smolders, E.J.; Colbers, A.; Kanter, C. de; Velthoven-Graafland, K.; Wolberink, L.T.; Ewijk-Beneken Kolmer, N.V. van; Drenth, J.P.H.; Aarnoutse, R.E.; Tack, C.J.J.; Burger, D.M.

    2017-01-01

    AIM: The aim of the present study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin. METHODS: This was an open-label, two-period, randomized, crossover trial in 20 healthy

  5. Circadian profile of QT interval and QT interval variability in 172 healthy volunteers

    DEFF Research Database (Denmark)

    Bonnemeier, Hendrik; Wiegand, Uwe K H; Braasch, Wiebke

    2003-01-01

    The limited prognostic value of QT dispersion has been demonstrated in recent studies. However, longitudinal data on physiological variations of QT interval and the influence of aging and sex are few. This analysis included 172 healthy subjects (89 women, 83 men; mean age 38.7 +/- 15 years). Beat...

  6. Steady-state plasma and cerebrospinal fluid pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine in healthy volunteers.

    Science.gov (United States)

    Nunes, Teresa; Rocha, José Francisco; Falcão, Amílcar; Almeida, Luis; Soares-da-Silva, Patrício

    2013-01-01

    To evaluate the pharmacokinetics and tolerability of once-daily eslicarbazepine acetate (ESL) and twice-daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration. Single-center, open-label, randomized, parallel-group study in healthy volunteers. Volunteers in ESL group (n = 7) received 600 mg on days 1-3 and 1,200 mg on days 4-9, once daily. Volunteers in the OXC group (n = 7) received 300 mg on days 1-3 and 600 mg on days 4-9, twice daily. Plasma and CSF sampling was performed following the last dose. Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R-licarbazepine and oxcarbazepine was approximately four-fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak-to-trough (ratio) in the CSF for both eslicarbazepine (ESL = 1.5; OXC = 1.2) and R-licarbazepine (ESL = 1.2; OXC = 1.2). In contrast, oxcarbazepine showed larger differences between peak and trough (ESL = 3.1; OXC = 6.4). A total of 84 and 24 treatment-emergent adverse events (TEAEs) were reported with OXC and ESL, respectively. In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R-licarbazepine, and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The smaller peak-to-trough fluctuation of eslicarbazepine in CSF (a measure of sustained delivery to the brain) than in plasma supports once-daily dosing of ESL. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  7. Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

    Science.gov (United States)

    Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

    2016-01-01

    To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞  were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  8. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica.

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Mator, Lugkana; Muchimapura, Supaporn; Tongun, Terdthai; Pasuriwong, Orapin; Piyawatkul, Nawanant; Yimtae, Kwanchanok; Sripanidkulchai, Bungorn; Singkhoraard, Jintana

    2008-03-05

    Centella asiatica has a reputation to restore decline cognitive function in traditional medicine and in animal model. However, little evidence regarding the efficacy of Centella asiatica from systematized trials is available. Therefore, the present randomized, placebo-controlled, double-blind study investigated the effect of Centella asiatica on cognitive function of healthy elderly volunteer. Twenty-eight healthy elderly participants received the plant extract at various doses ranging 250, 500 and 750 mg once daily for 2 months. Cognitive performance was assessed using the computerized test battery and event-related potential whereas mood was assessed using Bond-Lader visual analogue scales prior to the trial and after single, 1 and 2 months after treatment. The results showed that the high dose of the plant extract enhanced working memory and increased N100 component amplitude of event-related potential. Improvements of self-rated mood were also found following the Centella asiatica treatment. Therefore, the present findings suggest the potential of Centella asiatica to attenuate the age-related decline in cognitive function and mood disorder in the healthy elderly. However, the precise mechanism(s) underlying these effects still require further investigation.

  9. Reliability of side-to-side sonographic cross-sectional area measurements of upper extremity nerves in healthy volunteers.

