Pharmacokinetics and safety of eszopiclone in healthy Chinese volunteers.

PubMed

Wu, F; Zhao, X L; Wei, M J; Wang, S M; Zhou, H; Guo, S J; Zhang, P

2012-12-01

The main objective of this study was to investigate the pharmacokinetic characters of eszopiclone (CAS: 138729-47-2) after single and multiple-dose oral administration in healthy adult Chinese volunteers.In single-dose study, 12 subjects were given oral administrations of 1.5, 3 and 6 mg eszopiclone in an open-label, randomized, crossover fashion. In multiple-dose study, 8 subjects were given 3 mg eszopiclone once daily consecutively for 7 days. Blood samples were collected over 24 h and plasma eszopiclone were determined using a validated liquid chromatography/mass spectrometry (LC/MS/MS) assay. The safety and tolerability of eszopiclone was evaluated by adverse events recording, physical examination, laboratory testing, vital signs, and 12-lead ECG findings.The main pharmacokinetic parameters of eszopiclone after single-dose administration were as follows: doses of 1.5, 3 and 6 mg; Cmax of 18.08±4.65, 38.29±15.41 and 76.38±23.34 ng/ml; Tmax of 0.94±0.39, 1.04±0.63 and 1.08±0.51 h; AUC0-24 of 110.90±23.06, 227.36±62.41 and 504.10±140.13 ng*h/ml; elimination half-lives of 5.84±1.03, 5.53±1.91 and 6.17±1.23 h. After multiple-dose administration, the steady-state levels of eszopiclone were achieved by the 4th day, and the main pharmacokinetic parameters were Css_max at 33.43±5.63 ng/ml and AUCss (0-24) at 263.30±51.21 ng*h/ml. The most common adverse event was bitter or abnormal taste. All the adverse events were judged as mild to moderate and resolved without any medication.The pharmacokinetic character of eszopiclone is linear and dose-proportional over the range of 1.5-6 mg. The systemic exposure does not accumulate with once-daily administrations. Eszopiclone appears to have good safety and is well tolerated. © Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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 < 0.001 for all). The 149 trials included 101 non-interventional, 33 interventional, and 15 vaccine trials. The impact on study validity of recruiting NAFLD subjects as controls was estimated as likely, probable, and unlikely in 10, 41, and 98 trials, respectively. The proportion of pNF subjects (28%-29%) did not differ by impact. Only 14% of trials used both BMI and ALT for screening. ALT cutoffs for screening were based on local reference values. Grade 3-4 ALT elevations during the study period were rare but more common in pNF subjects than in 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

Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers

PubMed Central

Luo, Zhu; Nan, Feng; Miao, Jia; Chen, Zhihui; Li, Mei; Liang, Maozhi

2016-01-01

The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat 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. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0−∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0−∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in

Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers.

PubMed

Luo, Zhu; Nan, Feng; Miao, Jia; Chen, Zhihui; Li, Mei; Liang, Maozhi

2016-01-01

The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat 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. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0-∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0-∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in healthy

Effects of the Chinese herbal formula "Zuojin Pill" on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.

PubMed

Qiu, Furong; Liu, Songcan; Miao, Ping; Zeng, Jin; Zhu, Leilei; Zhao, TongFang; Ye, Yujie; Jiang, Jian

2016-06-01

Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype. A pharmacokinetics interaction study was carried out in three groups with CYP2D6*1/*1 (n = 6), CYP2D6*1/*10 (n = 6), and CYP2D6*10/*10 (n = 6) genotypes. Each participant received a single oral dose of dextromethorphan (15 mg) followed by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15 mg dextromethorphan in the last day. Blood samples (0-24 h) and urine samples (0-12 h) were collected at baseline and after the administration of Zuojin Pill, and the samples' concentration of dextromethorphan and its main metabolite dextrorphan was determined. Compared to baseline values, co-administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC0-24 of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49∼3.61) and 1.71-fold (1.42∼2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57-fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes, respectively. In contrast, no significant change was observed in these pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype. These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.

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

PubMed

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

2008-01-01

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

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

PubMed

Warot, D

1991-01-01

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

[Application of Fourier amplitude sensitivity test in Chinese healthy volunteer population pharmacokinetic model of tacrolimus].

PubMed

Guan, Zheng; Zhang, Guan-min; Ma, Ping; Liu, Li-hong; Zhou, Tian-yan; Lu, Wei

2010-07-01

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

Balancing justice and autonomy in clinical research with healthy volunteers.

PubMed

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

2007-08-01

In clinical research, ethics review generally first examines whether study risks are reasonable in light of benefits provided. Through informed consent, then, prospective subjects consider whether the risk/benefit balance and procedures are reasonable for them. Unique ethics issues emerge in clinical research with healthy volunteers. Certain types of studies only recruit healthy volunteers as participants. Phase 1 studies, for example, including first time in human studies of investigational drugs and vaccines, generally are conducted in healthy volunteers. Although such research carries inherent and often unknown risks, healthy subjects provide the most efficient target population in which to conduct such research, as these volunteers generally are free of concurrent diseases or medications that could confound interpretation of toxicity. Other studies enrolling healthy volunteers often are simply looking for the most scientifically sound population for the study of normal human physiology.

The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma.

PubMed

Tao, Jianfei; Jiang, Peng; Peng, Chengcheng; Li, Min; Liu, Runhui; Zhang, Weidong

2016-07-15

To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-∞), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of the Beliefs against Volunteering Scale among Chinese Adolescents in Hong Kong

ERIC Educational Resources Information Center

Law, Ben M. F.; Shek, Daniel T. L.

2011-01-01

Participation in volunteer service is an indicator of quality of life. This study attempts to validate the Beliefs Against Volunteering Scale (BAV), an assessment of the negative beliefs about volunteerism among Chinese adolescents in Hong Kong. The BAV was administered to 5,946 Chinese adolescents. The BAV and its subscales were found to be…

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

PubMed

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

2013-03-01

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

Psychometric Properties of the Volunteer Functions Inventory with Chinese Students

ERIC Educational Resources Information Center

Wu, Joseph; Lo, T. Wing; Liu, Elaine S. C.

2009-01-01

The authors report an evaluation of the psychometric properties of a Chinese version of the Volunteer Functions Inventory on a sample of university student volunteers. Reliabilities were high for four out of the six scales of the Inventory (Values, Career, Social, and Understanding) in terms of internal consistency. Items in these four scales also…

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

PubMed

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

2016-03-01

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

Safeguards for healthy volunteers in drug studies.

PubMed

Smith, R N

1975-09-06

Safeguards for healthy volunteers in drug studies have not been as strict as those involving patients. The shortcomings include the lack of surveillance over the scientific validity of the protocol and its ethical review, and over the financial inducements to volunteers. Recruitment is open to abuse because the volunteers may have some allegiance to the investigators. There is an urgent need to institute checks on these aspects. Most important, however, is the lack of legal safeguards for volunteers taking part in research done outside the pharmaceutical industry. The suggested procedure for obtaining consent, for health checks, and for providing compensation can be equitable to all concerned, and yet not restrict initiative, nor curtail research aims.

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

PubMed Central

Stunkel, Leanne; Grady, Christine

2016-01-01

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

Intestinal Microbial Community Differs between Acute Pancreatitis Patients and Healthy Volunteers.

PubMed

Zhang, Xi Mei; Zhang, Zheng Yu; Zhang, Chen Huan; Wu, Jing; Wang, You Xin; Zhang, Guo Xin

2018-01-01

A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S rRNA gene amplicon sequencing was used to profile the microbiological composition of the samples. In total, 27 microbial phyla were detected and the samples of pancreatitis patients contained fewer phyla. Samples from acute pancreatitis patients contained more Bacteroidetes and Proteobacteria and fewer Firmicutes and Actinobacteria than those from healthy volunteers. PCoA analyses distinguished the fecal microbial communities of acute pancreatitis patients from those of healthy volunteers. The intestinal microbes of acute pancreatitis patients are different from those of healthy volunteers. Modulation of the intestinal microbiome may serve as an alternative strategy for treating acute pancreatitis. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Sensation seeking amongst healthy volunteers participating in phase I clinical trials.

PubMed Central

Farré, M; Lamas, X; Camí, J

1995-01-01

1. Phase I clinical trials are usually carried out in healthy volunteers. In addition to economic gain, factors that may influence willingness to participate include scientific interest, curiosity and choice for risky activities. 2. We assessed the relationship between personality variables and volunteering for clinical pharmacology research. Two personality questionnaires, the Sensation Seeking Scale (SSS, form V) and the Eysenck Personality Questionnaire (EPQ), were administered to 48 male healthy university students who volunteered to participate in a phase I clinical trial and to 43 male university students who were not willing to participate in phase I clinical trials. General norm data were also used for the comparison of results. 3. When healthy volunteers were compared with unwilling subjects, significant differences were found in thrill-and-adventure seeking (7.9 vs 6.7, P = 0.0034), experience seeking (6.4 vs 5.2, P = 0.0012), disinhibition (6.2 vs 4.3, P < 0.0001), boredom susceptibility (3.9 vs 2.8, P = 0.0073), total sensation seeking trait (24.3 vs 19.0, P < 0.0001), extraversion (15.1 vs 13.3, P = 0.0490), and psychoticism (4.4 vs 3.5, P = 0.0086). When healthy volunteers were compared with general norm data similar statistically significant differences were found in all these scales, except for boredom susceptibility and psychoticism. 4. The personality profile of healthy volunteers was characterized by a higher sensation seeking trait and extraversion as compared with individuals who were not willing to participate in phase I clinical trials and general norm data. PMID:7640147

Family influence on volunteering intention and behavior among Chinese adolescents in Hong Kong.

PubMed

Law, Ben M F; Shek, Daniel T L

2009-01-01

Based on the responses of 5,946 adolescents (mean age = 14.77), the relationships among family influence, adolescents' volunteering intention, and volunteering behavior in a Chinese context were examined. A 9-item Chinese Family Influence on Adolescent Volunteerism Scale (C-FIAV) was used to measure nine kinds of influence of the family (such as family support) which could be subsumed under two underlying domains (positive family influence and extrinsic family influence). Results showed that family support, family belief, and family modeling were positively associated with both intention and behavior. Family reward and coercion were negatively associated with both intention and behavior. Family belief in volunteerism was the most critical factor. Grade and gender differences were found only in the associations between family influence and volunteering intention. Path models showed that positive and extrinsic family influence had an effect on volunteering behavior directly or via the mediation of volunteering intention. Implications and limitations are discussed.

The relative bioavailability and fasting pharmacokinetics of three formulations of olmesartan medoxomil 20-mg capsules and tablets in healthy Chinese male volunteers: An open-label, randomized-sequence, single-dose, three-way crossover study.

PubMed

Li, Kun-Yan; Liang, Jian-Ping; Hu, Bing-Qiang; Qiu, Yu; Luo, Chen-Hui; Jiang, Yun; Lin, Xiao-Ping; Yang, Nong

2010-08-01

Olmesartan medoxomil is an angiotensin II-receptor antagonist used in the treatment of hypertension. It is a prodrug and is converted to the pharmacologically active compound on de-esterification by arylesterase in the gastrointestinal tract. This study investigated the relative bioavailability and fasting pharmacokinetic properties of olmesartan after single doses of a 20-mg test tablet, a 20-mg test capsule, and a commercially available 20-mg reference tablet in healthy Chinese male volunteers. The study was conducted to satisfy Chinese State Food and Drug Administration regulatory requirements for approval of a generic formulation of olmesartan medoxomil. This study had an open-label, randomized-sequence, single-dose, 3-treatment, 3-period crossover design. Healthy volunteers were randomly assigned in a 1:1:1 ratio to receive a single 20-mg dose of the test tablet, test capsule, or reference tablet, each administered after a 12-hour overnight fast, followed by a 1-week washout period and administration of the alternate formulation. Blood samples were obtained at baseline and at 0.5, 1, 1.5,2,2.5,3,4,6,8,12,24,36, and 48 hours after dosing. Tolerability was assessed based on vital signs and laboratory values obtained before and after administration of study drug. The formulations were assumed to be bioequivalent if the 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-∞) were within the predetermined equivalence range (70%-143% for C(max); 80%-125% for AUC(0-t) and AUC(0-∞)), as established by the Chinese State Food and Drug Administration. Twenty-one healthy male subjects (mean age, 21 years [range, 18-25 years]; weight, 62.1 kg [range, 54.0-80.0 kg]) were enrolled in and completed the study. No period or sequence effect was observed. The mean AUC(0-∞) values for the test tablet, test capsule, and reference tablet were 3993 (1070), 3567 (850), and 3849 (872) ng/mL/h, respectively. The 90% CIs for the log-transformed ratios of test

The Volunteer Satisfaction Index: A Validation Study in the Chinese Cultural Context

ERIC Educational Resources Information Center

Wong, Lok Ping; Chui, Wing Hong; Kwok, Yan Yuen

2011-01-01

Using a Hong Kong-sourced sample of 261 participants, this study set out to validate the Volunteer Satisfaction Index (VSI) in the Chinese cultural context and to evaluate its psychometric properties. The VSI was originally developed by Galindo-Kuhn and Guzley (2001) to measure the outcomes of volunteer experiences. In this study, exploratory…

Pharmacokinetics and tolerability of oral dosage forms of huperzine a in healthy Chinese male volunteers: a randomized, single dose, three-period, six-sequence crossover study.

PubMed

Wu, San-Lan; Gan, Jun; Rao, Jing; He, Si-Jie; Zhu, Wen-Wen; Zhao, Ying; Lv, Yong-Ning; Huang, Jian-Geng; Liu, Ya-Ni

2017-10-01

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were C max , 1.550 (0.528) ng/mL; t 1/2 , 12.092 (1.898) h; AUC 0-72h , 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were C max , 1.412 (0.467), 1.521 (0.608) ng/mL; t 1/2 , 12.073 (2.068), 12.271 (1.678) h; AUC 0-72h , 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC 0-72h and C max were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers.

PubMed

Felton, T W; Ogungbenro, K; Boselli, E; Hope, W W; Rodvold, K A

2018-01-29

Severe infections of the respiratory tracts of critically ill patients are common and associated with excess morbidity and mortality. Piperacillin is commonly used to treat pulmonary infections in critically ill patients. Adequate antibiotic concentration in the epithelial lining fluid (ELF) of the lung is essential for successful treatment of pulmonary infection. To compare piperacillin pharmacokinetics/pharmacodynamics in the serum and ELF of healthy volunteers and critically ill patients. Piperacillin concentrations in the serum and ELF of healthy volunteers and critically ill patients were compared using population methodologies. Median piperacillin exposure was significantly higher in the serum and the ELF of critically ill patients compared with healthy volunteers. The IQR for serum piperacillin exposure in critically ill patients was six times greater than for healthy volunteers. The IQR for piperacillin exposure in the ELF of critically ill patients was four times greater than for healthy volunteers. The median pulmonary piperacillin penetration ratio was 0.31 in healthy volunteers and 0.54 in critically ill patients. Greater variability in serum and ELF piperacillin concentrations is observed in critically ill patients compared with healthy adult subjects and must be considered in the development of dosage regimens. Pulmonary penetration of antimicrobial agents should be studied in critically ill patients, as well as healthy volunteers, during drug development to ensure appropriate dosing of patients with pneumonia. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization.

PubMed

Cao, G; Zhang, J; Wu, X; Yu, J; Chen, Y; Ye, X; Zhu, D; Zhang, Y; Guo, B; Shi, Y

2013-10-01

The pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen. 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 fC(max) /MIC ≥5 and fAUC(24 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. The results of PK study showed that the C(max) and AUC(0-∞) 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 C(ss,max), C(ss,min) and AUC(0-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 fC(max) /MIC and fAUC/MIC targets. 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. © 2013 John Wiley & Sons Ltd.

Effects of an Al3+- and Mg2+-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers

PubMed Central

Zhang, Yi-fan; Dai, Xiao-jian; Wang, Ting; Chen, Xiao-yan; Liang, Li; Qiao, Hua; Tsai, Cheng-yuan; Chang, Li-wen; Huang, Ping-ting; Hsu, Chiung-yuan; Chang, Yu-ting; Tsai, Chen-en; Zhong, Da-fang

2014-01-01

Aim: To evaluate the effects of an Al3+- and Mg2+-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans. Methods: Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al3+ and 496 mg of Mg2+) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe2+) or calcium carbonate (containing 600 mg of Ca2+). Results: Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0–∞) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0–∞ for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0–∞ by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0–∞ by 17.8%, Cmax by 14.3%, and Ae by 18.4%. Conclusion: Metal ions, Al3+, Mg2+, and Fe2+ markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca2+ had much weaker effects. To avoid the effects of Al3+ and Mg2+-containing drugs, nemonoxacin should be administered ≥2 h before them. PMID:25327812

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

PubMed

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.

Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.

PubMed

Sheng, Yu-Cheng; Wang, Kun; He, Ying-Chun; Yang, Juan; Zheng, Qing-Shan

2010-11-01

To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach. Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition. The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease. The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.

CONCENTRATED AMBIENT AIR PARTICLES INDUCE PULMONARY INFLAMMATION IN HEALTHY HUMAN VOLUNTEERS

EPA Science Inventory

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

Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization

PubMed Central

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

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

PubMed Central

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

2013-01-01

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

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers.

PubMed

Wervers, K; Vis, M; Rasappu, N; van der Ven, M; Tchetverikov, I; Kok, M R; Gerards, A H; Hazes, Jmw; Luime, J J

2018-01-02

We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. New and established PsA patients and healthy volunteers (aged 20-30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10-22.5) in new PsA, 13.5 (9.5-18) in established PsA, and 3 (1-8.5) in healthy volunteers (p = 0.002). Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.

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

PubMed

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

2010-07-01

Citalopram (CITA) pharmacokinetics are enantioselective in healthy volunteers and the metabolism of (+)-(S)-CITA to (+)-(S)-DCITA is dependent on CYP2C19. Omeprazole is a potent CYP2C19 inhibitor. This study indicates that omeprazole induces a loss of enantioselectivity in the CITA pharmacokinetics because of the selective inhibition of (+)-(S)-CITA metabolism. The study assessed the influence of omeprazole on the kinetic disposition of the (+)-(S)-citalopram (CITA) and (-)-(R)-CITA enantiomers in healthy volunteers. 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. 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]. 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

Pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers.

PubMed

Vlase, Laurian; Popa, Adina; Neag, Maria; Muntean, Dana; Bâldea, Ioan; Leucuţa, Sorin E

2011-08-01

The objective of this study was to evaluate the pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers. The study consisted of 2 periods: period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem, and period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 400 mg carbamazepine. Between the 2 periods, the participants were treated for 15 days with a single daily dose of 400 mg carbamazepine. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using noncompartmental analysis. In the 2 periods of treatments, the mean peak plasma concentrations (C(max)) were 59 ng/mL (zolpidem alone) and 35 ng/mL (zolpidem after pretreatment with carbamazepine). The t(max), times taken to reach C(max), were 0.9 hours and 1.0 hour, respectively, and the total areas under the curve (AUC(0-∞)) were 234.9 ng·h/mL and 101.5 ng·h/mL, respectively. The half-life of zolpidem was 2.3 and 1.6 hours, respectively. Carbamazepine interacts with zolpidem in healthy volunteers and lowers its bioavailability by about 57%. The experimental data demonstrate the pharmacokinetic interaction between zolpidem and carbamazepine and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed.

Arterial blood pressure estimation using ultrasound: Clinical results on healthy volunteers and a medicated hypertensive volunteer.

PubMed

Zakrzewski, Aaron M; Anthony, Brian W

2017-07-01

This study presents a non-occlusive and non-invasive ultrasound-based technique to measure blood pressure. Most popular clinically-used arterial blood pressure measurement techniques suffer from important weaknesses including being inaccurate, invasive, or occlusive. In the proposed technique, an ultrasound probe is placed on the patient's carotid artery and the contact force between the probe and the tissue is slowly increased while ultrasound images and contact force data are recorded. From this data, the artery is segmented and the segmentation data is sent into an optimization procedure; after post-processing, blood pressure is displayed to the user. This technique was applied to 24 healthy single-visit volunteers, one multi-visit healthy volunteer, and one multi-visit medicated hypertensive volunteer. Compared to the oscillometric cuff, the accuracy and precision of the algorithm-reported systolic pressure is -2.4 ± 10.2 mmHg, and for diastolic pressure is -0.3 ± 8.2 mmHg. This method has the potential to occupy a clinical middle-ground between the arterial catheter and the oscillometric cuff.

Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study.

PubMed

Li, Jiapeng; Huang, Xiaojun; Wang, Qian; Jing, Shan; Jiang, Hao; Wei, Zhongna; Zang, Yannan; Liu, Yang; Zhao, Libo; Fang, Yi; Feng, Wanyu

2015-10-01

Histamine dihydrochloride (HDC) injection has been approved in Europe for the treatment of adults with acute myeloid leukemia, used in combination therapy with the T-cell-derived cytokine interleukin-2. Despite years of clinical applications of HDC in Europe, no data are available on its tolerability and pharmacokinetic properties in Chinese patients. The objective of this study was to determine the safety profile and pharmacokinetic properties of HDC in Chinese healthy volunteers (HVs). In this Phase I, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg HDC via a 10-minute subcutaneous injection. Whole-blood and urine samples were collected at designated time points after dosing. Plasma and urine concentrations of histamine and metabolite N-methyl histamine were measured using a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated through noncompartmental procedures based on concentration-time data. Adverse events and evaluation of clinical laboratory tests were used to assess the safety profile. The pharmacokinetic profile for a single-dose of 1.0 mg HDC in Chinese HVs was compared with that in Western HVs. No severe adverse events occurred in this study, and the severity of all adverse events was grade I according to the Common Terminology Criteria for Adverse Events, version 4.0. For the pharmacokinetic parameters of histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.50 and 1.02 hours; Tmax was 0.15 and 0.14 hours; mean Cmax was 26.59 and 71.01 nmol/L; AUC0-t was 8.35 and 20.43 nmol/h/L; AUC0-∞ was 9.61 and 22.69 nmol/h/L; accumulated amount excreted in urine within 24 hours was 125.93 and 145.52 nmol; and maximum urine excretion rates were 21.85 and 38.94 nmol/h, respectively. For N-methyl histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.58 and 0.66 hours; Tmax was 0.28 and 0.26 hours; mean Cmax was 17.01 and 23.54 nmol/L; AUC0-t was 7.72 and 17.08 nmol

Morphine Glucuronidation and Elimination in Intensive Care Patients: A Comparison with Healthy Volunteers.

PubMed

Ahlers, Sabine J G M; Välitalo, Pyry A J; Peeters, Mariska Y M; Gulik, Laura van; van Dongen, Eric P A; Dahan, Albert; Tibboel, Dick; Knibbe, Catherijne A J

2015-11-01

Although morphine is used frequently to treat pain in the intensive care unit, its pharmacokinetics has not been adequately quantified in critically ill patients. We evaluated the glucuronidation and elimination clearance of morphine in intensive care patients compared with healthy volunteers based on the morphine and morphine-3-glucuronide (M3G) concentrations. A population pharmacokinetic model with covariate analysis was developed with the nonlinear mixed-effects modeling software (NONMEM 7.3). The analysis included 3012 morphine and M3G concentrations from 135 intensive care patients (117 cardiothoracic surgery patients and 18 critically ill patients), who received continuous morphine infusions adapted to individual pain levels, and 622 morphine and M3G concentrations from a previously published study of 20 healthy volunteers, who received an IV bolus of morphine followed by a 1-hour infusion. For morphine, a 3-compartment model best described the data, whereas for M3G, a 1-compartment model fits best. In intensive care patients with a normal creatinine concentration, a decrease of 76% was estimated in M3G clearance compared with healthy subjects, conditional on the M3G volume of distribution being the same in intensive care patients and healthy volunteers. Furthermore, serum creatinine concentration was identified as a covariate for both elimination clearance of M3G in intensive care patients and unchanged morphine clearance in all patients and healthy volunteers. Under the assumptions in the model, M3G elimination was significantly decreased in intensive care patients when compared with healthy volunteers, which resulted in substantially increased M3G concentrations. Increased M3G levels were even more pronounced in patients with increased serum creatinine levels. Model-based simulations show that, because of the reduction in morphine clearance in intensive care patients with renal failure, a 33% reduction in the maintenance dose would result in morphine

Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy male volunteers.

PubMed

Ruan, Can-Jun; Liu, Dong-Yang; Jiang, Ji; Hu, Pei

2012-12-01

Icotinib hydrochloride {4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline hydrochloride}, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), was designed for the treatment of non-small cell lung cancer (NSCLC). In the present study, we investigated the influence of the CYP2C19*2 and CYP2C19*3 alleles on the pharmacokinetics of icotinib in healthy Chinese volunteers. In a single-dose pharmacokinetic study, 12 healthy Chinese volunteers received an oral dose of 600 mg of icotinib. Plasma was sampled for up to 72 h post-dose, followed by quantification of icotinib by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS). Five subjects genotyped as homozygous extensive metabolizers (CYP2C19*1/*1), 6 subjects genotyped as heterozygous extensive metabolizers (CYP2C19*1/*2 or CYP2C19*1/*3), and 1 subject genotyped as a poor metabolizer (CYP2C19*2/*3) and was withdrawn from the research because of urticaria. The mean icotinib AUC(0-∞) and C(max) (14.56 ±5.31 h mg/L and 2.32 ± 0.49 μg/mL) in homozygous EMs was 1.56 and 1.41-fold lower than that in heterozygous EMs (22.7 ± 6.11 and 3.28 ± 0.48, P = 0.046 and 0.047). The mean CL/F (44.18 ± 12.17 L/h) in homozygous EMs was 1.55-fold higher than that in heterozygous EMs (28.42 ± 9.23 L/h, P = 0.013). The data showed that the pharmacokinetics of icotinib differ significantly between homozygous EMs and heterozygous EMs in CYP2C19.

Using "clinical trial diaries" to track patterns of participation for serial healthy volunteers in U.S. phase I studies.

PubMed

Edelblute, Heather B; Fisher, Jill A

2015-02-01

Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers' Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that "clinical trial diaries" can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers' involvement in Phase I clinical trials. © The Author(s) 2015.

Exposure to wood smoke particles produces inflammation in healthy volunteers.

PubMed

Ghio, Andrew J; Soukup, Joleen M; Case, Martin; Dailey, Lisa A; Richards, Judy; Berntsen, Jon; Devlin, Robert B; Stone, Susan; Rappold, Ana

2012-03-01

Human exposure to wood smoke particles (WSP) impacts on human health through changes in indoor air quality, exposures from wild fires, burning of biomass and air pollution. This investigation tested the postulate that healthy volunteers exposed to WSP would demonstrate evidence of both pulmonary and systemic inflammation. Ten volunteers were exposed to filtered air and, 3 weeks or more later, WSP. Each exposure included alternating 15 min of exercise and 15 min of rest for a total duration of 2 h. Wood smoke was generated by heating an oak log on an electric element and then delivered to the exposure chamber. Endpoints measured in the volunteers included symptoms, pulmonary function tests, measures of heart rate variability and repolarisation, blood indices and analysis of cells and fluid obtained during bronchoalveolar lavage. Mean particle mass for the 10 exposures to air and WSP was measured using the mass of particles collected on filters and found to be below the detectable limit and 485±84 μg/m(3), respectively (mean±SD). There was no change in either symptom prevalence or pulmonary function with exposure to WSP. At 20 h after wood smoke exposure, blood tests demonstrated an increased percentage of neutrophils, and bronchial and bronchoalveolar lavage revealed a neutrophilic influx. We conclude that exposure of healthy volunteers to WSP may be associated with evidence of both systemic and pulmonary inflammation.

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

PubMed Central

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

Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers.

PubMed

Gutierrez, Sandra; Ang-Lee, Michael K; Walker, Diana J; Zacny, James P

2004-05-01

Valerian is the common name given to the genus Valeriana, an odiferous, herbaceous perennial plant widely distributed in the temperate regions of Asia, Europe, and North America. It is among the most widely used herbal medicines in the world. Numerous clinical studies have demonstrated valerian's ability to improve sleep; however, to the best of our knowledge, no study has systematically assessed subjective and psychomotor/cognitive effects of valerian in young healthy adults across a range of doses. In the present study, we sought to determine whether valerian extract (Valeriana officinalis) altered mood and/or impaired psychomotor/cognitive performance in young healthy volunteers. We examined the effects of valerian extract (600, 1200, and 1800 mg) and 10 mg diazepam (positive control) compared to placebo in 10 young healthy volunteers. Dependent measures included subjective and psychomotor variables. The valerian extract had no significant effects on any of the dependent measures. Diazepam, though, produced subjective effects as measured by four different rating scales, and impaired psychomotor/cognitive performance. The data suggest that acute administration of valerian does not have mood-altering or psychomotor/cognitive effects in young healthy volunteers.

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

PubMed Central

Anderlini, Paolo

2015-01-01

Purpose of Review Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. Recent Findings In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. G-CSF receptors were identified in a variety of non-myeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for PBPCs, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. Summary rhG-CSF effects in healthy volunteers, while normally transient and self-limiting, are now believed to be more complex and heterogeneous that previously thought. While rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals. PMID:19057203

The Influence of MDR1 G2677T/a genetic polymorphisms on the pharmacokinetics of repaglinide in healthy Chinese volunteers.

PubMed

Xiang, Qian; Cui, Yi Min; Zhao, Xia; Yan, Liang; Zhou, Ying

2012-01-01

The aim of this study was to evaluate the pharmacogenetic variability in the disposition of repaglinide in healthy Chinese subjects. A single dose of 2 mg repaglinide was orally administered to 24 healthy Chinese subjects. The serum concentrations of repaglinide were measured by using liquid chromatography/tandem mass spectrometry. We determined the polymorphic alleles of MDR1 C1236T, MDR1 G2677T/A, MDR1 C3435T, CYP3A4*18, OATP1B1 G388A, and OATP1B1 T521C in each subject. The area under the plasma concentration-time curve from time 0 to infinity (AUC((0-inf))) of repaglinide was significantly higher in subjects possessing the MDR1 2677GT and 2677TT alleles than in those with the MDR1 2677GG and 2677TA alleles (p = 0.007). The mean AUCs and peak plasma concentration were higher in subjects with the 521TC allele than in those with the OATP1B1 521TT allele, and the OATP1B1 388A allele is associated with a reduced trend of pharmacokinetic exposure; however, these trends were not statistically significant. The pharmacokinetics of repaglinide was not associated with MDR1 C1236T, MDR1 C3435T, and CYP3A4*18. This study shows that the genetic polymorphisms of MDR1 G2677T/A might explain the variability in the pharmacokinetics of repaglinide in the Chinese population. Copyright © 2012 S. Karger AG, Basel.

Comparative Bioavailability and Tolerability of a Single 2-mg Dose of 2 Repaglinide Tablet Formulations in Fasting, Healthy Chinese Male Volunteers: An Open-Label, Randomized-Sequence, 2-Period Crossover Study☆

PubMed Central

Zhai, Xue-jia; Hu, Kai; Chen, Fen; Lu, Yong-ning

2013-01-01

Background Repaglinide, an oral insulin secretagogue, was the first meglitinide analogue to be approved for use in patients with type 2 diabetes mellitus. Objective In our study, the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of repaglinide 2 mg were compared in a fasting, healthy Chinese male population. Methods This 2-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in 22 healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 2-mg dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. After an overnight fast, subjects received a single oral dose of repaglinide (2 mg). Blood samples were drawn at predetermined time points (0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 hours). All plasma concentrations of repaglinide were measured by LC-MS/MS. The observed Cmax, Tmax, t1/2, and AUC were assessed. The formulations were to be considered bioequivalent if the ln-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration of the People’s Republic of China. Tolerability was assessed throughout the study via subject interview, vital signs, and blood sampling. Results The mean (SD) age of the subjects was 24.2 (2.3) years; their mean (SD) weight was 62.6 (5.8) kg, their mean (SD) height was 172 (5.7) cm, and their mean (SD) body mass index was 21.0 (1.1). The mean (SD) Cmax for repaglinide with the test and reference formulations were 20.0 (5.1) and 18.7 (8.7) ng/mL. The AUC0–t for the test formulation was 46.3 (15.1) and AUC0–∞ was 47.9 (16.5) ng•h/mL. With the reference formulation, the corresponding values were 46.4 (26.1) and 49.0 (31.3) ng•h/mL. The mean (SD) Tmax values with the test and reference

Comparative Bioavailability and Tolerability of a Single 2-mg Dose of 2 Repaglinide Tablet Formulations in Fasting, Healthy Chinese Male Volunteers: An Open-Label, Randomized-Sequence, 2-Period Crossover Study.

PubMed

Zhai, Xue-Jia; Hu, Kai; Chen, Fen; Lu, Yong-Ning

2013-12-01

Repaglinide, an oral insulin secretagogue, was the first meglitinide analogue to be approved for use in patients with type 2 diabetes mellitus. In our study, the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of repaglinide 2 mg were compared in a fasting, healthy Chinese male population. This 2-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in 22 healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 2-mg dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. After an overnight fast, subjects received a single oral dose of repaglinide (2 mg). Blood samples were drawn at predetermined time points (0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 hours). All plasma concentrations of repaglinide were measured by LC-MS/MS. The observed Cmax, Tmax, t1/2, and AUC were assessed. The formulations were to be considered bioequivalent if the ln-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration of the People's Republic of China. Tolerability was assessed throughout the study via subject interview, vital signs, and blood sampling. The mean (SD) age of the subjects was 24.2 (2.3) years; their mean (SD) weight was 62.6 (5.8) kg, their mean (SD) height was 172 (5.7) cm, and their mean (SD) body mass index was 21.0 (1.1). The mean (SD) Cmax for repaglinide with the test and reference formulations were 20.0 (5.1) and 18.7 (8.7) ng/mL. The AUC0-t for the test formulation was 46.3 (15.1) and AUC0-∞ was 47.9 (16.5) ng(•)h/mL. With the reference formulation, the corresponding values were 46.4 (26.1) and 49.0 (31.3) ng(•)h/mL. The mean (SD) Tmax values with the test and reference formulations were 1.2 (0.7) hours and 1

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

PubMed

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 <0.05). Both RD and TD groups showed PI similar to controls during the recovery period. Selective REM 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.

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

PubMed

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

2015-10-28

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

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

PubMed

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 D 2 -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.

Immigrants as Active Citizens: Exploring the Volunteering Experience of Chinese Immigrants in Vancouver

ERIC Educational Resources Information Center

Guo, Shibao

2014-01-01

Despite the fact that immigration has played an important role in transforming Canada into an ethno-culturally diverse and economically prosperous nation, immigrants themselves are often criticised as passive citizens. This study attempts to deconstruct this myth by investigating the volunteering experiences of Chinese immigrants in Vancouver. The…

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

PubMed

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

2015-11-01

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

Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study.

PubMed

Breitschaft, Astrid; Hu, Ke; Hermosillo Reséndiz, Karina; Darstein, Christelle; Golor, Georg

2014-03-01

Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy in Cushing's disease and acromegaly, can affect glucose metabolism due to inhibition of insulin secretion and incretin hormone responses. A study was therefore conducted to evaluate different antihyperglycemic drugs in the management of pasireotide-associated hyperglycemia. This was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600 μg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide 60 mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6 mg sc qd. An oral glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and pharmacokinetic effects were also evaluated. Ninety healthy male volunteers were enrolled (n=18 per arm). After 7 days of treatment, plasma glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was reduced by 13%, 29%, 45% and 72% with co-administration of metformin, nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively). Minimal changes in plasma glucagon were observed. Adverse events were consistent with the safety profiles of the drugs used. Vildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Adapalene gel 0.1% is better tolerated than tretinoin gel 0.025% among healthy volunteers of various ethnic origins.

PubMed

Goh, Chee Leok; Tang, Mark B Y; Briantais, Philippe; Kaoukhov, Alexandre; Soto, Pascale

2009-01-01

The efficacious acne treatment adapalene gel 0.1% is significantly less irritating than tretinoin of various concentrations and formulations, according to several clinical studies conducted predominantly in Caucasian patients. To confirm the lower irritation potential of adapalene gel 0.1% compared to tretinoin gel 0.025% among volunteers of various ethnic origins and to explore the difference in the irritant susceptibility among ethnic groups. The study was a single-centre, randomized, investigator-masked and intra-individual comparison. Healthy volunteers applied adapalene and tretinoin daily to the face for 21 days and to the forearms for 4 days, and were then evaluated for the level of irritation. The irritation potential of adapalene gel 0.1% was significantly lower than that of tretinoin gel 0.025% in all tolerability assessments, irrespective of the volunteers' ethnic origins. The between-treatment differences were similar among various ethnic groups. Statistically significant but small inter-ethnicity differences were observed in the evaluation of facial signs, with Caucasians being less susceptible than Chinese, Asian Indians and Malays. Adapalene gel 0.1% was significantly better tolerated than tretinoin gel 0.025% among various ethnic groups. The patients' ethnic origins had no impact on the difference between adapalene and tretinoin treatments in terms of tolerability.

Effects of UDP-glucuronosyltransferase (UGT) polymorphisms on the pharmacokinetics of febuxostat in healthy Chinese volunteers.

PubMed

Lin, Meihua; Liu, Jian; Zhou, Huili; Wu, Minglan; Lv, Duo; Huang, Yujie; Zheng, Yunliang; Shentu, Jianzhong; Wu, Lihua

2017-02-01

The pharmacokinetics (PKs) of febuxostat varies among individuals, while the main causes are still unknown. We investigated whether the polymorphisms of UGT1A1 and UGT1A3 played an important role in the disposition of the drug after oral administration of febuxostat tablet in Chinese subjects. A total of 42 healthy subjects were from two previous independent clinical bioequivalence (BE) trials of febuxostat, in which the same reference formulation (ULORIC ® tablet, 80 mg) was taken, and thus the PK data were combined for the evaluation of pharmacogenomic effect on febuxostat PKs. Our study clearly indicated that the area under the plasma concentration-time curve (AUC) in the heterozygote and homozygote of UGT1A1*6 (c.211G > A, rs4148323) was significantly higher than that in the wild-type. Meanwhile, the clearance (CL/F) exhibited a significant reduction by 22.2%. Interestingly, UGT1A1*28, in perfect linkage disequilibrium (LD) with UGT1A3*2a, significantly increased its clearance. These results indicate that UGT1A1*6 was an important factor influencing the drug disposition, thus providing a probable explanation for interindividual variation of febuxostat PKs in Chinese subjects. In addition, by considering of the different allele distribution of UGT1A1*6 and *28 in Eastern and Western populations, these findings might further interpret the ethnic difference of febuxostat PKs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Oral versus rectal ibuprofen in healthy volunteers.

PubMed

Vilenchik, Rolanda; Berkovitch, Matitiahu; Jossifoff, Azaria; Ben-Zvi, Zvi; Kozer, Eran

2012-01-01

Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers

PubMed Central

Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

2016-01-01

Abstract The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited. Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results. The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found. The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin. PMID:27175645

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

PubMed

Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

2016-05-01

The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

Electrocardiographic effects of hawthorn (Crataegus oxyacantha) in healthy volunteers: A randomized controlled trial.

PubMed

Trexler, Stephanie E; Nguyen, Elaine; Gromek, Samantha M; Balunas, Marcy J; Baker, William L

2018-04-19

The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QT c I) at 4 and 6 hr. Maximum post-dose QT c I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QT c I were seen between hawthorn and placebo. Maximum post-dose QT c I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Exposure to wood smoke particles produces an inflammation in healthy volunteers

EPA Science Inventory

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

A bioequivalence study of two memantine formulations in healthy Chinese male volunteers
.

PubMed

Deng, Ying; Zhuang, Jialang; Wu, Jingguo; Chen, Jiangying; Ding, Liang; Wang, Xueding; Huang, Lihui; Zeng, Guixiong; Chen, Jie; Ma, Zhongfu; Chen, Xiao; Zhong, Guoping; Huang, Min; Zhao, Xianglan

2017-10-01

The aim of the current study is to evaluate the bioequivalence between the test and reference formulations of memantine in a single-dose, two-period and two-sequence crossover study with a 44-day washout interval. A total of 20 healthy Chinese male volunteers were enrolled and completed the study, after oral administration of single doses of 10 mg test and reference formulations of memantine. The blood samples were collected at different time points and memantine concentrations were determined by a fully validated HPLC-MS/MS method. The evaluated pharmacokinetic parameters (test vs. reference) including C_max (18 ± 3.2 vs. 17.8 ± 3.4), AUC_0-t (1,188.5 ± 222.2 vs. 1,170.9 ± 135.7), and AUC_0-∞ (1,353.3 ± 258.6 vs. 1,291.3 ± 136.7) values were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of memantine test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for C_max, AUC_0-t, and AUC_0-∞ were within the bioequivalence acceptance range of 80 - 125%. The results obtained from the healthy Chinese subjects in this study suggests that the test formulation of memantine 10 mg tablet is bioequivalent to the reference formulation (Ebixa^®10 mg tablet).
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Bioequivalence Study of Warfarin in Healthy Chinese Volunteers With a Validated High-Performance Liquid Chromatography-Mass Spectrometry Method.

PubMed

Li, Wenlong; Bu, Fanlong; Li, Rong; Wang, Benjie; Shaikh, Abdul Sami; Zhang, Yunyun; Guo, Ruichen; Zhang, Rui

2018-03-01

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t ½ , 103.5 ± 18.8 and 105.8 ± 21.3 hours; T max , 0.7 ± 0.5 and 1.3 ± 0.8 hours; C max , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC 0∼360 , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL -1 ·h; AUC 0∼∞ , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL -1 ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin. © 2017, The American College of Clinical Pharmacology.

Safety evaluation of Elixir Paregorico in healthy volunteers: a phase I study.

PubMed

de Moraes, Mea; Bezerra, Mm; Bezerra, Faf; de Moraes, Ra; Cavalcanti, Pp; Uchoa, Cra; Lima, Fav; Odorico de Moraes, M

2008-10-01

A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whether Elixir Paregorico administration causes any noticeable toxic effects in healthy volunteers. In all, 28 middle-aged healthy male (n = 14) and female (n = 14) were enrolled. After screening and a washout period, eligible subjects received four oral doses per day of Elixir Paregorico (3 mL diluted in 30 mL of water) over a 10-day period. Altogether, all 28 participants completed the study. The results of hematological and biochemical tests performed pre and post-treatment were within the normal range. In both male and female volunteers, there were no statistical differences (P > 0.05) in the results of clinical and laboratory tests performed at screening, on 5th and 10th day visits, and at final assessment. Although mild adverse events were related, which subsided spontaneously, no serious untoward reactions were reported following Elixir Paregorico administration. To our knowledge, this is the first demonstration that Elixir Paregorico administered four times a day for 10 days is safe and does not cause any noticeable toxic effect in healthy volunteers.

The acute (immediate) effects of reflexology on arterial compliance in healthy volunteers: A randomised study.

PubMed

Rollinson, Kirsty; Jones, Jenny; Scott, Norma; Megson, Ian L; Leslie, Stephen J

2016-02-01

Reflexology is a widely used complementary therapy. The effects of reflexology on the cardiovascular system are not well characterised. Arterial stiffness (compliance) is a marker of vascular health. This study aimed to evaluate the effects of reflexology on arterial compliance in healthy volunteers. 12 healthy volunteers (1 male; 11 female; mean age 44.8 ± 10.8 yrs) received 10 min of reflexology on each foot in a single-blind randomised study. The main outcome measures were measurements of cardiovascular parameters including heart rate, blood pressure and arterial compliance (augmentation index). Reflexology had no significant effect on heart rate, blood pressure or augmentation index (all p > 0.05). In healthy volunteers, there were no consistent changes in haemodynamic parameters with a single brief reflexology treatment. Thus from a cardiovascular point of view, reflexology (as delivered) would appear to have a limited (if any) effect on the cardiovascular system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of grapefruit juice and food on the pharmacokinetics of pirfenidone in healthy Chinese volunteers: a diet-drug interaction study.

PubMed

Hu, Jinqing; Shang, Dewei; Xu, Xinwen; He, Xiuling; Ni, Xiaojia; Zhang, Ming; Wang, Zhanzhang; Qiu, Chang; Deng, Shuhua; Lu, Haoyang; Zhu, Xiuqing; Huang, Wencan; Wen, Yuguan

2016-01-01

1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety.

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

PubMed

Nilsson, Matias; Poulsen, Jakob L; Brock, Christina; Sandberg, Thomas H; Gram, Mikkel; Frøkjær, Jens B; Krogh, Klaus; Drewes, Asbjørn M

2016-05-01

Opioid treatment is associated with numerous gastrointestinal adverse effects collectively known as opioid-induced bowel dysfunction (OIBD). Most current knowledge of the pathophysiology derives from animal studies limited by species differences and clinical studies, which have substantial confounders that make evaluation difficult. An experimental model of OIBD in healthy volunteers in a controlled setting is therefore highly warranted. The aim of this study was to assess bowel function in healthy volunteers during opioid treatment using subjective and objective methods. 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, patient assessment of constipation symptoms and the Bristol stool form scale. Colorectal volumes were determined using a newly developed MRI method. Compared with baseline, oxycodone increased pain detection thresholds by 8% (P=0.02). Subjective OIBD was observed as increased bowel function index (464% increase; P<0.001), gastrointestinal symptom rating scale (37% increase; P<0.001) and patient assessment of constipation symptoms (198% increase; P<0.001). Objectively, stools were harder and drier during oxycodone treatment (P<0.001) and segmental colorectal volumes increased in the caecum/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. Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies to discriminate the efficacies of different laxatives, peripheral morphine antagonists and opioid treatments.

A Study to Draw a Normative Database of Laryngopharynx pH Profile in Chinese

PubMed Central

Feng, Guijian; Wang, Junyao; Zhang, Lihong; Liu, Yulan

2014-01-01

Background/Aims To draw a normative database of laryngopharynx pH profile in Chinese subjects. Methods Normal volunteers were recruited from “www.Ganji.com” and People’s hospital between May 2008 and December 2009. The Restech pH Probes were calibrated in pH 7 and pH 4 buffer solutions according to the manufacturer's instructions. Each volunteer was asked to wear the device for a 24-hour period and was encouraged to participate in normal daily activities. Results The healthy volunteers consisted of 20 males and 9 females with a median age of 23 years (interquartile range, 21 to 32 years). The 95th percentiles for % total times at pH < 4, pH < 4.5, pH < 5.0 and pH < 5.5 for the oropharynx pH catheter were 0.06%, 1.01%, 7.23% and 27.34%, respectively. The 95th percentile for number of reflux events within the 24-hour period at pH < 4, pH < 4.5, pH < 5.0 and pH < 5.5 were 2.0, 18.0, 107.5 and 284.5, respectively. Conclusions This is the first study to systematically assess the degree of reflux detected by the new pH probe in healthy asymptomatic Chinese volunteers and to report normative values in Chinese people. Using an oropharyngeal pH catheter to monitor laryngopharyngeal reflux indicated that in healthy Chinese, reflux should be considered normal if the percent time at pH less than 4.5 is no more than 1%. PMID:24948130

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

PubMed Central

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

2009-01-01

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

Pharmacokinetics of 14C-etretinate in healthy volunteers and two patients with biliary T-tube drainage.

PubMed

Lucek, R W; Dickerson, J; Carter, D E; Bugge, C J; Crews, T; Vane, F M; Cunningham, W; Colburn, W A

1988-01-01

The pharmacokinetic profile of 14C-etretinate, a retinoid that is effective in the treatment of psoriasis, was studied in six healthy male volunteers and two biliary T-tube patients. Following a 100 mg oral dose of 14C-etretinate (20 microcurie), etretinate and its major blood metabolites (etretin, isoetretin) were measured by HPLC and total carbon-14 was measured in blood, bile, urine, and feces by liquid scintillation counting. Etretinate was extensively metabolized in healthy volunteers and in T-tube patients. During the absorption phase, 75 per cent of the total radioactivity in the blood could be accounted for as etretinate, etretin, and isoetretin whereas these compounds accounted for only approximately 12 per cent of the blood radioactivity in T-tube patients over the same time period. The blood concentrations of etretinate, etretin, and isoetretin appeared to be substantially reduced in T-tube patients compared to those in healthy volunteers. A higher proportion of the total drug was excreted in the feces and bile of the T-tube patients (84 per cent) than in the feces of healthy volunteers (62 per cent). The major factor responsible for the observed decrease in etretinate blood concentrations following biliary cannulation appears to be the reduced absorption of etretinate due to the elimination of solubilizing bile salts in the duodenum. Carbon-14 related material was detected in urine and feces for as long as 3 weeks in healthy subjects supporting the previous observation that a long terminal elimination half-life exists for etretinate, even following a single dose of the compound.

Dark chocolate inhibits platelet aggregation in healthy volunteers.

PubMed

Innes, Andrew J; Kennedy, Gwen; McLaren, Margaret; Bancroft, Anne J; Belch, Jill J F

2003-08-01

Cardiovascular disease is a leading cause of death in the UK. The flavonoids found in cocoa may produce a cardio-protective role for chocolate with a high cocoa content. Thirty healthy volunteers were randomised to receive 100 g of white, milk or dark chocolate, and assessments of platelet function were undertaken on venous blood samples before and after chocolate consumption. White and milk chocolate had no significant effect on platelets. However dark chocolate inhibited collagen-induced platelet aggregation in platelet rich plasma. In the future dark chocolate may have a role in prevention of cardiovascular and thromboembolic diseases.

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

EPA Science Inventory

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

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

PubMed

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.

Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

PubMed Central

Lima, Renata Monteiro; Ferreira, Maria Augusta Drago; de Jesus Ponte Carvalho, Teresa Maria; Dumêt Fernandes, Bruno José; Takayanagui, Osvaldo Massaiti; Garcia, Hector Hugo; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

2011-01-01

AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. PMID:21395645

Differential expression of immune factor between patients with chronic prostatitis/chronic pelvic pain syndrome and the healthy volunteers.

PubMed

Ye, Chen; Xiao, Guang'an; Xu, Jian; Qin, Shengfei; Luo, Yuhua; Chen, Guanghua; Lai, H Henry; Zhou, Tie

2018-03-01

Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers. This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4 + and CD8 + . There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8 + were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/μL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023). Differential levels of IgG and CD8 + between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.

Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers.

PubMed

Linssen, A M W; Vuurman, E F P M; Sambeth, A; Riedel, W J

2012-06-01

Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.

Determination of multiple sclerosis plaque size with diffusion-tensor MR Imaging: comparison study with healthy volunteers.

PubMed

Kealey, Susan M; Kim, Youngjoo; Whiting, Wythe L; Madden, David J; Provenzale, James M

2005-08-01

To use diffusion-tensor magnetic resonance (MR) imaging to measure involvement of normal-appearing white matter (WM) immediately adjacent to multiple sclerosis (MS) plaques and thus redefine actual plaque size on diffusion-tensor images through comparison with T2-weighted images of equivalent areas in healthy volunteers. Informed consent was not required given the retrospective nature of the study on an anonymized database. The study complied with requirements of the Health Insurance Portability and Accountability Act. Twelve patients with MS (four men, eight women; mean age, 35 years) and 14 healthy volunteers (six men, eight women; mean age, 25 years) were studied. The authors obtained fractional anisotropy (FA) values in MS plaques and in the adjacent normal-appearing WM in patients with MS and in equivalent areas in healthy volunteers. They placed regions of interest (ROIs) around the periphery of plaques and defined the total ROIs (ie, plaques plus peripheral ROIs) as abnormal if their mean FA values were at least 2 standard deviations below those of equivalent ROIs within equivalent regions in healthy volunteers. The combined area of the plaque and the peripheral ROI was compared with the area of the plaque seen on T2-weighted MR images by means of a Student paired t test (P = .05). The mean plaque size on T2-weighted images was 72 mm2 +/- 21 (standard deviation). The mean plaque FA value was 0.285 +/- 0.088 (0.447 +/- 0.069 in healthy volunteers [P < .001]; mean percentage reduction in FA in MS plaques, 37%). The mean plaque size on FA maps was 91 mm2 +/- 35, a mean increase of 127% compared with the size of the original plaque on T2-weighted images (P = .03). A significant increase in plaque size was seen when normal-appearing WM was interrogated with diffusion-tensor MR imaging. This imaging technique may represent a more sensitive method of assessing disease burden and may have a future role in determining disease burden and activity.

LSD enhances suggestibility in healthy volunteers.

PubMed

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.

Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy volunteers.

PubMed

Misaka, Shingen; Abe, Osamu; Sato, Hideyuki; Ono, Tomoyuki; Shikama, Yayoi; Onoue, Satomi; Yabe, Hirooki; Kimura, Junko

2018-05-01

The objective of this study is to assess the effects of green tea and its major catechin component, (-)-epigallocatechin gallate (EGCG), on CYP2C9-mediated substrate metabolism in vitro, and the pharmacokinetics of fluvastatin in healthy volunteers. The metabolism of diclofenac and fluvastatin in human recombinant CYP2C9 was investigated in the presence of EGCG. In a randomized three-phase crossover study, 11 healthy volunteers ingested a single 20-mg dose of fluvastatin with green tea extract (GTE), containing 150 mg of EGCG, along with water (300 mL), brewed green tea (300 mL), or water (300 mL) after overnight fasting. Plasma concentrations of fluvastatin and EGCG were measured by ultra-performance liquid chromatography with fluorescence detection and a single mass spectrometer. EGCG inhibited diclofenac 4'-hydroxylation and fluvastatin degradation with IC 50 of 2.23 and 48.04 μM, respectively. Brewed green tea used in the clinical study also dose-dependently inhibited the metabolism of diclofenac and fluvastatin in vitro. However, no significant effects of GTE and brewed green tea were observed in plasma concentrations of fluvastatin. The geometric mean ratios with 90% CI for area under the plasma concentration-time curve (AUC 0-∞ ) of fluvastatin were 0.993 (0.963-1.024, vs. brewed green tea) and 0.977 (0.935-1.020, vs. GTE). Although in vitro studies indicated that EGCG and brewed green tea produce significant inhibitory effects on CYP2C9 activity, the concomitant administration of green tea and fluvastatin in healthy volunteers did not influence the pharmacokinetics of fluvastatin.

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

PubMed

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

2018-01-01

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

Changes in Chinese hair growth along a full year.

PubMed

Liu, C; Yang, J; Qu, L; Gu, M; Liu, Y; Gao, J; Collaudin, C; Loussouarn, G

2014-12-01

To confirm the existence of seasonal hair growth cycle among Chinese subjects and objectivize the seasonal effect of hair loss; the hair growth parameters of Chinese volunteers were followed monthly for an entire year on the same area of vertex. The hair growth parameters of 41 Chinese volunteers (women and men), free from alopecia, were recorded monthly along an entire year using the phototrichogram technique. Results show an increased rate of telogen hairs (growing arrest) around August-September in the study group, as previously reported in European subjects albeit of a lower extent and remaining within the normal range of healthy head hair parameters. The possible effects of latitude and daylight duration are discussed. Data confirm that Chinese hairs present characteristics of the most developed and fast growing terminal fibres, as compared to other non-Asian ethnics. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

The haemodynamic effects of bolus versus slower infusion of intravenous crystalloid in healthy volunteers.

PubMed

Ukor, Ida F; Hilton, Andrew K; Bailey, Michael J; Bellomo, Rinaldo

2017-10-01

This pilot study aimed to characterise the haemodynamic effect of 1L of IV normal saline (NS) administered as a rapid versus slow infusion on cardiac output (CO), heart rate (HR), systemic blood pressures, and carotid blood flow in six healthy volunteers. Six healthy male volunteers aged 18-65years were randomized to receive 1L NS given over 30min or 120min. On a subsequent study session the alternate fluid regimen was administered. Haemodynamic data was gathered using a non-invasive finger arterial pressure monitor (Nexfin®), echocardiography and carotid duplex sonography. Time to micturition and urine volume was also assessed. Compared to baseline, rapid infusion of 1L of saline over 30min produced a fall in Nexfin®-measured CO by 0.62L/min (p<0.001), whereas there was a marginal but significant increase during infusion of 1L NS over 120min of 0.02L/min (p<0.001). This effect was mirrored by changes in HR and blood pressure (BP) (p<0.001). There were no significant changes in carotid blood flow, time to micturition, or urine volume produced. Slower infusion of 1L NS in healthy male volunteers produced a greater increase in CO, HR and BP than rapid infusion. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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 (p<0.05) however, it does not affect Clcr concentration (p>0.05). 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.

The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses.

PubMed

Chen, Xia; Wang, Hongyun; Jiang, Ji; Chen, Rui; Zhou, Ying; Zhong, Wen; Liu, Hongzhong; Hu, Pei

2014-03-01

Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males. This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol. Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed. The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.

PXR polymorphisms and their impact on pharmacokinetics/pharmacodynamics of repaglinide in healthy Chinese volunteers.

PubMed

Du, Qing-qing; Wang, Zhi-jun; He, Lin; Jiang, Xue-hua; Wang, Ling

2013-11-01

CYP3A4 is the main isoform of cytochrome P450 oxidases involved in the metabolism of approximately 60 % drugs, and its expression level is highly variable in human subjects. CYP3A4 is regulated by many transcription factors, among which the pregnane X receptor/steroid and xenobiotic receptor (PXR/SXR, NR1I2) have been identified as the most critical. Genetic polymorphisms (such as SNPs) in PXR may affect the expression level of CYP3A4. Although numerous SNPs have been identified in PXR and have appeared to affect PXR function, their impact on the expression of CYP3A4 in human subjects has not been well studied. Thus, a clinical study in healthy Chinese subjects was conducted to investigate the impact of PXR polymorphisms on repaglinide (an endogenous marker for CYP3A4 activity) pharmacokinetics used alone or in combination with a PXR inducer, flucloxacillin. Two SNPs, -298A>G and 11193T>C, were identified as the tag SNPs to represent the overall genetic polymorphic profile of PXR. To evaluate the potential functional change of these two SNPs, 24 healthy subjects were recruited in a pharmacokinetics/pharmacodynamics study of repaglinide with or without flucloxacillin. The pharmacokinetic parameters including AUC and T1/2 were significantly different among the PXR genotype groups. The SNPs of -298G/G and 11193C/C were found to be associated with a lower PXR activity resulting in reduction of CYP3A4 activity in vivo. After administration of flucloxacillin, a significant drug-drug interaction was observed. The clearance of repagnilide was significantly increased by concomitant flucloxacillin in a genotype dependent manner. The subjects with SNPs of -298G/G and 11193C/C appeared to be less sensitive to flucloxacillin. Our study results demonstrated for the first time the impact of genetic polymorphisms of PXR on the PK and PD of repaglinide, and showed that subjects with genotype of -298G/G and 11193C/C in PXR has a decreased elimination rate of 3A4/2C8. Furthermore

Shirodhara: A psycho-physiological profile in healthy volunteers.

PubMed

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

2013-01-01

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. 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. 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. 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. 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.

Shirodhara: A psycho-physiological profile in healthy volunteers

PubMed Central

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

2013-01-01

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

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

PubMed

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 < 0.01). Both thoracic kyphosis and lumbar lordosis were significantly greater in the osteoporosis group than in the volunteer group (p < 0.01). With regard to QOL, the 36-Item Short-Form Health Survey (SF-36) subscale scores of role physical, bodily pain, general health, and role emotional were all significantly lower in the osteoporosis group than in the volunteer group (p < 0.05 each). SF-36 physical component summary (PCS) score was significantly lower in the osteoporosis group than in the volunteer group (p < 0.001). SF-36 PCS score correlated positively with thoracic kyphosis and negatively with BMI only in the osteoporosis group (p < 0.05 each). These results indicated that lower QOL in osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean muscle

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

PubMed

Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2017-10-01

Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Influence of Panax ginseng on the steady state pharmacokinetic profile of lopinavir-ritonavir in healthy volunteers.

PubMed

Calderón, Mónica M; Chairez, Cheryl L; Gordon, Lori A; Alfaro, Raul M; Kovacs, Joseph A; Penzak, Scott R

2014-11-01

Panax ginseng has been shown in preclinical studies to modulate cytochrome P450 enzymes involved in the metabolism of HIV protease inhibitors. Therefore, the purpose of this study was to determine the influence of P. ginseng on the pharmacokinetics of the HIV protease inhibitor combination lopinavir-ritonavir (LPV-r) in healthy volunteers. Single-sequence, open-label, single-center pharmacokinetic investigation. Government health care facility. Twelve healthy human volunteers. Twelve healthy volunteers received LPV-r (400-100 mg) twice/day for 29.5 days. On day 15 of LPV-r administration, serial blood samples were collected over 12 hours for determination of lopinavir and ritonavir concentrations. On study day 16, subjects began taking P. ginseng 500 mg twice/day, which they continued for 2 weeks in combination with LPV-r. On day 30 of LPV-r administration, serial blood samples were again collected over 12 hours for determination of lopinavir and ritonavir concentrations. Lopinavir and ritonavir pharmacokinetic parameter values were determined using noncompartmental methods, and preadministration and postadministration ginseng values were compared using a Student t test, where p<0.05 was accepted as statistically significant. Neither lopinavir nor ritonavir steady-state pharmacokinetics were altered by 2 weeks of P. ginseng administration to healthy human volunteers. Thus, a clinically significant interaction between P. ginseng and LPV-r is unlikely to occur in HIV-infected patients who choose to take these agents concurrently. It is also unlikely that P. ginseng will interact with other ritonavir-boosted protease inhibitor combinations, although confirmatory data are necessary. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

PubMed

Li, Xueqing; Wang, Rutao; Liu, Yang; Liu, Yun; Zheng, Heng; Feng, Yabo; Zhao, Na; Geng, Hongbin; Zhang, Wanzhi; Wen, Aidong

2017-11-16

Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters. An open-label, randomized, and single- and multiple-dosing investigation was performed in healthy Chinese subjects. The investigation included 3 study groups: the 0.5 mg, 1 mg and 2 mg dose groups were the single-dose study groups in the first stage. Eligible volunteers were randomly and orally administered a single 0.5 mg, 1 mg, or 2 mg metolazone tablet. The 0.5 mg dose group was also part of the multiple-dose study group, and the 1 mg dose group was the food-effect study group in the second stage. Human plasma samples were gathered pre-dosing and up to 48 h after dosing. The human plasma sample concentration of metolazone was quantified using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic data were calculated by a noncompartmental analysis method using WinNonlin version 6.4. Tolerability was evaluated based on adverse events, medical examination, 12-lead ECG, and other clinical laboratory exams. Thirty eligible subjects (15 men and 15 women) were registered in our investigation and completed all of the study stages. The AUC and C max showed dose proportionality after a single dose based on the linear-regression analysis. A comparison of the pharmacokinetic data revealed that the differences between the male and female groups were not statistically significant. The t max of metolazone was increased by approximately 100% in the fed condition. Metolazone was

Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers

PubMed Central

Chiesa, Joseph; Lückermann, Mark; Fischer, Carsten; Dalhoff, Axel; Fuhr, Uwe

2017-01-01

ABSTRACT Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination

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

PubMed

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

2000-01-01

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

Serial Participation and the Ethics of Phase 1 Healthy Volunteer Research.

PubMed

Walker, Rebecca L; Cottingham, Marci D; Fisher, Jill A

2018-01-12

Phase 1 healthy volunteer clinical trials-which financially compensate subjects in tests of drug toxicity levels and side effects-appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on phase 1 trials. We show how participant experiences shift attention from discrete exchanges, behaviors, and events in the research enterprise to the ongoing and dynamic patterns of serial participation in which individual decision-making is embedded in collective social and economic conditions and shaped by institutional policies. We argue in particular for the ethical significance of structurally diminished voluntariness, routine powerlessness in setting the terms of exchange, and incentive structures that may promote pharmaceutical interests but encourage phase 1 healthy volunteers to skirt important rules. © The Author(s) 2018. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of propranolol on thyroid homeostasis of healthy volunteers.

PubMed Central

Wilkins, M. R.; Franklyn, J. A.; Woods, K. L.; Kendall, M. J.

1985-01-01

The effect of propranolol on thyroid status was investigated by administering the drug in 2 therapeutic doses (80 mg b.d. and 120 mg b.d.) to 8 healthy volunteers and serially measuring total and free thyroid hormones and their major binding protein. Mean free T3 fell by 1.2 pmol/l (P less than 0.05) whilst mean free T4 and mean rT3 rose by 3.3 pmol/l (P less than 0.01) and 0.16 nmol/l (P less than 0.01) respectively. Mean thyroxine binding globulin (TBG) fell by 1.2 mg/l (P less than 0.001). Despite the change in free hormone levels there was no significant change in TSH. For the first time the effect of propranolol on circulating thyroid hormones and binding proteins in healthy subjects is apparent within one study. The biological significance of the change in free hormone levels is discussed. PMID:3927277

Verbal learning in schizopsychotic outpatients and healthy volunteers as a function of cognitive performance levels.

PubMed

Karilampi, Ulla; Helldin, Lars; Hjärthag, Fredrik; Norlander, Torsten; Archer, Trevor

2007-02-01

The aim was to analyze and compare neurocognitive test profiles related to different levels of verbal learning performance among schizopsychotic patients and healthy volunteers. A single-center patient cohort of 196 participants was compared with an equal-sized volunteer group to form three cognitive subgroups based on the shared verbal learning performance. 43.9% of the patients had normal learning ability. Despite this, all patients underperformed the volunteers on all subtests with the exception of working memory, and, for those with high learning ability, even verbal facility. All patients also presented equally poor visuomotor processing speed/efficacy. A global neurocognitive retardation of speed-related processing in schizophrenia is suggested.

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

PubMed

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

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

PubMed

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

2017-02-01

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

[Pharmacokinetics of domestic actoprotector drug Metaprot in healthy volunteers].

PubMed

Kibal'chich, D A; Belolipetskaia, V G; Blagodatskikh, S V; Martsevich, S Iu; Rudenko, L I; Iatsuk, V R

2011-01-01

Pharmacokinetics of the actoprotector Metaprot, an original Russian drug, has been studied in a group of healthy adult volunteers. Metaprot in capsules was administrated orally as a single dose of 250 mg. The concentration of the active substance (ethylthiobenzimidazole) in the blood serum was determined by high-performance liquid chromatography (HPLC) with UV detection. The pharmacokinetic parameters were calculated by the model-independent method. The peak concentration of ethylthiobenzimidazole in plasma was Cmax = 0.91 +/- 1.05 microg/ml and the average time to peak concentration was t(max) = 1.06 +/- 0.16 h. A polymodal character of the distribution of pharmacokinetic parameters in the test group was revealed.

Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

PubMed

Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

2010-10-01

The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were <0.05 for the 90% CIs. Signs and symptoms of adverse effects of fluoxetine hydrochloride such as nausea, vomiting, insomnia, somnolence, anxiety, and nervousness, as well as any untoward effects, were collected using a daily written questionnaire and recorded by the study physicians. Tolerability was assessed using monitoring of vital signs, physical ex- amination, ECG, and routine blood and urine tests, along with blood biochemical tests, at the start as well as at the end of the study. Twenty-four subjects were

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

PubMed Central

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

2016-01-01

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

Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers

PubMed Central

Songisepp, Epp; Kals, Jaak; Kullisaar, Tiiu; Mändar, Reet; Hütt, Pirje; Zilmer, Mihkel; Mikelsaar, Marika

2005-01-01

Background In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. Methods Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. Results ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. Conclusion The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by

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

PubMed

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 < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 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 < 0.001) during the 30 min interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (± 4.3) min. The reacidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (± 33) and 77 (± 30) min, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions.

Giving Voice to Study Volunteers: Comparing views of mentally ill, physically ill, and healthy protocol participants on ethical aspects of clinical research

PubMed Central

Roberts, Laura Weiss; Kim, Jane Paik

2014-01-01

Motivation Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable. Methods Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation. Results Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives

Giving voice to study volunteers: comparing views of mentally ill, physically ill, and healthy protocol participants on ethical aspects of clinical research.

PubMed

Roberts, Laura Weiss; Kim, Jane Paik

2014-09-01

Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable. Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation. Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives regarding the ethical

Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers.

PubMed

Schück, Stéphane; Bentué-Ferrer, Danièle; Kleinermans, Diane; Reymann, Jean-Michel; Polard, Elisabeth; Gandon, Jean-Marc; Allain, Hervé

2002-02-01

Piribedil is a dopamine agonist acting on D2 and D3 central nervous system dopamine receptors. This drug has been administered to 12 young healthy male volunteers (age 22 +/- 2 years) according to a single center randomized, double-blind, two ways cross-over, placebo controlled trial, including a washout period of one week. Placebo and piribedil were administered by a single intravenous infusion over 2 h (3 mg). Psychomotor performance and cognitive functions were assessed through a standardized and computerized psychometric tests battery and a continuous electroencephalogram (EEG) mapping. Piribedil improved simple reaction time (P=0.02), immediate (P=0.045 and 0.004), and delayed free recall (P=0.05), dual coding test (P=0.02) and increased theta and fast beta waves on the EEG (P < 0.05 and 0.001, respectively). No deleterious effect was observed on the tests exploring attention and concentration via the other procedures. It is concluded that a single intravenous perfusion of piribedil 3 mg improves alertness and the information processing speed within the central nervous system, in healthy volunteers.

Single bright light exposure decreases sweet taste threshold in healthy volunteers.

PubMed

Srivastava, Shrikant; Donaldson, Lucy F; Rai, Dheeraj; Melichar, Jan K; Potokar, John

2013-10-01

Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.

Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake.

PubMed

Wen, Yu-Guan; Shang, De-Wei; Xie, He-Zhi; Wang, Xi-Pei; Ni, Xiao-Jia; Zhang, Ming; Lu, Wei; Qiu, Chang; Liu, Xia; Li, Fang-Fang; Li, Xuan; Luo, Fu-Tian

2013-03-01

The aim of the study was to better understand blonanserin population pharmacokinetic (PK) characteristics in Chinese healthy subjects. Data from two studies with 50 subjects were analyzed to investigate the population PK characteristics of blonanserin at single dose (4, 8, and 12 mg) under fasting, multidose (4 mg bid or 8 mg qd for 7 days) and under food intake condition (single dose, 8 mg). Blonanserin plasma concentrations were detected using the high performance liquid chromatography tandem mass spectrometry (LC/MS/MS). A nonlinear mixed-effects model was developed to describe the blonanserin concentration-time profiles. A two compartment model with first-order absorption was built to describe the time-course of blonanserin. The population-predicted system apparent clearance (CL/F), volume of apparent distribution in center (V(1)/F), and the first-order absorption rate constant (Ka) of blonanserin under fasting was 1230 L/h, 9500 L, and 3.02 h(-1), respectively. Food intake decreased Ka of blonanserin to 0.78 h(-1). The relative bioavailability between fasting and food intake estimated by the final model was 55%. No clinically significant safety issues were identified. This is the first study assessing the PK profile of blonanserin with population PKs method. The results can be used for simulation in further clinical trial and optimize individual dosage regimens using a Bayesian methodology in patients. Copyright © 2013 John Wiley & Sons, Ltd.

Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disorders.

PubMed

Hollenstein, Michael; Thwaites, Philip; Bütikofer, Simon; Heinrich, Henriette; Sauter, Matthias; Ulmer, Irina; Pohl, Daniel; Ang, Daphne; Eberli, Daniel; Schwizer, Werner; Fried, Michael; Distler, Oliver; Fox, Mark; Misselwitz, Benjamin

2017-09-01

The factors that determine how people eat when they are healthy or have disease have not been defined. We used high resolution manometry (HRM) to assess pharyngeal swallowing and oesophageal motility during ingestion of a solid test meal (STM) in healthy volunteers and patients with motility disorders. This study was based at University Hospital Zurich (Zürich, Switzerland). Healthy volunteers who responded to an advertisement completed HRM with ten single water swallows (SWS) in recumbent and upright positions followed by a 200 g rice STM in the upright position. Healthy volunteers were stratified for age and sex to ensure a representative population. For comparison, consecutive patients with major motility disorders on SWS and patients with dysphagia but no major motility disorders on SWS (disease controls) were selected from a database that was assembled prospectively; the rice meal data were analysed retrospectively. During STM, pharyngeal swallows were timed and oesophageal contractions were classified as representing normal motility or different types of abnormal motility in accordance with established metrics. Factors that could potentially be associated with eating speed were investigated, including age, sex, body-mass index, and presence of motility disorder. We compared diagnoses based on SWS findings, assessed with the Chicago Classification v3.0, with those based on STM findings, assessed with the Chicago Classification adapted for solids. These studies are registered with ClinicalTrials.gov, numbers NCT02407938 and NCT02397616. Between April 2, 2014, and May 13, 2015, 72 healthy volunteers were recruited and underwent HRM. Additionally, we analysed data from 54 consecutive patients with major motility disorders and 53 with dysphagia but no major motility disorders recruited between April 2, 2013, and Dec 18, 2014. We found important variations in oesophageal motility and eating speed during meal ingestion in healthy volunteers and patients. Increased

Predicting personality disorder functioning styles by the Chinese Adjective Descriptors of Personality: a preliminary trial in healthy people and personality disorder patients.

PubMed

Fan, Hongying; Zhu, Qisha; Ma, Guorong; Shen, Chanchan; Zhang, Bingren; Wang, Wei

2016-08-30

Cultural and personality factors might contribute to the clinical differences of psychiatric patients all over the world including China. One cultural oriented Chinese Adjective Descriptors of Personality (CADP) designed to measure normal personality traits, might be specifically associated with different personality disorder functioning styles. We therefore have invited 201 healthy volunteers and 67 personality disorder patients to undergo CADP, the Parker Personality Measure (PERM), and the Plutchik-van Praag Depression Inventory (PVP) tests. Patients scored significantly higher on PVP scale and all 11 PERM personality disorder functioning styles, as well as CADP Emotional and Unsocial traits. The PVP was significantly correlated with some CADP traits and PERM styles in both groups. In healthy volunteers, only one CADP trait, Unsocial, prominently predicted 11 PERM styles. By contrast in patients, CADP Intelligent predicted the PERM Narcissistic and Passive-Aggressive styles; CADP Emotional the PERM Paranoid, Borderline, and Histrionic styles; CADP Conscientious the PERM Obsessive-Compulsive style; CADP Unsocial the PERM Schizotypal, Antisocial, Narcissistic, Avoidant, Dependent, and Passive-Aggressive styles; CADP Agreeable the PERM Antisocial style. As a preliminary study, our results demonstrated that, in personality disorder patients, all five CADP traits were specifically associated with almost all 11 personality disorder functioning styles, indicating that CADP might be used as an aid to diagnose personality disorders in China.

Effects of different doses, enteric-coated preparation of aspirin, and sex on urinary 11-dehydrothromboxane B2 in healthy volunteers.

PubMed

Dharmasaroja, Pornpatr A; Sae-Lim, Suvaraporn

2010-10-01

There is scarce information about the effects of different doses and enteric-coated preparation of aspirin on platelet function, especially in Asian people, evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The objective of the present study was to assess the effects of different doses, enteric-coated preparation of aspirin, sex and also the effects of timing of urine collection on urinary dTXB2 level in healthy volunteers. Thirty healthy volunteers were included. Each volunteer took three preparations of aspirin (aspirin 81 mg, enteric-coated aspirin 300 mg and aspirin 300 mg) for 7 days. Urine dTXB2 level was measured at baseline, day 3, and day 7 after taking each preparation of aspirin. There was no significant difference in the effects of different doses of aspirin (81 vs. 300 mg, 50.7 vs. 61.8 ng/mmol creatinine, P = 0.248), preparations (enteric-coated vs. nonenteric-coated aspirin, 61.8 vs. 67.9 ng/mmol creatinine, P = 0.527) and time of urine collection (day 3 vs. day 7, 51.7 vs. 49.9 ng/mmol creatinine, P = 0.448). Female volunteers showed a trend to have higher urinary dTXB2 than male volunteers at baseline and after taking aspirin. This study showed no significant difference in urinary dTXB2 level after taking different doses and enteric-coated preparation of aspirin in healthy volunteers.

The prevalence and incidence of medical conditions in healthy pharmaceutical company employees who volunteer to participate in medical research

PubMed Central

Singh, S D; Williams, A J

1999-01-01

Aims Although clinical research in healthy volunteers is commonly performed there have been few studies of the value of the medical screening of subjects. The aim of this study was to investigate the prevalence and incidence of medical conditions found during the medical screening of ‘healthy’ subjects employed in a pharmaceutical company who volunteered to participate in medical research. Methods This was a retrospective study of the medical notes of all the subjects who volunteered for membership of the Zeneca Clinical Pharmacology Unit’s healthy volunteer panel over a 4 year period from 1990 to 1994. The prevalence of medical conditions found at presentation was determined. The incidence of medical conditions during the 4 year observation period was also ascertained. Medical screening included a full medical history and examination, clinical chemistry, haematology and urinalysis screens, pulmonary function tests, ECGs, 24 h ambulatory cardiac monitoring and a request for information from the volunteer’s General Practitioner. Results Prevalence-1293 subjects volunteered to join the panel of which 156 subjects (12%) were not accepted at presentation including 141 (10.9%) for medical reasons. The most medical common reasons were; previously diagnosed medical conditions (3.3%), cardiovascular abnormalities (1.9%), abnormal liver function tests (1.9%), anaemia (1.2%), hyperlipidaemia (1.1%), excess alcohol intake (0.6%) and thyroid disease (0.5%). Incidence—36 of the 1137 volunteers (0.8% per year) accepted onto the panel subsequently developed medical conditions of which the most common were; anaemia (0.29% per year), cardiovascular abnormalities (0.13% per year) and vasovagal syncope (0.13% per year). Conclusions This study demonstrates the importance of medical screening before healthy volunteers participate in clinical research. PMID:10383556

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-01-01

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug administered to treat injuries, joint pain, and recurrent muscular skeletal pain. The aim of this study was to determine the cutaneous irritancy of a medicated ibuprofen plaster compared with a placebo plaster in healthy volunteers. Healthy volunteers (N = 31) were treated at the same time with one ibuprofen and one placebo plaster. The ibuprofen and placebo plaster were applied in a randomized fashion to sites on the left or right side of subjects' lower backs. At each scheduled visit, the plasters and applications sites were assessed for degree of adhesion and skin irritancy, respectively. The plasters were applied on study Days 1, 2, 3, 5, 8, 10, 12, 15, 17, and 19, with final plaster removal on Day 22. The ibuprofen medicated plaster compared with placebo had a lower percentage of Grade 1 (23.3% vs. 46.7%, respectively), Grade 2 (10% vs. 20%), and ≥Grade 3 (3% vs. 16.1%) irritancy scores after 21 days of application. The mean irritation score across the study was 0.40 for the ibuprofen medicated plaster and 1.18 for the placebo plaster. The irritation score on Day 22 of the study was 0.53 for the ibuprofen medicated plaster and 1.50 for placebo. The placebo plaster was associated with a higher number of stopped applications due to Grade 3 or above skin reactions compared with the ibuprofen medicated plaster (5 vs. 1, respectively). The ibuprofen medicated plaster was well tolerated and was associated with lower irritancy than the placebo plaster.

Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

PubMed

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.

The ability of healthy volunteers to simulate a neurologic field defect on automated perimetry.

PubMed

Ghate, Deepta; Bodnarchuk, Brian; Sanders, Sheila; Deokule, Sunil; Kedar, Sachin

2014-03-01

To determine if volunteers can simulate and reproduce 3 types of neurologic field defects: hemianopia, quadrantanopia, and central scotoma. Cross-sectional study. Thirty healthy volunteers new to perimetry (including automated perimetry). After informed consent, volunteers were randomized to 1 of the 3 visual field defects listed above. All visual field testing was performed on the right eye using the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA) SITA Fast 24-2 protocol. Each volunteer was provided with standard new patient instructions and was shown a diagram of the defect to be simulated. Two sets of visual fields were performed on the right eye with 10 minutes between tests. Three experts used the Ocular Hypertension Treatment Study reading center criteria and determined if the simulation was successful. Proportion of volunteers able to simulate the assigned visual field. All 10 volunteers (100%) successfully simulated a hemianopia on the first and second fields. All 10 volunteers (100%) simulated a quadrantanopia on the first field and 9 (90%) did so on the second field. Eight volunteers (80%) successfully simulated a central scotoma in the first field and all 10 (100%) did so on in the second field. Reliability criteria were excellent. Forty-seven fields (78%) had 0 fixation losses, 48 (80%) had 0 false-positive results, and 44 (73%) had 0 false-negative results. It is easy to simulate reproducible and reliable neurologic field defects on automated perimetry using HFA. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Hypoglycemic and hypolipidemic activities of crude seeds of Centratherum anthelminticum in healthy volunteers and type 2 diabetic patients.

PubMed

Mudassir, Hina Akram; Qureshi, Shamim Akhter; Azmi, Muhammad Bilal; Ahsan, Muhammad; Kamran, Musab; Jafar, Sakina

2018-05-01

This study first time reports the hypoglycaemic activity of crude seeds powder (CSP) of Centratherum anthelminticum in healthy and type 2 diabetic volunteers. In addition, hypolipidemic effect of same CSP was also determined in healthy volunteers. Healthy individuals were divided into control and two test groups T1 and T2 treated with 200 & 400mg of CSP. Similarly, type 2 diabetic patients were also divided into positive control (PC) treated with metformin 600mg and two test groups DT1 (CSP 400mg + metformin 600mg) & DT2 (CSP 400mg). Each group has 6 individuals and each treatment was done orally. CSP 400mg was found more hypoglycaemic on all time intervals from 30 to 120min when oral glucose tolerance test was conducted in healthy volunteers. Both test quantities of CSP 200 & 400 mg were found successful in same healthy persons in decreasing the levels of triglycerides & total cholesterol (p<0.05), low & very low density lipoprotein cholesterols (p<0.01) and keeping the level of high density lipoprotein cholesterol as same as it was observed in control group. Similarly, CSP 400mg along with metformin and alone was also found helpful in lowering the fasting blood glucose levels in type 2 diabetic patients (DT1 & DT2) -24.99% and -20.62% respectively as compared to diabetic group only treated with metformin (PC), (p<0.01). Therefore, CSP of C antheminticum proves effective hypoglycaemic and hypolipidemic agent by possibly inducing glucose tolerance in healthy individuals and type 2 diabetic patients.

Effect of venous and lymphatic congestion on lymph capillary pressure of the skin in healthy volunteers and patients with lymph edema.

PubMed

Gretener, S B; Läuchli, S; Leu, A J; Koppensteiner, R; Franzeck, U K

2000-01-01

The aim of the present study was to assess the influence of venous and lymphatic congestion on lymph capillary pressure (LCP) in the skin of the foot dorsum of healthy volunteers and of patients with lymph edema. LCP was measured at the foot dorsum of 12 patients with lymph edema and 18 healthy volunteers using the servo-nulling technique. Glass micropipettes (7-9 microm) were inserted under microscopic control into lymphatic microvessels visualized by fluorescence microlymphography before and during venous congestion. Venous and lymphatic congestion was attained by cuff compression (50 mm Hg) at the thigh level. Simultaneously, the capillary filtration rate was measured using strain gauge plethysmography. The mean LCP in patients with lymph edema increased significantly (p < 0.05) during congestion (15.7 +/- 8.8 mm Hg) compared to the control value (12.2 +/- 8.9 mm Hg). The corresponding values of LCP in healthy volunteers were 4.3 +/- 2.6 mm Hg during congestion and 2.6 +/- 2.8 mm Hg during control conditions (p < 0.01). The mean increase in LCP in patients with lymph edema was 3.4 +/- 4.1 mm Hg, and 1.7 +/- 2.0 mm Hg in healthy volunteers (NS). The maximum spread of the lymph capillary network in patients increased from 13.9 +/- 6.8 mm before congestion to 18.8 +/- 8.2 mm during thigh compression (p < 0.05). No increase could be observed in healthy subjects. In summary, venous and lymphatic congestion by cuff compression at the thigh level results in a significant increase in LCP in healthy volunteers as well as in patients with lymph edema. The increased spread of the contrast medium in the superficial microlymphatics in lymph edema patients indicates a compensatory mechanism for lymphatic drainage during congestion of the veins and lymph collectors of the leg. Copyright 2000 S. Karger AG, Basel

The role of personal values in Chinese consumers' food consumption decisions. A case study of healthy drinks.

PubMed

Lee, Pui Yee; Lusk, Karen; Mirosa, Miranda; Oey, Indrawati

2014-02-01

Differences in culture, language, and behavior between Chinese and Western consumers make entering the Chinese market a challenge. Chinese consumers may desire similar product features (e.g. brand name, quality, and flavor) to Western consumers but the value that consumers attach to the same product may differ cross-nationally. Besides values, an understanding of desired product attributes and the consequences linking to these values is also important. To the authors' knowledge, there is no published scientific research that investigates how personal values influence Chinese consumers' food consumption decisions. The aim of this research was to identify the links among product attributes, consequences of these attributes, and personal values associated with healthy drink consumption decisions within the Chinese market. Specifically, this research employed means-end chain theory and used association pattern technique (APT) as the main data collection technique to identify these links. Focus groups (n=6) were held in Hangzhou, China to identify the important attributes and consequences involved in the consumption decisions of healthy drinks. These attributes and consequences along with Schwartz's 10 basic values were used to construct the matrices included in the APT survey. A total of 600 APT surveys were administered in six different companies in Hangzhou, with 570 returned. Construction of the hierarchical value map (HVM) identified four of Schwartz's personal values influencing Chinese consumers' healthy drink consumption decisions: security, hedonism, benevolence, and self-direction. Food safety was the foremost concern for Chinese consumers when choosing healthy drinks. Chinese consumers also sought a good tasting and nutritious drink that was good value for money. Results from this study provide food marketers with an in-depth understanding of Chinese consumers' healthy drink consumption decisions. Implications and recommendations are provided that will assist

Effect of Fresh Orange Juice Intake on Physiological Characteristics in Healthy Volunteers

PubMed Central

Asgary, Sedigheh; Keshvari, Mahtab; Afshani, Mohammad Reza; Javanmard, Shaghayegh Haghjooy

2014-01-01

Background. Impaired endothelial function is a predictor of cardiovascular events. Orange juice (OJ) is rich in dietary flavonoids and could inhibit oxidative stress and inflammatory responses. We examined the effects of commercial (COJ) and fresh orange juice (FOJ) on endothelial function and physiological characteristics in healthy humans. Materials and Methods. Twenty-two healthy volunteers years were enrolled in a single blind randomized crossover controlled trial. The two groups consumed either COJ for the first 4 weeks and then FOJ (CFOJ, 4 weeks), or FOJ for the first 4 weeks and then COJ (FCOJ, 4 weeks). We assessed endothelial function by measuring flow-mediated dilation, serum concentrations of lipids, apolipoproteins A and B (apo A-1 and apo B), and inflammatory markers such as vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6. Results. Consumption of both juices decreased VCAM, hs-CRP, and E-selectin but increased apo A-1. A decline in LDL occurred in the FOJ group. There were no differences between the characteristics of two groups, with the exception of apo A-1 levels that were increased with both forms of OJ. The largest variations occurred with hs-CRP, VCAM in both groups. Conclusion. Consumption of COJ and FOJ produced beneficial effects on the physiological characteristics of healthy volunteers. Although these results could encourage the consumption of OJ, intervention studies are needed to determine the long-term effects of these types of OJ on metabolic and cardiovascular endpoints. PMID:24967267

Effect of fresh orange juice intake on physiological characteristics in healthy volunteers.

PubMed

Asgary, Sedigheh; Keshvari, Mahtab; Afshani, Mohammad Reza; Amiri, Masoud; Laher, Ismail; Javanmard, Shaghayegh Haghjooy

2014-01-01

Background. Impaired endothelial function is a predictor of cardiovascular events. Orange juice (OJ) is rich in dietary flavonoids and could inhibit oxidative stress and inflammatory responses. We examined the effects of commercial (COJ) and fresh orange juice (FOJ) on endothelial function and physiological characteristics in healthy humans. Materials and Methods. Twenty-two healthy volunteers years were enrolled in a single blind randomized crossover controlled trial. The two groups consumed either COJ for the first 4 weeks and then FOJ (CFOJ, 4 weeks), or FOJ for the first 4 weeks and then COJ (FCOJ, 4 weeks). We assessed endothelial function by measuring flow-mediated dilation, serum concentrations of lipids, apolipoproteins A and B (apo A-1 and apo B), and inflammatory markers such as vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6. Results. Consumption of both juices decreased VCAM, hs-CRP, and E-selectin but increased apo A-1. A decline in LDL occurred in the FOJ group. There were no differences between the characteristics of two groups, with the exception of apo A-1 levels that were increased with both forms of OJ. The largest variations occurred with hs-CRP, VCAM in both groups. Conclusion. Consumption of COJ and FOJ produced beneficial effects on the physiological characteristics of healthy volunteers. Although these results could encourage the consumption of OJ, intervention studies are needed to determine the long-term effects of these types of OJ on metabolic and cardiovascular endpoints.

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

PubMed Central

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. PMID:28278231

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

PubMed

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.

Formative research to promote the Get Healthy Information and Coaching Service (GHS) in the Australian-Chinese community.

PubMed

Cranney, Leonie; Wen, Li Ming; Xu, Huilan; Tam, Nancy; Whelan, Anna; Hua, Myna; Ahmed, Nageen

2018-05-09

The free, telephone-based Get Healthy Information and Coaching Service (GHS) has made sustained improvements in healthy behaviours and weight change in the Australian population, but there is poor uptake of the GHS by culturally and linguistically diverse communities. This formative research study explored the Australian-Chinese community's awareness, perceptions and experiences of the GHS and their knowledge and cultural beliefs about healthy lifestyles. Conducted in Sydney, Australia, the research included 16 Chinese community-stakeholder interviews, a cross-sectional survey of 253 Chinese community members; and a review of Chinese participant GHS data. The study revealed poor uptake (<1%) and awareness (16%) of the GHS, but good intent (86%) to use it. The need for culturally appropriate and relevant information on healthy eating and physical activity was identified. Employment of a bilingual, bicultural coach, redesign and translation of written resources and targeted promotion in partnership with community organisations were recommended.

Influence of Panax ginseng on the Steady State Pharmacokinetic Profile of Lopinavir/Ritonavir (LPV/r) in Healthy Volunteers

PubMed Central

Calderón, Mónica M.; Chairez, Cheryl L.; Gordon, Lori A.; Alfaro, Raul M.; Kovacs, Joseph A.; Penzak, Scott R.

2014-01-01

Study Objective Panax ginseng has been shown in pre-clinical studies to modulate cytochrome P450 (CYP) enzymes involved in the metabolism of HIV protease inhibitors. Therefore, the purpose of this study was to determine the influence of Panax ginseng on the pharmacokinetics of the HIV protease inhibitor combination lopinavir/ritonavir (LPV/r) in healthy volunteers. Design Single sequence, open-label, single-center pharmacokinetic investigation. Setting Government healthcare facility. Subjects Twelve healthy human volunteers. Measurements and Main Results Thirteen healthy volunteers received LPV/r (400/100 mg) twice daily for 29.5 days. On day 15 of LPV/r administration, serial blood samples were collected over 12 hrs for determination of lopinavir and ritonavir concentrations. On study day 16, subjects began taking Panax ginseng 500 mg twice daily, which they continued for 2 weeks in combination with LPV/r. On day 30 of LPV/r administration, serial blood samples were again collected over 12 hrs for determination of lopinavir and ritonavir concentrations. Lopinavir and ritonavir pharmacokinetic parameter values were determined using noncompartmental methods and compared pre- and post-ginseng administration using a student’s t-test, where P < 0.05 was accepted as statistically significant. Conclusion Neither lopinavir nor ritonavir steady-state pharmacokinetics were altered by two weeks of Panax ginseng administration to healthy human volunteers. Thus, a clinically significant interaction between Panax ginseng and LPV/r is unlikely to occur in HIV-infected patients who choose to take these agents concurrently. It is also unlikely that Panax ginseng will interact with other ritonavir-boosted protease inhibitor combinations, although confirmatory data are necessary. PMID:25142999

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

PubMed Central

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

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

PubMed

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.

Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.

PubMed

Cheung, Tommy T; Salem, Ahmed Hamed; Menon, Rajeev M; Munasinghe, Wijith P; Bueno, Orlando F; Agarwal, Suresh K

2018-05-01

Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first-generation Han Chinese subjects received a single 100-mg dose of venetoclax following a low-fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD C max , AUC inf , and terminal half-life were 1.0 ± 0.32 μg/mL, 12.6 ± 5.4 μg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax C max and AUC inf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non-Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure-response relationship of venetoclax in non-Asian CLL subjects, a 400-mg once-daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open-label study in Chinese subjects with R/R CLL. © 2017, The American College of Clinical Pharmacology.

Intravenous strontium gluconate as a kinetic marker for calcium in healthy volunteers.

PubMed Central

Moraes, M E; Aronson, J K; Grahame-Smith, D G

1991-01-01

1. We have studied the pharmacokinetics of stable strontium in 10 healthy male volunteers. We gave each volunteer 5 mmol strontium gluconate by intravenous infusion over 1 h and measured strontium concentrations in plasma and urine samples for 20 days. The plasma strontium concentration vs time data for each volunteer were fitted by a triexponential function using NONLIN. Compartmental model-dependent and model-independent pharmacokinetic variables were then calculated. 2. The mean half-life we report (5.4 days) is longer than that previously reported (about 2 days), since we continued sampling for 20 days. However, the rates of clearance (CL 9.4 ml min-1. CLR 5.4 ml min-1, and CLNR 4.0 ml min-1) are similar to those previously reported, and the apparent volume of distribution at steady state (64 l) is similar to the values previously reported for the size of the exchangeable pool of both strontium and calcium. 3. The similarities in the pharmacokinetic behavior of strontium and calcium suggest that the in vivo disposition of strontium may be used as a marker of calcium disposition and for studying the effects of drugs such as the calcium antagonists. PMID:2049251

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

PubMed

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.

To Report or Not to Report: Exploring Healthy Volunteers' Rationales for Disclosing Adverse Events in Phase I Drug Trials.

PubMed

McManus, Lisa; Fisher, Jill A

2018-04-25

Phase I trials test the safety and tolerability of investigational drugs and often use healthy volunteers as research participants. Adverse events (AEs) are collected in part through participants' self-reports of any symptoms they experience during the trial. In some cases, experiencing AEs can result in trial participation being terminated. Because of the economic incentives underlying their motivation to participate, there is concern that healthy volunteers routinely fail to report AEs and, thereby, jeopardize the validity of the trial results. We interviewed 131 U.S. healthy volunteers about their experiences with AEs, including their rationales for reporting or failing to report symptoms. We found that participants have three primary rationales for their AE reporting behavior: economic, health-oriented, and data integrity. Participants often make decisions about whether to report AEs on a case-by-case basis evaluating what effects reporting or not reporting might have on the compensation they receive from the trial, the risk to their health, and the results of the particular clinical trial. Participants' interpretations of clinic policies, staff behaviors, and personal or vicarious experiences with reporting AEs also shape reporting decisions. Our findings demonstrate that participants' reporting behavior is more complex than previous portraits of healthy volunteers have suggested. Rather than finding participants who were so focused on the financial compensation that they were willing to subvert trial results, our study indicates that participants are willing in most cases to forgo their full compensation if they believe not reporting their symptoms jeopardizes their own safety or the validity of the research.

Influences of general and traditional Chinese beliefs on the decision to donate blood among employer-organized and volunteer donors in Beijing, China.

PubMed

Tison, Geoffrey H; Liu, Changli; Ren, Furong; Nelson, Kenrad; Shan, Hua

2007-10-01

For the past several decades, Chinese blood centers have relied on blood donations from employer-organized donors (blood donors who donate blood in groups with coworkers as prearranged by the employer and the local blood center). Recently the government has decided to phase out employer-organized donors and transition to the use of only volunteer donors (blood donors who donate individually independent of employers). Evaluating the beliefs and attitudes of employer-organized and volunteer donors is critical to maintain an adequate blood supply after this transition. The study population consisted of 431 volunteer donors and 527 employer-organized donors who completed a structured questionnaire in July 2005. Employer-organized donors tended to be older, male, and married, with higher education and higher income compared to volunteer donors. Volunteer donors were more often motivated by altruism (p < 0.001) and more likely to donate larger volumes (400 mL vs. 200 mL) of blood (volunteer 70.5% vs. employer-organized 7%; p < 0.001). Employer-organized donors were more inhibited by factors related to traditional Chinese beliefs, such as the belief that blood donation affects life energy "Qi" (volunteer 3.1% vs. employer-organized 12.7%; p < 0.001), and requested more time off from work after donating. Employer-organized donors also express a greater concern about contracting disease from donating blood. To recruit voluntary donors effectively in China and other countries with traditional cultures, efforts need to counteract traditional beliefs and perceptions of risk that discourage donation by emphasizing the benefits, safety mechanisms, physiology, and epidemiology of blood donation. In China, there is a rich opportunity to convert prior employer-organized donors into volunteer donors, and the institution of a confidential predonation screening system may help to facilitate truthful risk factor disclosure.

Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

PubMed Central

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

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

PubMed

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

2016-06-01

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. © 2015 The Authors. Andrologia Published by Blackwell Verlag GmbH.

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

PubMed Central

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

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

PubMed Central

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

2013-01-01

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

Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

PubMed

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.

Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques.

PubMed

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L; Merriman, Raphael B; Qayyum, Aliya

2012-01-01

To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Liver ADC (×10(-3) mm(2) /s) was lower on BH for all groups (mean difference 0.36 ± 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 ± 0.18; FB 2.24 ± 0.20) compared with NAFLD patients (BH 1.43 ± 0.27; FB 1.78 ± 0.28) (P < 0.001) and HCV patients (BH 1.63 ± 0.191; FB 1.88 ± 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. Copyright © 2011 Wiley-Liss, Inc.

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

PubMed Central

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

2012-01-01

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

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers.

PubMed

Avila-Rodriguez, M A; Rios, C; Carrasco-Hernandez, J; Manrique-Arias, J C; Martinez-Hernandez, R; García-Pérez, F O; Jalilian, A R; Martinez-Rodriguez, E; Romero-Piña, M E; Diaz-Ruiz, A

2017-12-12

In recent years, Copper-64 (T 1/2  = 12.7 h) in the chemical form of copper dichloride ([ 64 Cu]CuCl 2 ) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [ 64 Cu]CuCl 2 , using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model. The highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively. To the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [ 64 Cu]CuCl 2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis

Shear-wave sonoelastography for assessing masseter muscle hardness in comparison with strain sonoelastography: study with phantoms and healthy volunteers.

PubMed

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.

Effect of transdermic acetylsalicylic acid on hemostasis in healthy volunteers.

PubMed

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

2007-01-01

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

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

PubMed Central

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

2015-01-01

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

Executive functioning in healthy elderly Chinese people.

PubMed

Lin, Han; Chan, Raymond C K; Zheng, Liuning; Yang, Tianxiao; Wang, Ya

2007-05-01

This study aimed to explore the executive function of healthy elderly Chinese people. A sample of 58 healthy Chinese aged 60 and over was recruited from Guangzhou in China. They were divided into two age groups, a younger age group (aged 60-70) and an older age group (aged over 70). Executive function was measured by a battery of seven tests which were assumed to capture specific components of executive function. The tests were initiation (Hayling Sentence Completion Test (HSC)), sustained attention (Monotone Counting Test), switching and flexibility (word fluency and modified Wisconsin Card Sorting Test (WCST)), disinhibition (Modified Six Element Task (SET), Stroop Test, and HSC), attention allocation and planning (SET and modified version of WCST), and updating (Chinese Letter-Number Span). When independent neurocognitive tests were analyzed, there were significant age differences in the WCST (perseverative errors and category completed, p=0.025, 0.023) and the SET (raw score, p=0.050). The older age group tended to do worse in the total profile score of the SET and correct responses of the HSC Part A. However, when these tests were grouped into specific executive function components, a significant difference was found between the two groups in attention allocation and planning (p=0.007) and total component score (p=0.026). Regression analyses also indicated that age accounted for only very little variance of executive function in this narrow band of the elderly, whereas educational level accounted for a large part of the variance in initiation (R(2)=0.252, p<0.001), switching and flexibility (R(2)=0.211, p<0.001), and updating (R(2)=0.236, p<0.001) components of executive function. Our findings suggest that a significant decline in general executive functioning with advancing age was only evident in some putative tests in this sample. In addition, executive functions were selectively affected by older age, with attention location and planning and initiation

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

PubMed

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.

Effects of stellate ganglion block on sedation as assessed by bispectral index in normal healthy volunteers.

PubMed

Yeo, Jinseok; Jeon, Younghoon

2015-01-01

The sympathetic nervous system plays an important role in the arousal response. Recently, the stellate ganglion block (SGB) was found to effectively treat anxiety and night awakening in humans and decrease electroencephalogram (EEG) indices of arousal responses in rat. But, the role of the sympathetic block in human arousal responses has not yet been studied. We performed this prospective, double-blinded, controlled volunteer study to investigate the sedative effects and bispectral index (BIS) changes of SGB. A randomized, double-blind trial. Single academic medical center. This study was approved by the Ethics Committee of Kyungpook National University Hospital (ref: KNUH-10-1081) and registered with CRiS (Clinical Research Information Service, http://cris.cdc.go.kr, ref: KCT0000036, 2010. 9.24). Twenty healthy volunteers were enrolled in this study. The volunteers were randomly assigned to one of 2 groups: the SGB group (n = 10) and the sham group (n =10). Volunteers in SGB group received SGB and volunteers in the sham group received a sham procedure. BIS value, heart rate, and blood pressure were measured before and 5, 10, 20, and 30 minutes after the procedure. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed before and 10 and 30 minutes after the intervention. In the SGB group, BIS values and OAA/S scores significantly decreased after the intervention as compared to baseline (P < 0.05). The values were also significantly decreased in the SGB group when compared to the values in sham group after the intervention (P < 0.05). There was a significant change of mean blood pressure 10 to 30 minutes after SGB (P < 0.05). There were no differences in heart rate during study period between groups. This study is limited by a relatively small sample size. This study showed that SGB has a sedative effect in normal healthy volunteers, as evidenced by decreased OAA/S scores and BIS values.

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

PubMed Central

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

2009-01-01

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

Pharmacogenetics of healthy volunteers in Puerto Rico

PubMed Central

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

2016-01-01

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

Pharmacogenetics of healthy volunteers in Puerto Rico.

PubMed

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

2015-12-01

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

Pharmacokinetics of guaifenesin, pseudoephedrine and hydrocodone in a combination oral liquid formulation, administered as single and multiple doses in healthy Chinese volunteers, and comparison with data for individual compounds formulated as Antuss®.

PubMed

Deng, Shuhua; Huang, Wencan; Ni, Xiaojia; Zhang, Ming; Lu, Haoyang; Wang, Zhanzhang; Hu, Jinqing; Zhu, Xiuqing; Qiu, Chang; Shang, Dewei; Zhang, Yuefeng; Xiong, Linghui; Wen, Yuguan

2017-10-01

1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®. 2. In the single-dose period, exposure levels (AUC and C max ) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (∼0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering C max , there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®. 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.

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

PubMed

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 < 0.05 for all subregions, range: 11.9-15.7% at 40 Hz and 16.5-19.6% at 60 Hz). The 3D pancreatic MRE can provide promising and reproducible stiffness measurements throughout the pancreas, with more consistent data acquired at 40 Hz. © 2014 Wiley Periodicals, Inc.

Brazilian nut consumption by healthy volunteers improves inflammatory parameters.

PubMed

Colpo, Elisângela; Dalton D A Vilanova, Carlos; Reetz, Luiz Gustavo B; Duarte, Marta M M F; Farias, Iria Luiza G; Meinerz, Daiane F; Mariano, Douglas O C; Vendrusculo, Raquel G; Boligon, Aline A; Dalla Corte, Cristiane L; Wagner, Roger; Athayde, Margareth L; da Rocha, João Batista T

2014-04-01

The aim of this study was to investigate the effect of a single dose of Brazil nuts on the inflammatory markers of healthy individuals. A randomized crossover study was conducted with 10 healthy individuals (mean age 24.7 ± 3.4 y). Each individual was tested four times regarding intake of different portions of Brazil nuts: 0, 5, 20 and 50 g. At each testing period, peripheral blood was collected before and at 1, 3, 6, 9, 24, and 48 h after intake of nuts, as well as at 5 and 30 d after intake of various Brazil nut portions. Blood samples were tested for high-sensitivity to C-reactive protein, interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, aspartate and alanine aminotransferases, albumin, total protein, alkaline phosphatase, gamma-glutamyltransferase, urea, and creatinine. Consumption of nuts did not affect biochemical parameters for liver and kidney function, indicating absence of hepatic and renal toxicity. A single intake of Brazil nuts (20 or 50 g) caused a significant decrease in serum IL-1, IL-6, TNF-α, and IFN-γ levels (P < 0.05), whereas serum levels of IL-10 were significantly increased (P < 0.05). The results indicate a long-term decrease in inflammatory markers after a single intake of large portions of Brazil nuts in healthy volunteers. Therefore, the long-term effect of regular Brazil nut consumption on inflammatory markers should be better investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

Fecal antibodies to Cryptosporidium parvum in healthy volunteers.

PubMed

Dann, S M; Okhuysen, P C; Salameh, B M; DuPont, H L; Chappell, C L

2000-09-01

This study examined the intestinal antibody response in 26 healthy volunteers challenged with Cryptosporidium parvum oocysts. Fecal extracts were assayed for total secretory immunoglobulin A (IgA) and C. parvum-specific IgA reactivity. Specific IgA reactivity was standardized to IgA concentration and expressed as a reactivity index (RI). Anti-C. parvum fecal IgA (fIgA) increased significantly in 17 of 26 (65.4%) following oocyst ingestion. Of those with detectable responses, 59, 76.5, and 94.1% were positive by days 7, 14, and 30, respectively. Volunteers receiving high challenge doses (>1,000 and 300 to 500 oocysts) had higher RIs (RI = 5.57 [P = 0. 027] and RI = 1.68 [P = 0.039], respectively) than those ingesting low doses (30 to 100 oocysts; RI = 0.146). Subjects shedding oocysts and experiencing a diarrheal illness had the highest fIgA reactivity. When evaluated separately, oocyst excretion was associated with an increased fIgA response compared to nonshedders (RI = 1.679 versus 0. 024, respectively; P = 0.003). However, in subjects experiencing diarrhea with or without oocyst shedding, a trend toward a higher RI (P = 0.065) was seen. Extracts positive for fecal IgA were further examined for IgA subclass. The majority of stools contained both IgA1 and IgA2, and the relative proportions did not change following challenge. Also, no C. parvum-specific IgM or IgG was detected in fecal extracts. Thus, fecal IgA to C. parvum antigens was highly associated with infection in subjects who had no evidence of previous exposure and may provide a useful tool in detecting recent infections.

Reflexology has an acute (immediate) haemodynamic effect in healthy volunteers: a double-blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2012-11-01

Reflexologists claim that massage to specific points of the feet increases blood supply to internal organs. This study measured changes in cardiovascular parameters in subjects receiving reflexology to areas of their feet thought to correspond to the heart (intervention) compared with other areas which are not (control). 16 reflexology-naive healthy volunteers received an active and control reflexology treatment in an RCT, double-blind repeated measures study. 'Beat-to-beat' continuous measurement of selected cardiovascular parameters, State Anxiety Inventory. Cardiac index decreased significantly in the intervention group during left foot treatment (LFT) (baseline mean 2.6; standard deviation (SD) 0.75; 95% CI ± 0.38 vs. LFT mean 2.45; SD 0.68; CI 0.35), effect size (p = 0.035, omega squared effect (w2) = 0.002; w = 0.045). Reflexology massage applied to the upper part of the left foot may have a modest specific effect on the cardiac index of healthy volunteers. Copyright © 2012 Elsevier Ltd. All rights reserved.

The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers.

PubMed

Blazejewski, Sylvie; Georges, Agnès; Forest, Karelle; Corcuff, Jean-Benoît; Abouelfath, Abdelilah; Girodet, Pierre-Olivier; Kamagate, Mamadou; Jacquet, Alain; Pillet, Odile; Bordenave, Laurence; Moore, Nicholas

2009-06-01

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

Pharmacokinetic drug interaction between gemfibrozil and sitagliptin in healthy Indian male volunteers.

PubMed

K P, Arun; Meda, Venkata Subbaiah; Kucherlapati, V S P Raj; Dubala, Anil; M, Deepalakshmi; P R, Anand VijayaKumar; K, Elango; B, Suresh

2012-05-01

To study the impact of gemfibrozil co-administration on the pharmacokinetics of sitagliptin in healthy Indian male volunteers. A randomized open label two-period crossover study involving 12 healthy Indian male volunteers was conducted at a single center. In each phase, the volunteers were administered sitagliptin as 100 mg tablets, either alone or co-administered with gemfibrozil as 600 mg tablets twice daily for 3 days. There was a 2-week washout period between phases. The venous blood samples were serially collected at 0-12 h post-dose, and plasma concentrations of the study drugs were estimated by a validated high-performance liquid chromatography-ultraviolet method. Relative to the administration of sitagliptin alone, co-administration with gemfibrozil increased the AUC₀₋₁₂ (2,167 ± 82.9 vs. 2,970 ± 76.4 ng h/ml; p < 0.0001), AUC(0-∞) (3,621 ± 222.5 vs. 5,574 ± 249.6 ng h/ml; p < 0.0002), C(max) (282.9 ± 7.7 vs. 344.1 ± 5.9 ng/ml; p < 0.0001), and t(½) (7.4 ± 0.6 vs. 10 ± 0.6 h; p = 0.0076) to statistically significant levels. The interindividual differences in the pharmacokinetic parameters of sitagliptin were found to be within acceptable limits (coefficient of variation <20%). No adverse drug events associated with sitagliptin occurred in the subjects during the study period. Although the bioavailability of sitagliptin was increased by 54% when co-administered with gemfibrozil, this interaction may not have any clinical significance as sitagliptin has a wide therapeutic index. Hence, in clinical practice, sitagliptin as 100 mg tablets and gemfibrozil as 600 mg tablets may be co-prescribed without much threat of sitagliptin toxicity. However, these results may not hold if the dose of sitagliptin is increased or if is co-prescribed with other antidiabetic drugs and/or cytochrome P450 2C8/human organic anion transporter-3 inhibitors. Further studies are needed to confirm these results in patients.

Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.

PubMed

Ali, Ahmed; Farid, Samar; Amin, Mona; Kassem, Mohamed; Al-Garem, Nouman; Al-Ghobashy, Medhat

2016-02-01

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension, and can also be used for hepatorenal syndrome and cirrhotic patients with tense ascites. The objective of the present work was to study the clinical pharmacokinetic parameters of midodrine and its active metabolite desglymidodrine in cirrhotic patients with tense ascites, which may help in dose selection and improve treatment outcome. This was a prospective, open-label, single-dose, parallel-group study. At first, a pilot study was performed on one healthy volunteer by taking serial blood samples at scheduled time intervals to validate the method of analysis and sampling times. The full study was then conducted by selecting 12 cirrhotic patients with tense ascites in one group and taking nine blood samples. We also selected five healthy volunteers as the control group and took 11 blood samples. Statistically significant differences were observed between the healthy volunteer group and the patients group in the area under the concentration versus time curve (AUC0-t) and maximum plasma concentration (Cmax) values of midodrine and desglymidodrine. Based on the results of the pharmacokinetic analysis, the patient group was further subdivided into those receiving the interacting drug ranitidine (five patients) and those not receiving the interacting drug (seven patients). Pharmacokinetic parameters of midodrine can differ significantly in cirrhotic patients with tense ascites from those in healthy individuals. Drug monitoring, dose adjustments, and drug-drug interactions should all be considered during therapy in this vulnerable patient group.

Shear-wave sonoelastography for assessing masseter muscle hardness in comparison with strain sonoelastography: study with phantoms and healthy volunteers

PubMed Central

Nakayama, Miwa; Nishiyama, Wataru; Nozawa, Michihito

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. Results: 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. Conclusions: The hardness measured with shear-wave sonoelastography showed high-level reliability. Shear-wave sonoelastography may be suitable for evaluation of the masseter muscles. PMID:26624000

The effect of pH on citric acid cough challenge: A randomised control trial in chronic cough and healthy volunteers.

PubMed

Rai, Z L; Fowles, H E; Wright, C; Howard, Joseph; Morice, A H

2018-03-06

Citric acid has been used for over six decades to induce cough; however the mechanism of its pro-tussive effect is still not fully understood. We assessed the response to inhalation of citric acid at varying levels of acidity to determine if the pH of the solution plays a role in the induction of cough. Data was collected from both healthy volunteers and patients with chronic cough. 20 chronic cough patients and 20 healthy volunteers were recruited and underwent three cough challenges on separate days. Each visit involved 5 repeated one second inhalations of 300 mM citric acid solution. The concentration of the citrate cation remained constant, but the pH of the solution altered by the addition of sodium bicarbonate to 3, 5 and 6, representing the pK a values of the individual acid moieties. The total number of coughs elicited was recorded for each inhalation. Two subjects withdrew and were not included in the analysis. Participants were gender matched, each group consisting of 12 females. 74% of chronic coughers coughed at pH 3 (mean coughs 16), 89% coughed at pH 5 (18) and 63% coughed at pH 6 (7). In healthy volunteers, 60% of subjects coughed at pH 3 (9), 30% of subjects coughed at pH 5 (3), and 10% of subjects coughed at pH 6 (0). Thus chronic cough patients coughed more than healthy volunteers and did not exhibit a clear pH concentration response. There was also a greater variability in their response to individual challenges. Copyright © 2018 Elsevier B.V. All rights reserved.

Retinal vessel oxygen saturation in a healthy young Chinese population.

PubMed

Yang, Wei; Fu, Yue; Dong, Yanmin; Lin, Leilei; Huang, Xia; Li, Yujie; Lin, Xiaofeng; Gao, Qianying

2016-06-01

To measure retinal vessel oxygen saturation in a healthy young Chinese population and to determine the effects of multiple factors (gender, age, dioptre, vessel diameter and ocular perfusion pressure - OPP) on retinal oxygen saturation. A total of 126 healthy Chinese individuals aged from 19 to 30 were included in this study. A retinal oximeter (Oxymap T1) was used to measure retinal vessel oxygen saturation by retinal imaging at two different wavelengths. The mean retinal vessel oxygen saturation (Sat_O2 ) of arterioles, venules and arteriovenous (AV) difference overall and in four separate quadrants were measured. Intra-ocular pressure, blood pressure, finger pulse oximetry value, vessel diameter and dioptre were also measured. The correlations between OPP and dioptre, OPP and vessel diameter, and dioptre and vessel diameter were analysed. And the effects of multiple factors on the retinal oxygen saturation were analysed. The mean oxygen saturation was 93.2 ± 6.3% in the retinal arterioles, 60.4 ± 5.3% in venules and 32.9 ± 6.4% in AV difference. The temporal quadrants had lower measurements of arteriolar and venular oxygen saturation and AV difference compared with nasal quadrants (p < 0.001). The oxygen saturation of the arterioles, venules and AV difference were unaffected by any unique factor. Arteriolar and venular retinal oxygen saturation correlated negatively with the product of dioptre and OPP. Arteriolar retinal oxygen saturation correlated positively with the product of dioptre and vessel diameter. This study provided a normal reference of Sat_O2 in healthy young Chinese individuals. It was a reflection of the normal state of retinal oxygen metabolism affected by several factors. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

N400 elicited by incongruent ending words of Chinese idioms in healthy adults.

PubMed

Chen, Xing-shi; Tang, Yun-xiang; Xiao, Ze-ping; Wang, Ji-jun; Zhang, Ming-dao; Zhang, Zai-fu; Hu, Zhen-yu; Lou, Fei-ying; Chen, Chong; Zhang, Tian-hong

2010-03-20

Prior research about N400 has been mainly based on English stimuli, while the cognitive processing of Chinese characters is still unclear. The aim of the present study was to further investigate the semantic processing of Chinese idioms. Event related potentials (ERP) component N400 was elicited by 38 pairs of matching (congruent) and mismatching (incongruent) ended Chinese idioms: ending words with same phoneme but different shape and meaning (sPdSdM), with similar shape but different phoneme and meaning (sSdPdM), with same meaning but different phoneme and shape (sMdPdS), and words with different phoneme, shape and meaning (dPdSdM) and recorded by Guangzhou Runjie WJ-1 ERP instruments. In 62 right-handed healthy adults (age 19 - 50 years), N400 amplitudes and latencies were compared between matching and mismatching conditions at Fz, Cz and Pz. N400 showed a midline distribution and could be elicited in electrodes Fz, Cz and Pz. The mean values of N400 latencies and amplitudes were obtained for matching and mismatching ending words in healthy adults. Significant differences were found in N400 latencies and amplitudes in matching and mismatching ending-words idioms in healthy adults (P < 0.05). Compared with matching ending-words idioms, N400 latencies were prolonged and the amplitudes were increased in mismatching ones. N400s elicited by different types of stimuli showed different latencies and amplitudes, and longest N400 latency and largest N400 amplitude were elicited by ending-words with dPdSdM. No gender difference was found of N400 latency and amplitude in this study (P > 0.05). Compared with English stimuli, Chinese ideographic words could provide more flexible stimuli for N400 research in that the words have 3-dimension changes - phoneme, shape and meaning. Features of N400 elicited by matching and mismatching ending words in Chinese idioms are mainly determined by the meaning of the word. Some issues of N400 elicited by Chinese characters deserve further

T2 Relaxation Values of the Talar Trochlear Articular Cartilage: Comparison Between Patients With Lateral Instability of the Ankle Joint and Healthy Volunteers.

PubMed

Park, So Yoon; Yoon, Young Cheol; Cha, Jang Gyu; Sung, Ki Sun

2016-01-01

The purpose of this study was to evaluate the difference between the T2 relaxation values of the talar trochlear cartilage in patients with lateral instability of the ankle joint and the values in healthy volunteers. A retrospective assessment was conducted of images from 13 MRI examinations of the ankles of 12 patients who underwent lateral ankle ligament repair with an arthroscopically proven normal talar trochlear cartilage. Thirteen ankle MRI examinations of 12 healthy age- and sex-matched volunteers were prospectively performed. Two radiologists independently measured the T2 relaxation values of the talar trochlear cartilage in two layers (superficial and deep) in the following six compartments: medial anterior (M1), medial middle (M2), medial posterior (M3), lateral anterior (L1), lateral middle (L2), and lateral posterior (L3). The T2 relaxation values of patients were compared with those of healthy volunteers. Both readers found that the mean T2 relaxation values of all six compartments of the superficial layer were significantly higher in patients than in control subjects. For reader 1, the M1 findings were 46.2 for patients and 39.6 for healthy volunteers; M2, 50.4 and 41.1; M3, 52.1 and 46.2; L1, 43.1 and 37.9; L2, 47.8 and 41.8; and L3, 53.8 and 49.8. For reader 2, the M1 findings were 45.0 and 40.2; M2, 48.8 and 41.1; M3, 53.2 and 45.6; L1, 42.8 and 38.5; L2, 48.0 and 42.1; and L3, 55.0 and 49.0 (p < 0.05). For the deep layer, the mean T2 relaxation values of M2 (patients, 32.6; volunteers, 27.8 [p = 0.004]) and M3 (patients, 38.3; volunteers, 35.0 [p = 0.046]) for reader 1 and M2 (patients, 31.6; volunteers, 28.7 [p = 0.041]) for reader 2 were significantly higher in patients than in control subjects. Intraobserver and interobserver variability were excellent, except for interobserver variability for M1 deep (0.79) and L1 deep (0.75). The T2 relaxation values of arthroscopically proven normal talar trochlear cartilage of patients with lateral

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

PubMed

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

2015-02-01

Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. © 2014, The American College of Clinical Pharmacology.

Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial.

PubMed

Hartley, S L; Barbot, F; Machou, M; Lejaille, M; Moreau, B; Vaugier, I; Lofaso, F; Quera-Salva, M A

2013-06-01

To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light 10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+, C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C-L-. Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Repaglinide-irbesartan drug interaction: effects of SLCO1B1 polymorphism on repaglinide pharmacokinetics and pharmacodynamics in Chinese population.

PubMed

Pei, Qi; Liu, Jun-Yan; Yin, Ji-Ye; Yang, Guo-Ping; Liu, Shi-Kun; Zheng, Yi; Xie, Pan; Guo, Cheng-Xian; Luo, Mi; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2018-05-11

On account of the potential inhibition of OATP1B1 (organic anion transporting polypeptide) by angiotensin II receptor blockers (ARBs) and the effects of SLCO1B1 (solute carrier organic anion transporter family member) polymorphism, the aim of current study is to assess the impact of ARBs on the pharmacokinetics (PK) and pharmacodynamics (PD) of repaglinide in Chinese healthy volunteers with different SLCO1B1 genotypes. The in vitro study was conducted on irbesartan, valsartan, olmesartan, and losartan by using HEK293 cells transfected with OATP1B1. Data on drug interactions between repaglinide and irbesartan from 21 healthy Chinese-Han male volunteers were collected and analyzed. IC 50 from in vitro study suggested irbesartan was the most potent inhibitor of OATP1B1 transporter. Clinical data from single dose of repaglinide indicated SLCO1B1 c.521 T>C polymorphism influenced the PK and PD of repaglinide in healthy Chinese-Han male volunteers. In subjects with SLCO1B1 c.521 TT genotype, irbesartan comedication increased the exposure of repaglinide. In details, the peak plasma concentration [C max ] increased 84% (P = 0.003) and the area under the curve of plasma concentration 0-8 h [AUC 0-8 ] increased 34% (P = 0.004), while the minimum blood glucose concentration [C min ] decreased 33.8% (P = 0.005). No significant change was observed in repaglinide exposure in subjects with SLCO1B1 c.521 TC genotype in presence or absence of irbesartan. SLCO1B1 c.521 T>C polymorphism affects the PK of repaglinide in Chinese population. Irbesartan increased repaglinide exposure in subjects with SLCO1B1 c.521 TT genotype, but not SLCO1B1 c.521 TC genotype.

Esomeprazole 40 mg provides improved intragastric acid control as compared with lansoprazole 30 mg and rabeprazole 20 mg in healthy volunteers.

PubMed

Wilder-Smith, Clive H; Röhss, Kerstin; Nilsson-Pieschl, Catharina; Junghard, Ola; Nyman, Lars

2003-01-01

To compare the effects of standard-dose esomeprazole with those of standard doses of lansoprazole and rabeprazole on intragastric pH during repeated daily oral dosing in healthy volunteers. In two standardized, randomized crossover studies, Helicobacter pylori negative healthy volunteers (study A: 19 males, 5 females; study B: 13 males, 10 females) received esomeprazole 40 mg and either lansoprazole 30 mg (study A) or rabeprazole 20 mg (study B) orally once daily in the morning for 5 days. Continuous 24-hour intragastric pH recording was performed on day 5. The intragastric pH was maintained >4 for 65% (95% CI 59.5-71.3) of the 24-hour period with esomeprazole and for 53% of the time (95% CI 47.0-58.9) with lansoprazole in study A (p < 0.001). In study B, the proportion of time with pH >4 was 61% (95% CI 53.6-68.3) with esomeprazole versus 45% (95% CI 37.7-52.5) with rabeprazole (p = 0.005). The 24-hour median pH and the proportion of volunteers with intragastric pH >4 for > or =12 h and > or =16 h were significantly higher with esomeprazole than with either lansoprazole or rabeprazole. Esomeprazole 40 mg provides significantly more effective and more sustained gastric acid control than lansoprazole 30 mg or rabeprazole 20 mg in healthy volunteers. Copyright 2003 S. Karger AG, Basel

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

NASA Astrophysics Data System (ADS)

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

2004-06-01

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

Determination of lansoprazole in human plasma by rapid resolution liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study on Chinese volunteers.

PubMed

Wu, Guo-Lan; Zhou, Hui-Li; Shentu, Jian-Zhong; He, Qiao-Jun; Yang, Bo

2008-12-15

A simple, sensitive and rapid LC/MS/MS method was developed for the quantification of lansoprazole in human plasma. After a simple sample preparation procedure by one-step protein precipitation with acetonitrile, lansoprazole and the internal standard bicalutamide were chromatographed on a Zorbax SB-C(18) (3.0 mm x 150 mm, 3.5 microm, Agilent) column with the mobile phase consisted of methanol-water (70:30, v/v, containing 5 mM ammonium formate, pH was adjusted to 7.85 by 1% ammonia solution). Detection was performed on a triple quadrupole tandem mass spectrometry by multiple reaction monitoring (MRM) mode via negative eletrospray ionization source (ESI(-)). The lower limit of quantification was 5.5 ng/mL, and the assay exhibited a linear range of 5.5-2200.0 ng/mL. The validated method was successfully applied to investigate the bioequivalence between two kinds of preparation (test vs. reference product) in twenty-eight healthy male Chinese volunteers.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

PubMed

Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola

2018-03-22

This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers.

PubMed

Terai, Shiho; Iijima, Katsunori; Asanuma, Kiyotaka; Ara, Nobuyuki; Uno, Kaname; Abe, Yasuhiko; Koike, Tomoyuki; Imatani, Akira; Ohara, Shuichi; Shimosegawa, Tooru

2009-05-01

Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers.

Aspirin has little additional anti-platelet effect in healthy volunteers receiving prasugrel.

PubMed

Leadbeater, P D M; Kirkby, N S; Thomas, S; Dhanji, A-R; Tucker, A T; Milne, G L; Mitchell, J A; Warner, T D

2011-10-01

Strong P2Y(12) blockade, as can be achieved with novel anti-platelet agents such as prasugrel, has been shown in vitro to inhibit both ADP and thromboxane A(2) -mediated pathways of platelet aggregation, calling into question the need for the concomitant use of aspirin. The present study investigated the hypothesis that aspirin provides little additional anti-aggregatory effect in a group of healthy volunteers taking prasugrel. STUDY PARTICIPANTS/METHODS: In all, 9 males, aged 18 to 40 years, enrolled into the 21-day study. Prasugrel was loaded at 60 mg on day 1 and maintained at 10 mg until day 21. At day 8, aspirin 75 mg was introduced and the dose increased to 300 mg on day 15. On days 0, 7, 14 and 21, platelet function was assessed by aggregometry, response to treatments was determined by VerifyNow and urine samples were collected for quantification of prostanoid metabolites. At day 7, aggregation responses to a range of platelet agonists were reduced and there was only a small further inhibition of aggregation to TRAP-6, collagen and epinephrine at days 14 and 21, when aspirin was included with prasugrel. Urinary prostanoid metabolites were unaffected by prasugrel, and were reduced by the addition of aspirin, independent of dose. In healthy volunteers, prasugrel produces a strong anti-aggregatory effect, which is little enhanced by the addition of aspirin. The addition of aspirin as a dual-therapy with potent P2Y(12) receptor inhibitors warrants further investigation. © 2011 International Society on Thrombosis and Haemostasis.

Liver diffusivity in healthy volunteers and patients with chronic liver disease: Comparison of breath-hold and free-breathing techniques

PubMed Central

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L.; Merriman, Raphael B.; Qayyum, Aliya

2011-01-01

Purpose To compare liver ADC obtained with breath-hold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Materials and Methods Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breath-hold (BH) and free-breathing (FB) DWI MRI at 1.5T. Pearson’s correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Results Liver ADC (×10−3 mm2/sec) was lower on BH for all groups (mean difference 0.36±0.20; p<0.01). ADC was higher in healthy volunteers (BH 1.80±0.18; FB 2.24±0.20) compared to NAFLD patients (BH 1.43±0.27; FB 1.78±0.28) (p<0.001) and HCV patients (BH 1.63±0.191; FB 1.88±0.12). Overall correlation between BH and FB ADC was (r =0.75), greatest in NAFLD (r =0.90) compared to the correlation in HCV (r =0.24) and healthy subjects (r =0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Conclusion Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. PMID:22034200

Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers.

PubMed

Kropeit, D; Johnson, M; Cawello, W; Rudd, G D; Horstmann, R

2015-11-01

To determine whether lacosamide prolongs the corrected QT interval (QTc). In this randomized, double-blind, positive- and placebo-controlled, parallel-design trial, healthy volunteers were randomized to lacosamide 400 mg/day (maximum-recommended daily dose, 6 days), lacosamide 800 mg/day (supratherapeutic dose, 6 days), placebo (6 days), or moxifloxacin 400 mg/day (3 days). Variables included maximum time-matched change from baseline in QT interval individually corrected for heart rate ([HR] QTcI), other ECG parameters, pharmacokinetics (PK), and safety/tolerability. The QTcI mean maximum difference from placebo was -4.3 ms and -6.3 ms for lacosamide 400 and 800 mg/day; upper limits of the 2-sided 90% confidence interval were below the 10 ms non-inferiority margin (-0.5 and -2.5 ms, respectively). Placebo-corrected QTcI for moxifloxacin was +10.4 ms (lower 90% confidence bound >0 [6.6 ms]), which established assay sensitivity for this trial. As lacosamide did not increase QTcI, the trial is considered a negative QTc trial. There was no dose-related or clinically relevant effect on QRS duration. HR increased from baseline by ~5 bpm with lacosamide 800 mg/day versus placebo. Placebo-subtracted mean increases in PR interval at tmax were 7.3 ms (400 mg/day) and 11.9 ms (800 mg/day). There were no findings of second-degree or higher atrioventricular block. Adverse events (AEs) were dose related and most commonly involved the nervous and gastrointestinal systems. Lacosamide (≤ 800 mg/day) did not prolong the QTc interval. Lacosamide caused a small, dose-related increase in mean PR interval that was not associated with AEs. Cardiac, overall safety, and PK profiles for lacosamide in healthy volunteers were consistent with those observed in patients with partial-onset seizures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.

PubMed

Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kunz, Christina; Formella, Stephan; Kloft, Charlotte

2016-03-01

Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. Plasma and urine data after intravenous administration (0.5-25 μg) and oral inhalation (2.5-70 μg via the Respimat® inhaler) were available from a total of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied, using population pharmacokinetic modelling. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% [95% confidence interval (CI) 46.1, 52.7%] of the dose released from the device. A large proportion of the pulmonary bioavailable fraction [70.1% (95% CI 66.8, 73.3%)] was absorbed with a half-life of 21.8 h (95% CI 19.7, 24.4 h). The plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high proportion of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on the physicochemical properties of olodaterol. © 2015 The British Pharmacological Society.

Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers.

PubMed

Bagga, Deepika; Aigner, Christoph Stefan; Reichert, Johanna Louise; Cecchetto, Cinzia; Fischmeister, Florian Ph S; Holzer, Peter; Moissl-Eichinger, Christine; Schöpf, Veronika

2018-05-30

Experimental investigations in rodents have contributed significantly to our current understanding of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behaviour. However, clinical evidence to support such interactions is still scarce. The present study used a double-blind, randomized, pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers. Forty-five healthy volunteers were recruited for this study and were divided equally into three groups (PRP: probiotic, PLP: placebo, and CON: control). All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study, at the beginning (time point 1) and after 4 weeks (time point 2). MRI data were acquired using a 3T whole-body MR system (Magnetom Skyra, Siemens, Germany). Functional connectivity (FC) changes were observed in the default mode network (DMN), salience network (SN), and middle and superior frontal gyrus network (MFGN) in the PRP group as compared to the PLP and CON groups. PRP group showed a significant decrease in FC in MFGN (in frontal pole and frontal medial cortex) and in DMN (in frontal lobe) as compared to CON and PLP groups, respectively. Further, significant increase in FC in SN (in cingulate gyrus and precuneus cortex) was also observed in PRP group as compared to CON group. The significance threshold was set to p < 0.05 FWE corrected. No significant structural differences were observed between the three groups. This work provides new insights into the role of a multi-strain probiotic administration in modulating the behaviour, which is reflected as changes in the FC in healthy volunteers. This study motivates future investigations into the role of probiotics in context of major depression and stress disorders.

Effect of consuming a grape seed supplement with abundant phenolic compounds on the oxidative status of healthy human volunteers.

PubMed

Grases, Felix; Prieto, Rafel M; Fernández-Cabot, Rafel A; Costa-Bauzá, Antonia; Sánchez, Ana M; Prodanov, Marin

2015-09-09

Diverse enzymatic and non-enzymatic antioxidants provide protection against reactive oxygen species in humans and other organisms. The nonenzymatic antioxidants include low molecular mass molecules such as plant-derived phenols. This study identified the major phenolic compounds of a grape seed extract by HPLC and analyzed the effect of consumption of biscuits enriched with this extract on the urinary oxidative status of healthy subjects by measurement of urine redox potential. The major phenolic compounds were characterized in a red grape seed extract separated by HPLC with detection by a photodiode array (PDA), fluorescence (FL) and quadrupole mass spectrometer (MS). A nutritional study in a healthy volunteers group was done. Each volunteer ate eight traditional biscuits with no red grape seed extract supplementation. The second day each volunteer ate eight traditional biscuits supplemented with 0.6% (wt/wt) of grape seed extract. An overnight urine sample was obtained for each treatment. The redox potential was measured at 25 °C using a potentiometer in each urine sample. Epicatechin, catechin, procyanidin dimers B1 to B4, and the procyanidin trimer C2 were the major phenolic components in the extract. Epicatechin gallate and procyanidin dimers B1-3-G and B2-3'-G were the major galloylated flavan-3-ols. The forty-six healthy volunteers each shown a reduction of the urine redox potential after the treatment by traditional biscuits supplemented with the grape seed extract. This simple dietary intervention significantly reduced (33%) the urine redox potential, reflecting an overall increase in antioxidant status. Incorporation of plant-derived phenols in the diet may increase anti-oxidative status.

Population Pharmacokinetic-Pharmacodynamic Model of Oral Fludrocortisone and Intravenous Hydrocortisone in Healthy Volunteers.

PubMed

Hamitouche, Noureddine; Comets, Emmanuelle; Ribot, Mégane; Alvarez, Jean-Claude; Bellissant, Eric; Laviolle, Bruno

2017-05-01

This study aimed at describing the pharmacokinetics and the concentration-effect relationships of fludrocortisone and hydrocortisone on urinary sodium/potassium excretion in healthy volunteers. This was a placebo-controlled, randomized, double blind, crossover study, of oral fludrocortisone and intravenous hydrocortisone, given alone or in combination, in 12 healthy male volunteers. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships on urinary sodium/potassium ratio for each drug. A one-compartment model was used to describe fludrocortisone and hydrocortisone pharmacokinetics. Mean plasma half-life was 1.40 h (95%CI [0.80;2.10]) for fludrocortisone and 2.10 h (95%CI [1.78;2.40]) for hydrocortisone. Clearance was 40.8 L/h (95%CI [33.6;48]) for fludrocortisone and 30 L/h (95%CI [25.3;34.7]) for hydrocortisone. An indirect response model was used to describe effects on urinary sodium/potassium ratio. Fludrocortisone plasma concentrations showed a wider inter-individual dispersion than hydrocortisone plasma concentrations. Urinary sodium/potassium ratio variability was also higher with fludrocortisone as compared to hydrocortisone. The plasma concentration of drug producing 50% of maximal inhibition of urinary sodium/potassium (IC 50 ) was about 200 times lower for fludrocortisone (0.08 μg/L, 95%CI [0.035;0.125]) than for hydrocortisone (16.7 μg/L, 95%CI [10.5;22.9]). Simulations showed that a 4-time per day administration regimen allow to achieve steady fludrocortisone plasma concentrations with stable decrease in urinary sodium/potassium ratio after the second administration of fludrocortisone. Fludrocortisone and hydrocortisone have short and similar plasma elimination half-lives in healthy subjects. Fludrocortisone plasma concentrations and effect on urinary sodium/potassium ratio had a higher inter-individual variability as compared to hydrocortisone. The administration regimen of

The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria.

PubMed

Yago, Marc R; Frymoyer, Adam; Benet, Leslie Z; Smelick, Gillian S; Frassetto, Lynda A; Ding, Xiao; Dean, Brian; Salphati, Laurent; Budha, Nageshwar; Jin, Jin Y; Dresser, Mark J; Ware, Joseph A

2014-11-01

Many orally administered, small-molecule, targeted anticancer drugs, such as dasatinib, exhibit pH-dependent solubility and reduced drug exposure when given with acid-reducing agents. We previously demonstrated that betaine hydrochloride (BHCl) can transiently re-acidify gastric pH in healthy volunteers with drug-induced hypochlorhydria. In this randomized, single-dose, three-way crossover study, healthy volunteers received dasatinib (100 mg) alone, after pretreatment with rabeprazole, and with 1500 mg BHCl after rabeprazole pretreatment, to determine if BHCl can enhance dasatinib absorption in hypochlorhydric conditions. Rabeprazole (20 mg b.i.d.) significantly reduced dasatinib Cmax and AUC0-∞ by 92 and 78%, respectively. However, coadministration of BHCl significantly increased dasatinib Cmax and AUC0-∞ by 15- and 6.7-fold, restoring them to 105 and 121%, respectively, of the control (dasatinib alone). Therefore, BHCl reversed the impact of hypochlorhydria on dasatinib drug exposure and may be an effective strategy to mitigate potential drug-drug interactions for drugs that exhibit pH-dependent solubility and are administered orally under hypochlorhydric conditions.

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

PubMed Central

Kirby, S. M.; Smith, J.; Ventresca, G. P.

1995-01-01

BACKGROUND--Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a. METHODS--The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design. RESULTS--Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels. CONCLUSIONS--In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity. PMID:7638815

Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis.