    Science.gov (United States)

    Tagliafico, Alberto; Martinoli, Carlo

    2013-03-01

    In sonographic evaluations of peripheral nerves, the healthy, contralateral side may be used as an internal control for the pathologic one. Therefore, the inherent side-to-side differences must be minimal. The goal of this study was to determine the reliability of side-to-side measurements of upper extremity nerves in healthy volunteers. Forty participants with no upper extremity abnormalities were included. Upper limb nerves were evaluated bilaterally at the usual pathologic sites by 3 musculo-skeletal radiologists in separate sessions. To assess intraobserver and interobserver agreement, sonographic examinations were repeated 2 months after the first evaluations. The median nerve, ulnar nerve, musculocutaneous nerve, and radial nerve were considered. Nonparametric tests were used for statistical analysis. Minimum detectable differences with relative 95% confidence intervals were reported. Intraobserver and interobserver agreements were good (0.73 measurement was evaluated, the reliability was 80% to 87%. In general, the healthy contralateral side can be used as an internal control considering that changes in minimum detectable differences are related to the anatomic site considered.

  10. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI: initial results in animals and healthy volunteers.

    Science.gov (United States)

    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. Copyright © 2011 Wiley Periodicals, Inc.

  11. Pharmacokinetic and bioequivalence study comparing a candesartan cilexetil/rosuvastatin calcium fixed-dose combination with the concomitant administration of candesartan cilexetil and rosuvastatin calcium in healthy Korean subjects
.

    Science.gov (United States)

    Park, Dan-Bee; Jang, Kyungho; Lee, Jae-Won; Park, Cheol-Won; Lee, Back-Hwan; Kim, Min-Gul; Jeon, Ji-Young

    2017-03-01

    A fixed-dose combination (FDC) of candesartan and rosuvastatin was recently developed for the treatment of cardiovascular disease and expected to enhance patient compliance. This study was performed to compare the single-dose pharmacokinetic properties and tolerability of DP-R208 (candesartan and rosuvastatin FDC) to those of each component administered alone in healthy Korean male volunteers. A total of 40 healthy Korean volunteers were enrolled in this randomized, open-label, single-dose, two-treatment, two-way crossover study. During each treatment period, subjects received the test formulation (FDC tablet containing candesartan and rosuvastatin) or reference formulation (co-administration of candesartan and rosuvastatin). Plasma samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, and 48 hours post-dose. Safety and tolerability were assessed by the evaluation of adverse events (AEs), physical examinations, laboratory assessments, 12-lead electrocardiograms (ECGs), and vital sign measurements. The 90% confidence intervals (CIs) of the geometric least-square mean ratios of Cmax, AUClast, and AUCinf were 0.86 - 1.00, 0.92 - 1.04, and 0.92 - 1.03 for candesartan, and 0.88 - 1.06, 0.91 - 1.08, and 0.91 - 1.03 for rosuvastatin, respectively. All of the AEs were mild, and there was no significant difference in the incidence of AEs between the formulations. Furthermore, the pharmacokinetic properties of the test and reference formulations met the regulatory criteria for bioequivalence. Discussion and conclusion: Both formulations were safe and well tolerated, and no significant difference was observed in the safety assessments of the treatments.
.

  12. Randomized, Double-Blind Clinical Trial to Assess the Acute Diuretic Effect of Equisetum arvense (Field Horsetail in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Danilo Maciel Carneiro

    2014-01-01

    Full Text Available 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.

  13. Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers.

    Science.gov (United States)

    Nyrén, Sven; Radell, Peter; Lindahl, Sten G E; Mure, Margareta; Petersson, Johan; Larsson, Stig A; Jacobsson, Hans; Sánchez-Crespo, Alejandro

    2010-03-01

    The literature on ventilation (V) and lung perfusion (Q) distributions during general anesthesia and controlled mechanical ventilation in supine and prone position is contradictory. The authors aimed to investigate whether V, Q, and ventilation to perfusion ratio (V/Q ratio) matching in anesthetized and mechanically ventilated volunteers are gravity dependent irrespective of posture. Seven healthy volunteers were studied at two different occasions during general anesthesia and controlled mechanical ventilation. One occasion studied ventral to dorsal V and Q distributions in the supine posture and the other in the prone posture. Imaging was performed in supine posture at both occasions. A dual radiotracer technique and single photon emission computed tomography were used. V and Q were simultaneously tagged with Tc-Technegas (Tetley Manufacturing Ltd., Sydney, Australia) and In-labeled macroaggregates of human albumin (TechneScan LyoMAA, Mallinckrodt Medica, Petten, The Netherlands), respectively. No differences in V between postures were observed. Q differed between postures, being more uniform over different lung regions in prone posture and dependent in supine posture. The contribution of the vertical direction to the total V/Q ratio heterogeneity was larger in supine (31.4%) than in prone (16.4%) (P = 0.0639, two-tailed, paired t test) posture. During mechanical ventilation, prone posture favors a more evenly distributed Q between lung regions. V distribution is independent of posture. This results in a tendency toward lower V/Q gradients in the ventral to dorsal direction in prone compared with supine posture.

  14. Median nerve T2 assessment in the wrist joints: preliminary study in patients with carpal tunnel syndrome and healthy volunteers.

    Science.gov (United States)

    Cha, Jang Gyu; Han, Jong Kyu; Im, Soo Bin; Kang, Sung Jin

    2014-10-01

    To perform a prospective quantitative analysis of median nerve T2 values and cross-sectional area (CSA) in patients with carpal tunnel syndrome (CTS) as compared to asymptomatic volunteers. Twelve CTS patients with positive nerve conduction results and 12 healthy volunteers (controls) were enrolled and underwent axial T2 mapping of the wrist joints. Median nerve T2 values and CSAs at the distal radioulnar joint, pisiform, and hook of hamate levels were compared between the groups. The T2 values at the proximal and distal carpal tunnel were higher in the CTS patients than in the controls (P carpal tunnel were significantly larger in the CTS patients than in the controls (P carpal tunnel and has the potential to be a promising complementary method for evaluation of CTS patients. A future study with larger sample sizes is necessary to investigate the potential effect of median nerve T2 assessment to a reliable tool in the diagnosis of CTS. © 2013 Wiley Periodicals, Inc.

  15. Assessment of Combined Ascorbyl Palmitate (AP) and Sodium Ascorbyl Phosphate (SAP) on Facial Skin Sebum Control in Female Healthy Volunteers.

    Science.gov (United States)

    Khan, H; Akhtar, N; Ali, A

    2017-01-01

    The skin is fortified with a setup of lipophilic and hydrophilic, enzymatic and non-enzymatic antioxidant systems. Ascorbyl palmitate (AP) and sodium ascorbyl phosphate (SAP) are reported as lipophilic and hydrophilic antioxidants, respectively used for skin care. Present study was aimed to assess the combined AP (in oil phase) and SAP (in aqueous phase) via multiple emulsion (ME1) for controlling sebum secretions in healthy human females. FTIR analysis of AP and SAP was performed for identification. Multiple emulsions (ME1 and control) were prepared and analyzed for physical stability. Antioxidant activities of AP, SAP as well as ME1 (with combination of these compounds) were determined by DPPH method. 11 female volunteers were included in a single-blinded, placebo-controlled, split-face comparative study. Volunteers were instructed to apply ME1 on left cheek while control (without AP and SAP) on right cheek, for a period of 90 days. A non-invasive photometric device (Sebumeter®) was used for the measurement of sebum secretions on both sides of the face with subsequent time intervals. A good antioxidant activity of ME1 was observed. ME1 treatments reduced significant facial sebum secretions as compared with control/placebo treatments. It was concluded that combined AP and SAP supplementations to skin proved a promising choice for controlling facial sebum secretions and could be evaluated for undesired oily skin and acne reductions for beautifying the facial appearance. © Georg Thieme Verlag KG Stuttgart · New York.