PubMed

Ohba, Fuminori; Nomoto, Maiko; Hojo, Seiichiro; Akama, Hideto

2016-01-01

The purpose of the present studies was to assess the safety, tolerability and pharmacokinetics of topical application of a novel phosphodiesterase inhibitor, E6005, in healthy volunteers and in patients with atopic dermatitis (AD). In two randomized, investigator-blind, vehicle-controlled studies, we evaluated the topical application of E6005 ointment at concentrations ranging from 0.01% to 0.2% in healthy volunteers (Study 001) and in patients with AD (Study 101). Thirty-six subjects were enrolled in Study 001 and 40 in Study 101. Neither skin irritation nor photosensitization was observed with application of E6005 in Study 001. Four subjects receiving E6005 in Study 001 experienced a treatment-emergent adverse event (application site edema, increased alanine aminotransferase or erythema); three of these subjects discontinued the study. Two subjects receiving E6005 in Study 101 experienced an adverse event (gout or enterocolitis); one discontinued the study. Plasma concentrations of E6005 were below the limit of quantification (1 ng/ml) in both studies. E6005 ointment exhibited acceptable safety and tolerability. Topical application of E6005 ointment resulted in very low systemic exposure to E6005 in healthy volunteers and in patients with AD.

Assessing change in health professions volunteers' perceptions after participating in Special Olympics healthy athlete events.

PubMed

Freudenthal, Jacqueline J; Boyd, Linda D; Tivis, Rick

2010-09-01

This study assessed perceptions of health professions student and faculty volunteers who participated with athletes at the 2009 Special Olympics World Winter Games in Healthy Athlete venues. The volunteers' perceptions and expectations of the abilities of intellectually disabled athletes were measured by administering pre-event and post-event questionnaires consisting of demographic questions and the Prognostic Belief Scale (PBS). Invitations to participate in the study were sent to 165 students and faculty members; of those, eighty (48.5 percent response rate) responded to the pre-event questionnaire, and sixty-seven (40.6 percent response rate) responded to the post-event questionnaire. Of the eighty respondents to the pre-event questionnaire, fifty-five (68.7 percent) also completed the post-event questionnaire. The ANOVA comparing pre- and post-event PBS scores between groups found a trend towards higher scores among the volunteers, but analysis did not demonstrate a significant effect in either group (p=.68) or the interaction of group by time (p=.46). Despite the findings from the PBS, participants' statements suggest the experience had an impact on their perceptions and expectations. Although not statistically significant, this study found a positive trend pre- to post-event in the volunteers' perceptions of the abilities of athletes with intellectual disabilities. In addition to didactic and clinical education, volunteer experiences may enhance care providers' knowledge, skill, and confidence levels for treating clients with intellectual disabilities.

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

PubMed

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.

Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers.

PubMed

Li, Wei; Han, Lei; Yu, Pengbo; Ma, Chaofeng; Wu, Xiaokang; Moore, John E; Xu, Jiru

2014-04-01

Systemic inflammation contributes to both the development of cancer and of cachexia. The microenvironment of bacterial habitats might be changed during the progression of cancer cachexia. The aim of this study was to quantitatively and qualitatively compare the composition of the skin microbiota between cancer cachexia patients and healthy volunteers. Cutaneous bacteria were swabbed at the axillary fossa of 70 cancer cachexia patients and 34 healthy individuals from China. Nested-PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region and quantitative PCR (qPCR) for total bacteria, Corynebacterium spp., Staphylococcus spp., and Staphylococcus epidermidis were performed on all samples. Barcoded 454 pyrosequencing of the V3-V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, we found that the skin microbiome of cachectic cancer patients is less diverse than that of healthy participants, though these differences were not significant. The main microbes that reside on human skin were divided into four phyla: Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria at the genus level. Significantly fewer Corynebacterium spp. had been observed in cachexia patients compared to healthy subjects. These results suggest that the presence of cancer and cachexia alters human skin bacterial communities. Understanding the changes in microbiota during cancer cachexia may lead to new insights into the syndrome.

Relationship between Chinese adjective descriptors of personality and emotional symptoms in young Chinese patients with bipolar disorders.

PubMed

Yu, Enyan; Li, Huihui; Fan, Hongying; Gao, Qianqian; Tan, Yunfei; Lou, Junyao; Zhang, Jie; Wang, Wei

2015-12-01

To investigate whether personality traits are related to emotional symptoms (mania, hypomania, and depression) in Chinese patients with bipolar disorders. Patients with bipolar I and II disorders, and healthy volunteers, were assessed using the Chinese Adjective Descriptors of Personality (CADP) questionnaire, Mood Disorder Questionnaire (MDQ), Hypomanic Checklist (HCL-32), and Plutchik-van Praag Depression Inventory (PVP). Seventy-three patients with bipolar I disorder, 35 with bipolar II disorder and 216 healthy controls were included. Bipolar I and II groups scored significantly higher on MDQ, HCL-32 and PVP scales than controls; the bipolar II group scored lower on the MDQ, but higher on the HCL-32 and PVP than bipolar I. In the bipolar I group, the CADP Intelligent trait (β, 0.25) predicted MDQ; Intelligent (β, -0.24), Agreeable (β, 0.22) and Emotional (β, 0.34) traits predicted PVP. In the bipolar II group, Intelligent (β, 0.22), Agreeable (β, -0.24) and Unsocial (β, 0.31) traits predicted MDQ; Intelligent (β, -0.20), Agreeable (β, -0.31) and Emotional (β, -0.26) traits predicted HCL-32. Four out of five Chinese personality traits were associated with emotional symptoms in patients with bipolar I or II disorder, but displayed different associations depending on disorder type. © The Author(s) 2015.

Comparing fractional anisotropy in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers through DTI.

PubMed

Moran, Marcel E; Luscher, Zoe I; McAdams, Harrison; Hsu, John T; Greenstein, Deanna; Clasen, Liv; Ludovici, Katharine; Lloyd, Jonae; Rapoport, Judith; Mori, Susumu; Gogtay, Nitin

2015-01-01

Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls. To evaluate WM integrity in this population 39 patients diagnosed with COS, 39 of their healthy (nonpsychotic) siblings, and 50 unrelated healthy volunteers were scanned using a diffusion tensor imaging (DTI) sequence during a 1.5 T MRI acquisition. Each DTI scan was processed via atlas-based analysis using a WM parcellation map, and diffeomorphic mapping that shapes a template atlas to each individual subject space. Fractional anisotropy (FA), a measure of WM integrity was averaged over each of the 46 regions of the atlas. Eleven WM regions were examined based on previous reports of WM growth abnormalities in COS. Of those regions, patients with COS, and their healthy siblings had significantly lower mean FA in the left and right cuneus as compared to the healthy volunteers (P < .005). Together, these findings represent the largest DTI study in COS to date, and provide evidence that WM integrity is significantly impaired in COS. Shared deficits in their healthy siblings might result from increased genetic risk. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2014.

Comparing Fractional Anisotropy in Patients With Childhood-Onset Schizophrenia, Their Healthy Siblings, and Normal Volunteers Through DTI

PubMed Central

Moran, Marcel E.; Luscher, Zoe I.; McAdams, Harrison; Hsu, John T.; Greenstein, Deanna; Clasen, Liv; Ludovici, Katharine; Lloyd, Jonae; Rapoport, Judith; Mori, Susumu; Gogtay, Nitin

2015-01-01

Background: Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls. Methods: To evaluate WM integrity in this population 39 patients diagnosed with COS, 39 of their healthy (nonpsychotic) siblings, and 50 unrelated healthy volunteers were scanned using a diffusion tensor imaging (DTI) sequence during a 1.5 T MRI acquisition. Each DTI scan was processed via atlas-based analysis using a WM parcellation map, and diffeomorphic mapping that shapes a template atlas to each individual subject space. Fractional anisotropy (FA), a measure of WM integrity was averaged over each of the 46 regions of the atlas. Eleven WM regions were examined based on previous reports of WM growth abnormalities in COS. Results: Of those regions, patients with COS, and their healthy siblings had significantly lower mean FA in the left and right cuneus as compared to the healthy volunteers (P < .005). Together, these findings represent the largest DTI study in COS to date, and provide evidence that WM integrity is significantly impaired in COS. Shared deficits in their healthy siblings might result from increased genetic risk. PMID:25217482

Intestinal absorption of strontium chloride in healthy volunteers: pharmacokinetics and reproducibility

PubMed Central

SIPS, A. J. A. M.; van der VIJGH, W. J. F.; BARTO, R.; NETELENBOS, J. C.

1996-01-01

1The absorption kinetics of orally administered strontium chloride and its reproducibility were investigated in healthy volunteers after administering strontium either under fasting conditions (study I, n=8) or in combination with a standardized meal (study II, n=8). Each subject received strontium orally at day 0, 14, and 28 and intravenously at day 42. The study was performed as part of a project in which a simple clinical test for measuring intestinal calcium absorption is being developed, based on the use of stable strontium as a marker. 2Plasma strontium concentration–time curves were analysed by noncompartment analysis and a four compartment disposition model. Within a volunteer each oral curve was fitted simultaneously with the intravenous curve, by which means a two segment model for absorption was revealed. 3Mean absolute bioavailability of strontium was 25% without a meal and 19% with a meal, whereas the intraindividual variation was 24% and 20%, respectively. 4Various limited sampling absorption parameters were determined in order to select a potential test parameter for measuring intestinal calcium absorption using strontium as a marker. Fractional absorption at 4 h (Fc240), obtained after co-ingestion of strontium with a meal, appeared to be the best test parameter, because it represented bioavailability well (r=0.90). PMID:8799520

Frequency of functional bowel disorders among healthy volunteers in Mexico City.

PubMed

Schmulson, Max; Ortíz, Orianna; Santiago-Lomeli, Mariana; Gutiérrez-Reyes, Gabriela; Gutiérrez-Ruiz, María Concepción; Robles-Díaz, Guillermo; Morgan, Douglas

2006-01-01

The frequency of functional bowel disorders (FBD) in Mexico using the Rome II criteria is unknown. The Rome II Modular Questionnaire (RII-MQ) was translated into Spanish in coordination with the Rome Committee and their Latin American program. Volunteers were recruited by advertisement in Mexico City, and administered the RII-MQ. The study population consisted of 324 healthy volunteers, with a mean age of 35.7; 66% were female. The most prevalent disorders were heartburn 35%, irritable bowel syndrome (IBS) 35%, functional bloating 21%, proctalgia fugax 21%, and functional constipation 19%. Based on gender, IBS-C was 4 times more frequent in females than males (19 vs. 4.6%) and functional bloating 3 times more frequent (10 vs. 3.7%). Differences according to occupation included a higher prevalence of ulcer-like dyspepsia (p = 0.04), IBS-C (p = 0.018) and proctalgia fugax (p = 0.034) among students. This is the first study to use RII-MQ to determine the prevalence of FBD in urban Mexico. The prevalence of IBS was significant and is related to a number of factors, including the stress of living in an overpopulated city. Selection bias is likely operative. A community-based study is warranted. Copyright 2006 S. Karger AG, Basel

Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report was to determine the pharmacokinetic properties, safety, and tolerability of single and multiple doses of intravenous delafloxacin. In addition, the absolute bioavailability (BA) of the 450-mg tablet formulation of delafloxacin was determined. Three clinical trials are summarized. The first study was a randomized, double-blind, placebo-controlled, single- (300, 450, 600, 750, 900, and 1200 mg) ascending-dose study of IV delafloxacin in 62 (52 active, 10 placebo) healthy volunteers. The second study was a randomized, double-blind, placebo-controlled study of IV delafloxacin (300 mg) given as a single dose on day 1, followed by twice-daily dosing on days 2 through 14; 12 (8 active, 4 placebo) healthy volunteers were enrolled. The third study was an open-label, randomized, 2-period, 2-sequence crossover study in which 56 healthy volunteers were randomly assigned to 1 of 2 sequences of a single oral dose of delafloxacin (450-mg tablet) or IV delafloxacin (300 mg). Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were calculated. Delafloxacin Cmax values increased proportionally with increasing single IV dose for the dose range of 300 to 1200 mg, whereas the AUC values increased more than proportionally to dose for the same dose range. The mean terminal half-life of delafloxacin was approximately 12 hours (ranging from 8 to 17 hours). The volume of distribution (Vd) at steady state was approximately 35 L, which is similar to the volume of total body water. There was minimal accumulation of delafloxacin after twice-daily IV administration of 300 mg with an accumulation ratio of 1.09. The delafloxacin total exposure after a single 1-hour IV infusion of 300 mg and a single oral dose of a 450-mg tablet were equivalent with geometric least square mean ratio (90% CI) of 0.8768 (0.8356-0.9200) for AUC0-∞ and 0.8445 (0.8090-0.8815) for AUC0-t, respectively. The Cmax values of delafloxacin were not

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers

PubMed Central

Guarnieri, Regina V.; Ribeiro, Rafaela L.; de Souza, Altay A. Lino; Galduróz, José Carlos F.; Covolan, Luciene; Bueno, Orlando F. A.

2016-01-01

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model. PMID:27047394

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

PubMed Central

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

2014-01-01

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

Beliefs about Volunteerism, Volunteering Intention, Volunteering Behavior, and Purpose in Life among Chinese Adolescents in Hong Kong

PubMed Central

Law, Ben M. F.; Shek, Daniel T. L.

2009-01-01

The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect. PMID:19734959

Beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life among Chinese adolescents in Hong Kong.

PubMed

Law, Ben M F; Shek, Daniel T L

2009-09-01

The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect.

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

PubMed

Emri, Miklós; Glaub, Teodóra; Berecz, Roland; Lengyel, Zsolt; Mikecz, Pál; Repa, Imre; Bartók, Eniko; Degrell, István; Trón, Lajos

2006-05-01

Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the

Potential Mechanisms Leading to the Abnormal Lipid Profile in Patients With Rheumatoid Arthritis Versus Healthy Volunteers and Reversal by Tofacitinib†, ‡

PubMed Central

Fleischmann, Roy; Davignon, Jean; Schwartz, Howard; Turner, Scott M.; Beysen, Carine; Milad, Mark; Hellerstein, Marc K.; Luo, Zhen; Kaplan, Irina V.; Riese, Richard; Zuckerman, Andrea; McInnes, Iain B.

2015-01-01

Objective Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Systemic inflammation is proposed to play a fundamental role in the altered lipid metabolism associated with RA; however, the underlying mechanisms are unknown. We undertook this study to compare cholesterol and lipoprotein kinetics in patients with active RA with those in matched healthy volunteers. Methods This was a phase I open‐label mechanism‐of‐action study. Cholesterol and lipoprotein kinetics were assessed with 13C‐cholesterol and 13C‐leucine infusions. RA patients were reevaluated after receiving oral tofacitinib 10 mg twice daily for 6 weeks. Results Levels of high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, total cholesterol, and apolipoprotein A‐I (Apo A‐I) as well as HDL cholesterol particle number were lower in RA patients (n = 36) than in healthy volunteers (n = 33). In contrast, the cholesterol ester fractional catabolic rate was higher in RA patients, but no differences were observed in cholesterol ester transfer protein, cholesterol ester production rate, HDL‐associated Apo A‐I fractional catabolic rate, or LDL‐associated Apo B fractional catabolic rate. Following tofacitinib treatment in RA patients, the cholesterol ester fractional catabolic rate decreased and cholesterol levels increased. The decrease in cholesterol ester fractional catabolic rate correlated significantly with the increase in HDL cholesterol. Additionally, HDL cholesterol particle number increased and markers of HDL cholesterol function improved. Conclusion This is the first study to assess cholesterol and lipoprotein kinetics in patients with active RA and matched healthy volunteers. The data suggest that low cholesterol levels in patients with active RA may be driven by increases in cholesterol ester catabolism. Tofacitinib treatment reduced cholesterol ester catabolism, thereby increasing cholesterol levels toward those

Health effects of a subway environment in healthy volunteers.

PubMed

Klepczyńska Nyström, A; Svartengren, M; Grunewald, J; Pousette, C; Rödin, I; Lundin, A; Sköld, C M; Eklund, A; Larsson, B-M

2010-08-01

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter <10 microm, <2.5 microm or <1 microm (PM(10), PM(2.5) or PM(1)), is known to have a negative impact on the health of the population. Little is known about how the size and origin of particles influence the effects. We have previously shown that exposure to a road tunnel environment causes a cellular inflammatory response in the airways of healthy individuals. In the present study, our aim was to investigate potential airway health effects from exposure to a subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.

Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy volunteers.

PubMed

Antypa, N; Van der Does, A J W; Smelt, A H M; Rogers, R D

2009-09-01

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may be beneficial in the treatment of several psychiatric disorders, including depression. A small number of studies have suggested that there may also be cognitive and mood effects in healthy samples. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals. Fifty-four healthy university students were randomized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design. The test battery included measures of cognitive reactivity, attention, response inhibition, facial emotion recognition, memory and risky decision-making. Results showed few effects of n-3 PUFAs on cognition and mood states. The n-3 PUFA group made fewer risk-averse decisions than the placebo group. This difference appeared only in non-normative trials of the decision-making test, and was not accompanied by increased impulsiveness. N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure. No effects were found on the other cognitive tasks and no consistent effects on mood were observed. The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers, which is unrelated to impulsiveness.

Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males.

PubMed

Zhu, Jie; Song, Min; Tan, Hong-Yi; Huang, Li-Hua; Huang, Zhi-Jun; Liu, Chang; Fu, Zhi-Min; Huang, Yuan-Yuan; Tan, Zhi-Rong; Chen, Xiao-Ping; Yuan, Hong; Yang, Guo-Ping

2013-05-01

The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration (Cmax) of repaglinide (P=0.003) in SLCO1B1*1b homozygotes (P=0.015) and SLCO1B1*15 carriers (P=0.031). Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity (AUC0⇒∞) of repaglinide (P=0.091). There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the Cmax of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported.

[Development and evaluation of an educational program for promotion of healthy nutrition and physical activity by health volunteers].

PubMed

Yamaguchi, Yukio; Kai, Yuko; Kumamoto, Hiroko

2009-12-01

The purpose of the present trial was to develop and evaluate an educational program for promotion of healthy nutrition and physical activity by health volunteers. The educational program consisted of the following four phases: preliminary self-learning by mail (3 weeks), basic learning (3 sessions of 3 hours), practice of planned activities (2 months), and a report session (1 session of 3 hours). Beginner volunteers (n=18, mean age 63.3 +/- 6.4) were recruited from two volunteer health organizations in Kurume city. They then participated in a program that taught basic health knowledge regarding nutrition and physical activity, how to plan effective support activities, and methods for self-evaluation. In the preliminary self-learning phase, an assessment sheet, health information, and homework (goal setting, etc.) were delivered to the volunteers by mail. In the basic learning phase, volunteers attended a 3 day seminar on essential principles for behavioral change and assessment methods for volunteer activity. In addition, effective support activities were planned through group discussion. After a 2-month practice of support activities, each group reported and discussed the results of their activity in a 3-hour report session. Main outcome measures were health knowledge (15 items, 0-1 points), self-efficacy for life style support (5 items, 0-100%), and evaluation of the educational program (9 items, 1-5 points). All measures were self-administered. Significant increases in rate of true answers for health knowledge were observed during the preliminary self-learning and before basic learning phases (54.8% --> 67.1%, P < 0.05), and before and after basic learning phases (67.1% --> 87.6%, P < 0.05). Self-efficacy for life style support were significantly higher after the report session than before the preliminary self-learning phase (35.1% --> 53.1%, P < 0.05). In the two-month practice, all groups received feedback through questionnaires completed by participants who

[Meteoadaptogenic properties of peptide drugs in healthy volunteers].

PubMed

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

2007-01-01

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

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

PubMed

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.

Prediction of Psilocybin Response in Healthy Volunteers

PubMed Central

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

2012-01-01

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

Prediction of psilocybin response in healthy volunteers.

PubMed

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.

Ketamine-dependent neuronal activation in healthy volunteers.

PubMed

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 < 0.05; FWE-corrected). A significant decrease of neural activation in the 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 < 0.05, FWE-corrected). Using an approach combining pharmacological and fMRI data, important information about the neurobiological correlates of the clinical antidepressant effects of ketamine could be revealed.

Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies.

PubMed

Burghardt, Kyle J; Seyoum, Berhane; Mallisho, Abdullah; Burghardt, Paul R; Kowluru, Renu A; Yi, Zhengping

2018-04-20

Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required. Copyright © 2018 Elsevier Inc. All rights reserved.

A simplified ingestion procedure for esophageal capsule endoscopy: initial evaluation in healthy volunteers.

PubMed

Gralnek, I M; Rabinovitz, R; Afik, D; Eliakim, R

2006-09-01

Initial studies on esophageal capsule endoscopy (PillCam ESO) reported excellent sensitivity and specificity, but these were followed by mixed results in several subsequent studies, probably due to deviations from the recommended ingestion protocol and the inconvenience of capsule ingestion in the supine position. The aim of this study was therefore to test a simplified ingestion procedure (SIP) for PillCam ESO. Using a cross-over study design, the SIP was prospectively compared with the original ingestion procedure for PillCam ESO in 24 healthy volunteers (15 men, nine women; mean age 44, range 27 - 70) and evaluated for: bubbles/saliva interference at the Z-line, Z-line circumferential visualization (quadrants), and convenience and ease of the ingestion procedure. All Rapid 4 videos were reviewed in a randomized manner and read by an experienced PillCam ESO reader blinded to the ingestion procedure used. It was found that the SIP significantly improved visualization in comparison with the original ingestion procedure, with less interference due to bubbles/saliva observed at the gastroesophageal junction ( P = 0.002) and improved visualization of the Z-line ( P = 0.025). Although the esophageal transit time was significantly faster with the SIP (3 : 45 min vs. 0 : 38 min; P = 0.0001), there were no differences in the number of Z-line frames/images captured. This new, simplified ingestion procedure for PillCam ESO provides significantly improved visualization of the Z-line in healthy volunteers. The overall test characteristics of PillCam ESO using SIP should be tested in patients with esophageal disease.

Pharmacokinetic evaluation of a newly developed piperazine dithioctate formulation in healthy volunteers.

PubMed

Zheng, Renhua; Song, Hyung Ho; Kwon, Young Ee; Kim, Bo-Hyung

2014-12-01

The formulation investigated as reference contains thioctic acid which is known to be poorly soluble in water and have some instability during storage at high temperature. To overcome these limitations, a new piperazine dithioctate (PDT) tablet formulation was developed by a domestic pharmaceutical company in Korea. The aim of this clinical study was to evaluate the pharmacokinetic characteristics of PDT in healthy volunteers. This study consisted of two clinical trials. In the part 1 study, a randomized, singledose, parallel study was performed with 24 healthy volunteers. All of the subjects were administered one of the three study formulations, Thioctacid® HR (High Release) as the reference, PDT-1 or PDT-2 (each containing thioctic acid 600 mg), respectively. To determine the harmacokinetic characteristics, blood samples were serially collected at pre-dose and at pre-defined timepoints after dosing. In the part 2 study, a randomized, single-dose, two-way crossover study was conducted with 48 subjects. All of the subjects were administered both the reference and PDT-2 formulations, with a 7-day washout period between the two medications. Blood samples were collected at the same timepoints as in the part 1 study. Tolerability was evaluated throughout the study. 23 volunteers completed the part 1 study. The maximum plasma concentration (Cmax) of thioctic acid after administration of the reference tablet was 4.08 ± 2.35 μg/mL (means ± SD), and the Cmax of PDT-1 and PDT-2 was 3.53 ± 2.87 μg/mL and 4.15 ± 1.62 μg/mL, respectively. The AUClast value was 2.96 ± 1.13 μg x h/mL for the reference, 2.84 ± 1.12 μg x h/mL for PDT-1, and 3.30 ± 1.32 μg x h/mL for PDT-2. 42 volunteers completed the part 2 study. The Cmax of reference and PDT-2 was 5.59 ± 3.07 μg/mL and 5.14 ± 3.18 μg/mL, respectively. The AUClast value was 4.01 ± 1.65 μg x h/mL for the reference and 3.96 ± 1.47 μg x h/mL for PDT-2. The geometric mean ratios (PDT-2/reference) and the 90% CI

Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers

PubMed Central

Laviolle, Bruno; Donal, Erwan; Le Maguet, Pascale; Lainé, Fabrice; Bellissant, Eric

2013-01-01

Aims A single administration of hydrocortisone has been shown to enhance the pressor response to phenylephrine in healthy volunteers and to norepinephrine in septic shock patients. Similar data do not exist for fludrocortisone. Since there continues to be disagreement about the utility of fludrocortisone in septic shock, we assessed the effects of a single administration of low doses of hydrocortisone (50 mg intravenously) and fludrocortisone (50 μg orally), given either alone or in combination, on phenylephrine mean arterial pressure and cardiac systolic and diastolic function dose–response relationships in 12 healthy male volunteers with hypo-aldosteronism induced by intravenous sodium loading. Methods This was a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 × 2 factorial design. Subjects received first a 2000 ml infusion of NaCl 0.9% during 2 h. Then fludrocortisone 50 μg (or its placebo) was administered orally and hydrocortisone 50 mg (or its placebo) was injected intravenously. At 1.5 h after treatment administration, incremental doses of phenylephrine were infused (from 0.01 to 3 μg kg−1 min−1), each dose being infused during 5 min. Results Both fludrocortisone (P < 0.001) and hydrocortisone (P = 0.002) induced a significant decrease in pressor response to phenylephrine, their effects being additive (fludrocortisone × hydrocortisone interaction, P = 0.792). The two drugs did not induce any detectable cardiac effect. Conclusions Single administrations of fludrocortisone and hydrocortisone decreased the pressor response to phenylephrine in healthy volunteers with hypo-aldosteronism. These similar effects of hydrocortisone and fludrocortisone probably express a rapid non-genomic vasodilating effect of the two steroids in the context of acute volume loading. PMID:22703532

Effect of ensure on the oral bioavailability of gatifloxacin in healthy volunteers.

PubMed

Kays, Michael B; Overholser, Brian R; Lagvankar, Seema; Goldman, Mitchell; Sowinski, Kevin M

2005-11-01

To determine the effect of Ensure on the relative oral bioavailability of gatifloxacin in healthy volunteers. Single-dose, randomized, crossover study. University-affiliated research center. Twelve healthy volunteers (six men, six women) aged 18 years or older with no clinically significant abnormal findings on physical examination or in medical history. Intervention. Subjects consumed 120 ml of study liquid-water or Ensure-every 30 minutes for five doses. With the second dose, subjects ingested a single gatifloxacin 400-mg tablet that had been uniformly crushed and mixed into the study liquid. Serial blood samples were collected for 48 hours, and gatifloxacin concentrations were determined by high-performance liquid chromatography. Pharmacokinetic data were analyzed by using noncompartmental methods. Maximum serum concentration (Cmax) and area under the serum concentration-time curve from zero to infinity (AUC0-infinity) were tested for bioequivalence after log-transformation of the data. Comparison of parameters for gatifloxacin administered with water versus those with Ensure showed that Cmax (4.35 +/- 0.90 vs 2.41 +/- 0.58 mug/ml, p<0.0001) and AUC(0-infinity) (42.4 +/- 10.1 vs 31.3 +/- 8.3 mg*hr/L, p<0.0001) were significantly decreased with Ensure, and bioequivalence was not achieved for either parameter. The geometric least squares mean ratio was 0.553 (90% confidence interval [CI] 0.501-0.611) for Cmax and 0.730 (90% CI 0.664-0.802) for AUC0-infinity. The median time to reach Cmax was significantly prolonged when gatifloxacin was administered with Ensure versus that with water (2.5 hrs vs 1.0 hr, p=0.006). The Cmax and AUC0-infinity of gatifloxacin were significantly decreased when the drug was administered with Ensure. The clinical significance of these findings will depend on the offending pathogen and its susceptibility to gatifloxacin.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

PubMed

Robertson, Elaine V; Derakhshan, Mohammad H; Wirz, Angela A; Mitchell, David R; Going, James J; Kelman, Andrew W; Ballantyne, Stuart A; McColl, Kenneth E L

2017-07-01

Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux. 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/.

Direct effects of diazepam on emotional processing in healthy volunteers

PubMed Central

Murphy, S. E.; Downham, C.; Cowen, P. J.

2008-01-01

Rationale Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness. Objectives The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers. Materials and methods Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured. Results Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention. Conclusions At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety. PMID:18581100

Metronidazole immediate release formulations: a fasting randomized open-label crossover bioequivalence study in healthy volunteers.

PubMed

de Freitas Silva, M; Schramm, S G; Kano, E K; Koono, E E M; Manfio, J L; Porta, V; dos Reis Serra, C H

2012-10-01

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, ke, and t1/2 were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of Cmax, AUC0-t, and AUC0-∞ values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for Cmax (0.92-1.06), AUC0-t (0.97-1.02), and AUC0-∞ (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements. © Georg Thieme Verlag KG Stuttgart · New York.

Post-retirement voluntary work and psychological functioning among older Chinese in Hong Kong.

PubMed

Wu, Anise M S; Tang, Catherine S K; Yan, Elsie C W

2005-03-01

This study examined demographic and psychosocial differences between older Chinese volunteers and non-volunteers. The influences of work-related factors on older Chinese volunteers' post-retirement psychological functioning and life satisfaction were also explored. A total of 501 older Chinese in Hong Kong were individually interviewed. About 65% of them were involved in community voluntary work since their retirement, with an average of four hours per week. Compared to those without voluntary work experiences, older Chinese volunteers had higher educational attainment and reported better physical health, higher self-efficacy, greater life satisfaction, and less psychological distress. Results from hierarchical regression analyses showed that salient correlates of a low level of psychological distress in older Chinese volunteers were high educational attainment, high self-efficacy, perceived good physical health, and high levels of perceived rewards and satisfaction from voluntary work. Self-efficacy and perceived rewards from voluntary work were also salient correlates of life satisfaction for older Chinese volunteers. As hypothesized, work-related factors of perceived rewards and work satisfaction remained significant correlates of older volunteers' psychological well-being, even after controlling for demographic and individual psychosocial factors. Limitations and implications of the study were also discussed.

Do patients with OAB experience bladder sensations in the same way as healthy volunteers? A focus group investigation.

PubMed

Heeringa, R; van Koeveringe, G A; Winkens, B; van Kerrebroeck, P E V; de Wachter, S G G

2012-04-01

To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers. Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations. Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis. Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients. Copyright © 2012 Wiley Periodicals, Inc.

Development of population pharmacokinetics model of icotinib with non-linear absorption characters in healthy Chinese volunteers to assess the CYP2C19 polymorphism and food-intake effect.

PubMed

Hu, Pei; Chen, Jia; Liu, Dongyang; Zheng, Xin; Zhao, Qian; Jiang, Ji

2015-07-01

Icotinib is a potent and selective inhibitor of epidermal growth factor receptors (EGFR) approved to treat non-small cell lung cancer (NSCLC). However, its high variability may impede its application. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in icotinib absorption and/or disposition following single dose of icotinib in healthy volunteers. Data from two clinical studies (n = 22) were analyzed. One study was designed as three-period and Latin-squared (six sequence) trial to evaluate dose proportionality, and the other one was designed as two-way crossover trial to evaluate food effect on pharmacokinetics (PK) characters. Icotinib concentrations in plasma were analyzed using non-linear mixed-effects model (NONMEM) method. The model was used to assess influence of food, demographic characteristics, measurements of blood biochemistry, and CYP2C19 genotype on PK characters of icotinib in humans. The final model was diagnosed by goodness-of-fit plots and evaluated by visual predictive check (VPC) and bootstrap methods. A two-compartment model with saturated absorption character was developed to capture icotinib pharmacokinetics. Typical value of clearance, distribution clearance, central volume of distribution, maximum absorption rate were 29.5 L/h, 24.9 L/h, 18.5 L, 122.2 L and 204,245 μg/h, respectively. When icotinib was administrated with food, bioavailability was estimated to be increased by 48%. Inter-occasion variability was identified to affect on maximum absorption rate constant in food-effect study. CL was identified to be significantly influenced by age, albumin concentration (ALB), and CYP2C19 genotype. No obvious bias was found by VPC and bootstrap methods. The developed model can capture icotinib pharmacokinetics well in healthy volunteers. Food intake can increase icotinib exposure. Three covariates, age, albumin concentration, and CYP2C19 genotype, were identified to

Safety and Pharmacokinetics of Multiple 750-Milligram Doses of Intravenous Levofloxacin in Healthy Volunteers

PubMed Central

Chow, Andrew T.; Fowler, Cynthia; Williams, R. Rex; Morgan, Nancy; Kaminski, Susan; Natarajan, Jaya

2001-01-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation. PMID:11408234

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

PubMed

Chow, A T; Fowler, C; Williams, R R; Morgan, N; Kaminski, S; Natarajan, J

2001-07-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Gender- and Age-Specific REE and REE/FFM Distributions in Healthy Chinese Adults

PubMed Central

Cheng, Yu; Yang, Xue; Na, Li-Xin; Li, Ying; Sun, Chang-Hao

2016-01-01

Basic data on the resting energy expenditure (REE) of healthy populations are currently rare, especially for developing countries. The aims of the present study were to describe gender- and age-specific REE distributions and to evaluate the relationships among glycolipid metabolism, eating behaviors, and REE in healthy Chinese adults. This cross-sectional survey included 540 subjects (343 women and 197 men, 20–79 years old). REE was measured by indirect calorimetry and expressed as kcal/day/kg total body weight. The data were presented as the means and percentiles for REE and the REE to fat-free mass (FFM) ratio; differences were described by gender and age. Partial correlation analysis was used to analyze the correlations between REE, tertiles of REE/FFM, and glycolipid metabolism and eating behaviors. In this study, we confirmed a decline in REE with age in women (p = 0.000) and men (p = 0.000), and we found that men have a higher REE (p = 0.000) and lower REE/FFM (p = 0.021) than women. Furthermore, we observed no associations among glycolipid metabolism, eating behaviors, and REE in healthy Chinese adults. In conclusion, the results presented here may be useful to clinicians and nutritionists for comparing healthy and ill subjects and identifying changes in REE that are related to aging, malnutrition, and chronic diseases. PMID:27598192

Gender- and Age-Specific REE and REE/FFM Distributions in Healthy Chinese Adults.

PubMed

Cheng, Yu; Yang, Xue; Na, Li-Xin; Li, Ying; Sun, Chang-Hao

2016-09-01

Basic data on the resting energy expenditure (REE) of healthy populations are currently rare, especially for developing countries. The aims of the present study were to describe gender- and age-specific REE distributions and to evaluate the relationships among glycolipid metabolism, eating behaviors, and REE in healthy Chinese adults. This cross-sectional survey included 540 subjects (343 women and 197 men, 20-79 years old). REE was measured by indirect calorimetry and expressed as kcal/day/kg total body weight. The data were presented as the means and percentiles for REE and the REE to fat-free mass (FFM) ratio; differences were described by gender and age. Partial correlation analysis was used to analyze the correlations between REE, tertiles of REE/FFM, and glycolipid metabolism and eating behaviors. In this study, we confirmed a decline in REE with age in women (p = 0.000) and men (p = 0.000), and we found that men have a higher REE (p = 0.000) and lower REE/FFM (p = 0.021) than women. Furthermore, we observed no associations among glycolipid metabolism, eating behaviors, and REE in healthy Chinese adults. In conclusion, the results presented here may be useful to clinicians and nutritionists for comparing healthy and ill subjects and identifying changes in REE that are related to aging, malnutrition, and chronic diseases.

Dopaminergic modulation of semantic priming in healthy volunteers.

PubMed

Roesch-Ely, Daniela; Weiland, Stephan; Scheffel, Hans; Schwaninger, Markus; Hundemer, Hans-Peter; Kolter, Thomas; Weisbrod, Matthias

2006-09-15

Semantic priming is a function related to prefrontal cortical (PFC) networks and is lateralized. There is evidence that semantic priming underlies dopaminergic modulation. It is known that the D1-receptor is more abundant in prefrontal networks; however, until now there have been no studies investigating the selective modulation of semantic priming with dopamine agonists. Furthermore, D1 receptor dysfunction has been described in schizophrenia, and patients with formal thought disorder seem to have disturbed focusing of associations and increased indirect priming. With a subtraction design, we compared the influence of pergolide (D1/D2 agonist) with bromocriptine (D2 agonist) and placebo, in a randomized, double-blind, crossover design in 40 healthy male volunteers. Subjects performed a lateralized lexical decision task including direct and indirect related prime-target pairs (stimulus onset asynchrony = 750 msec). Only on pergolide a decrease of the indirect priming in the left hemisphere presentations was found. These findings point to a potential selective modulation of agonists with a D1 component on the focusing of semantic associations. The clinical relevance of this study is that it might help the development of therapeutic strategies for treating cognitive deficits in schizophrenia and Parkinson's disease, which are highly relevant to the functional outcome.

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

PubMed

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.

Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy.

PubMed

Brown, J; Haines, S; Wilding, I R

1997-08-01

Rectal administration of enemas, foams and suppositories is the most efficient method of delivering locally-acting drugs to the distal colon, sigmoid colon and rectum. Healthy volunteers provide an effective population to compare different formulations for rectal drug delivery. However, there is still only limited comparative information available on the dispersion of such dosage forms in human subjects. Therefore, the objective of this scintigraphic study was to compare colonic spread of an enema, a rectal foam and a suppository formulation in healthy volunteers. This was a randomized, crossover study in eight healthy male volunteers. Each received Pentasa rectal formulations as either a 100 mL suspension enema (1 g mesalazine), one actuation of a non-CFC propellant rectal foam (1 g mesalazine in 5 mL concentrate, expanding to 40 mL on actuation), or one suppository (1 g mesalazine) on three separate occasions. The spread of the radiolabelled formulations was assessed over a 4-h period by gamma scintigraphy. The formulations were retained by all subjects for the whole of the 4-h imaging period. The enema spread to the splenic flexure in 7 out of 8 subjects, but was retained in the rectum and sigmoid colon in one individual. The foam spread as far as the descending colon in four subjects. In the remaining individuals the foam was retained in the rectum and sigmoid colon. The spread of the suppository was limited and confined to the rectum. The findings of this study are consistent with previous research and support the intended clinical uses of the enema, foam and suppository formulations to treat distal ulcerative colitis, proctosigmoiditis and proctitis, respectively. The results highlight the potential of gamma scintigraphy in providing in vivo 'proof of concept' data to help verify the targeting of pharmaceutical products to their intended site of delivery.

CYP3A5*3 and MDR1 C3435T are influencing factors of inter-subject variability in rupatadine pharmacokinetics in healthy Chinese volunteers.

PubMed

Xiong, Yuqing; Yuan, Zhao; Yang, Jingzhi; Xia, Chunhua; Li, Xinhua; Huang, Shibo; Zhang, Hong; Liu, Mingyi

2016-04-01

Rupatadine (RUP) is an oral antihistamine and platelet-activating factor antagonist and is shown as the substrate of CYP3A5 and P-gp. The significant interindividual differences of CYP3A5 and P-gp often cause bioavailability differences of some clinical drugs. The present study is aimed to evaluate the effect of genetic polymorphisms of CYP3A5 and MDR1 on RUP pharmacokinetics in healthy male Chinese volunteer subjects. Blood samples were collected from 36 subjects before and after a single, oral RUP 10 mg dose. A PCR-RFLP assay was used to genotype CYP3A5*3 and assess MDR1 C3435T variation. A validated LC-MS/MS method quantified plasma RUP concentration. The relationship between RUP plasma concentration, pharmacokinetic parameters, and polymorphic alleles (CYP3A5 and MDR1) were assessed. Plasma RUP concentrations were lower for CYP3A5*1/*1 carriers than for CYP3A5*3/*3 and CYP3A5*1/*3 carriers. Mean C(max), AUC(0-t) and AUC(0-∞) were significantly lower, and the CLz and Vd were significantly higher in the CYP3A5 wild-type group, than in the CYP3A5 mutated group. MDR1 CT and MDR1 TT carriers had lower plasma RUP concentrations than MDR1 CC carriers. The mean C(max), AUC(0-t), AUC(0-∞) and T max were significantly lower in the TT group than in the CC and CT groups. The mean CLz was higher in the TT group than in the CC and CT groups, but not significantly. These results suggest that CYP3A5 and MDR1 may play a key role in the variability of RUP metabolism and transport, respectively. CYP3A5 and MDR1 polymorphisms may be the main explanation for the differences observed in RUP pharmacokinetics, and therefore may provide a rationale for safe and effective clinical use of RUP. Our research lays down a solid theory foundation to guide the safe and effective clinical use of RUP and a route to achieve individualized therapy.

Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers.

PubMed

Joeres-Nguyen-Xuan, Thai Hoa; Boehm, Stephan Karl; Joeres, Lars; Schulze, Juergen; Kruis, Wolfgang

2010-02-01

Mesalamine and the probiotic E. coli Nissle 1917 (EcN) are both effective agents for the treatment of ulcerative colitis. A combined therapy may have more than additive efficacy. However, mesalamine may have antimicrobial effects on EcN. In this prospective, randomized, double-blind, placebo-controlled study, 48 healthy volunteers took EcN in a run-in phase for 17 days (5-50 x 10(9) viable bacteria od). If stool samples became positive for EcN, volunteers received combination treatment with EcN plus either mesalamine (1500 mg twice a day) or placebo for 1 week. Fecal samples were further tested for EcN in 2- to 3-day intervals until a maximum of 48 weeks after treatment. Patient diaries, blood, and urine were checked to assess safety, compliance, and tolerance. During run-in, viable EcN were detected in 45 of the 48 volunteers (94%); 2 volunteers were positive before taking EcN. From days 1 to 7 of combination treatment (n = 40), the number of EcN-positive volunteers varied between 70% and 80% in the mesalamine group and between 85% and 95% in the placebo group. Differences between the groups were not significant (normal approximation: day 3, P > 0.15; day 5, P > 0.25; day 7, P > 0.076). At treatment discontinuation, 16 of 20 volunteers in the mesalamine group and 15 of 20 volunteers in the placebo group were EcN positive, whereas this figure dropped continuously up to week 12 after discontinuation (mesalamine, 7 of 20; placebo, 4 of 20). No differences between the groups were seen with regard to tolerance and safety. The combination of EcN and mesalamine has no significant effect on the survival of EcN in healthy volunteers.

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis.

PubMed

van Rijn, S P; Zuur, M A; van Altena, R; Akkerman, O W; Proost, J H; de Lange, W C M; Kerstjens, H A M; Touw, D J; van der Werf, T S; Kosterink, J G W; Alffenaar, J W C

2017-04-01

Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% T MIC ). To assess the 40% T MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentration-time curve from 0 to 24 h [AUC 0-24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation ( n = 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% T MIC with the free fraction ( f 40% T MIC ) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) in MDR-TB patients by 6.8% (range, -17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h ( r 2 = 0.78, mean prediction error = -0.33%, root mean square error = 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, -15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% T MIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis

PubMed Central

van Rijn, S. P.; Zuur, M. A.; van Altena, R.; Akkerman, O. W.; Proost, J. H.; de Lange, W. C. M.; Kerstjens, H. A. M.; Touw, D. J.; van der Werf, T. S.; Kosterink, J. G. W.

2017-01-01

ABSTRACT Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% TMIC). To assess the 40% TMIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentration-time curve from 0 to 24 h [AUC0–24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation (n = 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% TMIC with the free fraction (f 40% TMIC) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC0–24) in MDR-TB patients by 6.8% (range, −17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h (r2 = 0.78, mean prediction error = −0.33%, root mean square error = 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, −15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% TMIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

PubMed

Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability.

PubMed

Maurer, J M; Schellekens, R C A; van Rieke, H M; Stellaard, F; Wutzke, K D; Buurman, D J; Dijkstra, G; Woerdenbag, H J; Frijlink, H W; Kosterink, J G W

2013-12-28

ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in specific patient groups and not with a shorter interval between administration and breakfast. Information on bioavailability and release characteristics of ColoPulse tablets in Crohn's patients and the influence of food and time of food intake is a prerequisite to properly design future clinical studies with active substances in these patients. In the current cross-over study bioavailability and drug release characteristics of ColoPulse tablets were compared in healthy volunteers and in Crohn's patients in remission. Furthermore the influence of food and time of food intake on the in vivo drug release behavior of ColoPulse tablets was investigated. In this study the dual label isotope strategy was used which means that a ColoPulse tablet containing (13)C-urea and an uncoated, immediate release tablet containing (15)N2-urea were taken simultaneously. Breath and urine samples were collected during the test day for isotope analysis. The appearance of the stable isotopes in breath and/or urine provides information on the site of release from the dosage form, release characteristics and bioavailability. Both tablets were administered on two different days in a cross-over design: the first day with a breakfast (non-standardized) one hour after administration and the second day with a standardized breakfast three hours after administration of the tablets. There was no difference in instructions for administration between both days. Results of 16 healthy volunteers and 14 Crohn's patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets administered in this study released their contents at the desired intestinal region. There was no significant difference in

Clinical evaluation of liquid placebos for an herbal supplement, STW5, in healthy volunteers.

PubMed

Yoon, Saunjoo L; Grundmann, Oliver; Keane, Devan; Urbano, Theodore; Moshiree, Baharak

2012-10-01

Although clinical trials are needed to evaluate the efficacy of liquid herbal medicinal products, design of feasible placebos that mimic the appearance, taste, and smell of such products is particularly challenging. The design and feasibility of a liquid placebo for STW5, an herbal medicinal product used for various gastrointestinal problems, was explored in this study. Four sample products-STW5, a fresh and aged version of a placebo made from a seasoning mix (Maggi™), and a placebo with aged artificial flavor and food coloring-were compared in two organoleptic (sensory), single-blind trials with a total of 60 (N=60) healthy volunteers (n(1)=30, n(2)=30). The appearance, smell, and taste of each solution were evaluated using a Likert scale questionnaire. The liquid placebos evaluated were similar in regard to appearance, smell, and taste. However, participants indicated that for a clinical trial with STW5, the aged Maggi™ placebo would be more viable compared to the fresh Maggi placebo or the aged artificial food coloring placebo with licorice flavor. Participants also noted that the mint flavor and smell of STW5 was distinctly different from the placebo solutions. The trials were conducted in healthy volunteers, not in actual patients. The aged Maggi™ liquid mix may be more favorable as a placebo than the artificially created one. However, further adjustment will need to be made to the Maggi™ placebo to simulate the complex aromatic composition of STW5 for clinical studies in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of grape seed extract on the pharmacokinetics of dextromethorphan in healthy volunteers.

PubMed

Goey, Andrew K L; Meijerman, Irma; Beijnen, Jos H; Schellens, Jan H M

2013-11-01

Grape seed extract (GSE) has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. To determine the clinical effect of GSE on CYP2D6, the pharmacokinetic interaction between GSE and the sensitive CYP2D6 probe dextromethorphan in healthy adult volunteers was examined. In this open label, randomized, cross-over study, 30 subjects were assigned to cohort A or B. Both cohorts ingested 30 mg dextromethorphan hydrobromide on day 1 and day 10. Cohort A received 100 mg GSE capsules three times daily on days 8, 9 and 10, while cohort B started with GSE on day -1 until day 1. After urine collection (0-8 h) on day 1 and day 10, the urinary dextromethorphan to dextrorphan metabolic ratio was determined. Among 28 evaluable subjects, an increase of the urinary metabolic ratio was observed in 16 subjects (57 %). The mean metabolic ratio (± standard deviation) before and after GSE supplementation was 0.41 (± 0.56) and 0.48 (± 0.59), respectively. This result was neither statistically (P = 0.342) nor clinically [geometric mean ratio 1.10, 90 % CI (0.93-1.30)] significant. Further, the majority (73 %) of the included subjects did not experience any adverse events after intake of dextromethorphan or GSE. Supplementation of GSE did not significantly affect the urinary dextromethorphan to dextrorphan metabolic ratio in healthy volunteers. The results of this clinical study indicate that GSE appears to be safe to combine with drugs extensively metabolized by CYP2D6, such as dextromethorphan and tamoxifen.

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

PubMed

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 < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). I.v. 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.

Reference Range of Platelet Delta Granules in the Pediatric Age Group: An Ultrastructural Study of Platelet Whole Mount Preparations from Healthy Volunteers.

PubMed

Sorokin, Victoria; Alkhoury, Razan; Al-Rawabdeh, Sura; Houston, Ronald H; Thornton, David; Kerlin, Bryce; O'Brien, Sarah; Baker, Peter; Boesel, Carl; Uddin, Minhaj; Yin, Han; Kahwash, Samir

This study sought to determine delta granule normal ranges for children and to validate methodology for the appropriate diagnosis of delta granule deficiency (storage pool disease) by using the whole-mount technique in electron microscopy. Specimens obtained from 40 healthy volunteers (2 months of age through 21 years old, 21 females and 19 males) were tested. Results showed dense granules/platelet (DG/Plt) ranged from 1.78 to 5.25. The 5th percentile was 1.96 DG/Plt with an overall mean ± SEM 3.07 ± 0.12 DG/Plt. In comparison, a previously published lower cutoff value, 3.68 DG/Plt, was significantly higher than the mean from our volunteers (P < 0.0001). We found no variability in dense granules/platelet based on race or sex and no significant variation by age subgroup. Pending wider studies, the value of 2 DG/Plt is a more appropriate lower limit of normal. In the absence of wider studies (in healthy volunteers and patients), laboratories should consider establishing their own reference ranges.

High-resolution 3T Magnetic Resonance Imaging of the Triangular Fibrocartilage Complex in Chinese Wrists: Correlation with Cross-sectional Anatomy.

PubMed

Zhan, Hui-Li; Li, Wen-Ting; Bai, Rong-Jie; Wang, Nai-Li; Qian, Zhan-Hua; Ye, Wei; Yin, Yu-Ming

2017-04-05

The injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar-sided wrist pain. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) could demonstrate the detailed complex anatomy of TFCC in Chinese. Fourteen Chinese cadaveric wrists (from four men and three women; age range at death from 30 to 60 years; mean age at 46 years) and forty healthy Chinese wrists (from 20 healthy volunteers, male/female: 10/10; age range from 21 to 53 years with a mean age of 32 years) in Beijing Jishuitan Hospital from March 2014 to March 2016 were included in this study. All cadavers and volunteers had magnetic resonance (MR) examination of the wrist with coronal T1-weighted and proton density-weighted imaging with fat suppression in three planes, respectively. MR arthrography (MRAr) was performed on one of the cadaveric wrists. Subsequently, all 14 cadaveric wrists were sliced into 2 mm thick slab with band saw (six in coronal plane, four in sagittal plane, and four in axial plane). The MRI features of normal TFCC were analyzed in these specimens and forty healthy wrists. Triangular fibrocartilage, the ulnar collateral ligament, and the meniscal homolog could be best observed on images in coronal plane. The palmar and dorsal radioulnar ligaments were best evaluated in transverse plane. The ulnotriquetral and ulnolunate ligaments were best visualized in sagittal plane. The latter two structures and the volar and dorsal capsules were better demonstrated on MRAr. High-resolution 3T MRI is capable to show the detailed complex anatomy of the TFCC and can provide valuable information for the clinical diagnosis in Chinese.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial.

PubMed

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.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

PubMed Central

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. PMID:29387131

A randomised trial of the effect of the glycine reuptake inhibitor Org 25935 on cognitive performance in healthy male volunteers.

PubMed

Christmas, David; Diaper, Alison; Wilson, Sue; Rich, Ann; Phillips, Suzanne; Udo de Haes, Joanna; Sjogren, Magnus; Nutt, David

2014-03-01

Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers. A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken. There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild. A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.

Qualitative and quantitative assessment of nailfold capillaries by capillaroscopy in healthy volunteers.

PubMed

Hoerth, Christian; Kundi, Michael; Katzenschlager, Reinhold; Hirschl, Mirko

2012-01-01

Nailfold capillaroscopy (NVC) is a diagnostic tool particularly useful in the differential diagnosis of rheumatic and connective tissue diseases. Although successfully applied since many years, little is known about prevalence and distribution of NVC changes in healthy individuals. NVC was performed in 120 individuals (57 men and 63 women; age 18 to 70 years) randomly selected according to predefined age and sex strata. Diseases associated with NVC changes were excluded. The nailfolds of eight fingers were assessed according to standardized procedures. A scoring system was developed based on the distribution of the number of morphologically deviating capillaries, microhaemorrhages, and capillary density. Only 18 individuals (15 %) had no deviation in morphology, haemorrhages, or capillary density on any finger. Overall 67 % had morphological changes, 48 % had microhaemorrhages, and 40 % of volunteers below 40 years of age and 18 % above age 40 had less than 8 capillaries/mm. Among morphological changes tortous (43 %), ramified (47 %), and bushy capillaries (27 %) were the most frequently altered capillary types. A semiquantitative scoring system was developed in such a way that a score above 1 indicates an extreme position (above the 90th percentile) in the distribution of scores among healthy individuals. Altered capillaries occur frequently among healthy individuals and should be interpreted as normal unless a suspicious increase in their frequency is determined by reference to the scoring system. Megacapillaries and diffuse loss of capillaries were not found and seem to be of specific diagnostic value.

Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo.

PubMed

Kalbag, J B; Walter, Y H; Nedelman, J R; McLeod, J F

2001-01-01

This study was designed to compare the pharmacodynamic effects of single doses of nateglinide (A-4166), repaglinide, and placebo on mealtime insulin secretion and glycemic control in healthy subjects. Fifteen healthy volunteers participated in this open-label five-period crossover study. They received single 10-min preprandial doses of 120 mg nateglinide, 0.5 or 2 mg repaglinide, or placebo or 1 min preprandially of 2 mg repaglinide. Subjects received each dose only once, 48 h apart. Pharmacodynamic and pharmacokinetic assessments were performed from 0 to 12 h postdose. Nateglinide induced insulin secretion more rapidly than 2 and 0.5 mg repaglinide and placebo (10 min preprandial), with mean rates of insulin rise of 2.3, 1.3, 1.15, and 0.8 microU x ml(-1) x min(-1), respectively, over the 0- to 30-min postmeal interval. After peaking, insulin concentrations decreased rapidly in the nateglinide-treated group and were similar to placebo within 2 h postdose. After 2 mg repaglinide, peak insulin concentrations were delayed and returned to baseline more slowly than with nateglinide treatment. Nateglinide treatment produced lower average plasma glucose concentrations in the 0- to 2-h postdose interval than either dose of repaglinide and placebo (P < 0.05 vs. 0.5 mg repaglinide and placebo). Plasma glucose concentrations returned more rapidly to predose levels with nateglinide treatment than with either dose of repaglinide. Treatment with repaglinide produced a sustained hypoglycemic effect up to 6 h postdose. In this single-dose study in nondiabetic volunteers, nateglinide provided a more rapid and shorter-lived stimulation of insulin secretion than repaglinide, resulting in lower meal-related glucose excursions. If similar results are observed in diabetes, nateglinide may produce a more physiological insulin secretory response with the potential for a reduced risk of postabsorptive hypoglycemia.

Pharmacokinetics of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir in Healthy Chinese Subjects and HCV GT1b-Infected Chinese, South Korean and Taiwanese Patients.

PubMed

Zha, Jiuhong; Ding, Bifeng; Wang, Haoyu; Zhao, Weihan; Yu, Chen; Alves, Katia; Mobashery, Niloufar; Luo, Yan; Menon, Rajeev M

2018-06-16

The 3 direct-acting antiviral (3D) regimen of ombitasvir/paritaprevir/ritonavir plus dasabuvir has recently been approved in several Asian geographic regions for the treatment of hepatitis C virus (HCV) genotype (GT) 1 infection. The pharmacokinetics of the components of the 3D regimen with or without ribavirin were evaluated in healthy Chinese subjects and HCV GT1b-infected Chinese, South Korean, and Taiwanese patients, with or without cirrhosis, to determine how the drug exposures in Asian populations compare with historical data in Western populations. Participants received ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily plus dasabuvir 250 mg twice daily for 14 days (healthy subjects, n = 36) or 12 weeks (HCV patients, n = 754). Patients with compensated cirrhosis also received ribavirin 1000 or 1200 mg divided twice daily, per the local label. Intensive or sparse pharmacokinetic sampling was performed for assessments of plasma drug concentrations. The exposures [maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC)] of the components of the 3D regimen were comparable (< 20% difference) in healthy Chinese subjects residing in China or the United States. In addition, the trough plasma concentrations (C trough ) in HCV GT1b-infected Asian patients were either similar to (ombitasvir) or within 75% of (paritaprevir and dasabuvir) those in Western patients without cirrhosis, or similar to (ombitasvir and paritaprevir) or within 100% of (dasabuvir) those in Western patients with cirrhosis, with widely overlapping ranges of individual values. Generally comparable drug exposures were observed among Chinese, South Korean, and Taiwanese ethnicities for noncirrhotic and cirrhotic patients. Collectively, the results of these pharmacokinetic analyses support the use of the same dose of the 3D regimen for Asian and Western patients. CLINICALTRIALS.GOV: NCT02534870, NCT02517515, NCT02517528.

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

PubMed

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

2012-08-01

There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5mg alprazolam, 10mg oxycodone, and 0.5mg alprazolam combined with 10 mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Oxycodone by itself increased drug liking and "take again" ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers.

PubMed

Piscitelli, Stephen C; Formentini, Elizabeth; Burstein, Aaron H; Alfaro, Raul; Jagannatha, Shyla; Falloon, Judith

2002-05-01

To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Prospective open-label drug interaction study. Outpatient clinic. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11-day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Indinavir concentrations were measured by using a validated high-performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour-0 concentration, hour-8 concentration (C8), time to reach Cmax, and area under the plasma concentration-time curve over the 8-hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.

Assessment of tamsulosin as a potential male contraceptive in healthy volunteers.

PubMed

Wang, Jin; Zhao, Yong; Jiang, Shao-bo; Xia, Qing-hua; Wei, Chun-xiao; Wang, Mu-wen; Sun, Peng; Jin, Xun-bo

2012-09-01

To investigate the efficacy and safety of tamsulosin, an α(1A)-adrenoceptor antagonist, as a potential male contraceptive. Forty healthy male volunteers were equally divided into 2 groups, each of which received placebo and tamsulosin sequentially in a crossover manner. Ejaculatory profile was examined 4 to 6 hours after administration and adverse effects were noted. Anejaculation occurred in all subjects after taking 0.8-mg of tamsulosin. Total functional sperm count was significantly reduced in subjects after taking 0.4-mg of tamsulosin. Six subjects receiving 0.8-mg of tamsulosin complained of tolerated discomfort, which disappeared 10 hours after administration. When administered at 0.8 mg, tamsulosin can cause anejaculation with some transient side effects. Our results imply that tamsulosin and related drugs might potentially be used as male contraceptive agents in the future, which needs more studies to verify. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-06-01

We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Traditional measures of normal anal sphincter function using high-resolution anorectal manometry (HRAM) in 115 healthy volunteers.

PubMed

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.

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers

PubMed Central

Wesnes, K A; Garratt, C; Wickens, M; Gudgeon, A; Oliver, S

2000-01-01

Aims To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. Methods On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg−1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg−1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. Results Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl−1.Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.

PubMed

Allen, A P; Hutch, W; Borre, Y E; Kennedy, P J; Temko, A; Boylan, G; Murphy, E; Cryan, J F; Dinan, T G; Clarke, G

2016-11-01

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

Effects of ice massage of the head and spine on heart rate variability in healthy volunteers.

PubMed

Mooventhan, A; Nivethitha, L

2016-07-01

Ice massage (IM) is one of the treatment procedures used in hydrotherapy. Though its various physiological/therapeutic effects have been reported, effects of IM of the head and spine on heart rate variability (HRV) have not been studied. Thus, this study evaluated the effects of IM of the head and spine on HRV in healthy volunteers. Thirty subjects were randomly divided into 3 sessions: (1) IM, (2) tap water massage (TWM) and (3) prone rest (PR). Heart rate (HR) and HRV were assessed before and after each intervention session. A significant increase in the mean of the intervals between adjacent QRS complexes or the instantaneous HR (RRI), square root of mean of sum of squares of differences between adjacent normal to normal (NN) intervals (RMSSD), number of interval differences of successive NN intervals greater than 50 milliseconds (NN50), proportion derived by dividing NN50 by total number of NN intervals along with significant reduction in HR after IM session; significant increase in RRI along with significant reduction in HR after TWM, and a significant increase only in RMSSD after PR were observed. However, there was no significant difference between the sessions. Results of this study suggest that 20 min of IM of the head and spine is effective in reducing HR and improving HRV through vagal dominance in healthy volunteers.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

PubMed

Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

2014-07-01

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers.

PubMed

Kongpatanakul, S; Chatsiricharoenkul, S; Khuhapinant, A; Atipas, S; Kaewkungwal, J

2009-09-01

As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decrease in hemoglobin was detected after a single 200-mg oral dose. To explore further, a clinical study with an emphasis on hematological parameters was conducted. A single-center, randomized, single-blind, cross-over clinical study was conducted in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters on study Days 0, 2, 5, and 7 post drug administrations were analyzed. Eighteen volunteers completed both rounds of the study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA 47%, p < 0.001 for both drugs compared to baseline). The present study confirmed our previous finding on significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives.

Healthy Living Behaviors Among Chinese-American Preschool-Aged Children: Results of a Parent Survey.

PubMed

Chomitz, Virginia Rall; Brown, Alison; Lee, Victoria; Must, Aviva; Chui, Kenneth Kwan Ho

2017-07-17

Associations between diet, physical activity, parenting, and acculturation among Chinese-American children are understudied. Parents/caregivers of children attending child-care programs in Boston Chinatown completed a self-administered survey on demographics, child's diet, physical activities, anthropometrics, and parenting practices. Associations were evaluated in multivariable regression analysis, stratified by survey language preference, a proxy for acculturation. Responding Asian families = 132; 86.4% were immigrants; 75.8% completed the Chinese-version survey. Children (mean ± SD: 4.9 ± 1.1 years) did not eat vegetables (31.8%), or play actively outside (45.4%) daily, 64.8% watched television/screens daily; 32.6% were overweight/obese (based on parent report). Parenting practices associated with obesity were apparent. Although healthy-living behavioral outcomes were less prevalent among less acculturated parents; multivariable adjustment attenuated the observed significant differences. Findings suggest opportunities for improvement in study children's diet and healthy-living behaviors, and underscore the need for further research on acculturation, and parenting styles in this population.

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

PubMed

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.

Dreaming under antidepressants: a systematic review on evidence in depressive patients and healthy volunteers.

PubMed

Tribl, Gotthard G; Wetter, Thomas C; Schredl, Michael

2013-04-01

Sleep related symptoms of depression include sleep fragmentation, early morning awakening, decreased rapid eye movement (REM) sleep latency, increased REM density, and more negative dream content. Most tricyclic antidepressants (ADs) increase total sleep time and decrease wake time after sleep onset, while many selective serotonin reuptake inhibitors (SSRIs) have an opposite effect. However, almost all ADs prolong REM sleep latency and reduce the amount of REM sleep. Case reports and research data indicate a strong effect of ADs on dream recall and dream content. We performed a systematic review (1950 to August 2010) about ADs impact on dreaming in depressive patients and healthy volunteers. Twenty-one clinical studies and 25 case reports were eligible for review and document a clear AD effect on dreaming. The major finding, both in depressed patients and in healthy volunteers, is a decrease of dream recall frequency (DRF) under ADs. This is a rather consistent effect in tricyclic ADs and phenelzine, less consistently documented also for SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs). Tricyclic ADs induce more positive dream emotions. Withdrawal from tricyclic ADs and from the monoamine oxidase inhibitors phenelzine and tranylcypromine may cause nightmares. Intake and even more withdrawal of SSRIs/SNRIs seem to intensify dreaming, which may be experienced in different ways; a potential to cause nightmares has to be taken into account. Though there are clear-cut pharmacological effects of ADs on DRF and dream content, publications have been surprisingly scarce during the past 60 years. There is evidence of a gap in neuropsychopharmacological research. AD effects on dreams should be recognized and may be used in treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Efficacy and safety of topical depigmenting agent in healthy human fair skin female volunteers: A single-arm study.

PubMed

Shah, Saurabh; Chew, Soon-Keong

2017-11-28

Skin hyperpigmentation is the darkening of skin due to the increased production of melanin in the body. To evaluate the efficacy and safety of a botanical-based Rosa E pigmentation serum in healthy fair skin female volunteers with wrinkles, skin tone, and pigmentation. This was a single-arm, open label study conducted in healthy Indian females; 18 subjects aged 30-55, having fair Caucasian-like skin with at least 2 dark skin pigments with facial wrinkles diagnosed by dermatologist were selected. Rosa E pigmentation serum was applied twice a day for 84 days. Effect was evaluated by (i) instrumental technique (spectrophotometer ® 2600D), (ii) clinically by dermatologist regarding product efficacy (skin tone, antiwrinkle, pigmentation), and (iii) volunteers self-evaluation. The L* value of spectrophotometer reading represents lightness in the skin pigment. Reduction in the pigment was reported from day 14, with significant reductions observed till day 84 compared with baseline. Significant (P < .0001) skin pigmentation lightening was seen on day 14 (1.11) vastly improving on day 84 (1.94) based on photographic assessments. The significant reduction in skin pigment was 76.85%, Felix von Luschan skin color score was 30.24% (P < .0001) with a 7.38-fold reduction in skin tone and 57% reduction in facial wrinkles at day 84 from baseline. Rosa E pigmentation serum was found safe and effective in significant reduction in skin pigments, improvement of skin tone, and antiwrinkle properties instrumentally, clinically, and self-evaluation by volunteers. In these evaluations, best results were seen the longer the Rosa E was used. © 2017 Wiley Periodicals, Inc.

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

PubMed

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.

What is the normal haemodynamic response to passive leg raise? A study of healthy volunteers.

PubMed

Elwan, Mohammed H; Roshdy, Ashraf; Reynolds, Joseph A; Elsharkawy, Eman M; Eltahan, Salah M; Coats, Timothy J

2018-05-04

Passive leg raise (PLR) is used as self-fluid challenge to optimise fluid therapy by predicting preload responsiveness. However, there remains uncertainty around the normal haemodynamic response to PLR with resulting difficulties in application and interpretation in emergency care. We aim to define the haemodynamic responses to PLR in spontaneously breathing volunteers using a non-invasive cardiac output monitor, thoracic electrical bioimpedance, TEB (PLR-TEB). We recruited healthy volunteers aged 18 or above. Subjects were monitored using TEB in a semirecumbent position, followed by PLR for 3 min. The procedure was repeated after 6 min at the starting position. Correlation between the two PLRs was assessed using Spearman's r (r s ). Agreement between the two PLRs was evaluated using Cohen Kappa with responsiveness defined as ≥10% increase in stroke volume. Parametric and non-parametric tests were used as appropriate to evaluate statistical significance of baseline variables between responders and non-responders. We enrolled 50 volunteers, all haemodynamically stable at baseline, of whom 49 completed the study procedure. About half of our subjects were preload responsive. The ∆SV in the two PLRs was correlated (r s =0.68, 95% CI 0.49 to 0.8) with 85% positive concordance. Good agreement was observed with Cohen Kappa of 0.67 (95% CI 0.45 to 0.88). Responders were older and had significantly lower baseline stroke volume and cardiac output. Our results suggest that the PLR-TEB is a feasible method in spontaneously breathing volunteers with reasonable reproducibility. The age and baseline stroke volume effect suggests a more complex underlying physiology than commonly appreciated. The fact that half of the volunteers had a positive preload response, against the 10% threshold, leads to questions about how this measurement should be used in emergency care and will help shape future patient studies. © Article author(s) (or their employer(s) unless otherwise

Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients.

PubMed

Yoshihara, Kazutaka; Gao, Yuying; Shiga, Hiroshi; Wada, D Russell; Hisaoka, Masafumi

2005-01-01

Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype. To develop a population pharmacokinetic model for olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertensive patients, and to evaluate effects of covariates on the apparent oral clearance (CL/F), with particular emphasis on the effect of race. Retrospective analysis of data from 12 phase I-III trials in the US, Europe and Japan. Eighty-nine healthy volunteers and 383 hypertensive patients. Nonlinear mixed-effects modelling was used to evaluate 7911 olmesartan plasma sample concentrations. The covariates included age, bodyweight, sex, race (Westerners [including Caucasians and Hispanics] versus Japanese), patient status (hypertensive patients versus healthy volunteers), serum creatinine level as an index of renal function and serum chemistry data as indices of hepatic function. The pharmacokinetic data of olmesartan were well described by a two-compartment linear model with first-order absorption and an absorption lag-time, parameterised in terms of CL/F (6.66 L/h for a typical male Western hypertensive patient), absorption rate constant (1.46h-1), elimination rate constant (0.193h-1), rate constant from the central to peripheral compartment (0.061h-1), rate constant from the peripheral to central compartment (0.079h-1) and absorption lag-time (0.427h). Analysis of covariates showed that age, bodyweight, sex, patient status and renal function were factors influencing the clearance of olmesartan. The population pharmacokinetic analysis of olmesartan showed that: (i) severe renal impairment (serum creatinine >265 micromol/L [approximately 3 mg/dL]) could cause a clearance decrease of > or =30%; (ii) older age, lower bodyweight and being female were determinants of lower clearance but their effects on olmesartan clearance were within 20%; (iii) no statistically significant

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

PubMed

Blin, O; Jacquet, A; Callamand, S; Jouve, E; Habib, M; Gayraud, D; Durand, A; Bruguerolle, B; Pisano, P

1999-10-01

To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

The effects of moclobemide on autonomic and cognitive functions in healthy volunteers.

PubMed

Siepmann, M; Handel, J; Mueck-Weymann, M; Kirch, W

2004-03-01

Moclobemide, a reversible and selective inhibitor of the MAO-A isoenzyme, is marketed as an antidepressant that lacks autonomic and cognitive side effects. However, only few and inconclusive quantitative data on the effects of moclobemide on autonomic and cognitive functions have been reported in the literature. Therefore, a double-blind, randomized, placebo-controlled crossover trial was performed. Twelve healthy male volunteers (age 22-29 years) received orally 150 mg moclobemide b.i.d. and placebo for 14 days each. Heart rate variability (HRV) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed before the start of drug administration and repeatedly on the last treatment day. Parameters of HRV and SCR were not changed by multiple dosing with moclobemide (P > 0.05). Neither cognitive functions such as flicker fusion frequency, memory, choice reaction time, and psychomotor performance nor qEEG was significantly influenced, but subjective tiredness was decreased at all time points of measurement after multiple dosing with moclobemide (P < 0.05). In conclusion, moclobemide does not appear to influence autonomic functions or cognitive functions when given subchronically to healthy humans. In contrast, changes in subjective mood hint at a subtle activating effect.

Mixed effects of OATP1B1, BCRP and NTCP polymorphisms on the population pharmacokinetics of pravastatin in healthy volunteers.

PubMed

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 < 0.01) decrease in the apparent clearance from the central compartment (CL/F), while rs2296651 (NTCP) increased CL/F to a significant degree (p < 0.01). The combination of these three polymorphisms reduced the inter-individual variability of CL/F by 78.8%. 3. There was minimal effect of rs2231137 (BCRP) and rs2231142 (BCRP) on pravastatin pharmacokinetics (0.01 < p < 0.05), whereas rs11045819 (OATP1B1), rs1061018 (BCRP) and rs61745930 (NTCP) genotypes do not appear to be associated with pravastatin pharmacokinetics based on the population model (p > 0.05). 4. The current data suggest that the combination of rs4149056, rs2306283 and rs2296651 polymorphisms is an important determinant of pravastatin pharmacokinetics.

High-resolution 3T Magnetic Resonance Imaging of the Triangular Fibrocartilage Complex in Chinese Wrists: Correlation with Cross-sectional Anatomy

PubMed Central

Zhan, Hui-Li; Li, Wen-Ting; Bai, Rong-Jie; Wang, Nai-Li; Qian, Zhan-Hua; Ye, Wei; Yin, Yu-Ming

2017-01-01

Background: The injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar-sided wrist pain. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) could demonstrate the detailed complex anatomy of TFCC in Chinese. Methods: Fourteen Chinese cadaveric wrists (from four men and three women; age range at death from 30 to 60 years; mean age at 46 years) and forty healthy Chinese wrists (from 20 healthy volunteers, male/female: 10/10; age range from 21 to 53 years with a mean age of 32 years) in Beijing Jishuitan Hospital from March 2014 to March 2016 were included in this study. All cadavers and volunteers had magnetic resonance (MR) examination of the wrist with coronal T1-weighted and proton density-weighted imaging with fat suppression in three planes, respectively. MR arthrography (MRAr) was performed on one of the cadaveric wrists. Subsequently, all 14 cadaveric wrists were sliced into 2 mm thick slab with band saw (six in coronal plane, four in sagittal plane, and four in axial plane). The MRI features of normal TFCC were analyzed in these specimens and forty healthy wrists. Results: Triangular fibrocartilage, the ulnar collateral ligament, and the meniscal homolog could be best observed on images in coronal plane. The palmar and dorsal radioulnar ligaments were best evaluated in transverse plane. The ulnotriquetral and ulnolunate ligaments were best visualized in sagittal plane. The latter two structures and the volar and dorsal capsules were better demonstrated on MRAr. Conclusion: High-resolution 3T MRI is capable to show the detailed complex anatomy of the TFCC and can provide valuable information for the clinical diagnosis in Chinese. PMID:28345546

Cross-cultural comparison of perspectives on healthy eating among Chinese and American undergraduate students.

PubMed

Banna, Jinan C; Gilliland, Betsy; Keefe, Margaret; Zheng, Dongping

2016-09-26

Understanding views about what constitutes a healthy diet in diverse populations may inform design of culturally tailored behavior change interventions. The objective of this study was to describe perspectives on healthy eating among Chinese and American young adults and identify similarities and differences between these groups. Chinese (n = 55) and American (n = 57) undergraduate students in Changsha, Hunan, China and Honolulu, Hawai'i, U.S.A. composed one- to two-paragraph responses to the following prompt: "What does the phrase 'a healthy diet' mean to you?" Researchers used content analysis to identify predominant themes using Dedoose (version 5.2.0, SocioCultural Research Consultants, LLC, Los Angeles, CA, 2015). Three researchers independently coded essays and grouped codes with similar content. The team then identified themes and sorted them in discussion. Two researchers then deductively coded the entire data set using eight codes developed from the initial coding and calculated total code counts for each group of participants. Chinese students mentioned physical outcomes, such as maintaining immunity and digestive health. Timing of eating, with regular meals and greater intake during day than night, was emphasized. American students described balancing among food groups and balancing consumption with exercise, with physical activity considered essential. Students also stated that food components such as sugar, salt and fat should be avoided in large quantities. Similarities included principles such as moderation and fruits and vegetables as nutritious, and differences included foods to be restricted and meal timing. While both groups emphasized specific foods and guiding dietary principles, several distinctions in viewpoints emerged. The diverse views may reflect food-related messages to which participants are exposed both through the media and educational systems in their respective countries. Future studies may further examine themes that may

Influence of sex and CYP2D6 genotype on mirtazapine disposition, evaluated in Spanish healthy volunteers.

PubMed

Borobia, Alberto M; Novalbos, Jesús; Guerra-López, Pedro; López-Rodríguez, Rosario; Tabares, Beatriz; Rodríguez, Vanesa; Abad-Santos, Francisco; Carcas, Antonio J

2009-06-01

To evaluate the influence of sex and CYP2D6 genotype on mirtazapine disposition within two bioequivalence studies in healthy volunteers. Seventy-two healthy volunteers were included in two standard 2 x 2 crossover bioequivalence trials. Subjects received a single 30-mg oral dose of each mirtazapine formulation in each study period. Plasma concentrations were measured from 0 to 96 or 120 h by a HPLC with coupled mass spectrometry validated method. CYP2D6 genotyping was available for 68 subjects that were classified into three phenotypic groups depending on the number of active gene copies: extensive/ultrarapid metabolizers (UM-EM), intermediate (IM) and poor metabolizers (PM). To evaluate the influence of sex and genotype on mirtazapine disposition we performed a linear mixed model for repeated measures. Pharmacokinetic data were log-transformed and AUC and C(max) adjusted to the administered dose/weight. Factors included in the model were centre, formulation, period, sequence, sex and genotype as fixed effects, and subject nested sequence x sex x genotype as random one. A second model was also performed adding the interaction sex x genotype to the previous model. Mirtazapine disposition evaluated as AUC(0-infinity) is influenced by sex (p=0.007) and CYP2D6 phenotype group (p=0.01). Attending to the theoretical figures provided by the model, mean (95% CI) dose/weight adjusted AUC(0-infinity) (ng h/ml)/(mg/kg) is 1516.62 (1411.27-1628.22) in EM/UM, 1613.63 (1482.14-1758.55) in IM and 2049.28 (1779.78-2357.24) in PM. In the case of C(max) these figures also show a trend to higher values in PM, but it did not reach statistical significance. Females show a lower dose/weight adjusted AUC(0-infinity): 1594.39 (1477.70-1720.28) vs. 1837.65 (1694.67-1992.70). On the contrary dose/weight adjusted C(max) is higher in females than in males: 38.33 (34.79-42.28) vs. 32.66 (29.44-36.21). Both CYP2D6 genotype group and sex influence the disposition of mirtazapine in healthy

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

PubMed Central

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 < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP –0.15 mmHg, SBP +1.44 mmHg, DBP −–0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). Conclusions I.v. 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

The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers

PubMed Central

Wilner, Keith; Laboy, Lucia; LeBel, Marc

2002-01-01

Aims To examine the effect of concomitant cimetidine or antacid administration on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers in two open-label, randomized studies. Methods The first study was a parallel-group design in which 22 healthy male volunteers received sildenafil (50 mg) on days 1 and 5 and cimetidine (800 mg) or placebo on days 3, 4, 5, and 6. Blood samples were collected predose and at specified times up to 48 h postdose on days 1 and 5 to determine plasma levels of sildenafil and its metabolite, UK-103,320. The second study was a two-way crossover design in which 12 volunteers received sildenafil with or without a 30-ml dose of a magnesium hydroxide/aluminium hydroxide antacid. Blood samples were collected and analysed as in the first study. The two study periods were separated by at least 14 days. Results Coadministration of cimetidine had no statistically significant effect on the tmax or kel of sildenafil but caused a statistically significant increase in sildenafil AUCt and Cmax of 56% and 54%, respectively (P<0.01). Differences between the two treatment groups were smaller for the metabolite than for sildenafil, although cimetidine treatment did significantly (P<0.05) increase the AUCt for UK-103,320 by 30%. Antacid coadministration had no statistically significant effect on any pharmacokinetic parameter of sildenafil or UK-103,320. Whether taken alone, with cimetidine, or with an antacid, sildenafil was well tolerated. Most adverse events were mild in nature, and no subject withdrew from either study for any reason related to the drug. Conclusions Cimetidine co-administration produced an increase in sildenafil plasma levels; however, this increase is not sufficient to warrant dosage adjustment of either drug. Antacid coadministration had no effect on the pharmacokinetic profile of sildenafil. PMID:11879257

Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers.

PubMed

Bahra, M; Kapil, V; Pearl, V; Ghosh, S; Ahluwalia, A

2012-05-15

Ingestion of inorganic nitrate elevates blood and tissue levels of nitrite via bioconversion in the entero-salivary circulation. Nitrite is converted to NO in the circulation, and it is this phenomenon that is thought to underlie the beneficial effects of inorganic nitrate in humans. Our previous studies have demonstrated that oral ingestion of inorganic nitrate decreases blood pressure and inhibits the transient endothelial dysfunction caused by ischaemia-reperfusion injury in healthy volunteers. However, whether inorganic nitrate might improve endothelial function per se in the absence of a pathogenic stimulus and whether this might contribute to the blood pressure lowering effects is yet unknown. We conducted a randomised, double-blind, crossover study in 14 healthy volunteers to determine the effects of oral inorganic nitrate (8 mmol KNO(3)) vs. placebo (8 mmol KCl) on endothelial function, measured by flow-mediated dilatation (FMD) of the brachial artery, prior to and 3h following capsule ingestion. In addition, blood pressure (BP) was measured and aortic pulse wave velocity (aPWV) determined. Finally, blood, saliva and urine samples were collected for chemiluminescence analysis of [nitrite] and [nitrate] prior to and 3h following interventions. Inorganic nitrate supplementation had no effect on endothelial function in healthy volunteers (6.9±1.1% pre- to 7.1±1.1% post-KNO(3)). Despite this, there was a significant elevation of plasma [nitrite] (0.4±0.1 μM pre- to 0.7±0.2 μM post-KNO(3), p<0.001). In addition these changes in [nitrite] were associated with a decrease in systolic BP (116.9±3.8mm Hg pre- vs. 112.1±3.4 mm Hg post-KNO(3), p<0.05) and aPWV (6.5±0.1 m/s pre- to 6.2±0.1 post-KNO(3), p<0.01). In contrast KCl capsules had no effect on any of the parameters measured. These findings demonstrate that although inorganic nitrate ingestion does not alter endothelial function per se, it does appear to improve blood flow, in combination with a

Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers

PubMed Central

Bahra, M.; Kapil, V.; Pearl, V.; Ghosh, S.; Ahluwalia, A.

2012-01-01

Ingestion of inorganic nitrate elevates blood and tissue levels of nitrite via bioconversion in the entero-salivary circulation. Nitrite is converted to NO in the circulation, and it is this phenomenon that is thought to underlie the beneficial effects of inorganic nitrate in humans. Our previous studies have demonstrated that oral ingestion of inorganic nitrate decreases blood pressure and inhibits the transient endothelial dysfunction caused by ischaemia–reperfusion injury in healthy volunteers. However, whether inorganic nitrate might improve endothelial function per se in the absence of a pathogenic stimulus and whether this might contribute to the blood pressure lowering effects is yet unknown. We conducted a randomised, double-blind, crossover study in 14 healthy volunteers to determine the effects of oral inorganic nitrate (8 mmol KNO3) vs. placebo (8 mmol KCl) on endothelial function, measured by flow-mediated dilatation (FMD) of the brachial artery, prior to and 3 h following capsule ingestion. In addition, blood pressure (BP) was measured and aortic pulse wave velocity (aPWV) determined. Finally, blood, saliva and urine samples were collected for chemiluminescence analysis of [nitrite] and [nitrate] prior to and 3 h following interventions. Inorganic nitrate supplementation had no effect on endothelial function in healthy volunteers (6.9 ± 1.1% pre- to 7.1 ± 1.1% post-KNO3). Despite this, there was a significant elevation of plasma [nitrite] (0.4 ± 0.1 μM pre- to 0.7 ± 0.2 μM post-KNO3, p < 0.001). In addition these changes in [nitrite] were associated with a decrease in systolic BP (116.9 ± 3.8 mm Hg pre- vs. 112.1 ± 3.4 mm Hg post-KNO3, p < 0.05) and aPWV (6.5 ± 0.1 m/s pre- to 6.2 ± 0.1 post-KNO3, p < 0.01). In contrast KCl capsules had no effect on any of the parameters measured. These findings demonstrate that although inorganic nitrate ingestion does not alter endothelial function per se, it does appear to

Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men.

PubMed

Yang, Shu-Yu; Li, Xue-Jun; Zhang, Wei; Liu, Chang-Qin; Zhang, Hui-Jie; Lin, Jin-Rong; Yan, Bing; Yu, Ya-Xin; Shi, Xiu-Lin; Li, Can-Dong; Li, Wei-Hua

2012-06-01

To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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. 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. 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 r (2)≥0.700 for five of six biomarkers when evaluating biomarker concentration, but for only two biomarkers when evaluating concentration normalized to creatinine. Confidence intervals as well as intersubject and intrasubject

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine in healthy volunteers.

PubMed

Yassen, Ashraf; Olofsen, Erik; Romberg, Raymonda; Sarton, Elise; Danhof, Meindert; Dahan, Albert

2006-06-01

The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers. Data on the time course of the antinociceptive effect after intravenous administration of 0.05-0.6 mg/70 kg buprenorphine in healthy volunteers was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis. A three-compartment pharmacokinetic model best described the concentration time course. Four structurally different pharmacokinetic-pharmacodynamic models were evaluated for their appropriateness to describe the time course of buprenorphine's antinociceptive effect: (1) E(max) model with an effect compartment model, (2) "power" model with an effect compartment model, (3) receptor association-dissociation model with a linear transduction function, and (4) combined biophase equilibration/receptor association-dissociation model with a linear transduction function. The latter pharmacokinetic-pharmacodynamic model described the time course of effect best and was used to explain time dependencies in buprenorphine's pharmacodynamics. The model converged, yielding precise estimation of the parameters characterizing hysteresis and the relation between relative receptor occupancy and antinociceptive effect. The rate constant describing biophase equilibration (k(eo)) was 0.00447 min(-1) (95% confidence interval, 0.00299-0.00595 min(-1)). The receptor dissociation rate constant (k(off)) was 0.0785 min(-1) (95% confidence interval, 0.0352-0.122 min(-1)), and k(on) was 0.0631 ml . ng(-1) . min(-1) (95% confidence interval, 0.0390-0.0872 ml . ng(-1) . min(-1)). This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect

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

PubMed

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

2001-01-01

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. Sixteen healthy volunteers were examined at 1.5 T two times to obtain a repeated measurement in the same slice and a third time in three parallel slices. Single slice, two point Dixon SE (TR/TE 2,500/22.3) sequences were used, from which fat-fraction images were calculated. The fat-fraction results are presented as averages over regions of interest, which were derived from the contours of the vertebrae. Reproducibility measures related to repeated measurements on different days, slice position, and contour drawing were calculated. The mean fat fraction was 0.37 (SD 0.08). The SD due to repeated measurement was small (sigmaR = 0.013-0.032), almost all of which can be explained by slice-(re)-positioning errors. When used to evaluate the same person longitudinally in time, Dixon QCSI fat-fraction measurement has an excellent reproducibility. It is a powerful noninvasive tool in the evaluation of bone marrow composition.

Longitudinal changes in ventral and dorsal neck muscle layers during loading against gravity in healthy volunteers using speckle tracking.

PubMed

Peolsson, Anneli; Peolsson, Michael

2014-05-01

This study aimed to describe and compare the longitudinal mechanical activity, deformation, and deformation rate of the different layers of dorsal and ventral neck muscles in healthy volunteers during head lifts against gravity. The cross-sectional study included 19 healthy volunteers (mean age, 28 years; SD, 7 years). Ultrasound with speckle-tracking analysis was used to investigate longitudinal mechanical activation, deformation, and deformation rate of dorsal and ventral neck muscles in real time during a head lift. Significance levels were set as P = .025 or P = .0125, depending on the number of comparisons. The dorsal neck muscles did not significantly differ in deformation (P > .04); however, the multifidus had a higher deformation rate than all other dorsal muscles (P < .003). The sternocleidomastoid had significantly higher deformation than the longus capitis (P = .005) and colli (P = .001) but a lower deformation rate than the longus colli (P = .02). The sternocleidomastoid deformed more than the deeper muscles, but it did significantly slower than the longus colli. Among the dorsal muscles, the deepest (the multifidus) had the highest deformation rate. Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Engaging Stakeholders From Volunteer-Led Out-of-School Time Programs in the Dissemination of Guiding Principles for Healthy Snacking and Physical Activity.

PubMed

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

2015-12-24

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 to understand how successful implementation and dissemination of these principles could be accomplished. HKOS partnered with volunteer-led programs from 5 OST organizations in Maine, Massachusetts, and New Hampshire to create a regional "learning laboratory." We engaged partners in phases. In the first phase, we conducted focus groups with local volunteer program leaders; during the second phase, we held roundtable meetings with regional and state program administrators; and in the final phase, we conducted additional outreach to refine and finalize implementation strategies. Implementation strategies were developed based on themes and information that emerged. For enrichment programs, strategies included new patch and pin programs that were consistent with the organizations' infrastructure and usual practices. For sports programs, the main strategy was integration with online trainings for coaches. Through the engagement process, we learned that dissemination of the guiding principles in these large and complex OST organizations was best accomplished by using implementation strategies that were customized, integrated, and aligned with goals and usual practices. The lessons learned can benefit future efforts to prevent obesity in complex environments.

Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds.

PubMed Central

Reed, T. E.; Kalant, H.; Gibbins, R. J.; Kapur, B. M.; Rankin, J. G.

1976-01-01

Ethanol (0.4 to 0.8 g/kg in 30 minutes) was given by mouth to 102 healthy young volunteers (37 Caucasian men, 21 Caucasian women, 20 Chinese men and 24 Ojibwa men). Venous blood concentrations of ethanol and acetaldehyde 60, 90, 120 and 150 minutes after the end of drinking were measured by gas chromatography. The calculated rates of ethanol metabolism in the Caucasian men and women did not differ, but the overall group means for subgroups of Caucasians (103.6 mg/kg-h), Chinese (136.6 mg/kg-h) and Ojibwa (182.7 mg/kg-h) with decreasing postabsorption values differed significantly from each other. Mean acetaldehyde values paralleled the rates of ethanol metabolism: Ojibwa, 14.6 mug/ml; Chinese, 10.0 mug/ml; and Caucasians, 9.4 mug/ml. The high rate of ethanol metabolism in Amerind subjects differs from previous findings. Habitual level of alcohol consumption, proportion of body fat and genetic factors appear to account for most of the group differences. PMID:991030

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

NASA Astrophysics Data System (ADS)

Getty, Morgan

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

Independent effects of age and levodopa on reversal learning in healthy volunteers.

PubMed

Vo, Andrew; Seergobin, Ken N; MacDonald, Penny A

2018-05-18

The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson's disease. It posits that effects of dopaminergic therapy on cognition in Parkinson's disease depend on baseline dopamine levels in brain regions that support different functions. Although functions performed by more severely dopamine-depleted brain regions improve with medication, those associated with less dopamine deficient areas are actually worsened. It is presumed that medication-related worsening of cognition owes to dopamine overdose. We investigated whether age-related changes in baseline dopamine levels would modulate effects of dopaminergic therapy on reward learning in healthy volunteers. In a double-blind, crossover design, healthy younger and older adults completed a probabilistic reversal learning task after treatment with 100/25 mg of levodopa/carbidopa versus placebo. Older adults learned more poorly than younger adults at baseline, being more likely to shift responses after misleading punishment. Levodopa worsened stimulus-reward learning relative to placebo to the same extent in both groups, irrespective of differences in baseline performance and expected dopamine levels. When order effects were eliminated, levodopa induced response shifts after reward more often than placebo. Our results reveal independent deleterious effects of age group and exogenous dopamine on reward learning, suggesting a more complex scenario than predicted by the dopamine overdose hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnostic performance of the (1-3)-β-D-glucan assay in patients with Pneumocystis jirovecii compared with those with candidiasis, aspergillosis, mucormycosis, and tuberculosis, and healthy volunteers.