  16. LPS infusion suppresses serum FGF21 levels in healthy adult volunteers

    DEFF Research Database (Denmark)

    Lauritzen, Esben Stistrup; Rittig, Nikolaj; Bach, Ermina

    2017-01-01

    circulating levels of FGF21 after lipopolysaccharide (LPS) infusion. DESIGN: Two randomized, single blinded, placebo-controlled crossover trials were used. SETTING: The studies were performed at a university hospital clinical research center. PATIENTS AND INTERVENTIONS: Study 1 (LPS bolus): Eight young......, healthy, lean males were investigated two times: 1) after isotonic saline injection, and 2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 hours. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: 1) during continuously isotonic saline infusion, and 2......) during continuously LPS infusion (0.06 ng/kg/h). Each study day lasted 4 hours. Circulating FGF21 levels were quantified every second hour by an immunoassay. RESULTS: A LPS bolus resulted in a late suppression (t = 240 minutes) of serum FGF21 (P=0.035). Continuous LPS infusion revealed no significant...

  17. The correlation between mid-brain serotonin transporter availability and intelligence quotient in healthy volunteers.

    Science.gov (United States)

    Tseng, P Y; Lee, I H; Chen, K C; Chen, P S; Chiu, N T; Yao, W J; Chu, C L; Yeh, T L; Yang, Y K

    2015-02-01

    This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [(123)I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects' IQ using the WAIS-R. We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

    Science.gov (United States)

    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 (C max), median time to C max (t max), 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 C max 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

  19. Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers

    OpenAIRE

    Vissers, M.N.; Meyboom, S.; Wiseman, M.; Zock, P.L.; Katan, M B

    2001-01-01

    Objective: We studied whether consumption of phenol-rich extra virgin olive oil affects the susceptibility of low density lipoproteins (LDL) to oxidation and other markers of oxidation in humans. Design: Randomized cross-over intervention trial, stratified according to sex, age and energy intake. Setting: Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands. Subjects: Forty-six healthy men and women completed the study. Intervention: Subjects consumed two diets...

  20. COMPARISON OF WISCONSIN CARD SORTING TEST RESULTS BETWEEN CZECH SUBJECTS DEPENDENT ON METHAMPHETAMINE VERSUS HEALTHY VOLUNTEERS

    OpenAIRE

    Hosak, Ladislav; Preiss, Marek; Bazant, Jan; Tibenska, Andrea; Cermakova, Radka; Cermakova, Eva

    2012-01-01

    Background: Methamphetamine is a neurotoxic agent. Its chronic abuse may result in cognitive impairment with negative consequences for patients´ treatment and rehabilitation. The aim of the study was to compare Wisconsin Card Sorting Test profiles of Czech subjects dependent on methamphetamine with healthy individuals. Subjects and methods: Forty-three hospitalized Czech Caucasian patients including twenty-seven men at the average age of 25.3±5.2 years dependent on methamphetamine...

  1. Mood and cognitive function following repeated transcranial direct current stimulation in healthy volunteers: a preliminary report.

    Science.gov (United States)

    Motohashi, Nobutaka; Yamaguchi, Masayasu; Fujii, Tomokazu; Kitahara, Yuichi

    2013-01-01

    Although mood and cognitive function have been reported to change following transcranial direct current stimulation (tDCS) in patients with neurological and psychiatric diseases, little is known about the effects of repeated tDCS on mood and cognition in healthy humans. We recruited 11 healthy male participants for this single-blind, sham-controlled crossover trial. We used Profile of Mood States, brief-form (POMS), and CogHealth (Detection Task, Identification Task, One Back Task, One Card Learning Task and Continuous Monitoring Task) to evaluate the changes in mood and cognitive function, respectively, before and immediately after 4-daily, 20 min, 1 mA sham or anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). While there were no significant changes in six factors of POMS and performance (speed and accuracy) of CogHealth between sham and anodal stimulation, the accuracy of One Card Learning was increased at the end of the experiment. Signal detection analyses revealed that both hit rate and discriminability were improved in this task. These results suggest that 4-daily anodal tDCS over left DLPFC may not change mood and cognitive function in healthy subjects, and further support the safety of tDCS. A slight improvement in a visual recognition and learning task at the end of experiment may be susceptible to practice effects. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  2. Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers

    DEFF Research Database (Denmark)

    Ravn-Haren, Gitte; Dragsted, Lars Ove; Buch-Andersen, Tine

    2013-01-01

    of CVD. METHODS: Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood......PURPOSE: Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the '5 or more a day' campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors...... pressure in a group of 23 healthy volunteers. RESULTS: The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7 %), pomace (7.9 %) and cloudy juice (2.2 %) intake. On the other hand, LDL...