PubMed

Son, Hyo-Ju; Sung, Heungsup; Park, Se Yoon; Kim, Taeeun; Lee, Hyun Jeong; Kim, Sun-Mi; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2017-01-01

Diagnosis of pneumocystis pneumonia (PCP) relies on microscopic visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory specimens, which involves invasive procedures such as bronchoalveolar lavage. The (1-3)-β-D-glucan (BG) assay has been proposed as a less invasive and less expensive diagnostic test to rule out PCP. We therefore compared blood levels of BG in patients with PCP with those of patients with candidemia, chronic disseminated candidiasis (CDC), invasive aspergillosis, mucormycosis, and tuberculosis and those of healthy volunteers. Adult patients who were diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and tuberculosis whose blood samples were available, and healthy volunteers were enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period. The blood samples were assayed with the Goldstream Fungus (1-3)-β-D-glucan test (Gold Mountain River Tech Development, Beijing, China). A total of 136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15 invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy volunteers) were included. The mean±SD of the concentration of 1-3-β-D-glucan in the patients with PCP (290.08 pg/mL±199.98) were similar to those of patients with candidemia (314.14 pg/mL±205.60, p = 0.90 at an α = 0.005) and CDC (129.74 pg/mL±182.79, p = 0.03 at an α = 0.005), but higher than those of patients with invasive aspergillosis (131.62 pg/mL±161.67, p = 0.002 at an α = 0.005), mucormycosis (95.08 pg/mL±146.80, p<0.001 at an α = 0.005), and tuberculosis (103.31 pg/mL±140.81, p<0.001 at an α = 0.005) as well as healthy volunteers (101.18 pg/mL±197.52, p<0.001 at an α = 0.005). At a cut-off value > 31.25 pg/mL, which is highly sensitive for PCP versus tuberculosis plus healthy volunteers at the expense of specificity, the BG assay had a sensitivity of 92% (95% CI 81%-98%) and a specificity of 55% (95% CI 39%-71%). The BG assay

Evaluation of the Validity and Reliability of the Chinese Healthy Eating Index.

PubMed

Yuan, Ya-Qun; Li, Fan; Wu, Han; Wang, Ying-Chuan; Chen, Jing-Si; He, Geng-Sheng; Li, Shu-Guang; Chen, Bo

2018-01-24

The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective of the study was to evaluate the validity and reliability of the CHEI. Data from 12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3-day-24-h dietary recalls were used in this study. The CHEI was assessed by four exemplary menus developed by the DGC-2016, the general linear models, the independent t -test and the Mann-Whitney U -test, the Spearman's correlation analysis, the principal components analysis (PCA), the Cronbach's coefficient, and the Pearson correlation with nutrient intakes. A higher CHEI score was linked with lower exposure to known risk factors of Chinese diets. The CHEI scored nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and the healthy elderly (99.1), but not for young children (91.2). The CHEI was able to distinguish the difference in diet quality between smokers and non-smokers ( P < 0.0001), people with higher and lower education levels ( P < 0.0001), and people living in urban and rural areas ( P < 0.0001). Low correlations with energy intake for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the index assessed diet quality independently of diet quantity. The PCA indicated that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient α was 0.22. Components of dairy, fruits and cooking oils had the greatest impact on the total score. People with a higher CHEI score had not only a higher absolute intake of nutrients ( P < 0.001), but also a more nutrient-dense diet ( P < 0.001). Our findings support the validity and reliability of the CHEI when using the 3-day-24-h recalls.

Effects of Alcohol on the Pharmacokinetics of Blonanserin and N-Deethylated Blonanserin in Healthy Chinese Subjects.

PubMed

Deng, Shuhua; Ni, Xiaojia; Shang, Dewei; Wang, Zhanzhang; Zhang, Ming; Hu, Jinqing; Zhu, Xiuqing; Lu, Haoyang; Chen, Yuqing; Zhang, Yuefeng; Peng, Huan; Wen, Yuguan

2018-04-01

Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions. The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg). The average values of areas under the curve (AUCs) and mean peak plasma concentrations (Cmax) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0-24h, AUC0-∞, and Cmax were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0-∞ and Cmax were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach Cmax (Tmax) and half life time (t1/2) (P < 0.05). Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.

Cognitive effects of methylphenidate and levodopa in healthy volunteers.

PubMed

Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

2014-02-01

Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40 mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30 min delay, but it improved 24 h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory. © 2013 Published by Elsevier B.V. and ECNP.

[Functional and metabolic changes of healthy volunteers after cold exposure and administration of meteoadaptogen trekrezan].

PubMed

Zarubina, I V; Ganapol'skiĭ, V P; Shabanov, P D

2008-01-01

The effect of cold exposure (-10 degrees C, air speed--2.5 m/sec, 40 minutes) on physical activity, cognitive processes and metabolic status of 75 volunteers, healthy men of 20-24, was studied in termobarocomplex Tabaj (Japan). Cold exposure reduced physical and cognitive activity, the activity of kreatine phosphokinase, superoxide dismutase, the levels of redox glutation and pyruvate. Preliminary administration of adaptogenic drug trekrezan 0.2 g prior to cold exposure normalized the indexes studied of physical activity and metabolic status. It is suggested that trekrezan can be used as a meteoadaptogenic drug for rapid and effective adaptation to cold exposure of environment.

Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers.

PubMed

Murphy, Susannah E; Yiend, Jenny; Lester, Kathryn J; Cowen, Philip J; Harmer, Catherine J

2009-03-01

Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this study was to assess the effect of an SSRI on the processing of threat in healthy volunteers. A selective noradrenergic reuptake inhibitor (SNRI), which is not generally used in the treatment of anxiety, was used as a contrast to assess the specificity of SSRI effects on threat processing. Forty-two healthy volunteers were randomly assigned to 7 d double-blind intervention with the SSRI citalopram (20 mg/d), the SNRI reboxetine (8 mg/d), or placebo. On the final day, attentional and interpretative bias to threat was assessed using the attentional probe and the homograph primed lexical decision tasks. Citalopram reduced attentional vigilance towards fearful faces but did not affect the interpretation of ambiguous homographs as threatening. Reboxetine had no significant effect on either of these measures. Citalopram reduces attentional orienting to threatening stimuli, which is potentially relevant to its clinical use in the treatment of anxiety disorders. This finding supports a growing literature suggesting that an important mechanism through which pharmacological agents may exert their effects on mood is by reversing the cognitive biases that characterize the disorders that they treat. Future studies are needed to clarify the neural mechanisms through which these effects on threat processing are mediated.

[Event-related potentials in Chinese characters semantic priming and arithmetic tasks: comparative study between healthy children and children with cognitive disorder].

PubMed

Dong, Xuan; Wang, Su-hong; Yang, Yi-lin; Ren, Yan-ling; Meng, Ping; Yang, Yu-xia

2007-10-30

To explore the cognitive psychological process of healthy children and children with cognitive disorder. Single Chinese character semantic priming and arithmetic tasks were delivered to 20 8-year-old healthy children, and 20 11-year-old healthy children, and 30 children with attention deficit hyperactivity disorder, 23 children with epilepsy, and 22 age-matched normal children as controls. Electroencephalography was used. Event-related potential was distilled by BESA software. (1) During the Chinese character semantic priming, the amplitudes of N2 toward the non-related words and pseudo-words in the 8-year-old group were 12.1 microV and 11.7 microV respectively, both significantly larger than those of the 11-year-old group (3.7 microV and 4.8 microV, respectively, both P<0.05). The amplitudes of N2 and P2 toward the non-related words and pseudo-words among the children with attention deficit hyperactivity disorder were both significantly lower than those in the healthy children (both P<0.05). (2) During the arithmetic task, the latency values of P2 and P3 of addition, subtraction, and multiplication in the 8-year-old group of healthy children were all significantly longer than those of the 11-year-old group of healthy children (all P<0.05). The P3 latency of the children with epilepsy was significantly longer than that of the healthy children (P<0.05). Chinese character and arithmetic cognitive waves are steady. ERP can be used to estimate the healthy children's personality index. Quantitative indicators are helpful in diagnosis and treatment of cognitive and learning disorders.

Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.

PubMed

Harmer, Catherine J; Shelley, Nicholas C; Cowen, Philip J; Goodwin, Guy M

2004-07-01

Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material. Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. They also suggest a mechanism of

Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-week, randomized, double-masked, parallel-group study.

PubMed

Bartlett, Jimmy D; Holland, Edward J; Usner, Dale W; Paterno, Michael R; Comstock, Timothy L

2008-08-01

To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex) in healthy volunteers. In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n = 306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm. ClinicalTrials. gov, NCT 00532961. The 97.5% confidence intervals for the lower bound were within -10 for all of the seven comfort/ tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p < 0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p < or = 0.04); for pain, stinging/burning, and foreignbody sensation at visit 5 (p < or = 0.03), and for dryness and light sensitivity at visit 6 (p < or = 0.05). LE/T satisfied all conditions of noninferiority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T. The study population consisted of healthy volunteers.

Effects of high-tone external muscle stimulation on renal function in healthy volunteers.

PubMed

Peckova, Miroslava; Havlin, Jan; Charvat, Jiri; Horackova, Miroslava; Schück, Otto

2013-01-01

Hightone external muscle stimulation (HTEMS) ameliorates pain and discomfort of patients with polyneuropathy. Since some patients reported about an urge to urinate during these treatments, the potential effects of HTEMS application on renal function were investigated. For this purpose in healthy subjects, we analyzed in the current study the acute effects of electrotherapy on parameters of renal function. 24 healthy volunteers (14 women and 10 men), mean age 26 ± 4 years, were enrolled. The protocol was composed of a run-in period, a pre-treatment period, the active HTEMS treatment period of both lower extremities and the post-treatment period. The duration of each period was 60 min. Urine collection and blood samples were taken at the beginning and end of each period. To achieve a sufficient diuresis, the fluid intake was adapted to the amount of diuresis. Parameters of renal function included diuresis, glomerular filtration rate (endogenous creatinine clearance) and absolute and fractional sodium excretion. Moreover blood pressure and heart rate were monitored. HTEMS led to a significant increase of creatinine clearance and fractional sodium excretion which was limited to the active treatment period. These findings show for the first time that HTEMS can transiently increase glomerular filtration rate associated with a decreased tubular sodium reabsorption. The underlying mechanisms are to be elucidated.

Function in patients with cervical radiculopathy or chronic whiplash-associated disorders compared with healthy volunteers.

PubMed

Peolsson, Anneli; Ludvigsson, Maria Landén; Wibault, Johanna; Dedering, Åsa; Peterson, Gunnel

2014-05-01

The purposes of this study were to examine whether any differences in function and health exist between patients with cervical radiculopathy (CR) due to disk disease scheduled for surgery and patients with chronic whiplash-associated disorders (WADs) and to compare measures of patients' physical function with those obtained from healthy volunteers. This is a cross-sectional study of patients with CR (n = 198) and patients with chronic WAD (n = 215). Patient data were compared with raw data previously obtained from healthy people. Physical measures included cervical active range of motion, neck muscle endurance, and hand grip strength. Self-rated measures included pain intensity (visual analog scale), neck disability (Neck Disability Index), self-efficacy (Self-Efficacy Scale), and health-related quality of life (EuroQol 5-dimensional self-classifier). Patient groups exhibited significantly lower performance than the healthy group in all physical measures (P < .0005) except for neck muscle endurance in flexion for women (P > .09). There was a general trend toward worse results in the CR group than the WAD group, with significant differences in neck active range of motion, left hand strength for women, pain intensity, Neck Disability Index, EuroQol 5-dimensional self-classifier, and Self-Efficacy Scale (P < .0001). Patients had worse values than healthy individuals in almost all physical measures. There was a trend toward worse results for CR than WAD patients. Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

PubMed

Ashraf, Muhammad; Abid, Farah; Riffat, Sualeha; Bashir, Sajid; Iqbal, Javed; Sarfraz, Muhammad; Afzal, Attia; Zaheer, Muhammad

2015-01-01

The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study.

PubMed

Yan, Cunling; Hu, Jian; Yang, Jia; Chen, Zhaoyun; Li, Huijun; Wei, Lianhua; Zhang, Wei; Xing, Hao; Sang, Guoyao; Wang, Xiaoqin; Han, Ruilin; Liu, Ping; Li, Zhihui; Li, Zhiyan; Huang, Ying; Jiang, Li; Li, Shunjun; Dai, Shuyang; Wang, Nianyue; Yang, Yongfeng; Ma, Li; Soh, Andrew; Beshiri, Agim; Shen, Feng; Yang, Tian; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-04-01

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects. This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method. The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P < 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females. The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers.

PubMed

Sundby, Øyvind H; Høiseth, Lars Øivind; Mathiesen, Iacob; Jørgensen, Jørgen J; Weedon-Fekjær, Harald; Hisdal, Jonny

2016-09-01

Intermittent negative pressure (INP) applied to the lower leg and foot may increase peripheral circulation. However, it is not clear how different patterns of INP affect macro- and microcirculation in the foot. The aim of this study was therefore to determine the effect of different patterns of negative pressure on foot perfusion in healthy volunteers. We hypothesized that short periods with INP would elicit an increase in foot perfusion compared to no negative pressure. In 23 healthy volunteers, we continuously recorded blood flow velocity in a distal foot artery, skin blood flow, heart rate, and blood pressure during application of different patterns of negative pressure (-40 mmHg) to the lower leg. Each participant had their right leg inside an airtight chamber connected to an INP generator. After a baseline period at atmospheric pressure, we applied four different 120 sec sequences with either constant negative pressure or different INP patterns, in a randomized order. The results showed corresponding fluctuations in blood flow velocity and skin blood flow throughout the INP sequences. Blood flow velocity reached a maximum at 4 sec after the onset of negative pressure (average 44% increase above baseline, P < 0.001). Skin blood flow and skin temperature increased during all INP sequences (P < 0.001). During constant negative pressure, average blood flow velocity, skin blood flow, and skin temperature decreased (P < 0.001). In conclusion, we observed increased foot perfusion in healthy volunteers after the application of INP on the lower limb. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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

PubMed Central

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

1994-01-01

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

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

PubMed

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.

Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

PubMed

van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

2018-05-26

The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

Validation of the ERS standard citric acid cough challenge in healthy adult volunteers

PubMed Central

2010-01-01

Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive agent, single and dose response. A definitive method for measuring cough sensitivity needs to be established. The ERS guidelines recommend the KoKo DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of this citric acid (CA) cough challenge and previously established Mefar dosimeter (MD) protocol. 39 (female 26) volunteers mean age (40.4 yrs) were randomised to either KD or MD. Intra-day and inter-day reproducibility was compared. We calculated the concentration of citric acid evoking 2 coughs (C2). The geometric mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209 (151,288) mM respectively. The mean KD C2 was not significantly different. (F = 0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated significant variability (F = 7.85, P < 0.001) Measuring mean log C2 at baseline and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2 at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC = 0.41 Administering CA from KD offers a reproducible cough challenge in healthy volunteers. The results correlate well with the MD challenge but offer greater intra-day and inter-day reproducibility. Trial Registration Current controlled trials ISRCTN98385033 PMID:20698995

Dose-dependent effects of fish oil on cardio-metabolic biomarkers in healthy middle-aged and elderly Chinese people: a double-blind randomized controlled trial.

PubMed

Song, Jia; Hu, Manjiang; Li, Cheng; Yang, Bo; Ding, Qing; Wang, Chunhong; Mao, Limei

2018-06-20

n-3PUFA consumption has been widely accepted as a nutritional strategy for the secondary prevention of cardiovascular events in patients at high risk of cardiovascular disease (CVD), but little is known about the dose-response relationship between dietary n-3PUFA and serum biomarkers associated with cardiovascular health in the general population. The present study involved a 12-week double-blind, randomized controlled trial to explore the effects of fish oil with different doses (0.31, 0.62 and 1.24 g d-1 of EPA and DHA) on serum fatty acids and cardio-metabolic biomarkers including adiponectin, inflammatory markers, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people. 240 volunteers met our inclusion criteria. A total of 39 subjects dropped out and 201 finally completed the intervention. No significant differences in baseline characteristics and daily intakes of dietary nutrients were detected among all groups. After a 12-week intervention, fish oil dose-dependently enhanced serum EPA, DHA, n-3PUFA and adiponectin (except for 0.31 g d-1), but decreased serum n-6/n-3PUFA, TG and fasting glucose. Changes in the above indicators from the baseline to week 12 in fish oil groups significantly differed from those in the control. Meanwhile, all the doses of EPA and DHA led to decreases in serum CRP; only 1.24 g d-1 led to an increase in HDL-C with a concurrent decrease in TC/HDL-C even though these changes were not significantly different among all groups. All the findings suggested that fish oil dose-dependently regulated serum PUFA and cardio-metabolic biomarkers including adiponectin, CRP, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people who consumed insufficient dietary n-3PUFA, and the most desirable changes were observed for 1.24 g d-1.

Comparative polymorphism of BAT-26 between healthy individuals and cancer patients and its cancer risk implication for local Chinese.

PubMed

Zheng, Yanying; Liu, Li; Sun, Yi; Chen, Jie; Wang, Jianrong; Zhu, Changle; Lai, Rensheng; Xie, Ling

2016-07-30

BAT-26 is one of the representative markers for microsatellite instability evaluation and presents different polymorphisms in different ethnic populations. The current knowledge of its comparative polymorphism between healthy individuals and cancer patients in the Chinese population is insufficient. This study aims to analyze germline polymorphic variations of BAT-26 between healthy individuals and cancer patients in Chinese from Jiangsu province and the associated cancer risk implications. The various BAT-26 alleles and their percentages in cervical cells from 500 healthy women were assessed by direct sequencing. Twenty of these samples were also analyzed by fragment analysis. BAT-26 of blood DNA from 24 healthy individuals and 247 cancer patients was analyzed by fragment analysis. Compared with the sequencing results, 122.6-122.9 bp, 123.4-123.8 bp and 124.1-124.8 bp corresponded to the A25, A26 and A27 alleles, respectively. The 524 healthy individuals showed 4.58%, 92.18% and 3.24% of A25, A26 and A27, respectively. The variant alleles A18, A24, A28, A29 and A32 were only found in cancer patients, accounting for 0.81%, 0.40%, 0.40%, 0.40% and 0.40%, respectively; the A25, A26 and A27 alleles in cancer patients accounted for 6.48%, 77.33% and 13.77%. Healthy individuals had a stable BAT-26 profile within the quasimonomorphic variation range (QMVR), but cancer patients harbored variant alleles outside QMVR and showed a trend from quasimonomorph to polymonomorph, suggesting that variant alleles of BAT-26 in germline cells may be regarded as a potential marker of higher cancer risk in the Chinese population from Jiangsu province.

Healthy subjects volunteering for Phase I studies: influence of curiosity, exploratory tendencies and perceived self-efficacy.

PubMed

Almeida, L; Kashdan, T B; Coelho, R; Albino-Teixeira, A; Soares-da-Silva, P

2008-03-01

To test the hypothesis that trait-curiosity and perceived self-efficacy influence the willingness of healthy subjects to volunteer for participation in Phase I studies. A group of healthy subjects who had never participated in clinical studies ("index group") were invited to participate in a Phase I study. They were assessed with regard to trait curiosity (Curiosity and Exploration Inventory; CEI-T) and perceived self-efficacy (Self-Efficacy Scale; SES) and subjects who accepted the invitation to participate were compared with those who refused and with a group of healthy subjects who had previously participated in clinical studies ("validation group"). A significant positive correlation was found between the willingness to participate and the CEI-T total score (R=0.28; p<0.01), exploratory tendencies (R=0.34; p<0.001), SES total score (R=0.30, p<0.01), initiative and persistence (R=0.29, p<0.01), planning/goal setting (R=0.19, p<0.05) and social self-efficacy (R=0.29; p<0.01). The "index group" subjects who accepted the invitation to participate showed significantly greater CEI-T exploratory tendencies (Z=-3.334, p = 0.001, Mann-Whitney test) and total scores (Z=-2.703, p<0.01) and greater SES total score (Z=-3.131, p<0.01), initiative and persistence (Z=-3.065, p<0.01), planning/goal setting (Z=-2.173, p<0.05) and social self-efficacy (Z=-2.954, p<0.01) than subjects who refused. No differences were found between the subjects in the "index group" who accepted the invitation and subjects in the "validation group". Using a logistic regression model, both CEI-T exploratory tendencies and SES initiative/persistence were significant predictors of participation. Subjects higher in curiosity/exploration and in perceived initiative/persistence are more willing to volunteer for Phase I studies. The impact of these self-selection biases on Phase I study results is unknown but deserves further evaluation.

Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

PubMed

Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

2016-12-29

To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO 4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

PubMed

Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

2014-07-01

This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. © 2013, The American College of Clinical Pharmacology.

[Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

PubMed

Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

2009-06-01

To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

The ADRA2B gene in the production of false memories for affective information in healthy female volunteers.

PubMed

Fairfield, Beth; Mammarella, Nicola; Di Domenico, Alberto; D'Aurora, Marco; Stuppia, Liborio; Gatta, Valentina

2017-08-30

False memories are common memory distortions in everyday life and seem to increase with affectively connoted complex information. In line with recent studies showing a significant interaction between the noradrenergic system and emotional memory, we investigated whether healthy volunteer carriers of the deletion variant of the ADRA2B gene that codes for the α2b-adrenergic receptor are more prone to false memories than non-carriers. In this study, we collected genotype data from 212 healthy female volunteers; 91 ADRA2B carriers and 121 non-carriers. To assess gene effects on false memories for affective information, factorial mixed model analysis of variances (ANOVAs) were conducted with genotype as the between-subjects factor and type of memory error as the within-subjects factor. We found that although carriers and non-carriers made comparable numbers of false memory errors, they showed differences in the direction of valence biases, especially for inferential causal errors. Specifically, carriers produced fewer causal false memory errors for scripts with a negative outcome, whereas non-carriers showed a more general emotional effect and made fewer causal errors with both positive and negative outcomes. These findings suggest that putatively higher levels of noradrenaline in deletion carriers may enhance short-term consolidation of negative information and lead to fewer memory distortions when facing negative events. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrated Safety Assessment of 2′-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers

PubMed Central

Crooke, Stanley T; Baker, Brenda F; Kwoh, T Jesse; Cheng, Wei; Schulz, Dan J; Xia, Shuting; Salgado, Nelson; Bui, Huynh-Hoa; Hart, Christopher E; Burel, Sebastien A; Younis, Husam S; Geary, Richard S; Henry, Scott P; Bhanot, Sanjay

2016-01-01

The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2′-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2′-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied. PMID:27357629

Wavelet-based segmentation of renal compartments in DCE-MRI of human kidney: initial results in patients and healthy volunteers.

PubMed

Li, Sheng; Zöllner, Frank G; Merrem, Andreas D; Peng, Yinghong; Roervik, Jarle; Lundervold, Arvid; Schad, Lothar R

2012-03-01

Renal diseases can lead to kidney failure that requires life-long dialysis or renal transplantation. Early detection and treatment can prevent progression towards end stage renal disease. MRI has evolved into a standard examination for the assessment of the renal morphology and function. We propose a wavelet-based clustering to group the voxel time courses and thereby, to segment the renal compartments. This approach comprises (1) a nonparametric, discrete wavelet transform of the voxel time course, (2) thresholding of the wavelet coefficients using Stein's Unbiased Risk estimator, and (3) k-means clustering of the wavelet coefficients to segment the kidneys. Our method was applied to 3D dynamic contrast enhanced (DCE-) MRI data sets of human kidney in four healthy volunteers and three patients. On average, the renal cortex in the healthy volunteers could be segmented at 88%, the medulla at 91%, and the pelvis at 98% accuracy. In the patient data, with aberrant voxel time courses, the segmentation was also feasible with good results for the kidney compartments. In conclusion wavelet based clustering of DCE-MRI of kidney is feasible and a valuable tool towards automated perfusion and glomerular filtration rate quantification. Copyright © 2011 Elsevier Ltd. All rights reserved.

NK1 receptor antagonism and emotional processing in healthy volunteers.

PubMed

Chandra, P; Hafizi, S; Massey-Chase, R M; Goodwin, G M; Cowen, P J; Harmer, C J

2010-04-01

The neurokinin-1 (NK(1)) receptor antagonist, aprepitant, showed activity in several animal models of depression; however, its efficacy in clinical trials was disappointing. There is little knowledge of the role of NK(1) receptors in human emotional behaviour to help explain this discrepancy. The aim of the current study was to assess the effects of a single oral dose of aprepitant (125 mg) on models of emotional processing sensitive to conventional antidepressant drug administration in 38 healthy volunteers, randomly allocated to receive aprepitant or placebo in a between groups double blind design. Performance on measures of facial expression recognition, emotional categorisation, memory and attentional visual-probe were assessed following the drug absorption. Relative to placebo, aprepitant improved recognition of happy facial expressions and increased vigilance to emotional information in the unmasked condition of the visual probe task. In contrast, aprepitant impaired emotional memory and slowed responses in the facial expression recognition task suggesting possible deleterious effects on cognition. These results suggest that while antagonism of NK(1) receptors does affect emotional processing in humans, its effects are more restricted and less consistent across tasks than those of conventional antidepressants. Human models of emotional processing may provide a useful means of assessing the likely therapeutic potential of new treatments for depression.

Interaction between the LMWH reviparin and aspirin in healthy volunteers

PubMed Central

Klinkhardt, Ute; Breddin, Hans Klaus; Esslinger, Heinz Ulrich; Haas, Silvia; Kalatzis, Andreas; Harder, Sebastian

2000-01-01

Aims To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1–5). Methods In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 µg ml−1) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT). Results Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of Amax; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modified if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xa-activity and heptest compared with reviparin alone. Conclusions We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical significance. PMID:10759689

The effect of Na+/taurocholate cotransporting polypeptide (NTCP) c.800C > T polymorphism on rosuvastatin pharmacokinetics in Chinese healthy males.

PubMed

Lou, Xiao-Ya; Zhang, Wei; Wang, Guo; Hu, Dong-Li; Guo, Dong; Tan, Zhi-Rong; Zhou, Hong-Hao; Chen, Yao; Bao, Hei-Hua

2014-10-01

This study was designed to investigate the potential association between NTCP c.800C >T polymorphism and rosuvastatin pharmacokinetics in Chinese healthy males. 305 individuals were enrolled to identify NTCP c.800C > T, OATP1B1 c.521T > C and BCRP c.421C > A genotypes by direct sequencing and pyrosequencing methods, respectively. 17 healthy volunteers who were OATP1B1 c.521TT and BCRP c.421CC wild-type homozygotes with different NTCP c.800C > T genotype were selected to participate in this pharmacokinetic study. Nine were NTCP c.800CC wild-type homozygotes and the other eight subjects were carriers with at least one c.800T variant allele (seven subjects with c.800CT genotype and one was homozygote of c.800TT). All the subjects received a single oral dose of 10 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured up to 72 h by a LC-MS method. NTCP c.800C > T genetic polymorphism markedly effected rosuvastatin pharmacokinetics. The AUC(o-72) and AUC(0 --> ∞) in subjects with NTCP c.800CT + TT genotype were 56% (162.64 ± 37.55 vs. 103.99 ± 28.15 ng x h/ml, P = 0.016) and 57% greater (178.51 ± 42.75 vs. 113.60 ± 33.73 ng x h/ml, P = 0.020) than those in the c.800CC wild-type subjects, respectively. In the c.800CT + TT mutant group, the C(max) was about 78% higher than those in c.800CC genotype (14.31 ± 3.63 vs. 8.04 ± 1.72 ng x h/ml, P = 0.004). The oral clearance (CL/F) of rosuvastatin in subjects with the c.800CT+TT genotype was only 63% of those in the c.800CC genotype (58.32 ± 12.16 vs. 93.04 ± 20.61 ng x h/ml, P = 0.009). The half-time (T1/2) and the T(max) had no significant difference between two groups (p = 0.466 and 0.713, respectively). NTCP c.800C > T polymorphism play a critical role in the individual variability of rosuvastatin pharmacokinetics in Chinese healthy males after excluding the impact of OATP1B1 c.521T > C and BCRP c.421C > A polymorphisms.

The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin.

PubMed

Koning, Catherina J M; Jonkers, Daisy M A E; Stobberingh, Ellen E; Mulder, Linda; Rombouts, Frans M; Stockbrügger, Reinhold W

2008-01-01

One of the side effects of antimicrobial therapy is a disturbance of the intestinal microbiota potentially resulting in antibiotic-associated diarrhea (AAD). In this placebo-controlled double-blind study, the effect of a multispecies probiotic on the composition and metabolic activity of the intestinal microbiota and bowel habits was studied in healthy volunteers taking amoxycillin. Forty-one healthy volunteers were given 500 mg amoxycillin twice daily for 7 days and were randomized to either 5 g of a multispecies probiotic, Ecologic AAD (10(9) cfu/g), or placebo, twice daily for 14 days. Feces and questionnaires were collected on day 0, 7, 14, and 63. Feces was analyzed as to the composition of the intestinal microbiota, and beta-glucosidase activity, endotoxin concentration, Clostridium difficile toxin A, short chain fatty acids (SCFAs), and pH were determined. Bowel movements were scored according to the Bristol stool form scale. Mean number of enterococci increased significantly from log 4.1 at day 0 to log 5.8 (day 7) and log 6.9 (day 14) cfu/g feces (P < 0.05) during probiotic intake. Although no other significant differences were observed between both intervention groups, within each group significant changes were found over time in both microbial composition and metabolic activity. Moreover, bowel movements with a frequency >or=3 per day for at least 2 days and/or a consistency >or=5 for at least 2 days were reported less frequently in the probiotic compared to the placebo group (48%vs 79%, P < 0.05). Apart from an increase in enterococci no significant differences in microbial composition and metabolic activity were observed in the probiotic compared with the placebo group. However, changes over time were present in both groups, which differed significantly between the probiotic and the placebo arm, suggesting that the amoxycillin effect was modulated by probiotic intake. Moreover, the intake of a multispecies probiotic significantly reduced diarrhea

Muscle Activation During Grasping With and Without Motor Imagery in Healthy Volunteers and Patients After Stroke or With Parkinson's Disease

PubMed Central

Kobelt, Manuela; Wirth, Brigitte; Schuster-Amft, Corina

2018-01-01

Introduction: The present study assessed whether motor imagery (MI) produces electromyographic activation in specific muscles of the upper limb during a hand grasping and arm-lifting task in healthy volunteers, patients after stroke, or with Parkinson's disease. Electromyographic (EMG) activation was compared under three conditions: MI, physical execution (PE), and rest. The task is clinically relevant unilateral executed movement using open muscle chains. Methods: In a cross-sectional study EMG activation was measured in four muscles: M. deltoideus pars clavicularis, M. biceps brachii, M. extensor digitorum, M. flexor carpi radialis. MI ability was evaluated with mental rotation, mental chronometry and the Kinaesthetic and Visual Imagery Questionnaire. Cognitive performance was screened with the Mini-Mental State Examination. Results: Twenty-two participants (11 females, age 52.6 ±15.8, age range 21 to 72) were included: ten healthy volunteers, seven patients after stroke (time after stroke onset 16.3 ± 24.8 months), and five patients with Parkinson's disease (disease duration 60.4 ± 24.5 months). Overall Mini-Mental State Examination scores ranged between 27 and 30. An increased EMG activation during MI compared to rest condition was observed in M. deltoideus pars clavicularis and M. biceps brachii across all participants (p-value = 0.001, p = 0.007). Seven participants (two healthy volunteers, three patients after stroke and two patients with Parkinson's disease) showed a EMG activation during MI of the hand grasping and arm-lifting task in at least one of the target muscles. No correlation between EMG activation during MI and scores of three MI ability assessments were found. Conclusions: The findings suggest that MI can yield subliminal EMG activation. However, that might vary on individual basis. It remains unclear what parameters contribute to or inhibit an EMG activation during MI. Future investigations should determine factors that influence EMG

Tibiofemoral and patellofemoral joint 3D-kinematics in patients with posterior cruciate ligament deficiency compared to healthy volunteers.

PubMed

von Eisenhart-Rothe, Ruediger; Lenze, Ulrich; Hinterwimmer, Stefan; Pohlig, Florian; Graichen, Heiko; Stein, Thomas; Welsch, Frederic; Burgkart, Rainer

2012-11-26

The posterior cruciate ligament (PCL) plays an important role in maintaining physiological kinematics and function of the knee joint. To date mainly in-vitro models or combined magnetic resonance and fluoroscopic systems have been used for quantifying the importance of the PCL. We hypothesized, that both tibiofemoral and patellofemoral kinematic patterns are changed in PCL-deficient knees, which is increased by isometric muscle flexion. Therefore the aim of this study was to simultaneously investigate tibiofemoral and patellofemoral 3D kinematics in patients suffering from PCL deficiency during different knee flexion angles and under neuromuscular activation. We enrolled 12 patients with isolated PCL-insufficiency as well as 20 healthy volunteers. Sagittal MR-images of the knee joint were acquired in different positions of the knee joint (0°, 30°, 90° flexion, with and without flexing isometric muscle activity) on a 0.2 Tesla open MR-scanner. After segmentation of the patella, femur and tibia local coordinate systems were established to define the spatial position of these structures in relation to each other. At full extension and 30° flexion no significant difference was observed in PCL-deficient knee joints neither for tibiofemoral nor for patellofemoral kinematics. At 90° flexion the femur of PCL-deficient patients was positioned significantly more anteriorly in relation to the tibia and both, the patellar tilt and the patellar shift to the lateral side, significantly increased compared to healthy knee joints. While no significant effect of isometric flexing muscle activity was observed in healthy individuals, in PCL-deficient knee joints an increased paradoxical anterior translation of the femur was observed at 90° flexion compared to the status of muscle relaxation. Significant changes in tibiofemoral and patellofemoral joint kinematics occur in patients with isolated PCL-insufficiency above 30 degrees of flexion compared to healthy volunteers. Since

Facial nerve stimulation in normal pigs and healthy human volunteers: transitional development of a medical device for the emergency treatment of ischemic stroke.

PubMed

Sanchez, Olivia; García, Andrea; Castro-Prado, Fernando; Perez, Miriam; Lara-Estrada, Rafael; Ramirez-Meza, Martin; Godinez, Montserrat; Coco, Michael L; Azpiroz, Joaquín; Borsody, Mark K; Sacristán, Emilio

2018-02-15

Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients. Initial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer's ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period. In pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5-min duration. No clear dose-response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve

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

PubMed

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

2010-07-01

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

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

PubMed

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 < 0.05) compared to ESL BID (65.5) and 82.1% higher (p < 0.05) compared to OXC BID (48.0). The mean area under the curve (AUC)ss,0-τ (in μmol h/L) following the last dose of an 8-day repeated dosing was 1156.3, 1117.6, and 968.4 for ESL QD, ESL BID, and OXC BID, respectively. The ratio 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.

Time course for measuring endolymphatic size in healthy volunteers following intravenous administration of gadoteridol.

PubMed

Naganawa, Shinji; Suzuki, Kojiro; Yamazaki, Masahiro; Sakurai, Yasuo; Ikeda, Mitsuru

2014-01-01

We developed semi-quantitative methods to measure endolymphatic size on images obtained 4 hours after intravenous administration of single-dose gadolinium-based contrast medium (IV-SD-GBCM) and found little variation in results between observers. We used the methods to measure the size of the endolymph in healthy volunteers at various times after IV-SD-GBCM and attempted to determine the optimal timing for the evaluation. In 8 healthy male volunteers, we obtained heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) images 1.5, 3, 4.5, and 6 hours after IV-SD-GBCM as positive perilymph images (PPI) as well as acquiring positive endolymph images (PEI) and magnetic resonance cisternography (MRC). To evaluate the endolymph, we generated 2 kinds of processed images (HYDROPS-Mi2 and HYDROPS2-Mi2) by subtracting PEI or MRC from PPI as previously proposed. We semi-quantitatively measured the ratio of the area of the endolymph (%EL) to that of total lymph on the 2 kinds of generated images for the cochlea and vestibule according to the previously proposed method. We analyzed statistics to evaluate the change in %EL over time and used analysis of variance (ANOVA) for a 2 × 4 repeated-measures design to assess difference in image type. We adopted 5% as a significance level. The %EL was significantly larger at 1.5 hours after IV-SD-GBCM than at 3, 4.5, and 6 hours in both the cochlea and vestibule for both kinds of generated images. Between 4.5 and 6 hours, the %EL plateaued for both the cochlea and vestibule, and the 2 kinds of generated images did not differ significantly. A delay of 1.5 hours after IV-SD-GBCM is not sufficient to evaluate endolymphatic size. The %EL plateaus between 4.5 and 6 hours. These data might be valuable for further clinical studies.

Being healthy: a grounded theory study of help seeking behaviour among Chinese elders living in the UK.

PubMed

Liu, Zhenmi; Beaver, Kinta; Speed, Shaun

2014-01-01

The health of older people is a priority in many countries as the world's population ages. Attitudes towards help seeking behaviours in older people remain a largely unexplored field of research. This is particularly true for older minority groups where the place that they have migrated to presents both cultural and structural challenges. The UK, like other countries, has an increasingly aging Chinese population about who relatively little is known. This study used a qualitative grounded theory design following the approach of Glaser (1978). Qualitative data were collected using semi-structured interviews with 33 Chinese elders who were aged between 60 and 84, using purposive and theoretical sampling approaches. Data were analysed using the constant comparative method until data saturation occurred and a substantive theory was generated. "Being healthy" (the core category) with four interrelated categories: self-management, normalizing/minimizing, access to health services, and being cured form the theory. The theory was generated around the core explanations provided by participants and Chinese elders' concerns about health issues they face in their daily life. We also present data about how they direct their health-related activities towards meeting their physical and psychological goals of being healthy. Their differential understanding of diseases and a lack of information about health services were potent predictors of non-help seeking and "self" rather than medical management of their illnesses. This study highlights the need for intervention and health support for Chinese elders.

Impact of humic acids on the colonic microbiome in healthy volunteers.

PubMed

Swidsinski, Alexander; Dörffel, Yvonne; Loening-Baucke, Vera; Gille, Christoph; Reißhauer, Anne; Göktas, Onder; Krüger, Monika; Neuhaus, Jürgen; Schrödl, Wieland

2017-02-07

To test the effects of humic acids on innate microbial communities of the colon. We followed the effects of oral supplementation with humic acids (Activomin ® ) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin ® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were used. The sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation ( P < 0.001). The increase in the concentrations in each person was due to growth of preexisting groups. The individual microbial profile of the patients remained unchanged. Similarly, the bacterial diversity remained stable. Concentrations of 24 of the 35 substantial groups increased from 20% to 96%. Two bacterial groups detected with Bac303 ( Bacteroides ) and Myc657 (mycolic acid-containing Actinomycetes ) FISH probes decreased ( P > 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (< 0.1 × 10 9 /mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae , Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not significant. Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome.

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

PubMed

Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

2013-11-01

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Pharmacokinetics and food interaction of a novel prodrug of tenofovir, tenofovir dipivoxil fumarate, in healthy volunteers.

PubMed

Lu, C; Jia, Y; Chen, L; Ding, Y; Yang, J; Chen, M; Song, Y; Sun, X; Wen, A

2013-04-01

Tenofovir dipivoxil fumarate is a novel ester prodrug of tenofovir, a specific anti-hepatitis B virus (HBV) drug candidate. The pharmacokinetic properties and the effects of food intake on tenofovir dipivoxil have not yet been reported in healthy adults. The aim of this study was to evaluate the pharmacokinetic properties and food interaction of tenofovir dipivoxil in healthy Chinese volunteers. Pharmacokinetic studies included an ascending single dose of 150, 300, 600 mg and multiple doses of 300 mg. Food interaction was evaluated following a single oral dose of tenofovir dipivoxil fumarate 300 mg administered with a high-fat and high-energy standard breakfast or after a 12-h fast. Pharmacokinetic parameters of tenofovir given in each treatment period were calculated using non-compartmental analysis. After a single dose of 150, 300 and 600 mg, the main pharmacokinetic parameters for tenofovir were as follows: Cmax 209·6, 456·7, 989·8 ng/mL; AUClast 1744·9, 2663·5, 6010·2 ng h/mL, respectively. After multiple doses of 300 mg, the main pharmacokinetic parameters for tenofovir were Cmax 523·4 ng/mL, AUClast 4152·4 ng h/mL. After a single dose of 300 mg with a high-fat and high-energy standard breakfast, the main pharmacokinetic parameters for tenofovir were Cmax 448·5 ng/mL, AUClast 3286·8 ng h/mL. The plasma Cmax and AUC of tenofovir showed significance difference between a single dose of 300 mg and the accordingly multiple doses (P < 0·05). A standard high-fat meal enhanced mean AUClast values of tenofovir (relative AUClast  = 125·8%; 90% CI 114·5, 136·2); however, food did not show any significant on Cmax (relative Cmax  = 103·4%; 90% CI 94·6, 112·6). Oral tenofovir dipivoxil fumarate produced predictable and dose-proportional plasma tenofovir pharmacokinetics. The accumulation ratio was 1·51, suggesting tenofovir dipivoxil fumarate displayed accumulation after repeated administration. The bioavailability of tenofovir

Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study.

PubMed

Martin, Patrick; Wang, Phillip; Robinson, Antoine; Poole, Lynne; Dragone, Jeffrey; Smyth, Michael; Pratt, Raymond

2011-05-01

Lanthanum carbonate and sevelamer carbonate are noncalcium phosphate binders used to treat hyperphosphatemia in patients with chronic kidney disease. This is the first study to compare phosphate absorption from a standardized meal ingested with a typical clinical dose of these binders. Randomized open-label crossover study. Healthy volunteers were confined to a clinical research center during 4 study periods. Of 31 volunteers randomly assigned, 19 completed all treatments and 18 were analyzed in the pharmacodynamic set (1 was excluded because of vomiting). Participants were assigned in random order to meal alone, meal plus lanthanum carbonate (1 tablet containing 1,000 mg of elemental lanthanum), and meal plus sevelamer carbonate (three 800-mg tablets). The gastrointestinal tract was cleared, the meal was ingested (± treatment), and rectal effluent was collected. In a fourth period, volunteers repeated the study procedures while fasting. The primary end point, net phosphate absorption, was analyzed using a mixed-effect linear model. Phosphorus content of effluent and duplicate meal samples were measured using inductively coupled plasma-optical emission spectroscopy. The standard meal contained ∼375 mg of phosphate, 75% of which was absorbed (net absorption, 281.7 ± 14.1 mg [adjusted mean ± standard error]). Lanthanum carbonate decreased net phosphate absorption by 45% (net absorption, 156.0 ± 14.2 mg) compared with 21% (net absorption, 221.8 ± 14.1 mg) for sevelamer carbonate (P < 0.001). Lanthanum carbonate bound 135.1 ± 12.3 mg of phosphate, whereas sevelamer carbonate bound 63.2 ± 12.3 mg, a 71.9-mg difference (95% CI, 40.0-103.8; P < 0.001). Per tablet, this equates to 135 mg of phosphate bound with lanthanum carbonate versus 21 mg with sevelamer carbonate. A single-dose study. In healthy volunteers, 1,000 mg of lanthanum carbonate decreased phosphate absorption by 45% compared with a 21% decrease with 2,400 mg of sevelamer carbonate. Copyright © 2011

Effects of a short-term intervention with a paleolithic diet in healthy volunteers.

PubMed

Osterdahl, M; Kocturk, T; Koochek, A; Wändell, P E

2008-05-01

Prevention of cardiovascular diseases by paleolithic or hunter-gatherer diets has been discussed during recent years. Our aim was to assess the effect of a paleolithic diet in a pilot study on healthy volunteers during 3 weeks. The intention was to include 20 subjects, of whom 14 fulfilled the study. Complete dietary assessment was available for six subjects. Mean weight decreased by 2.3 kg (P<0.001), body mass index by 0.8 (P<0.001), waist circumference by 0.5 cm (P=0.001), systolic blood pressure by 3 mm Hg (P=0.03) and plasminogen activator inhibitor-1 by 72% (P=0.020). Regarding nutrient intake, intake of energy decreased by 36%, and other effects were also observed, both favourable (fat composition, antioxidants, potassium-sodium rate) and unfavourable (calcium). This short-term intervention showed some favourable effects by the diet, but further studies, including control group, are needed.

Dose-ranging study of the novel recombinant plasminogen activator BM 06.022 in healthy volunteers.

PubMed

Martin, U; von Möllendorff, E; Akpan, W; Kientsch-Engel, R; Kaufmann, B; Neugebauer, G

1991-10-01

The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 and protease domains of human tissue-type plasminogen activator and is unglycosylated because of its expression in Escherichia coli cells. Pharmacokinetics for activity and hemostatic effects of BM 06.022 were studied in 18 healthy male volunteers after an intravenous bolus injection over 2 minutes. BM 06.022 was administered successively at doses of 0.1125, 0.55, 2.2, 3.3, 4.4, and 5.5 MU to three volunteers. Plasma fibrinogen was unchanged; effects of BM 06.022 were observed on plasminogen only at higher doses, and dose-dependent effects were seen on alpha 2-antiplasmin and fibrin D-dimers. The concentration of plasminogen and alpha 2-antiplasmin was 87% +/- 3% and 79% +/- 3%, respectively, of baseline 2 hours after injection of 5.5 MU of BM 06.022. Fibrin D-dimers were highest with 1147 +/- 380 ng/ml at 5.5 MU of BM 06.022. The area under the activity concentration-time curve (AUC) increased dose-dependently and linearly. At 5.5 MU of BM 06.022, the AUC was 313 +/- 47 IU.hr.ml-1, the total plasma clearance was 306 +/- 40 ml/min, and the half-life was 14.4 +/- 1.1 minutes.

Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo.

PubMed

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.

Pain uncertainty in patients with fibromyalgia, yoga practitioners, and healthy volunteers.

PubMed

Bradshaw, David H; Donaldson, Gary W; Okifuji, Akiko

2012-01-01

Uncertainty about potentially painful events affects how pain is experienced. Individuals with fibromyalgia (FM) often exhibit anxiety and catastrophic thoughts regarding pain and difficulties dealing with pain uncertainty. The effects of pain uncertainty in predictably high odds (HO), predictably low odds (LO), and even odds (EO) conditions on subjective ratings of pain (PR) and skin conductance responses (SCR) following the administration of a painful stimulus were examined for individuals with fibromyalgia (IWFM), healthy volunteers (HVs), and yoga practitioners (YPs). We hypothesized IWFM would demonstrate the greatest physiological reactivity to pain uncertainty, followed by HVs and YPs, respectively. Nine IWFM, 7 YPs, and 10 HVs participated. Custom contrast estimates comparing responses for HO, LO, and EO pain conditions showed higher SCR for IWFM (CE = 1.27, p = 0.01) but not for HVs or for YPs. PR for the EO condition were significantly greater than for HO and LO conditions for IWFM (CE = 0.60, p = 0.012) but not for HVs or YPs. YPs had lower SCR and PR than did HVs. Results show that uncertainty regarding pain increases the experience of pain, whereas certainty regarding pain may reduce pain ratings for individuals with fibromyalgia.