  3. Mixed effects of OATP1B1, BCRP and NTCP polymorphisms on the population pharmacokinetics of pravastatin in healthy volunteers.

    Science.gov (United States)

    Lu, Xue-Feng; Zhou, Yang; Bi, Kai-Shun; Chen, Xiao-Hui

    2016-09-01

    1. Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of hyperlipidaemia. This study aims to investigate the effects of genetic polymorphisms in OATP1B1, BCRP and NTCP on pravastatin population pharmacokinetics in healthy Chinese volunteers using a non-linear mixed-effect modelling (NONMEM) approach. A two-compartment model with a first-order absorption and elimination described plasma pravastatin concentrations well. 2. Genetic polymorphisms of rs4149056 (OATP1B1) and rs2306283 (OATP1B1) were found to be associated with a significant (p  0.05). 4. The current data suggest that the combination of rs4149056, rs2306283 and rs2296651 polymorphisms is an important determinant of pravastatin pharmacokinetics.

  4. A Simple Method of Supplementation of Omega-3 Polyunsaturated Fatty Acids: Use of Fortified Yogurt in Healthy Volunteers

    Science.gov (United States)

    McCowen, Karen C.; Ling, Pei Ra; Decker, Eric; Djordjevic, D.; Roberts, R.F.; Coupland, J.N.; Bistrian, Bruce R.

    2011-01-01

    Background A relative dietary ω-3 fatty acid deficiency exists in Western diets, and this deficiency may be associated with some chronic diseases. The aim of the present study was to supplement yogurt with docosahexaenoic acid and assess whether this fatty acid could be incorporated into plasma lipids. Methods We developed a stable emulsion of docosahexaenoic acid that was incorporated into yogurt. Twelve healthy volunteers agreed to consume 1 serving daily that contained 600 mg of docosahexaenoic acid. Results After 3 weeks of supplementation, plasma phospholipid docosahexaenoic acid content increased significantly, by 32%, in parallel with a 16% rise in total ω-3 fatty acids. This result was associated with a significant 7% decline in phospholipid arachidonic acid. Conclusions Fortification of ordinary foods with docosahexaenoic acid is a potentially attractive method of increasing ω-3 fatty acid content of plasma lipids, and might even lower arachidonic acid concentrations. PMID:21139129

  5. Oral bioavailability and pharmacokinetic study of cetrizine HCl in Iranian healthy volunteers

    Science.gov (United States)

    Derakhshandeh, K.; Mohebbi, M.

    2009-01-01

    The objective of the present study was to evaluate the pharmacokinetic parameters and bioavailability of a selective histamine (H1)-receptor antagonist, cetirizine hydrochloride (CTZ), following administration of a single oral dose of the drug. The properties of a test compound were compared with those of a reference product in a randomized cross-over study in 12 volunteers. Blood samples were collected at selected time intervals up to 24 h and plasma concentrations of CTZ were determined using a validated HPLC method. Pharmacokinetic parameters including T1/2, T1/2(abs), K, Ka, Tmax, Cmax, Vd/F, Cl/F, AUC0-24, AUC 0-∞ and MRT were determined from plasma concentration-time profiles for tested products and found to be in good agreement with previous reports. The analysis of variance did not show any significant differences between the test and reference products. The confidence intervals for the ratio of Cmax (95-110%), AUC0-24 (91-112%) and AUC0-∞ (92-109%) for the test and reference products were within the acceptable interval of 80-125%. ANOVA assessment of logarithmically transformed data did not reveal any significant subject, period or sequence effects. It was, therefore, concluded that the two products were bioequivalent and could be used interchangeably. PMID:21589806

  6. Effects of Oral Lycopene Supplementation on Vascular Function in Patients with Cardiovascular Disease and Healthy Volunteers: A Randomised Controlled Trial

    Science.gov (United States)

    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, Plycopene-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

  7. Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

    Science.gov (United States)

    Andersson, Tommy; Nagy, Peter; Niazi, Mohammad; Nylander, Sven; Galbraith, Hal; Ranjan, Santosh; Wallentin, Lars

    2014-06-01

    The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

  8. Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial.

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    Parag R Gajendragadkar

    Full Text Available 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.

  9. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers

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    Morrow, Jasper M.; Reilly, Mary M.; Hanna, Michael G. [UCL Institute of Neurology, Medical Research Council Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, London (United Kingdom); Sinclair, Christopher D.J.; Yousry, Tarek A.; Thornton, John S. [UCL Institute of Neurology, Medical Research Council Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, London (United Kingdom); UCL Institute of Neurology, Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, London (United Kingdom); Fischmann, Arne [University of Basel Hospital, Department of Radiology, Division of Diagnostic and Interventional Neuroradiology, Basel (Switzerland)

    2014-07-15

    Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies. Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T{sub 1}-relaxometry, T{sub 2}-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. Mean between-muscle fat fraction and T{sub 2} differences were small, but significant (p < 0.001). Fat fraction and T{sub 2} correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively. Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials. (orig.)

  10. Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

    Science.gov (United States)

    Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

    2009-01-01

    The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

  11. A phase I dose-escalation and bioequivalence study of a trastuzumab biosimilar in healthy male volunteers.

    Science.gov (United States)

    Wisman, Liselijn A B; De Cock, Eduard P M; Reijers, Joannes A A; Kamerling, Ingrid M C; Van Os, Sandra H G; de Kam, Marieke L; Burggraaf, Jacobus; Voortman, Gerrit

    2014-12-01

    Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of HER2-overexpressing breast and gastric cancer. FTMB is being developed as a biosimilar of trastuzumab. In this combined dose-escalation and bioequivalence study of parallel design, the pharmacokinetic profile of FTMB was compared with Herceptin(®). Healthy male volunteers received single doses of 0.5, 1.5, 3.0 or 6.0 mg/kg FTMB, or placebo, in consecutive dose-escalation cohorts to assess the safety profile. Thereafter, the 6 mg/kg cohort was expanded to establish bioequivalence between FTMB (Test) and Herceptin(®) (Reference) based on an acceptance interval of 80.0-125.0 %. In total, 118 subjects were enrolled in the study. The mean area under the concentration-time curve from time zero to infinity (AUC∞) was 1,609 µg·day/mL (Test) and 1,330 µg·day/mL (Reference). The log-transformed geometric mean Test/Reference (T/R) ratio for AUC∞ was 89.6 % (90 % confidence interval [CI] 85.1-94.4), demonstrating bioequivalence. For the secondary endpoint, the maximum concentration observed (Cmax), the geometric mean T/R ratio was 89.4 % (90 % CI 83.4-95.9). Non-linear, target-mediated pharmacokinetics were also observed. Adverse events other than the documented side effects of Herceptin(®) (fever, influenza-like illness, and fatigue) did not occur. No signs of cardiotoxicity were observed. This bioequivalence study with a trastuzumab biosimilar in healthy male volunteers demonstrated bioequivalence of FTMB with Herceptin(®). FTMB was well tolerated in doses up to 6 mg/kg. Non-linear target elimination was also observed in the pharmacokinetic profile of trastuzumab.

  12. Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

    Science.gov (United States)

    Berteau, Cecile; Schwarzenbach, Florence; Donazzolo, Yves; Latreille, Mathilde; Berube, Julie; Abry, Herve; Cotten, Joël; Feger, Celine; Laurent, Philippe E

    2010-10-05

    A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects' preferred system for a final study injection or future treatment. A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment. This study indicated that the autoinjector used by the subject was similar to a syringe used by a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall acceptance, and preference.

  13. Lactobacillus gasseri SBT2055 stimulates immunoglobulin production and innate immunity after influenza vaccination in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    Jun Nishihira

    2016-09-01

    Full Text Available Background: Lactobacillus gasseri strain SBT2055 (LG2055 is a human intestine-originating probiotic bacterium and potent probiotic known to exert various health promotion effects, including prevention of abdominal adiposity in rats and humans. A recent finding in mice has suggested that oral administration of LG2055 induces a protective effect against influenza A virus infection. In this context, evidence for the efficacy of LG2055 using a human clinical trial was imminently required. Methods: To confirm this in humans, a randomized, double-blind, placebo-controlled, parallel- group study in healthy adult volunteers was conducted to examine the effect of drinkable yogurt (DY containing LG2055 on influenza, with vaccine-specific antibody responses as the primary objective and innate immune responses as the secondary objective. Subjects were asked to consume 100 g/day of DY with LG2055 (LG2055 group; n = 94 or without LG2055 (placebo group; n = 94 for 16 weeks. After 4 weeks, all subjects received a trivalent influenza vaccine. Results: We found that the intake of LG2055 DY increased hemagglutination inhibition titers against influenza viruses A/H1N1 and B and the rate of seroprotection against influenza B after vaccination as compared with the intake of placebo DY by healthy volunteers. In support of this result, we confirmed that total IgG and IgA levels in plasma and sIgA production in saliva were also higher in the LG2055 group than in the placebo group. Furthermore, the intake of LG2055 DY enhanced natural killer cell activity and myxovirus resistance A gene expression, which is one of the antiviral genes stimulated by type I or type III Interferons in peripheral blood mononuclear cells. Conclusions: These results strongly indicate that LG2055 activates both the innate and adaptive human immune responses, suggesting the potential to prevent influenza virus infections by providing specific probiotics as complementary foods.

  14. High-resolution myocardial perfusion imaging at 3 T: comparison to 1.5 T in healthy volunteers

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    Strach, K.; Meyer, C.; Thomas, D.; Naehle, C.P.; Cheng, B.; Schild, H.; Sommer, T. [University of Bonn, Department of Radiology, Bonn (Germany); Schmitz, C. [University of Bonn, Department of Cardiac Surgery, Bonn (Germany); Litt, H. [University of Pennsylvania Medical Center, Department of Radiology, Philadelphia, PA (United States); Bernstein, A. [Harvard School of Public Health, Department of Nutrition, Boston, MA (United States)

    2007-07-15

    The purpose of this study was to evaluate high-resolution (HR) myocardial first-pass perfusion in healthy volunteers at 3 T compared to a typical clinical imaging protocol at 1.5 T, with respect to overall image quality and the presence of subendocardial dark rim artifacts. Myocardial first-pass rest perfusion studies were performed at both field strengths using a T1-weighted saturation-recovery segmented k-space gradient-echo sequence combined with parallel imaging (Gd-DTPA 0.05 mmol/kg). Twenty-six healthy volunteers underwent (1) a HR perfusion scan at 3 T(pixel size 3.78 mm{sup 2}) and (2) a standard perfusion approach at 1.5 T(pixel size 9.86 mm{sup 2}). The contrast enhancement ratio (CER) and overall image quality (4-point grading scale: 4: excellent; 1: non-diagnostic) were assessed, and a semiquantitative analysis of dark rim artifacts was performed for all studies. CER was slightly higher (1.31 {+-} 0.32 vs. 1.14 {+-} 0.34; p<0.01), overall image quality was significantly improved (3.03 {+-} 0.43 vs. 2.37 {+-} 0.39; p<0.01), and the number of dark rim artifacts (139 {+-} 2.09 vs. 243 {+-} 2.33; p<0.01) was significantly reduced for HR perfusion imaging at 3 T compared to the standard approach at 1.5 T. HR myocardial rest perfusion at 3 T is superior to the typical clinical perfusion protocol performed at 1.5 T with respect to the overall image quality and presence of subendocardial dark rim artifacts. (orig.)

  15. Tibiofemoral and patellofemoral joint 3D