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

PubMed Central

Schmetterer, L; Wolzt, M; Salomon, A; Rheinberger, A; Unfried, C; Zanaschka, G; Fercher, A F

1996-01-01

AIMS/BACKGROUND: Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. METHODS: In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. RESULTS: Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. CONCLUSIONS: Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases. PMID:8703859

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

PubMed

Schmetterer, L; Wolzt, M; Salomon, A; Rheinberger, A; Unfried, C; Zanaschka, G; Fercher, A F

1996-03-01

Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases.

Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale.

PubMed

Montejo, Angel L; Deakin, J F W; Gaillard, Raphael; Harmer, Catherine; Meyniel, Florent; Jabourian, Artin; Gabriel, Cecilia; Gruget, Celine; Klinge, Corinna; MacFayden, Christine; Milligan, Holly; Mullings, Emma; Goodwin, Guy

2015-10-01

The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women. A total of 133 healthy volunteers (67 men, 66 women) were randomly assigned to agomelatine (25 or 50 mg) or escitalopram (20 mg) or placebo for nine weeks. Sexual acceptability was evaluated by using the psychotropic-related sexual dysfunction questionnaire 5-items total score and sexual dysfunction relative to each sub-score (in 110 volunteers with sexual activity). Sexual dysfunction was evaluated at baseline and after two, five and eight weeks of treatment and one week after drug discontinuation. The psychotropic-related sexual dysfunction questionnaire 5-items total score was significantly lower in both agomelatine groups versus escitalopram at all visits (p < 0.01 to p < 0.0001) with no difference between agomelatine and placebo nor between both agomelatine doses. Similar results were observed after drug discontinuation. The total score was significantly higher in the escitalopram group than in the placebo group at each post-baseline visit (p < 0.01 to p < 0.001). Similar results were observed regardless of volunteers' gender. Compared to placebo, only escitalopram significantly impaired dysfunction relative to "delayed orgasm or ejaculation" (p < 0.01) and "absence of orgasm or ejaculation" (p < 0.05 to p < 0.01). The percentage of participants with a sexual dysfunction was higher in the escitalopram group than in agomelatine groups (p < 0.01 to p < 0.05) and placebo (p < 0.01). The study confirms the better sexual acceptability profile of agomelatine (25 or 50 mg) in healthy men and women, compared to escitalopram. Evaluation of the effect of agomelatine and escitalopram on emotions and motivation in healthy male and female volunteers. ISRCTN75872983. © The Author(s) 2015.

Simultaneous dynamic blood oxygen level-dependent magnetic resonance imaging of foot and calf muscles: aging effects at ischemia and postocclusive hyperemia in healthy volunteers.

PubMed

Kos, Sebastian; Klarhöfer, Markus; Aschwanden, Markus; Scheffler, Klaus; Jacob, Augustinus Ludwig; Bilecen, Deniz

2009-11-01

To demonstrate the feasibility of simultaneous blood oxygen level-dependent (BOLD) magnetic resonance imaging of calf and foot muscles and investigate age-related changes of BOLD signal changes during ischemia and postocclusive hyperemia in healthy volunteers. In this study, 15 healthy elderly volunteers (mean age: 69.0 +/- 7.4 years) and 15 healthy young volunteers (mean age: 26.1 +/- 3.9 years) were enrolled. In both legs, simultaneous BOLD imaging of calf and foot muscles was performed at 1.5 Tesla. Short-term ischemia and consecutive reactive hyperemia were provoked by a cuff-compression paradigm. T2*-weighted signal time courses were obtained from foot and calf muscles simultaneously. Ischemia was assessed by T2* minimum ischemic value (MIV) and the time to half ischemic minimum (THIM). Reperfusion was assessed by the time to reach T2* half hyperemia peak (THHP). Reactive hyperemia was characterized by hyperemia peak value (HPV), time to peak (TTP), and relative T2* change from end of ischemia to HPV (deltaS). Parameter differences were assessed using a 2-sided Student t test. Dynamic BOLD measurement of foot and calf muscles was techniqually feasible and successful in all volunteers.In comparison, THIM was significantly longer in elderly than in young volunteers for calf (P < 0.01) muscles (young: 28.9 +/- 3.7 seconds; elderly: 57.8 +/- 31.4 seconds) and foot (P = 0.01) muscles (young: 36.8 +/- 25.5 seconds; elderly: 56.6 +/- 31.7 seconds). MIV relative to baseline T2*-signal was significantly (P < 0.01) lower in the elderly for calf (young: 96.0% +/- 2.6%; elderly: 91.3% +/- 4.4%) and foot (young: 95.8% +/- 2.5%; elderly: 91.1% +/- 8.2%) muscles. TTP was significantly (calf: P = 0.01; foot: P = 0.02) delayed in the elderly (elderly calf: 103.0 +/- 92.7 seconds and foot: 157.1 +/- 109.9 seconds vs. young calf: 54.8 +/- 42.1 seconds and foot: 95.1 +/- 77.6 seconds). HPV was significantly (calf: P < 0.01 and foot: P = 0.03) higher in (young calf: 114.1% +/- 7

Effects of 8-Week Hatha Yoga Training on Metabolic and Inflammatory Markers in Healthy, Female Chinese Subjects: A Randomized Clinical Trial.

PubMed

Chen, Neng; Xia, Xianghou; Qin, Liqiang; Luo, Li; Han, Shufen; Wang, Guiping; Zhang, Ru; Wan, Zhongxiao

2016-01-01

We aimed to determine the effects of an 8 wk Hatha yoga training on blood glucose, insulin, lipid profiles, endothelial microparticles (EMPs), and inflammatory status in healthy, lean, and female Chinese subjects. A total of 30 healthy, female Chinese subjects were recruited and randomized into control or yoga practice group. The yoga practice included 8 wks of yoga practice (2 times/wk) for a total of 16 times. Fasting blood samples were collected before and after yoga training. Plasma was isolated for the measurement of lipid profiles, glucose, insulin, EMPs, and inflammatory cytokines. Whole blood was cultured ex vivo and stimulated with lipopolysaccharide (LPS) and Pam3Cys-SK4. Peripheral blood mononuclear cells (PBMCs) were isolated for the measurement of TLR2 and TLR4 protein expression. Yoga practice significantly reduced plasma cholesterol, LDL-cholesterol, insulin levels, and CD31+/CD42b- EMPs. Cultured whole blood from the yoga group has reduced proinflammatory cytokines secretion both at unstimulated condition and when stimulated with Pam3Cys-SK4; this might be associated with reduced TLR2 protein expression in PBMCs after yoga training. Hatha yoga practice in healthy Chinese female subjects could improve hallmarks related to MetS; thus it can be considered as an ancillary intervention in the primary MetS prevention for the healthy population. This trial is registered with ChiCTR-IOR-14005747.

Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

PubMed

Martin-Santos, R; Crippa, J A; Batalla, A; Bhattacharyya, S; Atakan, Z; Borgwardt, S; Allen, P; Seal, M; Langohr, K; Farré, M; Zuardi, A W; McGuire, P K

2012-01-01

Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

The moderating role of age in the relationship between volunteering motives and well-being.

PubMed

Ho, Yuen Wan; You, Jin; Fung, Helene H

2012-12-01

Driven by socioemotional selectivity theory, this study examined whether age moderated the associations of volunteering motives with physical and psychological well-being in a sample of Hong Kong Chinese volunteers. Volunteering motives were measured by the volunteer functions inventory. Findings revealed that even after controlling for demographic characteristics and volunteering experience, age was related to higher social and value motives but lower career motives, and moderated the associations of social and protective motives with well-being. The associations of social motives with physical well-being were positive among older volunteers, but were negative among younger- and middle-aged volunteers. While protective motives were positively related to psychological well-being among all the volunteers, such effects were stronger among younger- and middle-aged volunteers than among older volunteers. Findings highlight the role of age in determining the relationship between volunteering motives and well-being.

Effects of caffeinated versus decaffeinated energy shots on blood pressure and heart rate in healthy young volunteers.

PubMed

Kurtz, Abigail M; Leong, Jessica; Anand, Monica; Dargush, Anthony E; Shah, Sachin A

2013-08-01

To evaluate the effects of a caffeinated 5-hour Energy shot compared with a decaffeinated 5-hour Energy shot as assessed by changes in blood pressure and heart rate in healthy, nonhypertensive volunteers. Randomized, double-blind, controlled, crossover study. University campus. Twenty healthy volunteers. Subjects were randomized to receive either the caffeinated 5-hour Energy shot or the decaffeinated 5-hour Energy shot; after a washout period of at least 6 days, subjects were given the alternate energy shot. Systolic (SBP) and diastolic (DBP) blood pressures were recorded for each subject at baseline and at 1, 3, and 5 hours after consumption of the energy shot. Heart rate, adverse effects, and energy levels were also assessed. Mean ± standard deviation (SD) baseline SBP for all study subjects was 114.06 ± 11.30 mm Hg and DBP was 69.53 ± 7.63 mm Hg. Mean changes in SBP between the caffeinated arm and the decaffeinated arm at the 1- and 3-hour time points were significantly increased compared with baseline (mean ± SD 6.08 ± 7.71 mm Hg at 1 hour [p=0.001] vs 3.33 ± 6.99 mm Hg at 3 hours [p=0.042]). Similarly, mean DBP changes between the caffeinated arm and the decaffeinated arm were significantly increased at the 1- and 3-hour time points compared with baseline (mean ± SD 5.18 ± 8.38 mm Hg at 1 hour [p=0.007] and 5.43 ± 7.21 mm Hg at 3 hours [p=0.005]). Heart rate, adverse effects, and energy levels were similar between the two groups. Caffeinated energy shots significantly increased SBP and DBP over a 3-hour period compared with decaffeinated energy shots in healthy, nonhypertensive individuals. © 2013 Pharmacotherapy Publications, Inc.

Sacral Peak Pressure in Healthy Volunteers and Patients With Spinal Cord Injury: With and Without Liquid-Based Pad.

PubMed

Duetzmann, Stephan; Forsey, Lynn M; Senft, Christian; Seifert, Volker; Ratliff, John; Park, Jon

2015-01-01

The prevalence of sacral pressure ulcers in patients with spinal cord injuries is high. The sacral area is vulnerable to compressive pressure because of immobility and because the sacrum and posterior superior iliac prominence lie closely under the skin with no muscle layer in between. The aim of this study was to assess peak sacral pressure before and after use of PURAP, a liquid-based pad that covers only the sacral area and can be applied on any bed surface. Healthy volunteers (n = 12) and patients with spinal cord injuries (n = 10) took part; the patients had undergone spine surgery within 7 days before data collection. Participants were in bed, pretest pressure maps were generated, PURAP was placed for 15 minutes, and then posttest pressure maps were generated. Peak pressure was obtained every second and averaged over the entire period. Patients rated whether their comfort had improved when PURAP was in use. For healthy volunteers, mean pretest peak sacral pressure was 74.7 (SD = 16.2) mmHg; the posttest mean was 49.1 (SD = 7.5) mmHg (p < .001, Wilcoxon signed-rank test). For patients with spinal cord injuries, mean pretest peak sacral pressure was 105.7 (SD = 22.4) mmHg; the posttest mean was 81.4 (SD = 18.3) mmHg (p < .001, Wilcoxon signed-rank test). The pad reduced the peak sacral pressure in the patient group by 23% (range = 11%-42%) and in the volunteers by 32% (range = 19%-46%). Overall, 70% of the patients reported increased comfort with PURAP. Peak sacral pressure was reduced when PURAP was used. It covers only the sacral area but could help many patients with spinal cord injury because the prevalence of sacral pressure ulcers is high in this group. PURAP may be economically advantageous in countries and hospitals with limited financial resources needed for more expensive mattresses and cushions.

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

PubMed Central

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

2016-01-01

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

Effect of Single-dose Rifampin on the Pharmacokinetics of Warfarin in Healthy Volunteers

PubMed Central

Frymoyer, A; Shugarts, S; Browne, M; Wu, AHB; Frassetto, L; Benet, LZ

2011-01-01

Based on in vitro rat and human hepatocyte uptake studies showing inhibition of warfarin uptake in the presence of the non-specific organic anion transporting polypeptide (OATP) inhibitor rifampin, a clinical study was conducted in 10 healthy volunteers. In a randomized, single-dose, two-period, crossover design, subjects received a 7.5 mg dose of warfarin alone or immediately following a 600 mg intravenous dose of rifampin. Rifampin did not significantly alter R- or S- warfarin area under the concentration-time curve (AUC) from 0–12 hours (period of hepatic OATP inhibition by rifampin) or Cmax (maximum plasma concentration). AUC0–∞ was decreased on rifampin days for both R- (25% reduction; p < 0.001) and S-warfarin (15% reduction; p < 0.05). No differences were seen on the area under the INR-time curve. Our study suggests hepatic uptake via OATPs may not be clinically important in the pharmacokinetics of warfarin. PMID:20703222

Bioequivalence of clavulanate potassium and amoxicillin (1:7) dispersible tablets in healthy volunteers.

PubMed

Hu, Guoxin; Dai, Zongshun; Long, Lihong; Han, Ying; Hou, Shuxian; Wu, Li

2002-01-01

To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross-over study was conducted in 18 healthy volunteers. A single oral dose of 1,000 mg Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main parameters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46 +/- 1.11 micrograms/ml and 18.81 +/- 7.26 micrograms/ml, Tmax: 1.12 +/- 0.23 h and 1.30 +/- 0.34 h, AUC(0-6 h): 5.18 +/- 2.24 micrograms.h/ml and 45.09 +/- 14.53 micrograms.h/ml, t1/2: 1.43 +/- 0.44 h and 1.09 +/- 0.22 h., respectively. The relative bioavailability of T to R were 96.5 +/- 19.2% and 98.4 +/- 26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.

[Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers].

PubMed

Saavedra S, Iván; Sasso A, Jaime; Quiñones S, Luis; Saavedra B, Mónica; Gaete G, Leonardo; Boza T, Ignacio; Carvajal H, Cristóbal; Soto L, Jorge

2011-07-01

The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex™) compared to the reference formulation (Cellcept™) to determine the bioequivalence between both formulations. A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. Linfonex™ 500 mg is bioequivalent to Cellcept™ 500 mg.

Impact of humic acids on the colonic microbiome in healthy volunteers

PubMed Central

Swidsinski, Alexander; Dörffel, Yvonne; Loening-Baucke, Vera; Gille, Christoph; Reißhauer, Anne; Göktas, Onder; Krüger, Monika; Neuhaus, Jürgen; Schrödl, Wieland

2017-01-01

AIM To test the effects of humic acids on innate microbial communities of the colon. METHODS We followed the effects of oral supplementation with humic acids (Activomin®) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were used. RESULTS The sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation (P < 0.001). The increase in the concentrations in each person was due to growth of preexisting groups. The individual microbial profile of the patients remained unchanged. Similarly, the bacterial diversity remained stable. Concentrations of 24 of the 35 substantial groups increased from 20% to 96%. Two bacterial groups detected with Bac303 (Bacteroides) and Myc657 (mycolic acid-containing Actinomycetes) FISH probes decreased (P > 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (< 0.1 × 109/mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae, Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not significant. CONCLUSION Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome. PMID:28223733

Cardiopulmonary and Metabolic Effects of Yoga in Healthy Volunteers.

PubMed

Divya, T Satheesh; Vijayalakshmi, M T; Mini, K; Asish, K; Pushpalatha, M; Suresh, Varun

2017-01-01

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. 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. 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. 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.

Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Min, Yang Won; Min, Byung-Hoon; Kim, Seonwoo; Choi, Dongil; Rhee, Poong-Lyul

2015-01-01

Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. ClinicalTrials.gov NCT02091635.

Evaluation of the health status of six volunteers from the Mars 500 project using pulse analysis.

PubMed

Shi, Hong-Zhi; Fan, Quan-Chun; Gao, Jian-Yi; Liu, Jun-Lian; Bai, Gui-E; Mi, Tao; Zhao, Shuang; Liu, Yu; Xu, Dong; Guo, Zhi-Feng; Li, Yong-Zhi

2017-08-01

To comprehensively evaluate the health status of 6 volunteers from the Mars 500 Project through analyzing their pulse graphs and determining the changes in cardiovascular function, degree of fatigue and autonomic nervous function. Six volunteers were recruited; all were male aged 26-38 years (average 31.83±4.96 years). Characteristic parameters reflflecting the status of cardiovascular functions were extracted, which included left ventricular contraction, vascular elasticity and peripheral resistance. The degree of fatigue was determined depending on the difference between the calendar age and biological age, which was calculated through the analysis of blood pressure value and characteristic parameters. Based on the values of pulse height variation and pulse time variation on a 30-s pulse graph, autonomic nervous function was evaluated. All parameters examined were marked on an equilateral polygon to form an irregular polygon of the actual fifigure, then health status was evaluated based on the coverage area of the actual fifigure. The results demonstrated: (1) volunteers developed weakened pulse power, increased vascular tension and peripheral resistance, and slight decreased ventricular systolic function; (2) the degree of fatigue was basically mild or moderate; and (3) autonomic nervous function was excited but generally balanced. These volunteers were in the state of sub-health. According to Chinese medicine theories, such symptoms are mainly caused by the weakening of healthy qi, Gan (Liver) failing in free coursing, and disharmony between Gan and Wei (Stomach), which manifests as a weak and string-like pulse.

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

PubMed

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

2014-03-01

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

Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.

PubMed

Dubowitz, G; Breyer, K; Lipnick, M; Sall, J W; Feiner, J; Ikeda, K; MacLeod, D B; Bickler, P E

2013-12-01

Pulse oximetry is a standard of care during anaesthesia in high-income countries. However, 70% of operating environments in low- and middle-income countries have no pulse oximeter. The 'Lifebox' oximetry project set out to bridge this gap with an inexpensive oximeter meeting CE (European Conformity) and ISO (International Organization for Standardization) standards. To date, there are no performance-specific accuracy data on this instrument. The aim of this study was to establish whether the Lifebox pulse oximeter provides clinically reliable haemoglobin oxygen saturation (Sp O2 ) readings meeting USA Food and Drug Administration 510(k) standards. Using healthy volunteers, inspired oxygen fraction was adjusted to produce arterial haemoglobin oxygen saturation (Sa O2 ) readings between 71% and 100% measured with a multi-wavelength oximeter. Lifebox accuracy was expressed using bias (Sp O2 - Sa O2 ), precision (SD of the bias) and the root mean square error (Arms). Simultaneous readings of Sa O2 and Sp O2 in 57 subjects showed a mean (SD) bias of -0.41% (2.28%) and Arms 2.31%. The Lifebox pulse oximeter meets current USA Food and Drug Administration standards for accuracy, thus representing an inexpensive solution for patient monitoring without compromising standards. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Scarce Evidence of Yogurt Lactic Acid Bacteria in Human Feces after Daily Yogurt Consumption by Healthy Volunteers

PubMed Central

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 experiments in only 10 (10.52%) of 96 individuals after consumption of fresh yogurt and in 2 (2.10%) of 96 individuals after consumption of pasteurized yogurt (P = 0.01). PMID:15640233

Frequency of inflammatory-like MR imaging findings in asymptomatic fingers of healthy volunteers.

PubMed

Agten, Christoph A; Rosskopf, Andrea B; Jonczy, Maciej; Brunner, Florian; Pfirrmann, Christian W A; Buck, Florian M

2018-02-01

To describe the frequency of inflammatory-like findings on MR imaging in asymptomatic volunteers and compare them with patients with known rheumatoid arthritis and psoriatic arthritis. MR images of fingers in 42 asymptomatic volunteers and 33 patients with rheumatoid/psoriatic arthritis were analyzed. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid/Psoriatic Arthritis MRI Scoring System (RAMRIS/PsAMRIS) and tenosynovitis scoring system were used to assess: bone marrow edema (BME), erosions, tendon sheath fluid/tenosynovitis, joint effusion, and soft-tissue edema. Findings and scores were compared between volunteers and patients. Inter-reader agreement was calculated (intraclass correlation coefficients, ICC). In volunteers, tendon sheath fluid was very common in at least one location (42/42 volunteers for reader 1, 34/42 volunteers for reader 2). BME, erosions, joint effusion, and soft-tissue edema were absent (except one BME in the 3rd proximal phalanx for reader 1). Tendon sheath fluid scores in volunteers and tenosynovitis scores in patients were high (reader 1, 7.17 and 5.39; reader 2, 2.31 and 5.45). Overall, inter-reader agreement was substantial (ICC = 0.696-0.844), except for tendon sheath fluid (ICC = 0.258). Fluid in the finger flexor tendon sheaths may be a normal finding and without gadolinium administration should not be interpreted as tenosynovitis. Bone marrow edema, erosions, joint effusion, and soft-tissue edema in the fingers most likely reflect pathology if present.

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

PubMed

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.

Effects on sleep stages and microarchitecture of caffeine and its combination with zolpidem or trazodone in healthy volunteers.

PubMed

Paterson, L M; Nutt, D J; Ivarsson, M; Hutson, P H; Wilson, S J

2009-07-01

Caffeine is the world's most popular stimulant and is known to disrupt sleep. Administration of caffeine can therefore be used in healthy volunteers to mimic the effects of insomnia and thus to test the hypnotic effects of medication. This study assessed the effects of caffeine on sleep architecture and electroencephalography (EEG) spectrum alone and in combination with two different sleep-promoting medications. Home polysomnography was performed in 12 healthy male volunteers in a double-blind study whereby subjects received placebo, caffeine (150 mg), caffeine plus zolpidem (10 mg) and caffeine plus trazodone (100 mg) at bedtime in a randomised crossover design. In addition to delaying sleep onset, caffeine decreased total sleep time (TST), sleep efficiency (SE) and stage 2 sleep without significantly altering wake after sleep onset or the number of awakenings. Zolpidem attenuated the caffeine-induced decrease in SE and increased spindle density in the caffeine plus zolpidem combination compared with placebo. Trazodone attenuated the decrease in SE and TST, and it also increased stage 3 sleep, decreased the number of awakenings and decreased the spindle density. No significant changes in rapid eye movement (REM) sleep were observed, neither was any significant alteration in slow wave activity nor other EEG spectral measures, although the direction of change was similar to that previously reported for caffeine and appeared to 'normalise' after trazodone. These data suggest that caffeine mimics some, but not all of the sleep disruption seen in insomnia and that its disruptive effects are differentially attenuated by the actions of sleep-promoting compounds with distinct mechanisms of action.

Advantages and disadvantages of graduated and inverse graduated compression hosiery in patients with chronic venous insufficiency and healthy volunteers: A prospective, mono-centric, blinded, open randomised, controlled and cross-over trial.

PubMed

Riebe, Helene; Konschake, Wolfgang; Haase, Hermann; Jünger, Michael

2018-02-01

Background The therapeutic effectiveness of compression therapy depends on the selection of compression hosiery. Objectives To assess efficacy and tolerability of graduated elastic compression stockings (GECS) and inverse graduated elastic compression stockings (PECS). Methods Thirty-two healthy volunteers and thirty-two patients with chronic venous insufficiency were analysed; wear period: one week for each stocking type (randomised, blinded). volume reduction of 'Lower leg' (Image3D®) and 'Distal leg and foot' (water plethysmography). clinical symptoms of chronic venous insufficiency assessed by the Venous Clinical Severity Score, side effects and wear comfort in both groups. Results Volume of 'Lower leg': significant reduction in healthy volunteers (mean GECS: -37.5 mL, mean PECS: -37.2 mL) and in patients (mean GECS: -55.6 mL, mean PECS: -41.6 mL). Volume of 'Distal lower leg and foot': significant reduction in healthy volunteers (mean GECS: -27 mL, mean PECS: -16.7 mL), significant reduction in patients by GECS (mean: -43.4 mL), but non-significant reduction by PECS (mean: -22.6 mL). Clinical symptoms of chronic venous insufficiency were improved significantly better with GECS than with PECS, p < 0.001. GECS led to more painful constrictions, p = 0.047, PECS slipped down more often, p < 0.001. Conclusion GECS and PECS reduce volume of the segment 'Lower leg' in patients and healthy volunteers. Patients' volume of the 'Distal lower leg and foot', however, were diminished significantly only by GECS ( p = 0.0001). Patients' complaints were improved by both GECS and PECS, and GECS were superior to PECS.

Comparison of Oseltamivir and Oseltamivir Carboxylate Concentrations in Venous Plasma, Venous Blood, and Capillary Blood in Healthy Volunteers

PubMed Central

Instiaty, Insti; Lindegardh, Niklas; Jittmala, Podjanee; Hanpithakpong, Warunee; Blessborn, Daniel; Pukrittayakamee, Sasithon; White, Nicholas J.

2013-01-01

Oseltamivir and oseltamivir carboxylate concentrations were measured in venous plasma, venous blood, and capillary blood taken simultaneously from 24 healthy volunteers. Median (range) venous-blood-to-plasma ratios were 1.42 (0.920 to 1.97) for oseltamivir and 0.673 (0.564 to 0.814) for oseltamivir carboxylate. Capillary blood/venous plasma ratios were 1.32 (0.737 to 3.16) for oseltamivir and 0.685 (0.502 to 1.34) for oseltamivir carboxylate. Oseltamivir concentrations in venous and capillary blood were similar. Oseltamivir carboxylate showed a time-dependent distribution between venous and capillary blood. PMID:23507284

Cardiopulmonary and Metabolic Effects of Yoga in Healthy Volunteers

PubMed Central

Divya, T Satheesh; Vijayalakshmi, MT; Mini, K; Asish, K; Pushpalatha, M; Suresh, Varun

2017-01-01

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. PMID:29422741

Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers

PubMed Central

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

2005-01-01

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

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

PubMed

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

2014-09-01

Amphetamine sensitisation (AS) is an established animal model of the hypersensitivity to psychostimulants seen in patients with schizophrenia. AS also models the dysregulation of mesolimbic dopamine signalling which has been implicated in the development of psychotic symptoms. Recent data suggest that the enhanced excitability of mesolimbic dopamine neurons in AS is driven by a hyperactivity of hippocampal (subiculum) neurons, consistent with a strong association between hippocampal dysfunction and schizophrenia. While AS can be modelled in human volunteers, its functional consequences on dopaminoceptive brain regions (i.e. striatum and hippocampus) remains unclear. Here we describe the effects of a sensitising dosage pattern of dextroamphetamine on the neural correlates of motor sequence learning in healthy volunteers, within a randomised, double-blind, parallel-groups design. Behaviourally, sensitisation was characterised by enhanced subjective responses to amphetamine but did not change performance (i.e. learning rate) during an explicit sequence learning task. In contrast, functional magnetic resonance imaging (fMRI) measurements showed that repeated intermittent amphetamine exposure was associated with increased blood-oxygen-level dependent (BOLD) signal within the medial temporal lobe (MTL) (subiculum/entorhinal cortex) and midbrain, in the vicinity of the substantia nigra/ventral tegmental area (SN/VTA) during sequence encoding. Importantly, MTL hyperactivity correlated with the sensitisation of amphetamine-induced attentiveness. The MTL-midbrain hyperactivity reported here mirrors observations in sensitised rodents and is consistent with contemporary models of schizophrenia and behavioural sensitisation. These findings of meso-hippocampal hyperactivity during AS thus link pathophysiological concepts of dopamine dysregulation to cognitive models of psychosis. © The Author(s) 2014.

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers.

PubMed

Alía, P; Villabona, C; Giménez, O; Sospedra, E; Soler, J; Navarro, M A

2006-09-01

No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.

Non-invasive positive-pressure ventilation with positive end-expiratory pressure counteracts inward air leaks during preoxygenation: a randomised crossover controlled study in healthy volunteers.

PubMed

Hanouz, J-L; Le Gall, F; Gérard, J-L; Terzi, N; Normand, H

2018-04-01

During preoxygenation, the lack of tight fit between the mask and the patient's face results in inward air leak preventing effective preoxygenation. We hypothesized that non-invasive positive-pressure ventilation and positive end-expiratory pressure (PEEP) could counteract inward air leak. Healthy volunteers were randomly assigned to preoxygenated through spontaneous breathing without leak (SB), spontaneous breathing with a calibrated air leak (T-shaped piece between the mouth and the breathing system; SB-leak), or non-invasive positive inspiratory pressure ventilation (inspiratory support +6 cm H 2 O; PEEP +5 cm H 2 O) with calibrated leak (PPV-leak). The volunteers breathed through a mouthpiece connected to an anaesthesia ventilator. The expired oxygen fraction (FeO 2 ) and air-leak flow (ml s -1 ) were measured. The primary end point was the proportion of volunteers with FeO 2 >90% at 3 min. The secondary end points were FeO 2 at 3 min, time to reach FeO 2 of 90%, and the inspiratory air-leak flow. Twenty healthy volunteers were included. The proportion of volunteers with FeO 2 >90% at 3 min was 0% in the SB-leak group, 95% in the SB group, and 100% in the PPV-leak group (P<0.001). At 3 min, the mean [standard deviation (sd)] FeO 2 was 89 (1)%, 76 (1)%, and 90 (0)% in the SB, SB-leak, and PPV-leak groups, respectively (P<0.001). The mean (sd) inward air leak was 59 (12) ml s -1 in the SB-leak group, but 0 (0) ml s -1 in the PPV-leak group (P<0.001). Preoxygenation through non-invasive positive-pressure ventilation and PEEP provided effective preoxygenation despite an inward air leak. NCT03087825. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

PubMed Central

García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L.; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

2005-01-01

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of ΔCTXΦ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain

The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteers.

PubMed

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

2005-05-01

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXPhi 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 10(9) CFU of freshly harvested 638 buffered with 1.3% NaHCO(3), 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 10(9) CFU of DeltaCTXPhi 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 x 10(5) CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO(3). 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 (10

Public interest in medical research participation: differences by volunteer status and study type.

PubMed

Cobb, Enesha M; Singer, Dianne C; Davis, Matthew M

2014-04-01

We assessed national levels of public interest in medical research participation (MRP) and factors associated with interest as a healthy volunteer; as a diagnosed volunteer; and in seven study types. Cross-sectional, Web-based survey of the US population in June 2012. Descriptive statistics estimated interest in MRP and multivariable logistic regression determined associations between respondent-level predictors and interest in MRP. Of 2,668 respondents (response rate = 61%), 41% were interested in MRP as healthy volunteers and 60% as diagnosed volunteers. Respondents with some college (OR = 1.54, 1.09-2.19) or higher education (OR = 1.86, 1.29-2.70) had higher adjusted odds of interest as healthy volunteers. Non-Hispanic black race (OR = 0.56, 0.37-0.86) and education below high school (OR = 0.57, 0.35-0.92) were associated with lower adjusted odds of interest as diagnosed volunteers. Non-Hispanic black race was associated with lower odds of interest in medication trials as diagnosed volunteers (OR = 0.61, 0.40-0.93). We found high levels of interest in MRP that contrast with low levels of prior research participation. Interest is higher in medical research involving noninvasive designs. Comparatively lower levels of interest in MRP among non-Hispanic blacks and those with less education raise concerns about disparities in future study enrollment. © 2014 Wiley Periodicals, Inc.

Remote magnetic control of a wireless capsule endoscope in the esophagus is safe and feasible: results of a randomized, clinical trial in healthy volunteers.

PubMed

Keller, Jutta; Fibbe, Christiane; Volke, Frank; Gerber, Jeremy; Mosse, Alexander C; Reimann-Zawadzki, Meike; Rabinovitz, Elisha; Layer, Peter; Swain, Paul

2010-11-01

Remote control of esophageal capsule endoscopes could enhance diagnostic accuracy. To assess the safety and efficacy of remote magnetic manipulation of a modified capsule endoscope (magnetic maneuverable capsule [MMC]; Given Imaging Ltd, Yoqneam, Israel) in the esophagus of healthy humans. Randomized, controlled trial. Academic hospital. This study involved 10 healthy volunteers. All participants swallowed a conventional capsule (ESO2; Given Imaging) and a capsule endoscope with magnetic material, the MMC, which is activated by a thermal switch, in random order (1 week apart). An external magnetic paddle (EMP; Given Imaging) was used to manipulate the MMC within the esophageal lumen. MMC responsiveness was evaluated on a screen showing the MMC film in real time. Safety and tolerability of the procedure (questionnaire), responsiveness of the MMC to the EMP, esophageal transit time, and visualization of the Z-line. No adverse events occurred apart from mild retrosternal pressure (n = 5). The ability to rotate the MMC around its longitudinal axis and to tilt it by defined movements of the EMP was clearly demonstrated in 9 volunteers. Esophageal transit time was highly variable for both capsules (MMC, 111-1514 seconds; ESO2, 47-1474 seconds), but the MMC stayed longer in the esophagus in 8 participants (P < .01). Visualization of the Z-line was more efficient with the ESO2 (inspection of 73% ± 18% of the circumference vs 33% ± 27%, P = .01). Magnetic forces were not strong enough to hold the MMC against peristalsis when the capsule approached the gastroesophageal junction. Remote control of the MMC in the esophagus of healthy volunteers is safe and feasible, but higher magnetic forces may be needed. Copyright © 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Randomized clinical trial studying effects of a personalized supervised lifestyle intervention program on cardiovascular status in physically inactive healthy volunteers

PubMed Central

Westergren, Helena U; Gan, Li-Ming; Månsson, Marianne; Svedlund, Sara

2018-01-01

Background The impact of personalized exercise training and a healthy dietary lifestyle in healthy volunteers on coronary flow reserve and cardiovascular function remains to be investigated in a controlled study setting. Purpose To examine the effects of a Mediterranean-inspired diet combined with regular physical exercise (standard) and a personalized supervised exercise program (DAPS) on coronary flow reserve and cardiovascular function. Results The number of males were 10 (59%) and 9 (47%) and mean age was 54 ± 12 and 55 ± 5 years in standard versus DAPS group, respectively. Primary outcomes were in addition to improved body composition and aerobic capacity, increased TDE-CFR (5.0%, CI:1.62,8.64, p = 0.005) and left ventricle ejection fraction (LVEF) during hyperemia (10.2%, CI:1.62,19.4, p = 0.022) in DAPS adjusted for the control period. Also, plasma fibrinogen decreased (−12.1%, CI:-22.0,–0.92, p = 0.035) in the DAPS group. Secondary outcomes, after adjusting DAPS intervention effects for the standard-training period, TDE-CFR and hyperemic LVEF remained significantly improved. Materials and Methods This randomized, controlled clinical trial (URL: http://www.clinicaltrials.gov NCT02713724) included 36 healthy volunteers who underwent exercise ECG before randomization to standard or DAPS groups. Standard-group was given gym-membership with limited instructions and general dietary advice. DAPS-group received personalized supervised exercise programs and more detailed dietary advice with regular contact with a personal trainer. Effects were evaluated after 3 months. All participants underwent coronary flow reserve by transthoracic ultrasound (TDE-CFR), blood marker analysis and examinations of vascular function. Standard-group was evaluated pre-control, post-control (=pre-intervention) and post-intervention. DAPS-group was examined at pre-intervention and post-intervention. Conclusions A personalized supervised training- and diet program improves

Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

PubMed

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.

Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers

PubMed Central

Oh, D Alexander; Parikh, Neha; Khurana, Varun; Cognata Smith, Christina; Vetticaden, Santosh

2017-01-01

Dronabinol is a pharmaceutical tetrahydrocannabinol originally developed as an oral capsule. A dronabinol oral solution was recently approved, and the effects of food on absorption and bioavailability of the oral solution versus capsules were compared in an open-label, single-dose, 3-period crossover study. Healthy volunteers were randomized to either dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted). Dosing was separated by a 7-day washout period. Plasma pharmacokinetics were evaluated for dronabinol and its major metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-Δ9-THC). Pharmacokinetic data were available for analysis in 54 volunteers. In the fed state, initial dronabinol absorption was faster with oral solution versus capsule (mean time to the first measurable concentration, 0.15 vs 2.02 hours, respectively), with 100% and 15% of volunteers, respectively, having detectable plasma dronabinol levels 30 minutes postdose. There was less interindividual variability in plasma dronabinol concentration during early absorption with oral solution versus capsule. Compared with the fasted state, mean area under the plasma concentration–time curve from time zero to the last measurable concentration (AUC0−t) increased by 2.1- and 2.4-fold for dronabinol oral solution and capsule, respectively, when taken with food. Mean time to maximum plasma concentration was similarly delayed for dronabinol oral solution with food (7.7 hours) and capsule with food (5.6 hours) versus capsule with fasting (1.7 hours). Under fed conditions, AUC0−t and area under the plasma concentration–time curve from time zero to infinity were similar for the oral solution versus capsule based on 11-OH-Δ9-THC levels. An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients, given its rapid and lower interindividual absorption variability versus dronabinol capsule

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

PubMed

Arancibia, A; Nella Gai, M; Paulos, C; Chávez, J; Pinilla, E; Angel, N; Ritschel, W A

2004-06-01

A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.

Effect of a modified guar gum preparation on glucose and lipid levels in diabetics and healthy volunteers.

PubMed

Smith, U; Holm, G

1982-10-01

Six healthy volunteers and 17 diabetics (6 insulin-dependent and 11 diet- and tablet-treated) were treated with a special processed, palatable guar gum (10 g b.i.d. immediately before meals) for periods of one or three weeks or, in some cases, up to 13 weeks. A standardized test meal was given to study the effect of the fiber on postprandial glucose levels. Ten g guar was stirred in water and taken immediately before the test meal. The postprandial blood glucose levels were similar in the healthy volunteers but significantly lower in the diabetics following treatment with guar for one and three weeks, respectively. Furthermore, the fasting blood glucose levels were significantly lower in the diabetics after three, but not one, weeks of treatment. The lower postprandial glucose levels were coupled with attenuated and delayed insulin levels in accordance with an effect of guar gum on the rate of carbohydrate absorption. The cholesterol levels were on average reduced with 14% in the diabetics following three weeks' treatment with guar. The higher the initial cholesterol level, the greater the reduction in cholesterol; 26% reduction was achieved in four patients with initial levels above 7 mM. The alpha-lipoprotein cholesterol levels were not significantly changed, thus an increase in the alpha-lipoprotein cholesterol/total serum cholesterol ratio was obtained. Neither plasma triglycerides nor body weights altered during treatment. The reported side-effects were as expected and were usually mild and transient (e.g. increased flatulence). The data show that guar gum also reduces postprandial glucose levels on a long-term basis and may improve the diabetic control. Additionally, treatment with this fiber leads to a concentration-dependent decrease in cholesterol levels.

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

PubMed

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.

Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers.

PubMed

Rubio, Amandine; Van Oudenhove, Lukas; Pellissier, Sonia; Ly, Huynh Giao; Dupont, Patrick; Lafaye de Micheaux, Hugo; Tack, Jan; Dantzer, Cécile; Delon-Martin, Chantal; Bonaz, Bruno

2015-02-15

The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary

[The effect of a single inhalation of mineral water on the blood hormonal status in healthy volunteers].

PubMed

Khinchagov, B P; Polushina, N D; Frolkov, V K

1998-01-01

Concentrations of ACTH, TTH, STH, LH, PSH, hydrocortisone, insulin, glucagone, triiodthyronine, thyroxine, aldosterone, glucose and unesterified fatty acids (NEFA) were measured in the blood of 23 healthy male volunteers aged 18 to 35 years 15, 30 and 60 min after a single nose inhalation and oral intake of mineral water Essentuki No. 17. Inhalation of Essentuki No. 17 stimulated secretion of the hormones and some parameters of metabolic reactions: the levels of glucose, NEFA, hydrocortisone, aldosterone, TTH, PSH and LH rose while those of insulin and growth hormone decreased. Oral intake of this water brought about the same changes in the hormone status except blood insulin the levels of which went up.

The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Gertsik, Lev; Dutta, Sandeep

2014-06-01

ABT-288 is a potent and selective H3 receptor antagonist with procognitive effects in several preclinical models. In previous studies, 3 mg once daily was the maximal tolerated dose in healthy volunteers. This study characterized the safety, tolerability and pharmacokinetics of ABT-288 in stable subjects with schizophrenia. This was a randomized, double-blind, placebo-controlled, dose-escalating study of ABT-288 (10 dose levels, from 1 to 60 mg once daily for 14 days) in stable subjects with schizophrenia treated with an atypical antipsychotic. In each dose group, five to seven and two to three participants were assigned to ABT-288 and placebo, respectively. Of the 67 participants enrolled, nine participants (on ABT-288) were prematurely discontinued, in seven of these due to adverse events. ABT-288 was generally safe and tolerated at doses up to 45 mg once daily. The most common adverse events, in decreasing frequency (from 31 to 5%), were abnormal dreams, headache, insomnia, dizziness, somnolence, dysgeusia, dry mouth, psychotic disorder, parosmia and tachycardia. Adverse events causing early termination were psychotic events (four) and increased creatine phosphokinase, pyrexia and insomnia (one each). The half-life of ABT-288 ranged from 28 to 51 h, and steady state was achieved by day 12 of dosing. At comparable multiple doses, ABT-288 exposure in subjects with schizophrenia was 45% lower than that previously observed in healthy subjects. At trough, ABT-288 cerebrospinal fluid concentrations were 40% of the total plasma concentrations. ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake. © 2013 The British Pharmacological Society.

Carpal tunnel syndrome assessment with ultrasonography: value of inlet-to-outlet median nerve area ratio in patients versus healthy volunteers.

PubMed

Fu, Tengfei; Cao, Manlin; Liu, Fang; Zhu, Jiaan; Ye, Dongmei; Feng, Xianxuan; Xu, Yiming; Wang, Gang; Bai, Yuehong

2015-01-01

To evaluate the diagnostic value of the Inlet-to-outlet median nerve area ratio (IOR) in patients with clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS). Forty-six wrists in 46 consecutive patients with clinical and electrodiagnostic evidence of CTS and forty-four wrists in 44 healthy volunteers were examined with ultrasonography. The cross-sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet (the level of scaphoid-pisiform) and outlet (the level of the hook of the hamate), and the IOR was calculated for each wrist. Ultrasonography and electrodiagnostic tests were performed under blinded conditions. Electrodiagnostic testing combined with clinical symptoms were considered to be the gold standard test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value between the inlet CSA and IOR. The study population included 16 men and 30 women (mean age, 45.3 years; range, 18-83 years). The control population included 18 men and 26 women (mean age, 50.4 years; range, 18-79 years). The mean inlet CSA was 8.7 mm2 in healthy controls and 14.6mm2 in CTS group (P<0.001). The mean IOR in healthy volunteers (1.0) was smaller than that in patients (1.6, P<0.001). Receiver operating characteristic analysis revealed a diagnostic advantage to using the IOR rather than the inlet CSA (P<0.01). An IOR cutoff value of ≥ 1.3 would yield 93% specificity and 91% sensitivity in the diagnosis of CTS. The IOR of median nerve area promises to be an effective means in the diagnosis of CTS. A large-scale, randomized controlled trial is required to determine how and when this parameter will be used.

Perceptions of Equipoise, Risk-Benefit Ratios, and "Otherwise Healthy Volunteers" in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry.

PubMed

Dubé, Karine; Dee, Lynda; Evans, David; Sylla, Laurie; Taylor, Jeff; Brown, Brandon; Miller, Veronica; Corneli, Amy; Skinner, Asheley; Greene, Sandra B; Tucker, Joseph D; Rennie, Stuart

2018-02-01

Early-phase HIV cure research is conducted against a background of highly effective antiretroviral therapy, and involves risky interventions in individuals who enjoy an almost normal life expectancy. To explore perceptions of three ethical topics in the context of HIV cure research-(a) equipoise, (b) risk-benefit ratios, and (c) "otherwise healthy volunteers"-we conducted 36 in-depth interviews (IDIs) with three groups of purposively selected key informants: clinician-researchers ( n = 11), policy-makers and bioethicists ( n = 13), and people living with HIV (PLWHIV; n = 12). Our analysis revealed variability in perceptions of equipoise. Second, most key informants believed there was no clear measure of risk-benefit ratios in HIV cure research, due in part to the complexity of weighing (sometimes unknown) risks to participants and (sometimes speculative) benefits to science and society. Third, most clinician-researchers and policy-makers/bioethicists viewed potential HIV cure study participants as "otherwise healthy volunteers," but this perception was not shared among PLWHIV in our study.

Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

PubMed

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.

[Genetic polymorphism in sparteine oxidation--occurrence in healthy volunteers in Slovakia].

PubMed

Holomán, J; Glasa, J; Veningerová, M; Prachar, V; Lukácsová, M

1997-02-01

The aim of this study was to estimate the occurrence of the phenotype of poor metabolizers of sparteine (in the frame of sparteine-debrisoquine-dextromethorphane polymorphism) in Slovakia. The authors examined a group of 216 of healthy volunteers (73 women and 143 men, average age of the group 24, 9 +/- 0.4 years), university students coming from various regions of Slovakia. The test substance-sparteine (1 x 100 mg tbl.) was administered perorally to all probands, in the evening after fasting. A 12-hour gathering of urine was subsequently performed. A sample of urine was subdued to examination. Isolation, separation, identification and assessment of the concentration of sparteine and its metabolites (2- and 5-dehydrosparteine) were performed by the method of gas chromatography. The metabolic MR ratio calculated from the ratio of the detected concentrations of sparteine and (2- and 5-dehydrosparteine) served for the assessment of the phenotype of poor (MR > 20), or rapid (MR < 20) metabolizers of sparteine in 8 authors found the poor metabolizer phenotype of 216 examined probands (i.e. in 3.75%). Its prevalence of the presented phenotype was lower than that anticipated on the basis of epidemiologic studies performed in other European countries. Study represents the first data on the phenotype of poor sparteine metabolizers in Slovakia. (Tab. 4, Fig. 1, Ref. 24.)

Pharmacokinetics and C-Reactive Protein Modelling of Anti-IL-6 Antibody (PF-04236921) in Healthy Volunteers and Patients with Autoimmune Disease.

PubMed

Li, Cheryl; Shoji, Satoshi; Beebe, Jean

2018-05-18

The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included. A 2-compartment model with first order absorption and linear elimination and a mechanism-based indirect response model adequately described the PK and PK/PD relationships, respectively. Central compartment volume of distribution (Vc) positively correlated with body weight. Clearance (CL) negatively correlated with baseline albumin concentration and positively correlated with baseline CRP and creatinine clearance, and was slightly lower in females. After correcting for covariates, CL in CD subjects was approximately 60% higher than other populations. Maximum inhibition of PF-04236921 on CRP production (I max ) negatively correlated with baseline albumin. I max positively correlated with baseline CRP and the relationship was captured as a covariance structure in the PK/PD model. Integrated population PK and PK/PD models of PF-04236921 have been developed using pooled data from healthy subjects and autoimmune patients. The current model enables simulation of PF-04236921 PK and PD profiles under various dosing regimens and patient populations and should facilitate future clinical study of PF-04236921 and other anti-IL6 monoclonal antibodies. This article is protected by copyright. All rights reserved.

Anatomical and metabolic assessment of prostate using a 3-Tesla MR scanner with a custom-made external transceive coil: healthy volunteer study.

PubMed

Kaji, Yasushi; Kuroda, Kagayaki; Maeda, Takaki; Kitamura, Yuri; Fujiwara, Toshitaka; Matsuoka, Yuichiro; Tamura, Mitsuru; Takei, Naoyuki; Matsuda, Tsuyoshi; Sugimura, Kazuro

2007-03-01

To examine the possibility of using a 3 Tesla (T) magnetic resonance (MR) scanner with a custom-made external coil to obtain ductal details of the prostate, high-quality spectra, and metabolite mapping corresponding to prostate zonal anatomy in healthy volunteers. MRI and two-dimensional (2D) chemical shift imaging (CSI) were performed in 16 healthy volunteers using a 3T scanner with a custom-made external transmit-receive (transceive) coil. Visualization of the prostatic duct-like structure was analyzed on T2-weighted (T2W) images. The resolution of the metabolite peaks and the distribution of metabolites in CSI were also assessed. In the axial plane, 3-mm-thick images were better than 4-mm-thick images with the same voxel volume for assessing duct-like structures and prostatic urethra. Differentiation between inner and outer citrate (Cit) peaks was frequently observed (29 out of 30). The mean peak area ratio of choline (Cho) plus creatine (Cr) over Cit in the peripheral zone (PZ) was significantly lower than in the transition zone (TZ) (P = 0.014). 3T MR examinations of the prostate using an external coil allow information to be collected about the details of duct-like structures, the high-quality spectra of Cit, and the zone-specific distribution of metabolites.

A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy volunteers: An open-label, parallel group, randomized clinical study.

PubMed

Chung, Hyewon; Oh, Jaeseong; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Chung, Jae-Yong

2018-01-01

The aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers. A total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration. The PK parameters after the second dose were evaluated through noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2-K, and OCT2 were genotyped, and their effects on PK characteristics were additionally evaluated. The plasma exposure of metformin increased as the metformin dose increased. The mean values for the area under the concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4 and 8808.2 h·μg/L for the low- and high-dose groups, respectively. Non-linear relationships were found between the glucose-lowering effect and PK parameters with a significant inverse trend at high metformin exposure. The PK parameters were comparable among subjects with the genetic polymorphisms. This study showed a non-linear PK-PD relationship on plasma glucose levels after the administration of metformin. The inverse relationship between systemic exposure and the glucose-lowering effect at a high exposure indicates a possible role for the intestines as an action site for metformin. ClinicalTrials.gov NCT02712619.

Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.

PubMed

Mundorf, Thomas K; Ogawa, Takahiro; Inui, Noritsugu; Naka, Hiroaki; Novack, Gary D; Crockett, R Stephens

2005-03-01

A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout. At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level. TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.

Comparison Thigh Skeletal Muscles between Snowboarding Halfpipe Athletes and Healthy Volunteers Using Quantitative Multi-Parameter Magnetic Resonance Imaging at Rest.

PubMed

Sun, He; Xu, Meng-Tao; Wang, Xiao-Qi; Wang, Meng-Hu; Wang, Bao-Heng; Wang, Feng-Zhe; Pan, Shi-Nong

2018-05-05

Magnetic resonance (MR) imaging provides a unique, noninvasive diagnostic platform to quantify the physiological and biochemical variables of skeletal muscle at rest. This study was to investigate the difference in thigh skeletal muscles between snowboarding halfpipe athletes and healthy volunteers via multiparametric MR imaging. A comparative study was conducted between 12 healthy volunteers and 14 snowboarding halfpipe athletes. MR scanning targeted the left leg at the level of the proximal thigh on a 3.0T MR system. The measured parameters compared between the two groups included T1, T2, T2* relaxation times, fat fraction (FF), and cross-sectional area (CSA) of the quadriceps femoris and the hamstring muscles. Statistical analysis was carried out using independent sample t-test. Interrater reliability was also assessed with intraclass correlation coefficients (ICCs). It was statistically equivalent between two groups in age, body mass index, thigh circumference, calf circumference, systolic blood pressure, and resting heart rate (all P > 0.05). However, the T1 and T2 values of the hamstring muscles in the athlete group were found to be significantly shorter than those in control group (T1: 1063.3 ± 24.1 ms vs. 1112.0 ± 38.2 ms in biceps femoris, 1050.4 ± 31.2 ms vs. 1095.0 ± 39.5 ms in semitendinosus, 1053.1 ± 31.7 ms vs. 1118.4 ± 40.0 ms in semimembranosus, respectively; T2: 33.4 ± 0.7 ms vs. 36.1 ± 1.9 ms in biceps femoris, 34.6 ± 2.0 ms vs. 37.0 ± 1.9 ms in semitendinosus, 36.9 ± 1.5 ms vs. 38.9 ± 2.4 ms in semimembranosus, respectively; all P < 0.05) although T2* relaxation time was detected with no significant difference. The FF of the hamstring muscles was obviously less than the control group (5.5 ± 1.9% vs. 10.7 ± 4.7%, P < 0.001). In addition, the quadriceps' CSA in the athlete group was substantially larger than the control group (8039.0 ± 1072.3 vs. 6258.2 ± 852.0 mm 2 , P < 0.001). Interrater reliability was excellent (ICC: 0

Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers.

PubMed

Bedada, Satish Kumar; Neerati, Prasad

2018-02-01

The purpose of present study was to evaluate the effect of quercetin on pharmacokinetics of diclofenac sodium (DIC) in healthy volunteers. The open-label, 2 period, sequential study was conducted in 12 healthy volunteers. DIC 100 mg was administered during control and after quercetin phases. Quercetin 500 mg was administered twice daily for 10 days during quercetin phase. Treatment with quercetin significantly enhanced maximum plasma concentration (C max ) , area under the curve (AUC 0-∞ ), and half life, while significantly decreased elimination rate constant (k el ) and apparent oral clearance (CL/F) of DIC compared with control. On the other hand, C max and AUC 0-∞ of 4-hydroxydiclofenac (4-OHDIC) were decreased after quercetin treatment. In addition, geometric mean ratios and 90% confidence intervals for C max and AUC 0-∞ of DIC and 4-OHDIC were both out of the no-effect limits of 0.80-1.25, which indicates a significant pharmacokinetic interaction between quercetin and DIC. Furthermore, quercetin treatment significantly decreased metabolic ratios of C max and AUC 0-∞ suggesting that reduced formation of DIC to 4-OHDIC. The results suggest that quercetin might have inhibited CYP2C9-mediated metabolism of DIC. Accordingly, caution should be taken when quercetin is used in combination with therapeutic drugs metabolized by CYP2C9, and dose adjustment of CYP2C9 substrates may be necessary. Copyright © 2017 John Wiley & Sons, Ltd.

Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.

PubMed

Cook, Mary R; Graham, Charles; Sastre, Antonio; Gerkovich, Mary M

2002-07-01

Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men). Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved. PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects. PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.

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

PubMed

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

2016-01-31

Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm(2)/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.

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

PubMed Central

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

2016-01-01

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

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

PubMed Central

2011-01-01

Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin. PMID:21466682

Social anxiety and perception of early parenting among American, Chinese American, and social phobic samples.

PubMed

Leung, A W; Heimberg, R G; Holt, C S; Bruch, M A

1994-01-01

Emotionally distant and controlling child-rearing attitudes have been reported to characterize the parents of American or western European social phobics in previous research. However, the notion that these parental attitudes may be associated with social anxiety only in some cultures has not been investigated. The present study examined social anxiety among American social phobics and American and Chinese/Chinese American volunteer samples and how it may relate to their parents' child-rearing attitudes. Multivariate analyses of variance revealed overall group differences. Both volunteer samples reported lower levels of anxiety than social phobics. Parents of Chinese/Chinese Americans and social phobics were reported to be similar in their (1) isolation of children from social activities; (2) over-emphasis of others' opinions; and (3) use of shame tactics for discipline (more so than American volunteers' parents). However, parents of nonsocial phobics were more likely to attend family social activities than social phobics' parents. Overall, the association between a reported parenting style emphasizing others' opinions and shame tactics and social anxiety in their adult children was more evident in both American samples than among Chinese/Chinese Americans.

Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.

PubMed

Georgiou, Leonidas; Penny, Jeffrey; Nicholls, Glynis; Woodhouse, Neil; Blé, François-Xavier; Hubbard Cristinacce, Penny L; Naish, Josephine H

2017-02-01

The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0

Pharmacokinetics in Healthy Volunteers of Sumatriptan 25-mg Oral Tablet Versus 25-mg Extemporaneous Suppository.

PubMed

Desai, Hiral D; Shriley, Kara L; Penzak, Scott R; Strom, J Grady; Hon, Yuen Yi; Spratlin, Vicky; Jann, Michael W

2003-01-01

The pharmacokinetics of an extemporaneous 25-mg suppository formulation of sumatriptan were compared to those of the marketed 25-mg oral tablet. Sixteen healthy volunteers enrolled in this open-label, two-way crossover study. Fifteen subjects completed the study. The pharmacokinetics of the suppository and the oral tablet were significantly different. Tmax was observed at 0.5 hours in 12 of 15 subjects with the extemporaneous suppository, compared with the range of 0.75 hours to 1.5 hours in 13 of 15 subjects with the oral tablet. The mean Cmax and area under the plasma concentration time curve were 5.4-fold and fourfold greater for the suppository than for the oral tablet. Both formulations were well tolerated, with mild headache experienced in only three subjects. Based upon its pharmacokinetic profile, the extemporaneous suppository may represent a useful alternative therapeutic administartion route for some patients.

A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs.

PubMed

McCarthy, James S; Sekuloski, Silvana; Griffin, Paul M; Elliott, Suzanne; Douglas, Nanette; Peatey, Chris; Rockett, Rebecca; O'Rourke, Peter; Marquart, Louise; Hermsen, Cornelius; Duparc, Stephan; Möhrle, Jörg; Trenholme, Katharine R; Humberstone, Andrew J

2011-01-01

Critical to the development of new drugs for treatment of malaria is the capacity to safely evaluate their activity in human subjects. The approach that has been most commonly used is testing in subjects with natural malaria infection, a methodology that may expose symptomatic subjects to the risk of ineffective treatment. Here we describe the development and pilot testing of a system to undertake experimental infection using blood stage Plasmodium falciparum parasites (BSP). The objectives of the study were to assess the feasibility and safety of induced BSP infection as a method for assessment of efficacy of new drug candidates for the treatment of P. falciparum infection. A prospective, unblinded, Phase IIa trial was undertaken in 19 healthy, malaria-naïve, male adult volunteers who were infected with BSP and followed with careful clinical and laboratory observation, including a sensitive, quantitative malaria PCR assay. Volunteers were randomly allocated to treatment with either of two licensed antimalarial drug combinations, artemether-lumefantrine (A/L) or atovaquone-proguanil (A/P). In the first cohort (n = 6) where volunteers received ∼360 BSP, none reached the target parasitemia of 1,000 before the day designated for antimalarial treatment (day 6). In the second and third cohorts, 13 volunteers received 1,800 BSP, with all reaching the target parasitemia before receiving treatment (A/L, n = 6; A/P, n = 7) The study demonstrated safety in the 19 volunteers tested, and a significant difference in the clearance kinetics of parasitemia between the drugs in the 13 evaluable subjects, with mean parasite reduction ratios of 759 for A/L and 17 for A/P (95% CI 120-4786 and 7-40 respectively; p<0.01). This system offers a flexible and safe approach to testing the in vivo activity of novel antimalarials. ClinicalTrials.gov NCT01055002.

Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

PubMed

Dumont, G J H; Wezenberg, E; Valkenberg, M M G J; de Jong, C A J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

2008-04-01

In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

Risk Factors for Helicobacter pylori Infection and Endoscopic Reflux Esophagitis in Healthy Young Japanese Volunteers.

PubMed

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

2017-11-15

Objective The aim of this study was to determine the prevalence and risk factors of reflux esophagitis and Helicobacter pylori (H.pylori) infection and their interrelationship in healthy young Japanese volunteers. Methods Between 2010 and 2016, 550 fifth-year medical students at Saga Medical School, aged 22 to 30 years, underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease). H. pylori infection was determined by detecting urinary immunoglobulin G antibodies. Results H. pylori antibodies were detected in 45 of the 550 subjects (8.2%). Endoscopic reflux esophagitis was detected in 38 out of 550 (6.9%): grade A in 37 subjects (97.3%) and grade B in 1. Most subjects with reflux esophagitis were H. pylori-negative (35/37). Nodular gastritis was observed in 33.3% (15/45) of H. pylori-positive subjects. The risk factors for H. pylori infection were drinking well water in childhood, nodular gastritis, and duodenal ulcer scars. The risk factors for endoscopic reflux esophagitis were male gender and obesity (body mass index ≥25). Conclusion This study describes the risk factors for H. pylori infection and reflux esophagitis in healthy young Japanese subjects. The prevalence of reflux esophagitis was relatively high, and the infection rate of H. pylori was low compared with the aged Japanese population.

The evaluation of potential pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers.

PubMed

Tortorici, Michael A; Parks, Virginia; Matschke, Kyle; Korth-Bradley, Joan; Patat, Alain

2013-04-01

Sirolimus and tacrolimus are immunosuppressive compounds that have been used concomitantly in renal transplant patients. Both drugs are dosed orally and have common intestinal and hepatic metabolism and intestinal transport mechanisms. As such, there is a potential for pharmacokinetic drug interaction. A single-dose, open-label, four-period, four-treatment, randomized crossover study was conducted in 27 healthy fasting volunteers. Each subject received a 15-mg oral dose of sirolimus alone, a 10-mg oral dose of tacrolimus alone, sirolimus and tacrolimus administered simultaneously, and tacrolimus administered 4 h before sirolimus. Whole blood and plasma samples for sirolimus and tacrolimus testing were analyzed by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were assessed using noncompartmental methods and were compared using analysis of variance (ANOVA). The geometric mean ratio and 90 % confidence interval (CI) area under the concentration-time curve from time 0 to infinity (AUCinf) for sirolimus administered simultaneously with tacrolimus versus sirolimus alone were 97 and 89-106, respectively, and, when administered in a staggered approach versus sirolimus alone, 107 and 98-117, respectively. The geometric mean ratio (%) and 90 % CI AUCinf for tacrolimus administered simultaneously with sirolimus versus tacrolimus alone were 92 and 82-102, respectively, and, when administered in a staggered approach versus tacrolimus alone, 94 and 84-105, respectively. The results of this study demonstrate a lack of any clinically important drug interaction between sirolimus and tacrolimus in healthy subjects after single-dose administration. However, due to the complexity of anti-rejection immunosuppressive therapy dosing, we suggest that sirolimus and tacrolimus concentration monitoring be performed when changes in dosing are made for either drug regimen.

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study.

PubMed

V V N Kothapalli, Satya; Altman, Michael B; Zhu, Lifei; Partanen, Ari; Cheng, Galen; Gach, H Michael; Straube, William; Zoberi, Imran; Hallahan, Dennis E; Chen, Hong

2018-01-04

Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.

Acetylsalicylic Acid Daily vs Acetylsalicylic Acid Every 3 Days in Healthy Volunteers: Effect on Platelet Aggregation, Gastric Mucosa, and Prostaglandin E2 Synthesis.

PubMed

Ferreira, Plinio Minghin Freitas; Gagliano-Jucá, Thiago; Zaminelli, Tiago; Sampaio, Marinalva Ferreira; Blackler, Rory Willian; Trevisan, Miriam da Silva; Novaes Magalhães, Antônio Frederico; De Nucci, Gilberto

2016-07-01

Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis. © 2015, The American College of Clinical Pharmacology.

Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers

PubMed Central

Kim, Tae-Eun; Ha, Na; Kim, Yunjeong; Kim, Hyunsook; Lee, Jae Wook; Jeon, Ji-Young; Kim, Min-Gul

2017-01-01

Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted. On Day 1, 20 mg of rosuvastatin was given to all subjects. After a 3-day washout period, the subjects received 20 mg of rosuvastatin plus 300 mg of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea (Day 4). After a 10-day pretreatment of EGCG up to Day 14, they received rosuvastatin (20 mg) plus EGCG (300 mg) once again (Day 15). Blood samples for the pharmacokinetic assessments were collected up to 8 hours after each dose of rosuvastatin. A total of 13 healthy volunteers were enrolled. Compared with the administration of rosuvastatin alone, the concomitant use at Day 4 significantly reduced the area under the concentration–time curve from time 0 to the last measurable time (AUClast) by 19% (geometric mean ratio 0.81, 90% confidence interval [CI] 0.67–0.97) and the peak plasma concentration (Cmax) by 15% (geometric mean ratio 0.85, 90% CI 0.70–1.04). AUClast or Cmax of rosuvastatin on Day 15 was not significantly different from that on Day 1. This study demonstrated that co-administration of EGCG reduces the systemic exposure of rosuvastatin by 19%, and pretreatment of EGCG can eliminate that effect of co-administration of EGCG. PMID:28533679

Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

PubMed

Yassen, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L; Danhof, M; Dahan, A

2007-01-01

The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62).

R-wave peak time at lead II in Chinese healthy adults.

PubMed

Deng, Jinhua; Chen, Tingting; Zeng, Chujuan; Lu, Nan; Zhou, Lihong; Tan, Xuerui; Yu, Min

2016-05-10

Wide QRS complex tachycardia (WCT) is a common arrhythmia. How to differentiate between WCTs is a challenge in clinical practice. Recently R-wave peak time (RWPT) at lead II was reported to be a helpful and simple tool for differentiating WCTs. However, it has remained unknown about the reference range of RWPT at lead II. In present study, we aimed to investigate the reference range of RWPT at lead II in Chinese healthy adults. A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in Southern China. Two thousand four hundred healthy adults aged 21-80 years with no history of structural heart diseases were included. RWPT at lead II was determined. Of 2400 healthy adults, 1200 men and 1200 women were included. The differences of age, mean heart rate and mean QRS duration at lead II between male and female were not significant. RWPT ranged from 16 to 42 ms in male while from 16 to 44 ms in female. The 95 % reference range of RWPT in normal male and female are 19.91 ~ 39.55 ms and 21.75 ~ 37.67 ms, respectively. Compared with the female, the male had a significantly longer RWPT at lead II (29.73 ± 5.01 ms vs 29.71 ± 4.06 ms in female, P = 0.000). Our study showed that RWPT at lead II is different between male and female. The male had a significantly longer RWPT at lead II than the female.

Detection of critical cerebral desaturation thresholds by three regional oximeters during hypoxia: a pilot study in healthy volunteers.

PubMed

Tomlin, Kerry L; Neitenbach, Anna-Maria; Borg, Ulf

2017-01-13

Regional oximetry is increasingly used to monitor post-extraction oxygen status of the brain during surgical procedures where hemodynamic fluctuations are expected. Particularly in cardiac surgery, clinicians employ an interventional algorithm to restore baseline regional oxygen saturation (rSO 2 ) when a patient reaches a critical desaturation threshold. Evidence suggests that monitoring cardiac surgery patients and intervening to maintain rSO 2 can improve postoperative outcomes; however, evidence generated with one manufacturer's device may not be applicable to others. We hypothesized that regional oximeters from different manufacturers respond uniquely to changes in oxygen saturation in healthy volunteers. Three devices were tested: INVOS™ 5100C (Medtronic), EQUANOX™ 7600 (Nonin), and FORE-SIGHT™ (CASMED) monitors. We divided ten healthy subjects into two cohorts wearing a single sensor each from INVOS and EQUANOX (n = 6), or INVOS and FORE-SIGHT (n = 4). We induced and reversed hypoxia by adjusting the fraction of inspired oxygen. We calculated the magnitude of absolute rSO 2 change and rate of rSO 2 change during desaturation and resaturation, and determined if and when each device reached a critical interventional rSO 2 threshold during hypoxia. All devices responded to changes in oxygen directionally as expected. The median absolute rSO 2 change and the rate of rSO 2 change was significantly greater during desaturation and resaturation for INVOS compared with EQUANOX (P = 0.04). A similar but nonsignificant trend was observed for INVOS compared with FORE-SIGHT; our study was underpowered to definitively conclude there was no difference. A 10% relative decrease in rSO 2 during desaturation was detected by all three devices across the ten subjects. INVOS met a 20% relative decrease threshold in all subjects of both cohorts, compared to 1 with EQUANOX and 2 with FORE-SIGHT. Neither EQUANOX nor FORE-SIGHT reached a 50% absolute rSO 2 threshold

Serum reference interval of ARCHITECT alpha-fetoprotein in healthy Chinese Han adults: Sub-analysis of a prospective multi-center study.

PubMed

Yan, Cunling; Yang, Jia; Wei, Lianhua; Hu, Jian; Song, Jiaqi; Wang, Xiaoqin; Han, Ruilin; Huang, Ying; Zhang, Wei; Soh, Andrew; Beshiri, Agim; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-02-01

Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study (ClinicalTrials.gov Identifier: NCT03047603). This analysis included a total of 530 participants (41.43±12.14years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0-7.07ng/mL (LOQ- 97.5th percentiles). The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Calcium carbonate does not affect nilotinib pharmacokinetics in healthy volunteers.

PubMed

Tawbi, Hussein A; Tran, An L; Christner, Susan M; Lin, Yan; Johnson, Matthew; Mowrey, Emily; Appleman, Leonard R; Stoller, Ronald; Miller, Brian M; Egorin, Merrill J; Beumer, Jan H

2013-11-01

Gastric upset is a common side effect of nilotinib therapy, and calcium carbonate is frequently used concomitantly, either as antacid or as calcium supplementation. With the increasing number of oral agents in cancer therapy, oral drug-drug interactions are becoming more relevant. Nilotinib has already been shown to be absorbed to a much lesser extent when co-administered with proton pump inhibitors. Because exposure to sub-therapeutic concentrations of anticancer drugs such as nilotinib may result in selection of resistant clones and ultimately relapse, we studied the effect of a calcium carbonate supplement (Tums Ultra 1000®) on nilotinib pharmacokinetics. Calcium carbonate may be co-administered with nilotinib without significantly affecting the pharmacokinetics of nilotinib and potentially impacting efficacy. Nilotinib is a second-generation oral tyrosine kinase inhibitor with superior efficacy compared with imatinib mesylate in the treatment for chronic phase chronic myelogenous leukemia. Calcium carbonate is commonly used as a source of calcium supplementation or as antacid to ameliorate the gastrointestinal side effects associated with nilotinib, which could have unknown effects on nilotinib absorption. The purpose of this study was to provide information on the effect of calcium carbonate on the PK of nilotinib in healthy volunteers. Healthy subjects were enrolled in a two-period, open-label, single-institution, randomized, cross-over, fixed-schedule study. In one period, each subject received 400 mg of nilotinib p.o. In the other period, 4,000 mg of calcium carbonate (4 X Tums Ultra 1000®) was administered p.o. 15 min prior to the nilotinib dose. Plasma samples were collected at specified timepoints, concentrations of nilotinib were quantitated by LC-MS, and data were analyzed non-compartmentally. Eleven subjects were evaluable. Calcium supplementation did not significantly affect nilotinib pharmacokinetic parameters including area under the plasma

Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

PubMed Central

King, D J; Devaney, N

1988-01-01

The cardiovascular, anticholinergic and central effects of single doses of 30, 45 and 60 mg of sibutramine hydrochloride (BTS 54524), a new potential antidepressant, were compared with amitriptyline (50 mg) and placebo given at weekly intervals in a randomised design to six healthy male volunteers. Sibutramine was associated with increases in both supine heart rate and systolic blood pressure at 1, 2 and 6 h after 60 mg (P less than 0.05). Amitriptyline caused a significant 50-60% decrease in salivation compared with placebo at 2 and 6 h but there were no changes with sibutramine. No significant changes in pupil size were detected with either drug. Visual analogue rating scales (VARS) revealed significant drowsiness with amitriptyline but neither sedative nor stimulant effects with sibutramine. Impairments of simple auditory and visual reaction times, visual two-choice reaction time, finger tapping and trail making, measured using an automated test battery, occurred with amitriptyline compared with sibutramine. If sibutramine proves to be an effective antidepressant it should be devoid of anticholinergic or central depressant effects. Chronic dosage studies are indicated to evaluate the clinical significance of its cardiovascular effects. PMID:3207566

Tryptophan Depletion and Emotional Processing in Healthy Volunteers at High Risk for Depression

PubMed Central

Feder, Adriana; Skipper, Jamie; Blair, James R.; Buchholz, Katherine; Mathew, Sanjay J.; Schwarz, Markus; Doucette, John T.; Alonso, Angelique; Collins, Katherine A.; Neumeister, Alexander; Charney, Dennis S.

2014-01-01

Background Studies in depressed patients have demonstrated the presence of emotional bias toward negative stimuli, as well as dysregulated brain serotonin function. The present study compared the effects of acute tryptophan depletion (ATD) on both an emotional processing and a planning task in never-depressed healthy volunteers at high and low familial risk for depression. Methods Young adults with no personal psychiatric history were stratified into two groups based on family history (n = 25). Participants were enrolled in a randomized, double-blind, placebo-controlled crossover ATD study and completed the affective go/no-go and Tower of London tasks once during each condition. Results There was a significant treatment by valence by group interaction on the affective go/no-go, driven primarily by a greater frequency of inappropriate responses to sad than to happy distracters in the high-risk group during ATD. No group differences were observed on the Tower of London. Conclusions Asymptomatic individuals at high familial risk for depression showed abnormalities in emotional processing while undergoing experimentally induced tryptophan depletion. These findings support emotional processing disturbances as potential trait-level abnormalities associated with the risk of mood disorder. PMID:21377656

Pharmacokinetics and bioequivalence study of two brands of loxoprofen tablets in healthy volunteers.

PubMed

Jhee, Ok Hwa; Lee, Min Ho; Shaw, Leslie M; Lee, Seo Eun; Park, Jin Hee; Kang, Ju Seop

2007-01-01

The aims of this study were to assess the pharmacokinetics and bioequivalence of two brands of loxoprofen (CAS 80832-23-6) 60 mg tablets in healthy male volunteers. The several pharmacokinetic parameters were evaluated after an oral administration after an overnight fast according to a single dose, two-sequence, and cross-over randomized design with a 1-week washout interval. Serial blood samples were collected throughout 10 h after administration of the reference and test drug. Plasma was analyzed by validated HPLC with UV detection. Several pharmacokinetic parameters, including AUC(infnity), AUC(t), C(max), T(max), T1/2, and Ke were determined from blood concentrations of both formulations. AUC(t), AUC(infinity) and C(max) were evaluated for bioequivalence after log-transformation of data using ANOVA with 90% confidence interval level. The parametric 90% confidence intervals of AUC(t), AUC(infinity), and C(max) were 90.13-106.34%, 91.43-106.94%, and 91.17-108.53%, respectively. All of the tested parameters were within the acceptable range of 80-125%. Based on these statistical considerations, it was concluded that the test drug was bioequivalent to the reference drug.

Is the Frequency in Somatosensory Electrical Stimulation the Key Parameter in Modulating the Corticospinal Excitability of Healthy Volunteers and Stroke Patients with Spasticity?

PubMed

Garcia, Marco Antonio Cavalcanti; Catunda, João Marcos Yamasaki; de Souza, Marcio Nogueira; Fontana, Ana Paula; Sperandei, Sandro; Vargas, Claudia D

2016-01-01

Somatosensory electrical stimulation (SES) has been proposed as an approach to treat patients with sensory-motor impairment such as spasticity. However, there is still no consensus regarding which would be the adequate SES parameters to treat those deficits. Therefore, the aim of this study was to evaluate the effects of applying SES over the forearm muscles at four different frequencies of stimulation (3, 30, 150, and 300 Hz) and in two intervals of time (5' and 30') by means of transcranial magnetic stimulation and Hoffmann's reflex (H-reflex) in healthy volunteers (Experiments  I and II). A group of stroke patients (Experiment  III) was also preliminary evaluated to ascertain SES effects at a low frequency (3 Hz) applied for 30' over the forearm spastic flexors muscles by measuring the wrist joint passive torque. Motor evoked potentials and the H-reflex were collected from different forearm and hand muscles immediately before and after SES and up to 5' (Experiment  I) and 10' (Experiments  I and II) later. None of the investigated frequencies of SES was able to operate as a key in switching modulatory effects in the central nervous system of healthy volunteers and stroke patients with spasticity.

Magnetic Resonance Elastography: Measurement of Hepatic Stiffness Using Different Direct Inverse Problem Reconstruction Methods in Healthy Volunteers and Patients with Liver Disease.

PubMed

Saito, Shigeyoshi; Tanaka, Keiko; Hashido, Takashi

2016-02-01

The purpose of this study was to compare the mean hepatic stiffness values obtained by the application of two different direct inverse problem reconstruction methods to magnetic resonance elastography (MRE). Thirteen healthy men (23.2±2.1 years) and 16 patients with liver diseases (78.9±4.3 years; 12 men and 4 women) were examined for this study using a 3.0 T-MRI. The healthy volunteers underwent three consecutive scans, two 70-Hz waveform and a 50-Hz waveform scans. On the other hand, the patients with liver disease underwent scanning using the 70-Hz waveform only. The MRE data for each subject was processed twice for calculation of the mean hepatic stiffness (Pa), once using the multiscale direct inversion (MSDI) and once using the multimodel direct inversion (MMDI). There were no significant differences in the mean stiffness values among the scans obtained with two 70-Hz and different waveforms. However, the mean stiffness values obtained with the MSDI technique (with mask: 2895.3±255.8 Pa, without mask: 2940.6±265.4 Pa) were larger than those obtained with the MMDI technique (with mask: 2614.0±242.1 Pa, without mask: 2699.2±273.5 Pa). The reproducibility of measurements obtained using the two techniques was high for both the healthy volunteers [intraclass correlation coefficients (ICCs): 0.840-0.953] and the patients (ICC: 0.830-0.995). These results suggest that knowledge of the characteristics of different direct inversion algorithms is important for longitudinal liver stiffness assessments such as the comparison of different scanners and evaluation of the response to fibrosis therapy.

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

PubMed

Padgaonkar, K A; Revankar, S N; Bhatt, A D; Vaz, J A; Desai, N D; D'Sa, S; Shah, V; Gandewar, K

1999-07-01

To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals.

PubMed

Istaces, Nicolas; Gulbis, Béatrice

2015-07-01

Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value. Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage. In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages. Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

In vivo interaction of ketoconazole and sucralfate in healthy volunteers.

PubMed Central

Carver, P L; Berardi, R R; Knapp, M J; Rider, J M; Kauffman, C A; Bradley, S F; Atassi, M

1994-01-01

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h. PMID:7910724

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey

PubMed Central

Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness–cognition relationship in Chinese older adults (OAs). Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness–cognition relationship. Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Discussion: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness–cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. PMID:27013536

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single and Multiple Doses of Trandolapril, an Effective Angiotensin-Converting Enzyme Inhibitor, in Healthy Chinese Subjects.

PubMed

Li, Xiaojiao; Liu, Chang; Wu, Min; Zhang, Hong; Sun, Yanfu; Cheng, Longmei; Chen, Hong; Liu, Chengjiao; Yang, Lizhi; Zhang, Qi; Cao, Yuchen; Gu, Jingkai; Ding, Yanhua

2016-08-01

Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor. This study was designed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six men and six women) were randomized into a single-dose, 3 × 3 crossover study (1-2-4 mg, 2-4-1 mg, and 4-1-2 mg), and a multiple-dose study (2 mg/day, 6 days). Serial blood and urine samples were collected after drug administration and analyzed using a validated LC-MS/MS method, and the trandolapril and trandolaprilat PK parameters were obtained. PD was evaluated by the changes in blood pressure and heart rates after dosing. Tolerability was assessed by monitoring adverse events, vital signs, ECGs, and changes in laboratory tests. In the single-dose study, trandolapril was absorbed rapidly, and peak plasma levels (C max, 1.57, 3.77, and 7.99 ng/mL) and AUCs (1.89, 3.46, and 6.47 ng/mL) were dose-dependent. The AUC0-∞ of trandolaprilat was dose-dependent, but in a non-linear fashion. The cumulative urine excretion of trandolapril and trandolaprilat was 5.51, 6.20, and 7.41 % for three doses, respectively. In the multiple-dose study, steady-state pharmacokinetics was observed; there was no trandolapril accumulation, but there was mild trandolaprilat accumulation (R = 1.67). Trandolapril was well tolerated. The most pronounced reductions in blood pressure were observed at 8 h after administration, which was later than T max. No orthostatic hypotension occurred. The pharmacokinetics and pharmacodynamics following single and multiple oral doses trandolapril in healthy Chinese subjects are similar to those observed in non-Chinese healthy subjects.

Vedolizumab Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability Following Administration of a Single, Ascending, Intravenous Dose to Healthy Volunteers.

PubMed

Rosario, Maria; Wyant, Timothy; Leach, Timothy; Sankoh, Serap; Scholz, Catherine; Parikh, Asit; Fox, Irving; Feagan, Brian G

2016-11-01

Vedolizumab, a humanized monoclonal antibody against the α 4 β 7 integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn's disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab were evaluated in healthy volunteers. Forty-nine participants (in five cohorts) were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of either vedolizumab (0.2, 0.5, 2.0, 6.0, or 10.0 mg/kg) or placebo. Blood samples were collected for measurement of vedolizumab serum concentrations and α 4 β 7 saturation on peripheral blood lymphocytes by vedolizumab. Pharmacokinetic parameters were computed using a non-compartmental approach. Adverse events were monitored. Vedolizumab maximum observed serum concentration (C max ) demonstrated dose proportionality over the dose range tested. Greater than dose-proportional increases in area under the serum concentration-time curve from time 0 to infinity (AUC 0-inf ) and shorter terminal elimination half-life (t 1/2 ) were observed from 0.2 to 2.0 mg/kg, suggestive of nonlinear pharmacokinetics at lower doses. At doses higher than 2.0 mg/kg, these parameters increased dose proportionally. Saturation of α 4 β 7 was at or near maximal levels (>90 %) at all doses and time points when vedolizumab was measurable in serum. A total of 21 of 39 (54 %) vedolizumab-treated participants were anti-drug antibody (ADA) positive, and 11 (28 %) were persistently ADA positive. Overall, no adverse event signals, including serious infections or malignancies, were apparent. Vedolizumab exhibited target-mediated disposition, characterized by a rapid, saturable, nonlinear elimination process at low concentrations and a slower linear elimination process at higher concentrations. Nearly complete α 4 β 7 saturation was observed at all doses. A single intravenous infusion of vedolizumab

Orange juice affects acylcarnitine metabolism in healthy volunteers as revealed by a mass-spectrometry based metabolomics approach.

PubMed

Moreira, Vanessa; Brasili, Elisa; Fiamoncini, Jarlei; Marini, Federico; Miccheli, Alfredo; Daniel, Hannelore; Lee, Jennifer Ji Hye; Hassimotto, Neuza Mariko Aymoto; Lajolo, Franco Maria

2018-05-01

Citrus juices, especially orange juice, constitute rich sources of bioactive compounds with a wide range of health-promoting activities. Data from epidemiological and in vitro studies suggest that orange juice (OJ) may have a positive impact on lipid metabolism. However, the effect of orange juice intake on blood lipid profile is still poorly understood. We have used two different blood samples, Dried Blood Spots (DBS) and plasma, to assess the effect of two-week orange juice consumption in healthy volunteers by a mass-spectrometry based metabolomics approach. DBS were analysed by liquid chromatography mass spectrometry (LC-MS) and plasma samples were analysed by the gas chromatography mass spectrometry (GC-MS). One hundred sixty-nine lipids including acylcarnitines (AC), lysophosphatidylcholines (LysoPC), (diacyl- and acyl-alkyl-) phosphatidylcholines (PC aa and PC ae) and sphingomyelins (SM) were identified and quantified in DBS. Eighteen fatty acids were identified and quantified in plasma. Multivariate analysis allowed to identify an increase in C3:1, C5-DC(C6-OH), C5-M-DC, C5:1-DC, C8, C12-DC, lysoPC18:3, myristic acid, pentadecanoic acid, palmitoleic and palmitic acid and a decrease in nervonic acid, C0, C2, C10, C10:1, C16:1, C16-OH, C16:1-OH, C18-OH, PC aa C40:4, PC ae C38:4, PC ae C42:3, PC ae C42:4 and cholesterol levels after orange juice intake. A two-week period of orange juice intake could affect fatty acids β-oxidation through mitochondrial and peroxisomal pathways, leading to an increase of short-chain acylcarnitines and a decrease of medium and long-chain acylcarnitines. This is the first report analyzing the effect of orange juice intake in healthy volunteers using a dried blood spot-based metabolomics approach. Copyright © 2018 Elsevier Ltd. All rights reserved.

Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

PubMed

Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

2018-05-01

Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

Aqueous humour dynamics and biometrics in the ageing Chinese eye.

PubMed

Guo, Tao; Sampathkumar, Sruthi; Fan, Shan; Morris, Nathan; Wang, Fang; Toris, Carol B

2017-09-01

This study evaluates ocular biometrics and aqueous humour dynamics (AHD) in healthy Chinese volunteers to determine how the various ocular parameters interact to maintain physiological intraocular pressure (IOP) at all ages. Sixty-nine volunteers enrolled in this cross-sectional study and were categorised into young (20-30 years) and old (≥50 years) groups. Measurements included IOP, ocular biometrics and AHD. Data were analysed using mixed model with random sampling to account for both eyes from the same individual. Spearman's rank correlation with bootstrap resampling was used to find associations between parameters. Compared with young subjects, old subjects had significantly (p<0.05) thinner corneas (CCT; 549.7±5.7 vs 530.6±5.3 µm; mean±SEM), shallower anterior chambers (3.14±0.05 vs 2.37±0.05 mm) and slower aqueous flow (Fa; 3.0±0.1 vs 2.7±0.1 µL/min). Uveoscleral outflow slowed (Fu; 1.0±0.2 vs 0.7±0.1) but not significantly. A positive linear association between IOP and episcleral venous pressure was found (young: R 2 =0.16; old: R 2 =0.08). Negative correlation between Fa and CCT (R 2 =0.06) and positive correlation between Fa and outflow facility (R 2 =0.08) was found in old participants. In the healthy ageing Chinese eye, IOP remains unchanged, while Fa slows, which is counterbalanced by slowing of Fu. Aqueous humour exits the eye preferentially through the trabecular route at all ages. Ageing is also associated with shallowing of the anterior chamber and thinning of the cornea. A slower Fa with lower outflow facility supports existence of autoregulatory mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pharmacokinetics of Empagliflozin and Pioglitazone After Coadministration in Healthy Volunteers.

PubMed

Macha, Sreeraj; Mattheus, Michaela; Pinnetti, Sabine; Broedl, Uli C; Woerle, Hans J

2015-07-01

The aim was to investigate the effects of coadministration of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin with the thiazolidinedione pioglitazone. In study 1, 20 healthy volunteers received 50 mg of empagliflozin alone for 5 days, followed by 50 mg of empagliflozin coadministered with 45 mg of pioglitazone for 7 days and 45 mg of pioglitazone alone for 7 days in 1 of 2 treatment sequences. In study 2, 20 volunteers received 45 mg of pioglitazone alone for 7 days and 10, 25, and 50 mg of empagliflozin for 9 days coadministered with 45 mg of pioglitazone for the first 7 days in 1 of 4 treatment sequences. Pioglitazone exposure (Cmax and AUC) increased when coadministered with empagliflozin versus monotherapy in study 1. The geometric mean ratio (GMR) for pioglitazone Cmax at steady state (Cmax,ss) and for AUC during the dosing interval at steady state (AUCτ,ss) when coadministered with empagliflozin versus administration alone was 187.89% (95% CI, 166.35%-212.23%) and 157.97% (95% CI, 148.02%-168.58%), respectively. Because an increase in pioglitazone exposure was not expected, based on in vitro data, a second study was conducted with the empagliflozin doses tested in Phase III trials. In study 2, pioglitazone exposure decreased marginally when coadministered with empagliflozin. The GMR for pioglitazone Cmax,ss when coadministered with empagliflozin versus administration alone was 87.74% (95% CI, 73.88%-104.21%) with empagliflozin 10 mg, 90.23% (95% CI, 66.84%-121.82%) with empagliflozin 25 mg, and 89.85% (95% CI, 71.03%-113.66%) with empagliflozin 50 mg. The GMR for pioglitazone AUCτ,ss when coadministered with empagliflozin versus administration alone was 90.01% (95% CI, 77.91%-103.99%) with empagliflozin 10 mg, 88.98% (95% CI, 72.69%-108.92%) with empagliflozin 25 mg, and 91.10% (95% CI, 77.40%-107.22%) with empagliflozin 50 mg. The effects of empagliflozin on pioglitazone exposure are not considered to be clinically relevant

Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate-Amodiaquine and Artemisinin-Piperaquine in Healthy Volunteers for Preselection Malaria Therapy.

PubMed

Quang, Nguyen Ngoc; Chavchich, Marina; Anh, Chu Xuan; Birrell, Geoffrey W; van Breda, Karin; Travers, Thomas; Rowcliffe, Kerryn; Edstein, Michael D

2018-05-07

The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick ® ] and artesunate-amodiaquine [ARS-AQ] [Coarsucam ™ ]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs. The area under the concentration-time curve (AUC 0-∞ ) was 3.6-fold higher for dihydroartemisinin (active metabolite of ARS) than that for ARN, whereas the AUC 0-∞ of desethylamodiaquine (active metabolite of AQ) was 2.0-fold lower than that of PPQ. Based on the 50% inhibitory dilution values of the volunteers' plasma samples collected from 0.25 to 3 hours after the last dose, the ex vivo activity of ARS-AQ was 2.9- to 16.2-fold more potent than that of ARN-PPQ against the drug-sensitive D6 Plasmodium falciparum line. In addition, at 1.5, 4.0, and 24 hours after the last dose, the ex vivo activity of ARS-AQ was 20.8-, 3.5-, and 8.5-fold more potent than that of ARN-PPQ against the ARN-sensitive MRA1239 line. By contrast, at 1.5 hours, the ex vivo activity of ARS-AQ was 5.4-fold more active than that of ARN-PPQ but had similar activities at 4 and 24 hours against the ARN-resistant MRA1240 line. The PK-PD data suggest that ARS-AQ possesses superior antimalarial activity than that of ARN-PPQ and would be the preferred ACT for further in vivo efficacy testing in multidrug-resistant falciparum malaria areas.

The Effect of Nizatidine, a MATE2K Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin in Healthy Volunteers

PubMed Central

Morrissey, Kari M.; Stocker, Sophie L.; Chen, Eugene C.; Castro, Richard A.; Brett, Claire M.; Giacomini, Kathleen M.

2015-01-01

Background and Objectives In the proximal tubule, basic drugs are transported from the renal cells to the tubule lumen through the concerted action of the H+/organic cation antiporters, multidrug and toxin extrusion 1 (MATE1) and 2K (MATE2K). Dual inhibitors of the MATE transporters have been shown to have a clinically relevant effect on the pharmacokinetics of concomitantly administered basic drugs. However, the clinical impact of selective renal organic cation transport inhibition on the pharmacokinetics and pharmacodynamics of basic drugs, such as metformin, is unknown. This study sought to identify a selective MATE2K inhibitor in vitro and to determine its clinical impact on the pharmacokinetics and pharmacodynamics of metformin in healthy subjects. Methods A strategic cell-based screen of 71 U.S. Food and Drug Administration (FDA)-approved medications was conducted to identify selective inhibitors of renal organic cation transporters that are capable of inhibiting at clinically relevant concentrations. From this screen, nizatidine was identified and predicted to be a clinically potent and selective inhibitor of MATE2K-mediated transport. The effect of nizatidine on the pharmacokinetics and pharmacodynamics of metformin was evaluated in 12 healthy volunteers in an open-label, randomized, two-phase crossover drug-drug interaction (DDI) study. Results In healthy volunteers, the MATE2K-selective inhibitor, nizatidine, significantly increased the apparent volume of distribution, half-life and hypoglycemic activity of metformin. However, despite achieving unbound maximum concentrations greater than the in vitro inhibition potency (IC50) of MATE2K-mediated transport, nizatidine did not affect the renal clearance or net secretory clearance of metformin. Conclusion This study demonstrates that a selective inhibition of MATE2K by nizatidine, affected the apparent volume of distribution, tissue levels and peripheral effects of metformin. However, nizatidine did not alter

Adolescents' Perceptions of Healthy Eating and Communication about Healthy Eating

ERIC Educational Resources Information Center

Chan, Kara; Prendergast, Gerard; Gronhoj, Alice; Bech-Larsen, Tino

2009-01-01

Purpose: The purpose of this paper is to explore Chinese adolescents' perceptions of healthy eating, their perceptions of various socializing agents shaping their eating habits, and their opinions about various regulatory measures which might be imposed to encourage healthy eating. Design/methodology/approach: Four focus group interview sessions…

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania.