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Sample records for healthy human volunteers

  1. Effects of botropase on clotting factors in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    Ashok K Shenoy

    2014-01-01

    Full Text Available Objective: To evaluate the effects of botropase on various clotting factors in human volunteers. Materials and Methods: It was a prospective open label study conducted on human healthy volunteers. After the baseline screening, subjects fulfilling inclusion criteria were enrolled. On the study day, 1 ml of botropase was administered intravenously and after an hour same dose of botropase (1 ml was given by intramuscular (IM route. The efficacy and safety parameters were monitored up to 72 h from the time of intravenous (IV administration. Results: A total of 15 volunteers, belonging to 24-35 years of age were included in the study. Botropase significantly reduced the plasma level of fibrinogen and fibrin degradation products after 5 min of IV administration (P < 0.05. In addition, factor X was observed to reduce constantly by botropase administration suggesting enhanced turnover between 5 and 20 min of IV administration. Although botropase reduced clotting and bleeding time in all the volunteers, the data remains to be statistically insignificant. Conclusion: Present study demonstrated the safety and efficacy of botropase in human healthy volunteers. The study has shown that it is a factor X activator and reduces effectively clotting and bleeding time.

  2. Endostatin concentration in plasma of healthy human volunteers

    International Nuclear Information System (INIS)

    Shah, I.; Malik, M.O.; Khan, M.J.; Fatima, S.; Habib, S.H.

    2017-01-01

    Angiogenesis is involved in many cardiovascular and cancerous diseases, including atherosclerosis and is controlled by a fine balance between angiogenic and angiostatic mediators. Endostatin is one of the main angiostatic mediators, and inhibits angiogenesis and prevents progression of atherosclerosis. The available literature shows a broad range of concentrations in relatively small samples of healthy controls and is calculated by using different techniques. This study was aimed to determine the basal endostatin concentration in plasma of healthy volunteers, to fully understand its physiological role. Methods: Fifty healthy adult volunteers were recruited to the study. Participants were advised not to participate in any physical activity on the day before the blood sampling. The volunteers' physical activity, height, weight, heart rate and blood pressure were recorded. The samples were analysed for plasma endostatin concentration, using ELISA. The participants were divided by gender and ethnic groups to calculate any difference. Results: Endostatin and other variables were normally distributed. Most of the participants had a moderate level of physical activity with no gender related difference (p=0.370). The mean value for plasma endostatin in all samples was 105+-12 ng/ml with range of 81-132 ng/ml. For males, it was 107+-13 ng/ml, while for females; 102+-12 ng/ml. There were no significant gender or ethnicity related differences in endostatin concentration. Moreover, endostatin was not significantly related with any anthropometric and physical variable. Conclusion: This study gives endostatin levels in normal healthy people and show no gender and ethnicity related differences in endostatin levels. Endostatin was not related with any anthropometric and physical variable. (author)

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Effect of Resveratrol Treatment on the Pharmacokinetics of Diclofenac in Healthy Human Volunteers.

    Science.gov (United States)

    Bedada, Satish Kumar; Yellu, Narsimha Reddy; Neerati, Prasad

    2016-03-01

    The purpose of the present study was to assess the effect of resveratrol (RSV) treatment on the pharmacokinetics of diclofenac (DIC) in healthy human volunteers. The open-label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered daily for 10 days during treatment phase. A single dose of DIC 100 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after DIC dosing and analyzed by HPLC. Treatment with RSV significantly enhanced maximum plasma concentration (Cmax) (1.73 to 2.91 µg/mL), area under the curve (AUC) (5.05 to 9.95 g h/mL), half life (T1/2) (1.12 to 1.76 h) and significantly decreased elimination rate constant (Kel ) (0.71 to 0.41 h(-1)), apparent oral clearance (CL/F) (14.58 to 6.48 L/h) of DIC as compared to control. The geometric mean ratios for Cmax, AUC, T1/2, Kel and CL/F of DIC were 1.75, 2.12, 1.65, 0.61 and 0.47, respectively were outside the limits of 0.8-1.25, which indicates clinically significant interaction between DIC and RSV. The results suggest that the altered pharmacokinetics of DIC might be attributed to RSV mediated inhibition of CYP2C9 enzyme. Therefore, combination therapy of DIC along with RSV may represent a novel approach to reduce dosage and results in reduced gastrointestinal side effects of DIC. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2013-07-30

    Experimental evidences have demonstrated that Nigella sativa Linn. seed (NS) has positive modulation effects on aged rats with memory impairments, prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats. NS has neuroprotective, nephroprotective, lung protective, cardioprotective, hepatoprotective activities as established by previous studies on animals. Several clinical trials with NS on human have also demonstrated beneficial effect. The present study was designed to investigate the effects of NS on memory, attention and cognition in healthy elderly volunteers. Furthermore, safety profile of NS was assessed during the nine-week study period. Forty elderly volunteers were recruited and divided randomly into group A and group B--each consisting of 20 volunteers. The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner. All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks. The neuropsychological tests were logical memory test, digit span test, Rey-Osterrieth complex figure test, letter cancellation test, trail making test and stroop test. Safety profile was assessed by measuring biochemical markers of Cardiac (total cholesterol, triglycerides and high density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein cholesterol, creatine kinase-MB); Liver (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin) and Kidney (creatinine and blood urea nitrogen) through using commercial kits. There was significant difference (p0.05) in any of the biochemical markers of cardiac, liver, kidney function during this nine-week study period. The current study demonstrates the role of NS in enhancing memory, attention and cognition. Therefore, whether NS

  8. Scintigraphic evaluation of floating, gastroretentive formulation of clarithramycin in healthy human volunteers

    International Nuclear Information System (INIS)

    Ali, Raisuddin; Aji Alex, M.R.; Dutta, M.; Singh, Thakuri; Bhatnagar, A.; Bajaj, M.; Singla, Y.P.; Ahmad, F.J.; Khar, R.K.

    2010-01-01

    Full text: Objective of the present study concerns formulation and evaluation of oral buoyant effervescent tablets of clarithromycin for prolongation of gastric residence time (GRT) and to enhance eradication of Helicobacter pylori (H. pylori) for longer period of time. Materials and Methods: Clarithromycin (CLA) a macrolide antibiotic was chosen as the candidate drug for its immense potential as an Anti H. pylori agent. HPMC and/or xanthan gum were used as release-retarding polymer(s) whereas sodium bicarbonate (NaHCO 3 ) was utilized as a gas former. The tablets were prepared by wet granulation method. Formulations were evaluated for physicochemical properties, in vitro drug release as well as drug release kinetics and stability studies. In vivo gamma scintigraphic studies were assessed for the optimized buoyant gastroretentive tablets in six healthy human volunteers to study influence of nature of the dosage form i.e. conventional or sustained release gastroretentive tablets and the presence of food in the stomach on intragastric performance of gastroretentive tablets. Result: The fabricated tablets showed acceptable physiochemical properties. Non-fickian release transport was confirmed as the drug release mechanism from the prepared tablets. Optimized tablets composed of HPMC K15M, xanthan gum, and NaHCO 3 were promising systems exhibiting excellent floating properties. The overall performance was found to be highly sustained. Scintigraphic imaging revealed GRT of 320 min or more in fed state on the other hand GRT of 180 min or less in case of unfed state. Conclusion: The developed gastroretentive system has potential to increase efficacy of the therapy and improve patient

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

    Science.gov (United States)

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

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Scarce Evidence of Yogurt Lactic Acid Bacteria in Human Feces after Daily Yogurt Consumption by Healthy Volunteers

    OpenAIRE

    del Campo, Rosa; Bravo, Daniel; Cantón, Rafael; Ruiz-Garbajosa, Patricia; García-Albiach, Raimundo; Montesi-Libois, Alejandra; Yuste, Francisco-Javier; Abraira, Victor; Baquero, Fernando

    2005-01-01

    In a double-blind prospective study including 114 healthy young volunteers, the presence in human feces of the yogurt organisms Lactobacillus delbrueckii and Streptococcus thermophilus after repeated yogurt consumption (15 days) was analyzed by culture, specific PCR, and DNA hybridization of total fecal DNA. Detection of yogurt lactic acid bacteria in total fecal DNA by bacterial culture and PCR assay was consistently negative. DNA compatible with yogurt bacteria was found by hybridization ex...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

  13. Scarce Evidence of Yogurt Lactic Acid Bacteria in Human Feces after Daily Yogurt Consumption by Healthy Volunteers

    Science.gov (United States)

    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

  14. Effects of melatonin on prepulse inhibition, habituation and sensitization of the human startle reflex in healthy volunteers

    DEFF Research Database (Denmark)

    Lehtinen, Emilia K; Ucar, Ebru; Glenthøj, Birte Y

    2014-01-01

    Prepulse inhibition of the startle reflex (PPI) is an operational measure of sensorimotor gating, which is demonstrated to be impaired in patients with schizophrenia. In addition, a disruption of the circadian rhythm together with blunted melatonin secretion is regularly found in patients...... with schizophrenia and it is theorized that these may contribute to their attentional deficits. The aim of this study was to assess the effects of acute melatonin on healthy human sensorimotor gating. Twenty-one healthy male volunteers were administered melatonin or placebo after which their levels of PPI were...... assessed. Melatonin significantly reduced startle magnitude and ratings of alertness, but did not influence PPI, nor sensitization and habituation. However, when taking baseline scores in consideration, melatonin significantly increased PPI in low scoring individuals while significantly decreasing...

  15. Pain perception in healthy volunteers

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. Analysis of human blood plasma proteome from ten healthy volunteers from Indian population.

    Directory of Open Access Journals (Sweden)

    Poonam Gautam

    Full Text Available Analysis of any mammalian plasma proteome is a challenge, particularly by mass spectrometry, due to the presence of albumin and other abundant proteins which can mask the detection of low abundant proteins. As detection of human plasma proteins is valuable in diagnostics, exploring various workflows with minimal fractionation prior to mass spectral analysis, is required in order to study population diversity involving analysis in a large cohort of samples. Here, we used 'reference plasma sample', a pool of plasma from 10 healthy individuals from Indian population in the age group of 25-60 yrs including 5 males and 5 females. The 14 abundant proteins were immunodepleted from plasma and then evaluated by three different workflows for proteome analysis using a nanoflow reverse phase liquid chromatography system coupled to a LTQ Orbitrap Velos mass spectrometer. The analysis of reference plasma sample a without prefractionation, b after prefractionation at peptide level by strong cation exchange chromatography and c after prefractionation at protein level by sodium dodecyl sulfate polyacrylamide gel electrophoresis, led to the identification of 194, 251 and 342 proteins respectively. Together, a comprehensive dataset of 517 unique proteins was achieved from all the three workflows, including 271 proteins with high confidence identified by ≥ 2 unique peptides in any of the workflows or identified by single peptide in any of the two workflows. A total of 70 proteins were common in all the three workflows. Some of the proteins were unique to our study and could be specific to Indian population. The high-confidence dataset obtained from our study may be useful for studying the population diversity, in discovery and validation process for biomarker identification.

  17. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing; Pan, Donghui; Xu, Yuping; Yang, Min; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    We report the biodistribution and radiation dosimetry of an integrin α v β 3 specific PET tracer 18 F-AlF-NOTA-E[PEG 4 -c(RGDfk)] 2 (denoted as 18 F-Alfatide II). We also assessed the value of 18 F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of 18 F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18 F-FDG (5.55 MBq/kg) and 18 F-Alfatide II. Injection of 18 F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18 F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18 F-Alfatide II PET, while only ten lesions were visualized by 18 F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18 F-Alfatide II is feasible for human studies. 18 F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  18. A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers.

    Science.gov (United States)

    Okour, Malek; Derimanov, Geo; Barnett, Rodger; Fernandez, Esther; Ferrer, Santiago; Gresham, Stephanie; Hossain, Mohammad; Gamo, Francisco-Javier; Koh, Gavin; Pereira, Adrian; Rolfe, Katie; Wong, Deborah; Young, Graeme; Rami, Harshad; Haselden, John

    2018-03-01

    GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4) pathway, is being considered for development in humans. However, a key problem encountered during the preclinical evaluation of the compound was its inconsistent pharmacokinetic (PK) profile across preclinical species (mouse, rat and dog), which prevented reliable prediction of PK parameters in humans and precluded a well-founded assessment of the potential for clinical development of the compound. Therefore, an open-label microdose (100 μg, six subjects) first time in humans study was conducted to assess the human PK of GSK3191607 following intravenous administration of [14C]-GSK3191607. A human microdose study was conducted to investigate the clinical PK of GSK3191607 and enable a Go/No Go decision on further progression of the compound. The PK disposition parameters estimated from the microdose study, combined with preclinical in vitro and in vivo pharmacodynamic parameters, were all used to estimate the potential efficacy of various oral dosing regimens in humans. The PK profile, based on the microdose data, demonstrated a half-life (~17 h) similar to other antimalarial compounds currently in clinical development. However, combining the microdose data with the pharmacodynamic data provided results that do not support further clinical development of the compound for a single dose cure. The information generated by this study provides a basis for predicting the expected oral PK profiles of GSK3191607 in man and supports decisions on the future clinical development of the compound. © 2017 The British Pharmacological Society.

  19. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  20. Initial Evaluation of (99m)Tc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers.

    Science.gov (United States)

    Lipowska, Malgorzata; Klenc, Jeffrey; Folks, Russell D; Taylor, Andrew T

    2014-09-01

    Preclinical studies in rats showed that two of (99m)Tc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of (131)I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of (99m)Tc(CO)3(ASMA) isomers in healthy human subjects. Three ASMA ligands (rac-, L- and D-ASMA) were labeled with (99m)Tc(CO)3 using an IsoLink kit (Covidien), and each formed (99m)Tc(CO)3(ASMA) tracer was co-injected with (131)I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC. Image quality was excellent with all three agents. Each (99m)Tc(CO)3(ASMA) preparation was excreted unchanged in the urine. The plasma clearance ratio ((99m)Tc(CO)3(ASMA)/(131)I-OIH) was 81 ± 3 % for D-ASMA compared to only 20 ± 4 % for L-ASMA and 37 ± 7 % for rac-ASMA; the 81 % clearance ratio for D-ASMA isomer is still ∼ 30 % higher than the (99m)Tc-MAG3/(131)I-OIH clearance ratio (∼50-60 %). Red cell uptake was similar for all three tracers (6-9 %), and all tracers had a relatively rapid renal excretion; at 3 h, the (99m)Tc(CO)3(ASMA)/(131)I-OIH urine ratio was 100 ± 3 % for D-ASMA, 80 ± 2 % for L-ASMA and 88 ± 1 % for rac-ASMA. The renal excretion characteristics of (99m)Tc(CO)3(D-ASMA) in humans are superior to those of the other two (99m)Tc(CO)3(ASMA) isomers studied, but are still inferior to (131)I-OIH, even though there was no difference in the clearance of two of (99m)Tc(CO)3(ASMA) isomers and (131)I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of (99m)Tc(CO)3(ASMA) isomers to their subtle structural differences.

  1. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective.

    Science.gov (United States)

    Persson, Ingrid A L; Persson, Karin; Hägg, Staffan; Andersson, Rolf G G

    2011-01-01

    Evidence suggests that cocoa from the bean of Theobroma cacao L. has beneficial effects on cardiovascular disease. The aim of this study was to investigate if cocoa extract and dark chocolate influence angiotensin-converting enzyme (ACE) and nitric oxide (NO) in human endothelial cells (in vitro) and in healthy volunteers (in vivo). ACE activity was analyzed with a commercial radioenzymatic assay and measured in human endothelial cells from umbilical veins (HUVEC) after 10 minutes of incubation with cocoa extract. NO was measured after 24 hours of incubation. ACE activity and NO were measured at baseline and after 30, 60, and 180 minutes in 16 healthy volunteers after a single intake of 75 g of dark chocolate containing 72% cocoa. Significant inhibition of ACE activity (P cocoa inhibits ACE activity in vitro and in vivo.

  2. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. Safeguards for healthy volunteers in drug studies.

    Science.gov (United States)

    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.

  5. Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    18 F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate 18 F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods: 18 F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BP ND ), and SUVR. BP ND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased 18 F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R 2 > 0.93 was found between BP ND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although 18 F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BP ND , whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  6. Reference intervals for putative biomarkers of drug-induced liver injury and liver regeneration in healthy human volunteers.

    Science.gov (United States)

    Francis, Ben; Clarke, Joanna I; Walker, Lauren E; Brillant, Nathalie; Jorgensen, Andrea L; Park, B Kevin; Pirmohamed, Munir; Antoine, Daniel J

    2018-05-02

    The potential of mechanistic biomarkers to improve the prediction of drug-induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration as well as to characterize their natural variability and impact of diurnal variation. Serum samples from 200 healthy volunteers were recruited as part of a cross sectional study; of these, 50 subjects had weekly serial sampling over 3 weeks, while 24 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA-122 (miR-122), high mobility group box-1 (HMGB1), total keratin-18 (FL-K18), caspase cleaved keratin-18 (cc-K18), glutamate dehydrogenase (GLDH) and colony stimulating factor-1 (CSF-1) were assessed by validated assays. Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models (ALT 50 (41-50) U/l, miR-122 3548 (2912-4321) copies/µl, HMGB1 2.3 (2.2-2.4) ng/ml, FL-K18 475 (456-488) U/l, cc-K18 272 (256-291) U/l, GLDH 27 (26-30) U/l and CSF-1 2.4 (2.3-2.9) ng/ml). There was a small but significant intra-individual time random effect detected but no significant impact of diurnal variation was observed, with the exception of GLDH. Reference intervals for novel DILI biomarkers have been described for the first time. An upper limit of a reference range might represent the most appropriate method to utilize these data. Regulatory authorities have published letters of support encouraging further qualification of leading candidate biomarkers. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification. Drug-induced liver injury (DILI) has a big impact on patient health and the development of new medicines. Unfortunately, currently used blood-based tests to assess liver injury and recovery suffer from insufficiencies. Newer blood

  7. The Effect of Chronic Alprazolam Intake on Memory, Attention, and Psychomotor Performance in Healthy Human Male Volunteers

    Directory of Open Access Journals (Sweden)

    Zahid Sadek Chowdhury

    2016-01-01

    Full Text Available Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL and Delayed Matching to Sample (DMS tests for memory, Rapid Visual Information Processing (RVP for attention, and Choice Reaction Time (CRT for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.

  8. Availability and dose response of phytophenols from a wheat bran rich cereal product in healthy human volunteers.

    Science.gov (United States)

    Neacsu, Madalina; McMonagle, Jolene; Fletcher, Reg J; Hulshof, Toine; Duncan, Sylvia H; Scobbie, Lorraine; Duncan, Gary J; Cantlay, Louise; Horgan, Graham; de Roos, Baukje; Duthie, Garry G; Russell, Wendy R

    2017-03-01

    Phytophenols present in cereals are metabolised to compounds that could be partly responsible for the reduced risk of chronic diseases and all-cause mortality associated with fibre-rich diets. The bioavailability, form and in vivo concentrations of these metabolites require to be established. Eight healthy volunteers consumed a test meal containing a recommended dose (40 g) and high dose (120 g) of ready-to-eat wheat bran cereal and the systemic and colonic metabolites determined quantitatively by LC-MS. Analysis of the systemic metabolomes demonstrated that a wide range of phytophenols were absorbed/excreted (43 metabolites) within 5 h of consumption. These included 16 of the 21 major parent compounds identified in the intervention product and several of these were also found to be significantly increased in the colon. Not all of the metabolites were increased with the higher dose, suggesting some limitation in absorption due to intrinsic factors and/or the food matrix. Many compounds identified (e.g. ferulic acid and major metabolites) exhibit anti-inflammatory activity and impact on redox pathways. The combination of postprandial absorption and delivery to the colon, as well as hepatic recycling of the metabolites at these concentrations, is likely to be beneficial to both systemic and gut health. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Development and scintigraphic evaluation of submicron sized dry powder inhalation formulation of fluticasone propionate in healthy human volunteers

    International Nuclear Information System (INIS)

    Ali, Sultana S.; Ahmad, F.J.; Khar, R.K.; Rathore, V.P.; Ali, Rashid; Rawat, H.S.; Chopra, M.K.; Mittal, G.; Bhatnagar, A.

    2010-01-01

    Full text: Objective of the present study concerns formulation and evaluation of submicron sized dry powder inhalation formulation of Fluticasone propionate for the treatment of bronchial asthma, COPD and a new life saving treatment option in restrictive lung diseases such as Interstitial Lung Disease (ILD), toxic and non-cardiogenic pulmonary inflammations or pulmonary edema, which have no effective treatment presently. Materials and Methods: The submicron sized particles were prepared by precipitation method using acetone as solvent and water as antisolvent. Poloxamer F127 was used as stabilizer. Both submicronized and micronized particles were characterized using FTIR, XRD, DSC, SEM and TEM. The mass median aerodynamic diameter (MMAD) of the submicronized and micronized API was calculated using Andersen cascade impactor. The prepared particles and micronized Active Pharmaceutical Ingredient (API) were radiolabeled with 99m Tc. Size3 HPMC capsules were filled with the 12.5 mg radiolabeled blend (100μg Fluticasone propionate and 12.4mg inhalable lactose) and given to healthy volunteers to assess the comparative pulmonary deposition. Results: The prepared formulation has shown better lung deposition as compared to micronized API. The MMAD of submicronized particles was in the range of 1 - 5 μm while the MMAD of micronized API was in the range of 5 - 15μm. Conclusion: The developed submicron sized dry powder inhalation formulation has better lung deposition as compared to micron sized API and it will become a better treatment option for the bronchial asthma, COPD and ILDs

  10. The Effect of Chronic Alprazolam Intake on Memory, Attention, and Psychomotor Performance in Healthy Human Male Volunteers.

    Science.gov (United States)

    Chowdhury, Zahid Sadek; Morshed, Mohammed Monzur; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Islam, Sardar Mohd Ashraful; Bin Sayeed, Muhammad Shahdaat

    2016-01-01

    Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.

  11. A first‐in‐human pharmacodynamic and pharmacokinetic study of a fully human anti‐glucagon receptor monoclonal antibody in normal healthy volunteers

    Science.gov (United States)

    Kostic, Ana; King, Thomas Alexander; Yang, Feng; Chan, Kuo‐Chen; Yancopoulos, George D.; Gromada, Jesper

    2017-01-01

    Aims Glucagon receptor (GCGR) blockers are being investigated as potential therapeutics for type 1 and type 2 diabetes. Here we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of REGN1193, a fully human glucagon receptor blocking monoclonal antibody from a first‐in‐human healthy volunteer randomized double‐blinded trial. Methods Healthy men and women received single ascending doses of REGN1193 ranging from 0.05 to 0.6 mg/kg (n = 42) or placebo (n = 14) intravenously. Safety, tolerability and PK were assessed over 106 days. The glucose‐lowering effect of REGN1193 was assessed after induction of hyperglycaemia by serial glucagon challenges. Results REGN1193 was generally well tolerated. There were small (50 mg/dL, and did not require treatment or medical assistance. Concentration‐time profiles suggest a 2‐compartment disposition and marked nonlinearity, consistent with target‐mediated clearance. REGN1193 inhibited the glucagon‐stimulated glucose increase in a dose‐dependent manner. The 0.6 mg/kg dose inhibited the glucagon‐induced glucose area under the curve for 0 to 90 minutes (AUC0‐90 minutes) by 80% to 90% on days 3 and 15, while blunting the increase in C‐peptide. REGN1193 dose‐dependently increased total GLP‐1, GLP‐2 and glucagon, with plasma levels returning to baseline by day 29 in all dose groups. Conclusion REGN1193, a GCGR‐blocking monoclonal antibody, produced a safety, tolerability and PK/PD profile suitable for further clinical development. The occurrence of transient elevations in serum hepatic aminotransferases observed here and reported with several small molecule glucagon receptor antagonists suggests an on‐target effect of glucagon receptor blockade. The underlying mechanism is unknown. PMID:28755409

  12. Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl in Human Healthy Volunteers: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Rocío García-Villalba

    2015-12-01

    Full Text Available The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.

  13. Brain Magnetic Resonance Elastography on Healthy Volunteers: A Safety Study

    International Nuclear Information System (INIS)

    Guang-Rui Liu; Pei-Yi Gao; Yan Lin; Jing Xue; Xiao-Chun Wang; Bin-Bin Sui; Li Ma; Zhi-Nong Xi; Qin Bai; Hao Shen

    2009-01-01

    Background: Magnetic resonance elastography (MRE) is a recently developed imaging technique that can directly visualize and quantitatively measure tissue elasticity. Purpose: To evaluate the safety of brain MRE on human subjects. Material and Methods: The study included 20 healthy volunteers. MRE sequence scan (drive signal not applied to external force actuator) and MRE study were separately performed on each volunteer at an interval of more than 24 hours. The heart rate and blood pressure of each volunteer were measured immediately before and after MRE sequence scan and MRE study. Electroencephalography (EEG) was also performed within 2 hours after each scan. The volunteers were asked about their experience of the two scans. Randomized-block analysis of variance (ANOVA) was used to analyze the data of blood pressure and heart rate. Paired t test was used to analyze the data of the two EEG examinations. The volunteers were followed up 1 week after the examination. Results: All procedures were performed on each volunteer, and no one complained of obvious discomfort. No related adverse events were reported during follow-up. There was no statistically significant difference in heart rate or blood pressure. There was a statistically significant difference (P<0.05) in EEG results in the right temporoparietal region. Increased power was found in the theta, delta, alpha, and beta2 bands. No brain injury was detected by the EEG examinations. Conclusion: Based on the study results, brain MRE examinations are safe to perform on human subjects

  14. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-02-01

    The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

  15. Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

    Science.gov (United States)

    Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

    2012-01-01

    The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system. PMID:21956447

  16. Fate and effects of Camembert cheese micro-organisms in the human colonic microbiota of healthy volunteers after regular Camembert consumption.

    Science.gov (United States)

    Firmesse, Olivier; Alvaro, Elise; Mogenet, Agnès; Bresson, Jean-Louis; Lemée, Riwanon; Le Ruyet, Pascale; Bonhomme, Cécile; Lambert, Denis; Andrieux, Claude; Doré, Joël; Corthier, Gérard; Furet, Jean-Pierre; Rigottier-Gois, Lionel

    2008-07-15

    The objective of this study was to determine i) if Camembert cheese micro-organisms could be detected in fecal samples after regular consumption by human subjects and ii) the consequence of this consumption on global metabolic activities of the host colonic microbiota. An open human protocol was designed where 12 healthy volunteers were included: a 2-week period of fermented products exclusion followed by a 4-weeks Camembert ingestion period where 2x40 g/day of Camembert cheese was consumed. Stools were collected from the volunteers before consumption, twice during the ingestion period (2nd and 4th week) and once after a wash out period of 2 weeks. During the consumption of Camembert cheese, high levels of Lactococcus lactis and Leuconostoc mesenteroides were measured in fecal samples using real-time quantitative PCR, reaching median values of 8.2 and 7.5 Log(10) genome equivalents/g of stool. For Ln. mesenteroides, persistence was observed 15 days after the end of Camembert consumption. The survival of Geotrichum candidum was also assessed and the fecal concentration reached a median level of 7.1 Log(10) CFU/g in stools. Except a decreasing trend of the nitrate reductase activity, no significant modification was shown in the metabolic activities during this study.

  17. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.

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

    Science.gov (United States)

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

    2015-06-16

    This study will develop the first human challenge model of paratyphoid infection which may then be taken forward to evaluate paratyphoid vaccine candidates. Salmonella Paratyphi A is believed to cause a quarter of the estimated 20 million cases of enteric fever annually. Epidemiological evidence also suggests that an increasing proportion of the enteric fever burden is attributable to S. Paratyphi infection meriting further attention and interest in vaccine development. Assessment of paratyphoid vaccine efficacy in preclinical studies is complicated by the lack of a small animal model and the human-restricted nature of the infection. The use of experimental human infection in healthy volunteers provides an opportunity to address these problems in a cost-effective manner. Volunteers will ingest virulent S. Paratyphi A bacteria (NVGH308 strain) with a bicarbonate buffer solution to establish the infectious dose resulting in an 'attack rate' of 60-75%. Using an a priori decision-making algorithm, the challenge dose will be escalated or de-escalated to achieve the target attack rate, with the aim of reaching the study end point while exposing as few individuals as possible to infection. The attack rate will be determined by the proportion of paratyphoid infection in groups of 20 healthy adult volunteers, with infection being defined by one or more positive blood cultures (microbiological end point) and/or fever, defined as an oral temperature exceeding 38 °C sustained for at least 12 h (clinical end point); 20-80 participants will be required. Challenge participants will start a 2-week course of an oral antibiotic on diagnosis of infection, or after 14 days follow-up. The strict eligibility criterion aims to minimise risk to participants and their close contacts. Ethical approval has been obtained. The results will be disseminated in a peer-reviewed journal and presented at international congresses. NCT02100397. Published by the BMJ Publishing Group Limited. For

  19. LSD enhances suggestibility in healthy volunteers.

    Science.gov (United States)

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

    2015-02-01

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

  20. Pharmacogenetics of healthy volunteers in Puerto Rico.

    Science.gov (United States)

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

    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.

  1. Pharmacogenetics of healthy volunteers in Puerto Rico

    Science.gov (United States)

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

    2016-01-01

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

  2. Prediction of psilocybin response in healthy volunteers.

    Science.gov (United States)

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

    2012-01-01

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

  3. Prediction of psilocybin response in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Erich Studerus

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

  4. A randomized two-way crossover comparative pharmacokinetic study of two different tablet formulations containing ilaprazole in healthy human Indian volunteers

    Directory of Open Access Journals (Sweden)

    Shubhasis Dan

    2014-01-01

    Full Text Available Background: Proton Pump Inhibitors (PPI are observed to be great healer in gastroesophageal reflux disorder (GERD and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t , Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵, Peak plasma concentration (C max , and time to reach peak plasma concentration (t max . Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence

  5. Calcitonin gene-related peptide modulates heat nociception in the human brain - An fMRI study in healthy volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B.W.

    2016-01-01

    Background: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...... cortex. Sumatriptan injection reversed these changes. Conclusion: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli....

  6. The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

    Science.gov (United States)

    Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

    2017-09-20

    A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

  7. Gluten-degrading bacteria are present in the human small intestine of healthy volunteers and celiac patients.

    Science.gov (United States)

    Herrán, Alexandra R; Pérez-Andrés, Jénifer; Caminero, Alberto; Nistal, Esther; Vivas, Santiago; Ruiz de Morales, José María; Casqueiro, Javier

    2017-09-01

    Gluten is the only known environmental factor that triggers celiac disease. Several studies have described an imbalance between the intestinal microbiota of different individuals based on diagnoses. Moreover, recent studies have suggested that human bacteria may play an important role in gluten hydrolysis. However, there has been no research focusing on the small intestine. This study aimed to characterize the adult small intestine microbiota possibly implicated in gluten hydrolysis. Duodenal biopsies from different diagnosed individuals were cultured in a gluten-containing medium, and the grown microbiota was analyzed by culture dependent/independent methods. Results showed that gluten-degrading bacteria can be found in the human small intestine. Indeed, 114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. We found that there are no differences based on the diagnosis, but each individual has its own population of gluten-hydrolyzing bacteria. These bacteria or their gluten-degrading enzymes could help to improve the quality of life of celiac disease patients'. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Determination of bifendate in human plasma by HPLC-MS and bioequivalence on bifendate pills in healthy volunteers.

    Science.gov (United States)

    Zhou, Lingjie; Gu, Lihua; Wang, Yijian; Liang, Jianying

    2006-03-03

    A sensitive and specific method for the determination of bifendate in human plasma was developed, based on high-performance liquid chromatography (HPLC)-mass spectrometry (MS). The samples were extracted from plasma with diethyl ether, followed by separation and evaporation after addition of internal standard diazepam. The residue was reconstituted in methanol and injected into the HPLC-MS. Chromatography was performed on an Inertsil ODS column with a mobile phase consisting of methanol-distilled water (70/30, v/v) at a flow rate of 0.3 mL/min. Quantitative analysis was achieved by MS detection, using a mass spectrometer equipped with an electrospray ionization interface (ESI) and operated in selected ion monitoring (SIM) and positive-ionization mode using target ions at m/z 419 for bifendate and m/z 285 for internal standard, respectively. The linearity was confirmed in the concentration range of 2-200 ng/mL in human plasma and the precision of this assay was not more than 6.79% over the entire concentration range. The method was sensitive and repeatable enough to be used in pharmacokinetic and bioavailability studies.

  9. Human dosimetry and preliminary tumor distribution of 18F-fluoropaclitaxel in healthy volunteers and newly diagnosed breast cancer patients using PET/CT.

    Science.gov (United States)

    Kurdziel, Karen A; Kalen, Joseph D; Hirsch, Jerry I; Wilson, John D; Bear, Harry D; Logan, Jean; McCumisky, James; Moorman-Sykes, Kathy; Adler, Stephen; Choyke, Peter L

    2011-09-01

    (18)F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that (18)F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, (18)F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of (18)F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ (18)F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection. Dosimetry calculations showed that the gallbladder received the highest dose (229.50 μGy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 μGy/MBq [0.597 rad/mCi] and 184.59 μGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 μGy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of (18)F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min. This study demonstrates the feasibility of using (18)F

  10. Human Dosimetry and Preliminary Tumor Distribution of 18F-Fluoropaclitaxel in Healthy Volunteers and Newly Diagnosed Breast Cancer Patients Using PET/CT

    International Nuclear Information System (INIS)

    Kurdziel, K.A.; Logan, J.; Kalen, J.D.; Hirsch, J.I.; Wilson, J.D.; Bear, H.D.; McCumisky, J.; Moorman-Sykes, K.; Adler, S.; Choyke, P.L.

    2011-01-01

    18 F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that 18 F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, 18 F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of 18 F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ 18 F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection. Dosimetry calculations showed that the gallbladder received the highest dose (229.50 μGy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 μGy/MBq [0.597 rad/mCi] and 184.59 μGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 μGy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of 18 F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min. This study demonstrates the feasibility of using 18 F

  11. Blanching improves anthocyanin absorption from highbush blueberry ( Vaccinium corymbosum L.) purée in healthy human volunteers: a pilot study.

    Science.gov (United States)

    Del Bo', Cristian; Riso, Patrizia; Brambilla, Ada; Gardana, Claudio; Rizzolo, Anna; Simonetti, Paolo; Bertolo, Gianni; Klimis-Zacas, Dorothy; Porrini, Marisa

    2012-09-12

    Blueberries ( Vaccinium corymbosum L.) are rich sources of phenolics and anthocyanins (ACNs). We investigated the absorption of ACNs after consumption of one portion (300 g) of minimally processed blueberry purée (P) obtained from blanched (BL) or unblanched (NB) berries. A repeated-measures, crossover design study was conducted on healthy human volunteers. Blood was drawn between baseline and 24 h after BL-P or NB-P consumption, while urine were collected from the day before the experiment up to 48 h. Total plasma ACN content was not significantly different, while phenolics content was higher in BL-P with respect to NB-P. The maximum ACN absorption in plasma was observed after 1.5 h from the intake of the purées and was significantly higher (p ≤ 0.05) after the intake of BL-P. Both products increased the excretion of hippuric acid in urine. In conclusion, blanching had no significant effect on total ACN content and enhanced their absorption from minimally processed purées.

  12. A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

    Directory of Open Access Journals (Sweden)

    Wael Abu Dayyih

    2017-01-01

    Full Text Available Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS. The method was accurate for the within- and between-days analysis, and precise CV% was 85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

  13. Human volunteer study with PGME: Eye irritation during vapour exposure

    NARCIS (Netherlands)

    Emmen, H.H.; Muijser, H.; Arts, J.H.E.; Prinsen, M.K.

    2003-01-01

    The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated

  14. Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers.

    Science.gov (United States)

    Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil; Jacobsen, Jette; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette

    2016-03-10

    Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Psychopharmacology of theobromine in healthy volunteers.

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Kalpana D Dhuri

    2013-01-01

    Full Text Available Background: Shirodhara is a classical and a well-established ayurvedic procedure of slowly and steadily dripping medicated oil or other liquids on the forehead. This procedure induces a relaxed state of awareness that results in a dynamic psycho-somatic balance. Objectives: The objective of the study is to evaluate the psychological and physiological effects of Shirodhara in healthy volunteers by monitoring the rating of mood and levels of stress, electrocardiogram (ECG, electroencephalogram (EEG, and selected biochemical markers of stress. Materials and Methods: The study was conducted in the human pharmacology laboratory. The study design was open labeled, comparing the baseline variables with values after Shirodhara. The subjects (n = 16 chosen were healthy human volunteers who gave an informed consent. Shirodhara was preceded by Abhyanga - whole body massage. The Shirodhara method was standardized for rate of dripping with peristaltic pump and temperature was controlled with a thermostat. Mood and stress levels were assessed by validated rating scales. The pre- and post-Shirodhara ECG and EEG records were evaluated. Results: Student′s paired "t" test was applied to the means + SE of the variables to calculate statistical significance at P <0.05. There was a significant improvement in mood scores and the level of stress (P <0.001. These changes were accompanied by significant decrease in rate of breathing and reduction in diastolic blood pressure along with reduction in heart rate. The relaxed alert state, after Shirodhara, was co-related with an increase in alfa rhythm in EEG. Conclusion : A standardized Shirodhara leads to a state of alert calmness similar to the relaxation response observed in meditation. The clinical benefits observed with Shirodhara in anxiety neurosis, hypertension, and stress aggravation due to chronic degenerative diseases could be mediated through these adaptive physiological effects.

  18. Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

    Science.gov (United States)

    Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

    2014-10-01

    Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate

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

    Directory of Open Access Journals (Sweden)

    Mads U Werner

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  1. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    Dose regimens in perioperative fluid management are rarely evidence based. Therefore, we investigated responses to an IV fluid infusion in healthy volunteers to assess basic physiologic effects of a fluid infusion per se. In a prospective, double-blinded, cross-randomized study, 12 healthy...... volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

  2. Effects of short term changes in the blood glucose level on the autofluorescence lifetime of the human retina in healthy volunteers

    Science.gov (United States)

    Klemm, Matthias; Nagel, Edgar; Schweitzer, Dietrich; Schramm, Stefan; Haueisen, Jens

    2016-03-01

    Purpose: Fluorescence lifetime imaging ophthalmoscopy (FLIO) provides in vivo metabolic mapping of the ocular fundus. Changes in FLIO have been found in e.g. diabetes patients. The influence of short term metabolic changes caused by blood glucose level changes on is unknown. Aim of this work is the detection of short-term changes in fundus autofluorescence lifetime during an oral glucose tolerance test. Methods: FLIO was performed in 10 healthy volunteers (29+/-4 years, fasting for 12h) using a scanning laser ophthalmoscope (30° fundus, 34μm resolution, excitation with 473nm diode laser with 70 ps pulses at 80 MHz repetition rate, detection in two spectral channels 500-560nm (ch1) and 560-720nm (ch2) using the timecorrelated single photon counting method). The blood glucose level (BGL) was measured by an Accu-Chek® Aviva self-monitoring device. Before and after a glucose drink (300ml solution, containing 75g of glucose (Accu-Chek® Dextrose O.G.T.), BGL and FLIO were measured every 15min. The FLIMX software package was applied to compute the average fluorescence lifetime τ on the inner ring of the ETDRS grid using a modified 3-exponential approach. Results: The results are given as mean +/- standard deviation over all volunteers in ch1. Baseline measurement: BGL: 5.3+/-0.4 mmol/l, τ1: 49+/-6ps. A significant reduction (α=5% Wilcoxon rank-sum test) in τ1 is detected after 15min (BGL: 8.4+/-1.1 mmol/l, τ1: 44+/-5ps) and after 90min (BGL: 6.3+/-1.4 mmol/l, τ1: 41+/-5ps). Results of ch2 show smaller reductions in the fluorescence lifetimes over time.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Junfeng eLi

    2015-11-01

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

  5. MORPHOMETRICAL PARAMETERS OF GUT MICROFLORA IN HUMAN VOLUNTEERS

    NARCIS (Netherlands)

    Wilkinson, M.H.F.; Meijer, B.C

    1991-01-01

    The morphology of faecal microflora of nine healthy human volunteers was studied by digital image analysis of microscopic slides. Weekly specimens were collected during an 8-week period. Seven morphometrical parameters were derived: the means and medians of components 1, 2 and 3, and morphometrical

  6. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Normal range values for thromboelastography in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    S. Scarpelini

    2009-12-01

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

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

    OpenAIRE

    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...

  9. The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

    Science.gov (United States)

    Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

    2007-09-01

    Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

  10. Development and validation of LC-MS/MS assay for the determination of Butoconazole in human plasma: Evaluation of systemic absorption following topical application in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Eman G. Nouman

    2017-12-01

    Full Text Available Butoconazole is an imidazole antifungal that is more effective than miconazole and clotrimazole for treatment of vaginal candidiasis. A highly sensitive tandem mass spectrometric assay was developed and validated to evaluate systemic absorption of Butoconazole following intravaginal administration. Chromatographic separation was achieved using Waters Xterra C18 column (3 µm, 3.0 × 50.0 mm. Liquid-liquid extraction using tert-butyl methyl ether was used for preparation of plasma samples. The mobile phase was solvent A: 0.1% formic acid in water and solvent B: acetonitrile: methanol (30:70, v/v, using gradient elution mode at 0.5 mL/min. Detection at positive electrospray ionization in the MRM mode was then employed. Analysis was carried out within 5.5 min over a linear concentration range of 0.10–30.00 ng/mL. Validation was carried out according to US FDA guidelines for bioanalytical method validation. Matrix effect, recovery efficiency and process efficiency have been investigated for the analyte and internal standard in neat solvent, post-extraction matrix and plasma. The mean percentage recoveries were higher than 80%, the accuracy was 93.51–106.85% and the RSD was below 10% throughout the studied concentration range. Results indicated sufficient stability of the target analyte in plasma at the employed experimental conditions. Results of incurred sample re-analysis and incurred sample stability revealed less than 5% variability. The applicability of the assay for monitoring of the systemic absorption of Butoconazole following intra vaginal application to healthy volunteers was demonstrated. Results confirmed that Butoconazole was detected shortly after intra vaginal administration with Cmax and tmax of 30 ng/mL and 6 h, respectively. Keywords: Butoconazole, LC-MS/MS, Matrix effect, Process efficiency, Recovery efficiency

  11. A comparative pharmacokinetic study of a fixed dose combination for essential hypertensive patients: a randomized crossover study in healthy human volunteers.

    Science.gov (United States)

    Gorain, B; Choudhury, H; Halder, D; Sarkar, A K; Sarkar, P; Biswas, E; Ghosh, B; Pal, T K

    2013-04-01

    This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects. The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days. Plasma concentration of the analytes were assayed in timed samples with a simple, highly sensitive and rapid validated method using HPLC coupled to tandem mass spectrometry that had a lower limit of quantification of 1 ng/mL for all the 3 components. Test and reference formulations gave a mean Cmax of 5.234±0.914 ng/mL and 4.991±0.563 ng/mL, 108.839±13.601 ng/mL and 114.783±12.315 ng/mL and 97.814±10.779 ng/mL and 93.731±10.018 ng/mL for amlodipine, telmisartan and hydrochlorothiazide respectively. The AUC0-t of amlodipine, telmisartan and hydrochlorothiazide was 161.484 ng.h/mL, 1 917.644 ng.h/mL and 822.847 ng.h/mL for test formulation and 162.108 ng.h/mL, 2 014.764 ng.h/mL and 829.323 ng.h/mL for reference in the fasting state. The 90% confidence intervals for the test/reference ratio of the pharmacokinetic parameters in fasting state (mean Cmax, AUC0-t, and AUC0-∞) were within the acceptable range of 80.00-125.00. Thus, these findings clearly indicate that the FDC product is bioequivalent with the individual marketed products in terms of rate and extent of drug absorption and is well tolerated with no significant adverse reactions. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Cardiopulmonary and metabolic effects of yoga in healthy volunteers

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    T Satheesh Divya

    2017-01-01

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

  13. Cardiopulmonary and Metabolic Effects of Yoga in Healthy Volunteers.

    Science.gov (United States)

    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.

  14. Steroid hormones and peptide hormones in atopic eczema. Radioimmunological determination of diurnal plasma level variations of testosterone, cortisol, prolactin and human growth factor in healthy volunteers and patients showing atopic eczemae

    International Nuclear Information System (INIS)

    Bock, B.

    1986-01-01

    An analysis of hormone measurements in sera from healthy volunteers and patients that was carried out on the basis of different criteria yielded the following results: 1) The testosterone levels determined in the patients sera were significantly lower than those of the healthy individuals and the daily rhythmic variations seen here did not attain statistical significance. 2) There were no statistically relevant differences in the serum concentrations of cortisol between healthy individuals and patients, nor was the amplitude of the daily variations observed to be changed in a consistent way. 3) In the patients, as compared to the healthy individuals, the prolactin level was considerably increased, as was the amplitude of the daily rhythmic variations. 4) The values determined for the human growth hormone (HCG) varied considerably between the individuals of either group. Since this held true for both the fluctuations with time and the height of the serum concentrations, a statistical analysis of the results appeared pointless. The results confirm that central and autonomous components have an important role in ectopic eczemae. (TRV) [de

  15. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    Kabeerdoss Jayakanthan

    2011-12-01

    Full Text Available Abstract Background Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. Findings 26 women aged 18-21 (median 19 years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (109 in 200 ml for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184 and returned to normal after cessation of probiotic yoghurt intake. Conclusions Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  16. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

    Science.gov (United States)

    Taylor, Claribel P; Tummala, Sanjeev; Molrine, Deborah; Davidson, Lisa; Farrell, Richard J; Lembo, Anthony; Hibberd, Patricia L; Lowy, Israel; Kelly, Ciaran P

    2008-06-25

    Recent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults. Five cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis. Thirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers. Administration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing......Q (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o.administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile....

  18. Dark chocolate inhibits platelet aggregation in healthy volunteers.

    Science.gov (United States)

    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.

  19. Population pharmacokinetics of adefovir dipivoxil tablets in healthy Chinese volunteers.

    Science.gov (United States)

    Huang, Jihan; Zhang, Yaping; Huang, Xiaohui; Li, Lujin; Li, Yunfei; Wang, Kun; Yang, Juan; He, Yingchun; Lv, Yinghua; Zheng, Qingshan

    2014-01-01

    To develop a population pharmacokinetic model of adefovir dipivoxil in healthy volunteers and evaluate the effect of individual factors on the pharmacokinetics of adefovir dipivoxil. Plasma concentration data collected from 32 healthy Chinese subjects in a Phase I clinical study was pooled. Subjects received a single oral dose of 10 mg, 20 mg, or 30 mg adefovir dipivoxil, or multiple doses of 10 mg once a day for 9 days. Plasma concentrations of adefovir dipivoxil were measured using a validated liquid chromatography-mass spectrometric method. A nonlinear mixed-effect model was used to analyze the plasma concentration data of adefovir dipivoxil in healthy volunteers and to calculate the relevant parameters as well as inter- and intra-individual variability. The time course of adefovir dipivoxil concentration is best described by a first-order absorption and first-order elimination two-compartment model with lag time. The final estimate of total body clearance (CL) is 56.9 L/h and 78.7 L/h for single and multiple dosing regimen, respectively; the volume distribution of the central compartment (V2) is 106 L; inter-compartmental clearance (Q) is 220 L/h; volume distribution of the peripheral compartment (V3) is 498 L and 800 L for single and multiple dosing regimen, respectively; absorption rate is 0.509 h-1; and lag time is 0.315 hours. The inter-individual variabilities of CL and V2 were 22.4% and 58.9%, respectively. The proportional error of residual variability is 14.1% and the additive error is 0.30 ng/L. The final pharmacokinetic model was evaluated using a bootstrap method. A nonlinear mixed effect model for oral adefovir dipivoxil formulations was developed in healthy Chinese subjects. A multiple dosing regimen may significantly increase the body clearance and volume distribution of the peripheral compartment compared to a single dosing regimen. *These authors contribute equally to this work.

  20. MR elastography study of the brain in healthy volunteers

    International Nuclear Information System (INIS)

    Liu Guangrui; Gao Peiyi; Lin Yan; Wang Xiaochun; Xue Jing; Sui Bingbing; Ma Li; Wang Chen; Shen Mi

    2009-01-01

    Objective: To evaluate the shear stiffness of brain by MR elastography (MRE) in healthy Chinese volunteers and to assess the association between the cerebral shear stiffness and age. Methods: Brain MRE studies were performed on 105 healthy volunteers. The shear stiffness of brain parenchyma was measured by local frequency estimation (LFE) algorithm. The differences of the shear stiffness between white matter (WM) and grey matter (GM) were analyzed by independent sample t test; the differences of brain parenchyma shear stiffness between male and female were estimated by independent sample t test. Spearman test was used to analyze the correlation between age and the shear stiffness of parenchyma; the volunteers were divided into two groups (age ≤40 and age > 40) and the correlation between age and shear stiffness of parenchyma in each group were analyzed separately. Results: The shear stiffness of whiter matter [(23.1±5.7) kPa] was higher than that of grey matter [(11.3±2.6) kPa], and the difference was significant (t=19.34, P 0.05). An age-dependent trend was observed in the stiffness of grey matter (r= 0.315, P 0.05). When the shear stiffness of subjects no more than 40 years old was analysed, the age-dependent trend of shear stiffness was found both in white matter and gray matter (r=0.251, 0.235, P 0.05). Conclusions: The shear stiffness of WM is significantly higher than that of GM. No obvious sex difference was found in the stiffness of brain parenchyma. The shear stiffness of GM increases with age; the age-related increase of shear stiffness of WM was only found in subjects under 40 years old. (authors)

  1. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  2. Population pharmacokinetics of olprinone in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kunisawa T

    2014-03-01

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

  3. Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

    Science.gov (United States)

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

    1998-01-01

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

  4. Health effects of a subway environment in healthy volunteers.

    Science.gov (United States)

    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 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.

  5. Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2010-01-01

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

  7. Exercise increases endostatin in circulation of healthy volunteers

    Directory of Open Access Journals (Sweden)

    Makey Ian

    2004-01-01

    Full Text Available Abstract Background Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis. Results We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2 was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF, and basic fibroblast growth factor (bFGF were determined using ELISA. The total peak VO2 (L in 7 male subjects was 29.5 ± 17.8 over a 4–10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise were 20.3 ± 3.2 pg/ml, the plasma levels increased to 29.3 ± 4.2, 35.2 ± 1.8, and 27.1 ± 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (% and the total peak VO2 (L related to exercise (R2 = 0.9388; P Conclusions The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as atherosclerosis.

  8. Healthy human gut phageome.

    Science.gov (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

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

    Science.gov (United States)

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

    2015-10-28

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

  10. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sandhya Vasan

    Full Text Available DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.

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

    Science.gov (United States)

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

    2017-11-01

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

  12. Exercise increases endostatin in circulation of healthy volunteers.

    Science.gov (United States)

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

    2004-01-16

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

  13. Effect of bidirectional rotation of an acupuncture needle at LI10 on acupuncture needle sensation and experimentally-induced contact heat pain in healthy human volunteers.

    Science.gov (United States)

    Benham, Alex; Johnson, Mark I

    2014-06-01

    There is insufficient evidence of a relationship between acupuncture needle sensations (de qi) and hypoalgesia. The aim of this study was to investigate the effects of bidirectional needle rotation at LI10 on acupuncture needle sensations and heat pain thresholds. Twenty-two healthy participants received one acupuncture needle at LI10 with bidirectional rotation of the needle in one experimental session and one acupuncture needle at LI10 with mock rotation in a separate session, in a randomised order. Measurements of heat pain thresholds were taken before needle insertion, during needle retention and 15 min after needle removal. At each measurement time point, participants rated needle sensations using the Massachusetts Acupuncture Sensation Scale (MASS) and a visual analogue scale (VAS) of overall intensity of needle sensation. Bidirectional needle rotation produced significantly higher scores for VAS, MASStotal, MASSpain and MASSsensation compared with mock rotation (all psensation and change in pain threshold after needling was only found when data from mock and rotation interventions were combined. Needle rotation increases the magnitude of hypoalgesia. There is tentative evidence that needle sensation may be associated with the amount of change in pain threshold. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Gender differences of heart rate variability in healthy volunteers

    International Nuclear Information System (INIS)

    Saleem, S.; Majeed, S.M.I.; Khan, M.A.

    2012-01-01

    Objective: To identify the basic values of heart rate variability in Pakistani population and to verify our hypothesis that there are gender differences in cardiovascular autonomic modulation. Methods: The descriptive cross sectional study based on convenience probability sampling was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC/NIHD) Pakistan. The duration of the study was from December 2009 to July 2010. It involved 24-hour holter monitoring of 45 healthy individuals using holter electrocardiography (ECG) recorder. Heart rate variability was analysed in time (SDNN, SDANN, SDNNi, rMSSD, pNN50) and frequency domains (power, VLF, LF, and HF). Results: The time domain indices; SDNN (male=140 +- 36 ms vs. females=122 +- 33 ms; p =0.09), SDANN (male=123 +- 34 ms vs. females=111+- 34 ms; P= 0.23), SDNNi (male=64 +-19 ms vs. females=52 +- 14 ms; P= 0.03), and pNN50 (male=14 +- 10 ms vs. females=12 +- 7 ms; P= 0.43) were decreased in female volunteers when compared with males. Comparison of frequency domain indices; Total power (male=4041 +- 3150 ms/sup 2/ vs. females=2750 +- 1439 ms/sup 2/; P= 0.07), VLF (male=291 2675 ms/sup 2/ vs. females=1843 +- 928 ms/sup 2/; P= 0.06), LF (male=788 +- 397 ms/sup 2/ vs. females=556 +- 346 ms/sup 2/; P= 0.04) and HF (male=318 +- 251 ms/sup 2/ vs. females=31 277 ms/sup 2/; P= 0.94) amongst males and females showed attenuated heart rate variability in females. Of all the observed values, SDNNi and LF were found significantly (p <0.05) decreased in women. Conclusion: In healthy population, heart rate variability is low in women than men. It reflects sympathetic dominance in women in our population. (author)

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

    Science.gov (United States)

    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 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.

  16. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  17. Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers.

    Science.gov (United States)

    Brazier, David; Perry, Robert; Keane, Jim; Barrett, Katie; Elmaleh, David R

    2017-11-01

    BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers. In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study. For cromolyn, the mean (±SD) maximum observed concentration (C max ) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C max (t max ) ~22 min for each; terminal elimination half-life (t ½ ) ~1.8 h for each]. For ibuprofen, the plasma C max was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t max ~1.6-1.8 h; t ½ ~1.9 h for each). For cromolyn, the CSF C max was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C max was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug. The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response

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

    Science.gov (United States)

    Pickering, Gisèle; Macian, Nicolas; Dubray, Claude; Pereira, Bruno

    2016-01-01

    Acetaminophen (APAP, paracetamol) mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467) was carried out from May 30, 2011 to July 12, 2011. Forty healthy volunteers were included and analyzed. Nociceptive thresholds, core temperature (body temperature), and a battery of cognitive tests were recorded before and after oral APAP (2 g) or placebo: Information sampling task for predecisional processing, Stockings of Cambridge for spatial memory, reaction time, delayed matching of sample, and pattern recognition memory tests. Analysis of variance for repeated measures adapted to crossover design was performed and a two-tailed type I error was fixed at 5%. APAP improved information sampling task (diminution of the number of errors, latency to open boxes, and increased number of opened boxes; all P memory initial thinking time were decreased ( P =0.04). All other tests were not modified by APAP. APAP had an antinociceptive effect ( P body temperature did not change. This study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance and antinociception are independent of APAP effect on thermogenesis. We suggest that cognitive performance mirrors the analgesic rather than thermic cascade of events, with possibly a central role for serotonergic and cannabinoid systems that need to be explored further in the context of pain and cognition.

  19. Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in healthy volunteers

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Klitgaard, Niels A; Brosen, Kim

    2004-01-01

    OBJECTIVES: To investigate different dose combinations of amprenavir and delavirdine in order to assess an optimal dose suitable for clinical use. METHODS: This was a prospective, open-label, controlled, three-period, multiple-dose study with nine healthy volunteers. The volunteers received three...

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

    Science.gov (United States)

    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.

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

    African Journals Online (AJOL)

    ... African volunteers in a randomized double masked, placebo controlled, crossover, single centre study. Pulse rate, systolic and diastolic blood pressure, and respiratory rate were also measured. Mean IOP was lower than baseline values up to 72 hours after instillation but the mean IOP was significantly lower in the eyes ...

  2. Study on influence of piperine treatment on the pharmacokinetics of diclofenac in healthy volunteers.

    Science.gov (United States)

    Bedada, Satish Kumar; Boga, Praveen Kumar; Kotakonda, Harish Kaushik

    2017-02-01

    1. Diclofenac sodium (DIC) is a widely used anti-inflammatory drug and its administration in humans receiving long-term therapy with herbal drugs containing piperine (PIP) may occur, which leads to drug-phytochemical interactions. The purpose of the present study was to investigate the influence of PIP treatment on the pharmacokinetics of DIC in healthy volunteers. 2. The open-label, two period, sequential study was conducted in 12 healthy volunteers. PIP 20 mg was administered once daily for 10 days during treatment phase. A single dose of DIC 100 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after DIC dosing at predetermined time intervals and analyzed by HPLC. 3. Treatment with PIP significantly enhanced maximum plasma concentration (C max ) (2.24-3.68 μg/mL, p pharmacokinetics of DIC might be attributed to PIP mediated inhibition of CYP2C9 enzyme, which indicates the clinically significant interaction present between DIC and PIP. Therefore, the combination therapy of DIC along with PIP may represent a novel approach to reduce dosage and result in reduced incidence of gastrointestinal side effects seen with DIC alone at higher doses.

  3. The irradiation of human volunteer subjects in research

    International Nuclear Information System (INIS)

    Rosen, R.

    1980-01-01

    In medical research radiation is sometimes used to obtain data from healthy individuals. These subjects gain no specific benefit from the research. To safeguard their welfare, constraints are imposed on the dose to be received, on the selection of volunteer subjects, on ensuring their understanding of the procedures and risks, and on obtaining their free consent to participate. The research proposals are assessed by peer review prior to being approved by the host institution. The first example presented describes the use of diagnostic radiography to obtain in vivo data on the femur bone. Conservative dosimetry indicates an expected dose-equivalent per film of 0.5 mSv in bone and 0.18 mSv in bone marrow and gonad tissue. The critical organ total dose-equivalent is estimated to be 7% of the dose-equivalent limit for a volunteer. The second example involves the internal administration of radioactive tracers. Dosimetric calculations indicate an expected whole-body dose-equivalent of 0.5 mSv in the case of C-14 and 0.37 mSv in the case of H-3, these values bejng 10% and 7% of the relevant dose-equivalent limit. Both proposals were given conditional approval. In the generalized research use of volunteer human subjects the rights of the subject, the investigator and the institution need to be protected. At the University of New South Wales procedures have been introduced to govern all experjmental procedures involving human subjects. Some interesting problems which have arisen are discussed. (author)

  4. Radiosensitiviness of blood lymphocytes from skin cancer patients and healthy volunteers as determined by micronucleus assay

    International Nuclear Information System (INIS)

    Lohmann, Tania Helena Ochi.

    1995-01-01

    Cancer, a major death cause in developed countries, has been related to somatic mutations that could be detected by cytogenetic analysis. Among the tools used in these tests, the micronucleus assay has been largely applied at population surveillance, biological dosimetry and early detection of groups with higher risks to developing cancers. In this study, we analysed the chromosome susceptibility of blood lymphocytes from basocellular skin cancer patients and healthy volunteers. The cytogenetic analysis was performed by a micronucleus assay, using progressive doses of ionizing radiation from a 60 Co source as mutagen. Briefly, the blood lymphocytes were irradiated in vitro, as processed by the cytokinesis-blocked method. The micronucleus frequency and distribution, cell cycle kinetics, nucleation index and dose-response relationship were determined in each patient. The results showed that the basocellular skin cancer patients lymphocytes presented higher spontaneous micronucleus frequency as compared with those from healthy young volunteers but lower than healthy now young volunteers . The radiation-induced micronucleus analysis showed that the basocellular skin cancer patients' lymphocytes presented similar proportion of damage lymphocytes as compared with those from healthy volunteers. Nevertheless, the magnitude of this damage was higher in this group with doses. Higher than 400 c Gy, which was not occurred in healthy volunteers. Cell cycle kinetics, as determined by the nucleation index, was lower in basocellular skin cancer patients as compared with healthy volunteers, indicating a more slow cell cycle. Our data showed that the lymphocytes from carcinoma basocellular patients were more radiosensitive as compared with those form healthy volunteers. (author). 159 refs., 21 figs., 16 tabs

  5. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    , infusion of the fluid over 3 h in the morning, and additionally 24-h hospitalization under standardized conditions. Primary outcome assessments were pulmonary function (spirometry), exercise capacity (submaximal treadmill test), balance function (BalanceMaster), and weight. Infusion of 40 mL/kg of lactated...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers

    DEFF Research Database (Denmark)

    Birk, Steffen; Sitarz, John Thomas; Petersen, Kenneth Ahrend

    2007-01-01

    .9+/-22.4% (Peffect on rCBF in healthy volunteers. The marked increase in heart rate and the reduction in rCBF caused by decreased P(et)CO(2) are important dose-limiting factors to consider in future clinical studies.......PACAP38 is an endogenous peptide located in trigeminal perivascular nerve fibers in the brain. It reduces neuronal loss and infarct size in animal stroke models and has been proposed a candidate substance for human clinical studies of stroke. The effect on systemic hemodynamics and regional......CBF was measured with SPECT and (133)Xe inhalation and mean blood flow velocity in the middle cerebral artery was measured with transcranial Doppler ultrasonography. End tidal partial pressure of CO(2) (P(et)CO(2)) and vital parameters were recorded throughout the 2 hour study period. PACAP38 decreased rCBF in all...

  9. Psychological effects of ketamine in healthy volunteers - Phenomenological study

    NARCIS (Netherlands)

    Pomarol-Clotet, E.; Honey, G. D.; Murray, G. K.; Corlett, P. R.; Absalom, A. R.; Lee, M.; McKenna, P. J.; Bullmore, E. T.; Fletcher, P. C.

    Background: The psychosis-inducing effect of ketamine is important evidence supporting the glutamate hypothesis of schizophrenia. However, the symptoms the drug produces have not been described systematically. Aim: To examine the effects of ketamine in healthy people using a structured psychiatric

  10. Risk and Emotion Among Healthy Volunteers in Clinical Trials

    NARCIS (Netherlands)

    Cottingham, M.D.; Fisher, J.A.

    2016-01-01

    Theorized as objective or constructed, risk is recognized as unequally distributed across social hierarchies. Yet the process by which social forces shape risk and risk emotions remains unknown. The pharmaceutical industry depends on healthy individuals to voluntarily test early-stage,

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

    Directory of Open Access Journals (Sweden)

    Pickering G

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Jang K

    2017-03-01

    (oseltamivir carboxylate AUC0–48h/oseltamivir AUC0–48h was 0.92 (0.87–0.97. The amount of unchanged oseltamivir excreted in urine increased by 14% after dexamethasone treatments. Conclusion: Coadministration of dexamethasone with oseltamivir slightly decreased systemic exposure to oseltamivir and oseltamivir carboxylate in healthy volunteers. This result suggests that CES1 is inhibited by dexamethasone in humans. However, coadministration of oseltamivir and dexamethasone did not appear to have a clinically relevant effect on the PK of oseltamivir; based on these results, dexamethasone can be coadministered with oseltamivir. Keywords: carboxylesterase, steroid, influenza, ARDS

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

    Science.gov (United States)

    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 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-04-10

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

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

    OpenAIRE

    Rollinson, K; Jones, J; Scott, N; Megson, IL; Leslie, SJ

    2016-01-01

    BACKGROUND: 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. METHODS: 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 ...

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

    Directory of Open Access Journals (Sweden)

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

    2015-10-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  19. Magnetic resonance elastography: Feasibility of liver stiffness measurements in healthy volunteers at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Mannelli, L., E-mail: mannellilorenzo@yahoo.it [Department of Radiology, Addenbrooke' s Hospital and University of Cambridge, Cambridge (United Kingdom); Department of Radiology, University of Washington, Seattle, WA (United States); Godfrey, E.; Graves, M.J.; Patterson, A.J.; Beddy, P.; Bowden, D.; Joubert, I.; Priest, A.N.; Lomas, D.J. [Department of Radiology, Addenbrooke' s Hospital and University of Cambridge, Cambridge (United Kingdom)

    2012-03-15

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

  20. Increased Set Shifting Costs in Fasted Healthy Volunteers

    Science.gov (United States)

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

    2014-01-01

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

  1. Effect of body posture on involuntary swallow in healthy volunteers.

    Science.gov (United States)

    Shiino, Yoshitaka; Sakai, Shogo; Takeishi, Ryosuke; Hayashi, Hirokazu; Watanabe, Masahiro; Tsujimura, Takanori; Magara, Jin; Ito, Kayoko; Tsukada, Tetsu; Inoue, Makoto

    2016-03-01

    Clinically, reclining posture has been reported to reduce risk of aspiration. However, during involuntary swallow in reclining posture, changes in orofacial and pharyngeal movement before and during pharyngeal swallow should be considered. Further, the mechanisms underlying the effect of body posture on involuntary swallow remain unclear. The aim of the present study was to determine the effect of body posture on activity patterns of the suprahyoid muscles and on patterns of bolus transport during a natural involuntary swallow. Thirteen healthy male adults participated in a water infusion test and a chewing test. In the water infusion test, thickened water was delivered into the pharynx at a very slow rate until the first involuntary swallow was evoked. In the chewing test, subjects were asked to eat 10 g of gruel rice. In both tests, the recording was performed at four body postures between upright and supine positions. Results showed that reclining changed the location of the bolus head at the start of swallow and prolonged onset latency of the swallowing initiation. Muscle burst duration and whiteout time measured by videoendoscopy significantly increased with body reclining and prolongation of the falling time. In the chewing test, reclining changed the location of the bolus head at the start of swallow, and the frequency of bolus residue after the first swallow increased. Duration and area of EMG burst and whiteout time significantly increased with body reclining. These data suggest that body reclining may result in prolongation of pharyngeal swallow during involuntary swallow. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

    Science.gov (United States)

    Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

    2013-10-01

    To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

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

    DEFF Research Database (Denmark)

    Werner, Mads U; Petersen, Karin; Rowbotham, Michael C

    2013-01-01

    Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repe...... repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models.......Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following...

  4. Effect of ketamine on endogenous pain modulation in healthy volunteers.

    Science.gov (United States)

    Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y

    2011-03-01

    Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (Ppain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Effect of body posture on chewing behaviours in healthy volunteers.

    Science.gov (United States)

    Iizumi, T; Magara, J; Tsujimura, T; Inoue, M

    2017-11-01

    Mastication is essential to the eating process and forms an important part of feeding behaviour. Many factors related to the food bolus, such as bolus texture and size, are known to influence mastication. The aim of this study was to determine the effects of body posture on (i) chewing duration prior to the first swallow and (ii) patterns of mastication-related EMG activity. We asked 10 healthy adults to chew 8 g of steamed rice with barium sulphate while we recorded masseter, suprahyoid and infrahyoid muscle activity and simultaneously collected videofluorographic images. Participants chewed in either an upright or reclining position. Chewing duration, which was defined as the time from the start of mastication to the first swallow, was not different between the positions. However, the variability of chewing duration was larger in the upright versus reclining position, and the chewing duration in the reclining position was distributed around 15 s. Masseter activity gradually decreased in a time-dependent manner and was significantly larger at the early versus late stage of mastication. Suprahyoid activity was significantly larger at the early versus middle stage of mastication in the upright position only. Finally, masseter activity per second was negatively correlated with changes in chewing duration, that is, the larger the increase in chewing duration in the reclining position, the more the decrease in masseter activity per second. These results suggest that position-dependent changes in chewing behaviours, as described by chewing duration and EMG activity, may vary among participants. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Gerards, A.H.; Lathouder, de S; Groot, E.R.; Dijkmans, B.A.C.; Aarden, L.A.

    2003-01-01

    OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients.

  8. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Gerards, A. H.; de Lathouder, S.; de Groot, E. R.; Dijkmans, B. A. C.; Aarden, L. A.

    2003-01-01

    Objectives. To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. Methods. Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients.

  9. Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues : a study in healthy volunteers

    NARCIS (Netherlands)

    Burm, A.G.D.; de Boer, A G; van Kleef, J.W.; Vermeulen, N P; de Leede, L G; Spierdijk, J; Breimer, D D

    1988-01-01

    The pharmacokinetics of lidocaine and bupivacaine and tri-deuteromethyl-labelled lidocaine and bupivacaine were investigated in healthy volunteers. The deuterium-labelled and the unlabelled form of the drug to be investigated were simultaneously infused in 10 min. Plasma concentrations were

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

    NARCIS (Netherlands)

    Wervers, K. (K.); M. Vis (M.); Rasappu, N. (N.); M. van der Ven (Myrthe); I. Tchetverikov (Ilja); Kok, M. (M.); A.H. Gerards (Andreas); J.M.W. Hazes (Mieke); J.J. Luime (Jolanda)

    2017-01-01

    textabstractObjectives: 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

  11. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock

    NARCIS (Netherlands)

    Edul, Vanina S. Kanoore; Enrico, Carolina; Laviolle, Bruno; Vazquez, Alejandro Risso; Ince, Can; Dubin, Arnaldo

    2012-01-01

    The microcirculation of septic patients has been characterized only semiquantitatively. Our goal was to characterize the sublingual microcirculation in healthy volunteers and patients with septic shock quantitatively. Our hypotheses were that 1) hyperdynamic blood flow is absent in septic shock; 2)

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

    African Journals Online (AJOL)

    ... as the test product while another silymarin tablet brand, Silliver® (Abbott Laboratories Pak Ltd) was the reference product. The tablets were administered to healthy male volunteers orally at a dose of 200 mg following an overnight fast according to a randomized cross-over design. Scheduled blood samples were collected ...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Relative bioavailability of three newly developed albendazole formulations : a randomized crossover study with healthy volunteers

    NARCIS (Netherlands)

    Rigter, I M; Schipper, H G; Koopmans, R P; van Kan, H J M; Frijlink, H W; Kager, P A; Guchelaar, H-J

    2004-01-01

    This study of healthy volunteers shows that the relative bioavailability of albendazole formulations that use arachis oil-polysorbate 80 or hydroxypropyl-beta-cyclodextrin as an excipient was enhanced 4.3- and 9.7-fold compared to the results seen with commercial tablets. Administration of macrogol

  15. Relative bioavailability of three newly developed albendazole formulations: a randomized crossover study with healthy volunteers

    NARCIS (Netherlands)

    Rigter, I. M.; Schipper, H. G.; Koopmans, R. P.; van Kan, H. J. M.; Frijlink, H. W.; Kager, P. A.; Guchelaar, H.-J.

    2004-01-01

    This study of healthy volunteers shows that the relative bioavailability of albendazole formulations that use arachis oil-polysorbate 80 or hydroxypropyl-beta-cyclodextrin as an excipient was enhanced 4.3- and 9.7-fold compared to the results seen with commercial tablets. Administration of macrogol

  16. Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

    Science.gov (United States)

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

    2018-04-01

    To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

  17. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers

    Science.gov (United States)

    Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

    2017-01-01

    Introduction A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. Methods A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. Results HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. Conclusions This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response. PMID:28045995

  18. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

    Science.gov (United States)

    Goldberg, Shmuel; Ollila, Hanna Maria; Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

    2017-01-01

    A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

  19. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

    Directory of Open Access Journals (Sweden)

    Shmuel Goldberg

    Full Text Available A previous study has suggested that the Human Leukocyte Antigen (HLA allele DQB1*06:02 affects hypoxic ventilatory response (HVR but not hypercapnic ventilatory response (HCVR in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians. HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5 were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2 compared to 0.429±0.266 (liter/minute/%SpO2 in men, p<0.001 (55.4% higher HVR in men. Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001, higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001, and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025. One hundred and two (18.5% of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866 and HCVR.This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

  20. Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

    International Nuclear Information System (INIS)

    Laarman, G.J.; Niemeyer, M.G.; Ascoop, C.A.P.L.; Bruschke, A.V.G.; Wall, E.E. van der; Verzijlbergen, F.J.; Liam Go, T.

    1989-01-01

    To establish test specific normal limits for quantitative analysis of uptake and washout of 201 Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as ≤ 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201 Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70 0 LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30 0 LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of 201 Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201 Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201 Tl derived from healthy volunteers who underwent the same combined protocol. (orig.)

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

    Science.gov (United States)

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

    2014-10-01

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

  2. The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

    Science.gov (United States)

    Englund, Amir; Atakan, Zerrin; Kralj, Aleksandra; Tunstall, Nigel; Murray, Robin; Morrison, Paul

    2016-02-01

    Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. Ten male cannabis users (THC on the fifth day. THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031). In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose. © The Author(s) 2015.

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

    Directory of Open Access Journals (Sweden)

    Amir Houshang Mohamadpour

    2013-01-01

    Full Text Available 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.

  4. Digestive tract microbiota in healthy volunteers Microbiota no trato digestivo em voluntários saudáveis

    Directory of Open Access Journals (Sweden)

    Bruno Zilberstein

    2007-02-01

    Full Text Available PURPOSE: The aim of this study was to standardize the methods of sample collection of mucus from the digestive tract and to determine the microbiota in healthy volunteers from Brazil, collecting samples from the mouth, esophagus, stomach, duodenum, jejunum, ileum, colon, and rectum. METHODS: Microbiota of selected healthy volunteers from the oral cavity (n=10, the esophagus (n=10, the upper digestive tract (n=20, and the lower digestive tract (n=24 were evaluated through distinct collection methods. Collection methods took into account the different sites, using basic scraping and swabbing techniques, stimulated saliva from the oral cavity, irrigation-aspiration with sterile catheters especially designed for the esophagus, a probe especially designed for upper digestive tract, and a special catheter for the lower digestive tract. RESULTS: (i Mixed microbiota were identified in the oral cavity, predominantly Gram-positive aerobic and anaerobic cocci; (ii transitional flora mainly in the esophagus; (iii Veillonella sp, Lactobacillus sp, and Clostridium sp in the stomach and duodenum; (iv in the jejunum and upper ileum, we observed Bacteroides sp, Proteus sp, and Staphylococcus sp, in addition to Veillonella sp; (v in the colon, the presence of "nonpathogenic" anaerobic bacteria Veillonella sp (average 10(5 UFC indicates the existence of a low oxidation-reduction potential environment, which suggests the possibility of adoption of these bacteria as biological markers of total digestive tract health. CONCLUSIONS: The collection methods were efficient in obtaining adequate samples from each segment of the total digestive tract to reveal the normal microbiota. These procedures are safe and easily reproducible for microbiological studies.OBJETIVO: Padronizar os métodos de coleta do muco do trato digestivo e determinar a microbiota, em voluntários saudáveis no Brasil, coletando amostras da boca, esôfago, estômago, duodeno, jejunos e íleo, c

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

    Directory of Open Access Journals (Sweden)

    Miguel Pinilla-Vera

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

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

    Directory of Open Access Journals (Sweden)

    Bhupendra Kumar Basnet

    2014-03-01

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

  7. Correlation of nasal geometry with aerosol deposition in human volunteers

    International Nuclear Information System (INIS)

    Cheng, Yung-Seng; Simpson, S.Q.; Cheng, Kuo-His; Swift, D.L.; Yeh, Hsu-Chi; Guilmette, R.A.

    1994-01-01

    The nasal airways act as the first filter in the respiratory tract to remove very large or small particles, that would otherwise penetrate to the lower airways. Aerosol deposition data obtained with human volunteers vary considerably under comparable experimental conditions. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. Because there is no direct proof of this hypothesis, nasal deposition of ultrafine particles in human volunteers has been studied in our laboratory. Preliminary results obtained with four adult volunteers also vary considerably between subjects. The purpose of this part of the study was to establish a theoretical equation relating diffusional deposition in nasal airways to the geometrical dimensions of the individual nasal airways. This relationship was then applied to the experimental deposition data and measurement of airway morphometry for correlation

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Stolker, Robert Jan; Mik, Egbert

    2016-01-01

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

  10. Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers.

    Science.gov (United States)

    Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Okada, Hiroki; Kikuchi, Shojiro; Sasako, Mitsuru; Matsumoto, Takayuki; Knowles, Charles H; Miwa, Hiroto

    2013-03-15

    Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P heartburn.

  11. Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

    Directory of Open Access Journals (Sweden)

    Propping Peter

    2004-03-01

    Full Text Available Abstract Background Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. Methods We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C, the serotonin 3A receptor (HTR3A, the dopamine D4 receptor (DRD4, and the dopamine β-hydroxylase (DBH genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA, homovanillic acid (HVA, and 3-methoxy-4-hydroxyphenylglycol (MHPG in healthy volunteers (n = 90. Results The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02. The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005 and HVA (p = 0.009 concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. Conclusions The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.

  12. Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

    Science.gov (United States)

    Hamidovic, Ajna; Kang, Un Jung; de Wit, Harriet

    2008-02-01

    The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers. Healthy men and women (N = 10) received placebo and 2 doses of pramipexole, 0.25 and 0.50 mg, in a within-subject, double-blinded study. Outcome measures included changes in cognitive performance, assessed by the Automated Neuropsychological Assessment Metrics, several behavioral measures related to impulsive behavior, including the Balloon Analogue Risk Task, Delay Discounting Task, Go/No-Go Task, Card Perseveration Task, and subjective ratings of mood assessed by Addiction Research Center Inventory, Profile of Mood States, and Drug Effects Questionnaire. Pramipexole decreased positive ratings of mood (euphoria, intellectual efficiency, and energy) and increased both subjectively reported sedation and behavioral sedation indicated by impaired cognitive performance on several measures of the Automated Neuropsychological Assessment Metrics. Single low to medium doses of this drug did not produce a decrease in impulsive responding on behavioral measures included in this study. The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects.

  13. comparison of various cholesterol lowering diets in young healthy volunteers : effects on serum lipoproteins and on other risk indicators for cardiovascular diseases

    NARCIS (Netherlands)

    Brussaard, J.H.

    1981-01-01

    This thesis deals with the effect of type and amount of dietary fat on the concentration and composition of serum lipoproteins, colonic function, plasma glucose and serum insulin levels and blood pressure in healthy human volunteers.

    Two experiments were carried out. In the first experiment

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

    DEFF Research Database (Denmark)

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie

    2013-01-01

    lateralis, deltoid, and infrapatellar fat pad. Quadriceps and hamstring muscle strength was assessed isometrically at 60-degree knee flexion using a dynamometer. Associations between pain sensitivity and muscle strength were investigated using multiple regressions including age, gender, and body mass index...... as covariates. Results. Knee extension strength was associated with computer-controlled PPT on the vastus lateralis muscle. Computer-controlled PPTs were significantly correlated between sites (r > 0.72) and with cuff PPT (r > 0.4). Saline induced pain intensity and duration were correlated between sites (r > 0......Objectives. To investigate associations between muscle strength and pain sensitivity among healthy volunteers and associations between different pain sensitivity measures. Methods. Twenty-eight healthy volunteers (21 females) participated. Pressure pain thresholds (PPTs) were obtained from 1...

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

    Science.gov (United States)

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

    2010-07-30

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

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

    Science.gov (United States)

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

    2017-01-01

    Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine 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.

  17. NASOPHARYNGEAL CONCENTRATIONS IN THE HUMAN VOLUNTEER BREATHING ACETONE

    Science.gov (United States)

    In an effort to examine the absorption of a common chemical into the nasopharyngeal region in humans, a 57 year old male volunteer inhaled uniformly labeled 13C-acetone at 1.4 ppm for 30 min while performing different breathing maneuvers; nose inhale, nose exhale (NINE); mouth ...

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2010-08-01

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

  20. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.

    OpenAIRE

    Gerards, A.H.; Lathouder, de, S; Groot, E.R.; Dijkmans, B.A.C.; Aarden, L.A.

    2003-01-01

    OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate monocytes or with monoclonal antibodies to CD3 and CD28 to in...

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

    OpenAIRE

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

    2013-01-01

    Objectives: we found only effects of at least a short term practice extended over a period of a few days to weeks of pranayama (alternate nostril breathing) rather than acute effects of unilateral right nostril breathing (suryanadi pranayama). Keeping this in mind the present study was designed to test the hypothesis that 10 min. of right nostril breathing have any immediate effect on ventilatory volumes and capacities in healthy volunteers. Methodology: Forced vital capacity (FVC), Forced ex...

  2. Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Rebecca J Hodge

    Full Text Available Nutritional agents have modest efficacy in reducing weight and blood glucose in animal models and humans, but combinations are less well characterized. GSK2890457 (GSK457 is a combination of 4 nutritional agents, discovered by the systematic assessment of 16 potential components using the diet-induced obese mouse model, which was subsequently evaluated in a human study.In the diet-induced obese mouse model, GSK457 (15% w/w in chow given with a long-acting glucagon-like peptide -1 receptor agonist, exendin-4 AlbudAb, produced weight loss of 30.8% after 28 days of treatment. In db/db mice, a model of diabetes, GSK457 (10% w/w combined with the exendin-4 AlbudAb reduced glucose by 217 mg/dL and HbA1c by 1.2% after 14 days.GSK457 was evaluated in a 6 week randomized, placebo-controlled study that enrolled healthy subjects and subjects with type 2 diabetes to investigate changes in weight and glucose. In healthy subjects, GSK457 well tolerated when titrated up to 40 g/day, and it reduced systemic exposure of metformin by ~ 30%. In subjects with diabetes taking liraglutide 1.8 mg/day, GSK457 did not reduce weight, but it slightly decreased mean glucose by 0.356 mmol/L (95% CI: -1.409, 0.698 and HbAlc by 0.065% (95% CI: -0.495, 0.365, compared to placebo. In subjects with diabetes taking metformin, weight increased in the GSK457-treated group [adjusted mean % increase from baseline: 1.26% (95% CI: -0.24, 2.75], and mean glucose and HbA1c were decreased slightly compared to placebo [adjusted mean glucose change from baseline: -1.22 mmol/L (95% CI: -2.45, 0.01; adjusted mean HbA1c change from baseline: -0.219% (95% CI: -0.910, 0.472].Our data demonstrate remarkable effects of GSK457 in rodent models of obesity and diabetes, but a marked lack of translation to humans. Caution should be exercised with nutritional agents when predicting human efficacy from rodent models of obesity and diabetes.ClinicalTrials.gov NCT01725126.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2004-11-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-11-01

    The purpose of this study was to evaluate the effect of tamsulosin (0.2 mg) on the pharmacokinetics of dutasteride (0.5 mg) in a group of healthy Chinese male volunteers. This was an open-label, single-sequence, 3-period, drug-drug interaction phase 1 study. Twenty-four healthy Chinese male volunteers were enrolled and administered a single dose of 0.5 mg dutasteride and, following a 28- to 30-day washout period, 0.2 mg tamsulosin once daily for 7 days. On day 5, subjects received 0.2 mg tamsulosin coadministered with 0.5 mg dutasteride. Serum dutasteride and tamsulosin concentrations were monitored. In the presence or absence of tamsulosin, there were no apparent changes in dutasteride AUC and Cmax . Adverse events reported were mild to moderate in intensity and resolved by the end of the study. In healthy Chinese male volunteers, tamsulosin 0.2 mg at steady state had no apparent effect on dutasteride pharmacokinetics. Dutasteride and tamsulosin when administered alone or in combination were well tolerated. © 2015, The American College of Clinical Pharmacology.

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

    Science.gov (United States)

    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.

  8. Influence of ondansetron on gastric sensorimotor responses to short duodenal acid infusion in healthy volunteers.

    Science.gov (United States)

    Vanuytsel, T; Karamanolis, G; Van Oudenhove, L; Oudenhove, L V; Vos, R; Tack, J

    2011-03-01

    Duodenal acid infusion induces gastric relaxation and sensitization to distension in healthy volunteers. The acid-sensitive mechanism is still unknown. We hypothesized that 5HT(3)-blockade can inhibit the acid-induced duodenogastric sensorimotor reflex in healthy volunteers. Fourteen healthy volunteers were included in a randomized, double-blind placebo-controlled cross-over trial. An infusion tube with attached pH-electrode was positioned in the duodenum and a barostat balloon was located in the gastric fundus. Proximal gastric volume and sensitivity to distension were assessed before and during duodenal acid infusion and after pretreatment with intravenous (i.v.) ondansetron (a 5HT(3)-receptor antagonist, 8 mg) or saline. An overall perception score (0-6) and an assessment of nine dyspeptic symptoms by visual analogue scales (VAS) were obtained. Results are given as mean ± SEM. Ondansetron had no effect on duodenal pH and on the acid-induced increase of proximal gastric volume (increase of 80 ± 20 vs 83 ± 15 mL after ondansetron and placebo; effect of acid acid infusion and gastric distension. 5HT(3)-receptors are involved in acid-induced duodenogastric sensitization, but not in the duodenogastric inhibitory motor reflex. © 2010 Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-10-15

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

  11. Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Cavallone LF

    2013-11-01

    Full Text Available Laura F Cavallone,1 Karen Frey,1 Michael C Montana,1 Jeremy Joyal,1 Karen J Regina,1 Karin L Petersen,2 Robert W Gereau IV11Department of Anesthesiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA; 2California Pacific Medical Center Research Institute, San Francisco, CA, USAIntroduction: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2.Study design and methods: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A. In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B.Results: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo.Conclusion: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of

  12. Improved lipid profile and increased serum antioxidant capacity in healthy volunteers after Sambucus ebulus L. fruit infusion consumption.

    Science.gov (United States)

    Ivanova, Diana; Tasinov, Oskan; Kiselova-Kaneva, Yoana

    2014-09-01

    This study aimed to establish the effect of Sambucus ebulus L. (SE) ripe fruit infusion on body weight, blood pressure, glucose levels, lipid profile and antioxidant markers in healthy volunteers in respect of its possible protective activity against cardiovascular diseases and other oxidative stress-related diseases. The study involved 21 healthy volunteers, aged between 20 and 59, BMI 23.12 ± 1.31, who consumed 200 ml SE infusion/day for a period of 30 d. Blood samples were collected before and at the end of the intervention. Significant decrease in triglycerides (14.92%), total cholesterol (15.04%) and LDL-C (24.67%) was established at the end of the study. In addition, HDL-C/LDL-C ratio increased by 42.77%. Improved serum antioxidant capacity and total thiol levels were also established. The results presented in this first human intervention study with SE fruit infusion indicate the potential of the plant to improve lipid profile and serum antioxidant capacity in humans.

  13. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers

    DEFF Research Database (Denmark)

    Madsen, Jan L; Linnet, Jan; Rumessen, Jüri J

    2006-01-01

    Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...

  14. Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers

    DEFF Research Database (Denmark)

    Madsen, Jan L; Linnet, Jan; Rumessen, Jüri J

    2006-01-01

    transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test......Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal...... solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after...

  15. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers

    International Nuclear Information System (INIS)

    Lavalaye, J.; Booij, J.; Reneman, L.; Habraken, J.B.A.; Royen, E.A. van

    2000-01-01

    Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [ 123 I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [ 123 I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [ 123 I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [ 123 I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [ 123 I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [ 123 I]FP-CIT binding ratios than males. This effect of gender on [ 123 I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies. (orig.)

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    Science.gov (United States)

    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

  18. Reproducibility of the serum lipid response to coffee oil in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Katan Martijn B

    2003-10-01

    Full Text Available Abstract Background Humans and animals show a certain consistency in the response of their serum lipids to fat-modified diets. This may indicate a genetic basis underlying this response. Coffee oil might be used as a model substance to investigate which genes determine differences in the serum lipid response. Before carrying out such studies our objective was to investigate to what extent the effect of coffee oil on serum lipid concentrations is reproducible within subjects. Methods The serum lipid response of 32 healthy volunteers was measured twice in separate five-week periods in which coffee oil was administered (69 mg cafestol / day. Results Total cholesterol levels increased by 24% in period 1 (range:0;52% and 18% in period 2 (1;48%, LDL cholesterol by 29 % (-9;71% and 20% (-12;57%, triglycerides by 66% (16;175% and 58% (-13;202%, and HDL cholesterol did not change significantly: The range of the HDL response was -19;25% in period 1 and -20;33% in period 2. The correlation between the two responses was 0.20 (95%CI -0.16, 0.51 for total cholesterol, 0.16 (95%CI -0.20, 0.48 for LDL, 0.67 (95%CI 0.42, 0.83 for HDL, and 0.77 (95%CI 0.56, 0.88 for triglycerides. Conclusions The responses of total and LDL cholesterol to coffee oil were poorly reproducible within subjects. The responses of HDL and triglycerides, however, appeared to be highly reproducible. Therefore, investigating the genetic sources of the variation in the serum-lipid response to coffee oil is more promising for HDL and triglycerides.

  19. Safety and Immunogenicity Testing of an Intranasal Group B Meningococcal Native Outer Membrane Vesicle Vaccine in Healthy Volunteers

    National Research Council Canada - National Science Library

    Drabick, Joseph

    1998-01-01

    An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain and tested in 32 healthy adult volunteers...

  20. Bioequivalence studies of two brands of meloxicam tablets in healthy Pakistani volunteers.

    Science.gov (United States)

    Hasan, Syed Muhammad Farid; Shoaib, Muhammad Harris; Hassan, Fouzia; Rehman, Inam-Ur

    2009-04-01

    The pharmacokinetic parameters of two oral formulations of meloxicam tablets were compared in a randomized, single oral dose; two treatments cross over design in 12 healthy male volunteers belonging to Pakistan under fasting conditions. After an overnight fast, the volunteers received 30 mg meloxicam and the blood samples were collected up to 96 hours and drug concentrations were determined by a validated HPLC method. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The 90% confidence intervals obtained by analysis of variance were 87-94% for C(max) and 88-97% for AUC(0-t), that fell well within the acceptance range of 80-125%. Also, no significant difference (a=0.05, Wilcoxon Signed rank test) were detected between T(max) of both formulations. The two formulations were well tolerated and no adverse effect was reported during the study.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml...... of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also......-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects. CONCLUSION: The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  5. Effect of royal jelly ingestion for six months on healthy volunteers

    Directory of Open Access Journals (Sweden)

    Morita Hiroyuki

    2012-09-01

    Full Text Available Abstract Background Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. Methods We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31 and a control group (n = 30. Three thousand mg of royal jelly (RJ or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. Results Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x106 /μL for the RJ group vs. -0.01x106 /μL for the control group, P = 0.0134, hematocrit (+0.9% vs. -0.8%, P = 0.0251, log (fasting plasma glucose (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297, log (insulinogenic index (+0.25 vs. -0.13, P = 0.0319, log dehydroepiandrosterone sulfate (DHEA-S (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483, log testosterone (T (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416, log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015, and in one of the SF-36 subscale scores, mental health (MH (+4 vs. -7, P = 0.0276. Conclusions Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  9. Influence of kinnow juice on the bioavailability of carbamazepine in healthy male volunteers.

    Science.gov (United States)

    Garg, S K; Bhargava, V K; James, H; KuJan-Mar, N; Prabhakar, S; Naresh, Ku

    1998-01-01

    Kinnow juice produces a marked and variable increase in carbamazepine bioavailability. The pharmacokinetics of carbamazepine was studied after drug administration with 300 ml water or kinnow juice in a randomized cross over trial on nine healthy male volunteers. With kinnow juice peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) was significantly (P kinnow juice enhances carbamazepine bioavailability could be due to inhibition of cytochrome P-450 enzyme, since kinnow juice contains naringin which is considered to be inhibitor of liver microsomal dihydropyridine oxidation.

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

    OpenAIRE

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

    2015-01-01

    Objectives: The variation of luminal pH and transit time in an individual is unknown, yet is necessary to interpret single measurements. This study aimed to assess the intrasubject variability of gut pH and transit time in healthy volunteers using SmartPill devices (Covidien, Minneapolis, MN). Methods: Each subject (n=10) ingested two SmartPill devices separated by 24?h. Mean pH values were calculated for 30?min after gastric emptying (AGE), before the ileocecal (BIC) valve, after the ileocec...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml ...... for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice. Sponsorship: Funded by the Scottish Executive Rural Affairs Department and the Danish Government....

  12. Determination of piperphentonamine and metabolites M1 and M6 in human plasma and urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese healthy volunteers.

    Science.gov (United States)

    Shi, Aixin; Hu, Xin; Li, Kexin; Li, Jian; Han, Liping; Wan, Huayin; Li, Rubing

    2012-11-01

    Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of piperphentonamine and its metabolites M1 and M6 was developed for the first time and applied to a pharmacokinetics study. Protein precipitation was used for pre-treatment of plasma samples, and solid phase extraction method was used for pre-treatment of urine samples. The chromatographic separation was achieved on a C(18) column using gradient elution in this study: A: 1% acetic acid aqueous solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the gradient flow rate was 0.25mL/min constantly. The detection was performed of a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via a positive electrospray ionization source. The results were that the m/z ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0→191.8, 356.0→148.7 and 358.0→148.7, respectively. From the standard curve, the concentration ranges of both PPTA and M1 in blood and urine samples were 0.1-500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the correlation coefficient of standard curve was r>0.99. A total of 31 healthy Chinese subjects participated in the pharmacokinetic study of single bolus intravenous injection of piperphentonamine hydrochloride. They were divided into three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug administration, concentrations of PPTA, M1 and M6 in human plasma and urine samples were determined to evaluation the pharmacokinetic characteristics of PPTA and its metabolites M1 and M6. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Laffon, Eric; Jimenez, Maria; Choussat, Alain; Latrabe, Valerie; Ducassou, Dominique; Marthan, Roger; Laurent, Francois

    2004-01-01

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

  14. The Survey on Knowledge of Shiraz District Health Volunteers Over Healthy Life Style in Aging

    Directory of Open Access Journals (Sweden)

    Masoomeh Saffari

    2006-10-01

    Full Text Available Objectives: The education promotion of elderly health is an Important preference of health that should be planned for it. Several problems of elderly are supposed to be due to life style so the community education of healthy life style should be considered. The appropriate approach to achieve those objectives is to use of female health volunteers for transformation of this education to families. Methods & Materials: To determine the level of knowledge of health voluntaries about healthy life style for prevention of problems in elderly period, in Shiraz. Method & Materials: In a cross-sectional study, 320 health voluntaries were selected by randomized method. The sample size was calculated with the results.  A pilot study on one hundred with use of a questionnaire contain of 5 demographic questions and 32 questions about life style including nutrition, prevention of disease, oral health's and health advices. They filled the questionaries' and the data were entered in EPI 2002 software and were analyzed by descriptive tests. Results: The mean age all of 320 health were 33.7 years, with standard deviation of 8.6 years. The knowledge level of them in health advices were 15% weak, 66.9% medium and 18.2% well. In oral health 21.6% well, 61.3% medium & 7.2% well. In prevention of disease 37% weak, 62.2% medium and 9% well, in nutrition 24.6% weak, 69.3% medium and 5.9% well. Overall the level of knowledge of health volunteers about life style were 20.9% weak, 65.5% medium and 13.8% well. Conclusion: In the aim achieving to their approaches program of health, volunteers was started by Ministry of Health in 1990. This program was performed by the aim of health promotion in these group with participation of themselves. Till now they have trained in the recognition of health problems and healthy approach to them. So, the volunteers transfer their knowledge to community specially to under their coverage. At present the health problems are not only due to

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Lindsey Tilling

    2014-01-01

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

  18. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    International Nuclear Information System (INIS)

    Fellner, C.; Friedrich-Alexander-Univ., Erlangen-Nuernberg; Schlaier, J.; Schwerdtner, J.; Brawanski, A.; Fellner, F.; Oberoesterreichische Landesnervenklinik, Linz; Held, P.; Blank, M.; Kalender, W.A.

    1999-01-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [de

  19. Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sisse R Ostrowski

    Full Text Available Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG.Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour, with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest were recorded. Mixed models with Tukey post hoc tests and correlations were applied.Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05. Platelet aggregation decreased (all tests, p<0.05, whereas TEG whole blood clot firmness increased (G, p = 0.05. Furthermore, during endotoxemia (4 h, whole blood fibrinolysis increased (clot lysis time (CLT, p<0.001 and Functional Fibrinogen clot strength decreased (p = 0.049. After endotoxemia (6 h, whole blood fibrinolysis was reduced (CLT, p<0.05. In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001.Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are

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

    Directory of Open Access Journals (Sweden)

    Pickering G

    2015-07-01

    Full Text Available Gisèle Pickering,1–3 Adrian Kastler,4 Nicolas Macian,1,2 Bruno Pereira,5 Romain Valabrègue,6 Stéphane Lehericy,6 Louis Boyer,4,7 Claude Dubray,1–3 Betty Jean4 1CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, 2Centre d’Investigation Clinique – Inserm 1405, 3Clermont Université, Laboratoire de Pharmacologie, Faculté de médecine, 4CHU Gabriel Montpied, Clermont-Ferrand, Service d’Imagerie Ostéo-articulaire thoracique et neurologique, 5CHU Clermont-Ferrand, Délégation Recherche Clinique et à l’Innovation, Clermont-Ferrand, France; 6Institut du Cerveau et de la Moelle epiniere – ICM, Centre de NeuroImagerie de Recherche CENIR, Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris, Paris, France, Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 7UMR CNRS UdA 6284, Clemont-Ferrand, France Background: Paracetamol’s (APAP mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans.Methods and results: This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704 aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter.Conclusion: These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated

  1. Successful application of large microneedle patches by human volunteers

    OpenAIRE

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F.

    2017-01-01

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600??m), were prepared from aqueous blends of 15% w/w Gantrez? S97 and 7.5% w/w poly(ethyleneglycol) 10,000?Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500??m. Ten human volunteers successfully self-inserted the microneedl...

  2. Application of human volunteer studies in setting exposure limits

    International Nuclear Information System (INIS)

    Bailey, M.R.

    1989-01-01

    Human volunteer studies can provide many of the quantitative data on human radionuclide biokinetics needed to relate organ doses to intakes. They are best suited to characterising parameters that apply to a wide range of compounds, e.g. particle deposition in the respiratory tract, and the retention and excretion of elements after injection into the blood. Their application to quantifying particle clearance from the respiratory tract is discussed, with particular reference to recent findings and the NRPB's programme of volunteer investigations. Evidence to support the view that particle clearance rates are similar for different materials is summarised. Rates of particle clearance from the human lung to the GI tract are calculated from the results of two recent studies. The fraction of the remaining lung content cleared per day is estimated to decrease from ∼ 3 x 10 -3 d -1 at 25 days to ∼ 5 x 10 -4 d -1 at 350 days. There is a large degree of inter-subject variation, with most results conforming to a log-normal distribution with σ g of 1.6. There remains considerable uncertainty about subsequent clearance, and about sites of long-term lung retention. (author)

  3. A comparative bioavailability study of two formulations of pregabalin in healthy Chilean volunteers.

    Science.gov (United States)

    Quiñones, Luis; Sasso, Jaime; Tamayo, Evelyn; Catalán, Johanna; González, Juan Paplo; Escala, Mario; Varela, Nelson; León, Jorge; Cáceres, Dante Daniel; Saavedra, Iván

    2010-07-01

    The aim of this study was to compare the pharmacokinetic parameters between two brands of pregabalin in healthy Chilean volunteers. A randomized, single-dose, two-period, two-sequence, crossover study design with a 2-week washout period was conducted in healthy Chilean males. Plasma samples were collected over a 12-hour period after administration of 150 mg pregabalin in each period. A validated ultra-performance liquid chromatography with positive ionization mass spectrometric detection method was used to analyze pregabalin concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products was determined when the ratio for the 90% confidence intervals (CIs) of the difference in the means of the log-transformed area under the curve (AUC)(0-t), AUC(0-∞), and maximum concentration (C(max)) of the two products were within 0.80 and 1.25. The study was carried out on 22 healthy Chilean volunteers. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the test formulation (Pregobin™) of pregabalin were 2.10 (0.56) μg/ml, 10.35 (2.00) μgxh/ml and 13.92 (2.74) μgxh/ml, respectively. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the reference formulation (Lyrica™) of pregabalin were 2.15 (0.52) μg/ml, 10.31 (1.85) μgxh/ml and 13.78 (2.25) μgxh/ml, respectively. The parametric 90% CIs for C(max), AUC(0-t), and AUC(0-∞) were 0.97-1.13, 1.01-1.04, and 0.98-1.02, respectively. These results suggest that both products are bioequivalent and can be used as interchangeable options in the clinical setting.

  4. Bright-light intervention induces a dose-dependent increase in striatal response to risk in healthy volunteers

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Fisher, Patrick M; Madsen, Martin K

    2016-01-01

    Bright-light interventions have successfully been used to reduce depression symptoms in patients with seasonal affective disorder, a depressive disorder most frequently occurring during seasons with reduced daylight availability. Yet, little is known about how light exposure impacts human brain...... function, for instance on risk taking, a process affected in depressive disorders. Here we examined the modulatory effects of bright-light exposure on brain activity during a risk-taking task. Thirty-two healthy male volunteers living in the greater Copenhagen area received 3weeks of bright......-light intervention during the winter season. Adopting a double-blinded dose-response design, bright-light was applied for 30minutes continuously every morning. The individual dose varied between 100 and 11.000lx. Whole-brain functional MRI was performed before and after bright-light intervention to probe how...

  5. The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers

    DEFF Research Database (Denmark)

    Petersen, K A; Birk, S; Lassen, L H

    2005-01-01

    CBF(MCA)) was measured by 133-Xenon inhalation SPECT. The diameter of the temporal and radial artery was measured by high-resolution ultrasound. Systemic haemodynamics and partial pressure of CO(2) (P(et)CO(2)), and adverse events were monitored regularly. BIBN4096BS had no influence on global or regional cerebral blood......BIBN4096BS is a CGRP-antagonist effective in the treatment of migraine. Blocking the receptor of a strong vasodilator involves a theoretical risk of causing cerebral vasoconstriction, a probability not previously investigated with BIBN4096BS. Seven healthy volunteers completed this double...... flow, or on the blood flow velocity in the middle cerebral artery. There was no effect on systemic haemodynamics and adverse events were minor. We conclude that there is no effect of CGRP-receptor blockade on the cerebral or systemic circulation in humans. Circulating CGRP is therefore not likely...

  6. Lack of association between joint hyperlaxity and, I: panic disorder, and II: reactivity to carbon dioxide in healthy volunteers.

    Science.gov (United States)

    Benjamin, Jonathan; Ben-Zion, Itzhak Z; Dannon, Pinhas; Schreiber, Shaul; Meiri, Gal; Ofek, Andre; Palatnik, Alex

    2001-03-01

    This study attempted to replicate previous reports of associations between panic disorder and joint hyperlaxity. The authors also examined possible associations between reacitivity to carbon dioxide (CO(2)), a model for panic vulnerability, and hyperlaxity in healthy volunteers. One hundred and one patients with DSM-IV panic disorder and 39 healthy volunteers were assessed for hyperlaxity by Beighton's criteria. Healthy volunteers also received two vital capacity inhalations of CO(2). Thirteen (13%) patients had five or more hyperlax joints. This rate did not differ from that in the healthy volunteers. Anxiety in healthy volunteers, as measured by the NIMH self-rating scale, DSM-IV panic symptom scores, and 100 mm visual analog scales of anxiety, increased after CO(2) from a mean of 1.8 to 2.8 (not significant); from 0.5 to 4 ( p < 0.001) and from 8.7 to 11.6 mm ( p < 0.1), respectively. There were no associations between responses to CO(2) and hyperlaxity. Copyright 2001 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Hütt Pirje

    2005-08-01

    Full Text Available Abstract 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

  8. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo

    Directory of Open Access Journals (Sweden)

    Oei Gezina TML

    2012-09-01

    Full Text Available Abstract Background 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. Methods Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O2 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. Results 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. Conclusions We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Trial registration Dutch Trial Register: http://www.trialregister.nl/ NTR2152

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Noisel, Nolwenn; Bouchard, Michèle; Carrier, Gaétan

    2010-05-01

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

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

    Science.gov (United States)

    Nielsen, Signe Tellerup; Harder-Lauridsen, Nina Majlund; Benatti, Fabiana Braga; Wedell-Neergaard, Anne-Sophie; Lyngbæk, Mark Preben; Møller, Kirsten; Pedersen, Bente Klarlund; Krogh-Madsen, Rikke

    2016-03-15

    Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect. Copyright © 2016 the American Physiological Society.

  12. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-05-01

    Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. © 2016 The Association of Anaesthetists of Great Britain and Ireland.

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

    Science.gov (United States)

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

    2002-01-01

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

  16. Percutaneous absorption of diclofenac in healthy volunteers after single and repeated topical application of diclofenac Emulgel.

    Science.gov (United States)

    Sioufi, A; Pommier, F; Boschet, F; Godbillon, J; Lavoignat, D; Salliere, D

    1994-08-01

    The percutaneous absorption of diclofenac was studied in ten healthy volunteers treated with Emulgel containing 1.16% diclofenac diethylammonium for 8 d as follows: a single application of 5 g Emulgel on days 1 and 8, and two applications d-1 on days 2-7. Plasma concentration profiles of unchanged diclofenac and urinary concentrations of total diclofenac and metabolites (sum of free and conjugated) were determined. High inter-individual variations in plasma and urine data were recorded, due probably to the permeability and the hydration of the skin. Steady state was reached after 2 d of twice-daily administration. Plasma concentrations were low but remained in the range 10-50 nmol L-1 over the full day for most of the subjects, indicating prolonged absorption from the application site.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: Ischaemia-reperfusion (IR) injury is partly caused by the release of reactive oxygen species and cytokines and may result in remote organ injury. Surgical patients are exposed to surgical stress and anaesthesia, both of which can influence the IR response. An IR model without these int......OBJECTIVE: Ischaemia-reperfusion (IR) injury is partly caused by the release of reactive oxygen species and cytokines and may result in remote organ injury. Surgical patients are exposed to surgical stress and anaesthesia, both of which can influence the IR response. An IR model without...... at any sampling time. CONCLUSION: Twenty minutes of lower limb ischaemia does not result in an ischaemia-reperfusion injury in healthy volunteers, measurable by oxidative and pro- and anti-inflammatory biomarkers in muscle biopsies and in the systemic circulation....

  18. Ocular effects of acute ingestion of Cola nitida(Linn on healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    S. A. Igwe

    2007-12-01

    Full Text Available Cola nitida Linn (Sterculiaceae is an economic plant widely distributed throughout West Africa and possibly other parts of Africa.Members are malvalves because of their lobular nature. Because of its ubiquity, the plant plays an important role in commerce, and in social activities where it is casually eaten without prescription or restriction. The ethnopharmacological effects of bolus ingestion of 30g of Cola nitida was investigated on visually acute and healthy volunteers in order to determine its ocular implications or effects. Results showed that Cola nitida had no effecton the pupil diameter, visual acuity and intraocular pressure but improved the near point of convergence by 43% and increased the amplitude of accommodation by 11% while existing heterophorias are ameliorated. The stimulating effect of Cola nitida might overcome asthenopic symptoms with convergence insufficiency and allows near work to be donewithout stress. Somnolence and ocular muscle imbalance common features of the elderly canbe ameliorated or relieved.

  19. Ethical issues in recruitment of "healthy volunteers": study of a clinical research organisation in Hyderabad.

    Science.gov (United States)

    Krishna, Shilpa; Prasad, N Purendra

    2014-01-01

    This paper raises some of the ethical issues involved in the recruitment of healthy volunteers (HVs) by clinical research organizations (CROs) for bioavailability and bioequivalent (BA/BE) studies. It also explores the underlying reasons for the participation of the HVs and their interaction with the CROs. The findings are based on the data collected from 50 HVs participating in a BA/BE study conducted by a CRO in Hyderabad and from the key officials involved in it. The findings indicate the existence of various complex networks, throw some light on the role of middlemen ("Anna") and the negotiation process, and give us an insight into the social norms and values that compelled the HVs to participate in the study. The paper offers a critical analysis of a few ethical concerns.

  20. Renal effects of the non-ionic contrast medium iopentol after intravenous injection in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsen, J.A.; Berg, K.J.; Waaler, A.; Andrew, E. (Rikshospitalet, Oslo (Norway). Dept. of Radiology Rikshospitalet, Oslo (Norway). Renal Section Nycomed A/S, Oslo (Norway). Dept. of Clinical Research and Development)

    1990-01-01

    Renal effects of the new non-ionic contrast medium iopentol in increasing doses were assessed and compared with the effects of physiologic saline. Twenty-four healthy male volunteers, allocated to three dose groups, were given iopentol intravenously in doses of 0.3, 0.6, and 1.2 g I/kg body weight, respectively. The highest dose group was also given physiologic saline separately as a control. The diuresis increased in all groups, most in the highest dose group, and with a concomitant fall of urine osmolality and increase in osmolar clearance. A slight decrease of serum osmolality, creatinine and urea occurred at 3 hours due to hemodilution. The glomerular filtration rate was unaffected by iopentol. The urinary excretion of albumin and {beta}{sub 2}-microglobulin was unchanged. However, urinary N-acetyl-{beta}-glucosaminidase and alkaline phosphatase increased significantly, most in the highest dose group. All changes were reversible. (orig.).

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

    Science.gov (United States)

    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.

  2. Non-uniform versus uniform attenuation correction in brain perfusion SPET of healthy volunteers

    International Nuclear Information System (INIS)

    Van Laere, K.; Versijpt, J.; Dierckx, R.; Koole, M.

    2001-01-01

    Although non-uniform attenuation correction (NUAC) can supply more accurate absolute quantification, it is not entirely clear whether NUAC provides clear-cut benefits in the routine clinical practice of brain SPET imaging. The aim of this study was to compare the effect of NUAC versus uniform attenuation correction (UAC) on volume of interest (VOI)-based semi-quantification of a large age- and gender-stratified brain perfusion normal database. Eighty-nine healthy volunteers (46 females and 43 males, aged 20-81 years) underwent standardised high-resolution single-photon emission tomography (SPET) with 925 MBq 99m Tc-ethyl cysteinate dimer (ECD) on a Toshiba GCA-9300A camera with 153 Gd or 99m Tc transmission CT scanning. Emission images were reconstructed by filtered back-projection and scatter corrected using the triple-energy window correction method. Both non-uniform Chang attenuation correction (one iteration) and uniform Sorenson correction (attenuation coefficient 0.09 cm -1 ) were applied. Images were automatically re-oriented to a stereotactic template on which 35 predefined VOIs were defined for semi-quantification (normalisation on total VOI counts). Small but significant differences between relative VOI uptake values for NUAC versus UAC in the infratentorial region were found. VOI standard deviations were significantly smaller for UAC, 4.5% (range 2.6-7.5), than for NUAC, 5.0% (2.3-9.0) (P 99m Tc-ECD uptake values in healthy volunteers to those obtained with NUAC, although values for the infratentorial region are slightly lower. NUAC produces a slight increase in inter-subject variability. Further study is necessary in various patient populations to establish the full clinical impact of NUAC in brain perfusion SPET. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Del Tacca M

    2013-07-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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, pinfinity) (42.4 +/- 10.1 vs 31.3 +/- 8.3 mg*hr/L, pinfinity. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

    2009-01-01

    The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

  8. Successful application of large microneedle patches by human volunteers.

    Science.gov (United States)

    Ripolin, Anastasia; Quinn, James; Larrañeta, Eneko; Vicente-Perez, Eva Maria; Barry, Johanne; Donnelly, Ryan F

    2017-04-15

    We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600μm), were prepared from aqueous blends of 15% w/w Gantrez ® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm 2 will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  10. Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

    Science.gov (United States)

    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.

  11. Patterns in the Parathyroid Response to Sodium Bicarbonate Infusion Test in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Theodossis S. Papavramidis

    2014-01-01

    Full Text Available Background. The sodium bicarbonate infusion test evaluates the function of the parathyroid glands. The present study aims to evaluate the range of parathyroid response in healthy individuals and the potential influence of various factors. Methods. Fifty healthy volunteers were subjected to the test. Levels of vitamin D, calcium, albumin, and PTH were measured before infusion. PTH was measured at 3, 5, 10, 30, and 60 minutes after infusion. Results. A curve describing the response of parathyroids to the test was drawn. Twenty percent of the subjects had blunted PTH response. No significant difference was observed between normal and blunted responders concerning age, BMI, baseline PTH, or calcium levels. Nonetheless, there was a significant difference in vitamin D levels (P=0.024. Interpretation. The test is easy to perform and may be used for everyday screening. It has to be clarified whether our observations are, at least partly, produced due to the presence of individuals with a constitutively blunted response or if low levels of vitamin D decrease the ability of the parathyroids to respond. Whichever the case, PTH response of normal individuals to sodium bicarbonate infusion test is more varied than previously thought and vitamin D levels influence it.

  12. Physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers

    International Nuclear Information System (INIS)

    Nishizawa, Sadahiko; Inubushi, Masayuki; Okada, Hiroyuki

    2005-01-01

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

  13. Diffusion-weighted MRI of kidneys in healthy volunteers and living kidney donors

    International Nuclear Information System (INIS)

    Sulkowska, K.; Palczewski, P.; Duda-Zysk, A.; Szeszkowski, W.; Wojcik, D.; Kownacka-Piotrowska, D.; Gołebiowski, M.

    2015-01-01

    Aim: To establish the normal apparent diffusion coefficient (ADC) values in healthy kidneys, comparing them with the literature, and assessing the correlation between ADC values, creatinine blood level, and glomerular filtration rate (GFR). Materials and methods: Twenty-four healthy volunteers and 26 living kidney donors were examined on a 1.5 T magnetic resonance imaging (MRI) unit. Two diffusion-weighted imaging (DWI) sequences were included in the study protocol (protocol 1 with 16 b-values, protocol 2 with 10 b-values) before the examination blood and urine samples were collected. The GFR was calculated using Cockcroft & Gault and MDRD (Modification of Diet In Renal Disease) formulas and the ADC values were measured separately for the cortex and medulla of each kidney by two independent observers. All statistical analyses were performed using the STATISTICA (version 10.0) software package. Data were analysed using an unpaired t-test; p<0.05 indicated a statistically significant difference. Results: The average ADC value for protocol 1 for the cortex was 2.26×10 −3  mm 2 /s, for the medulla 2.21×10 −3  mm 2 /s. In protocol 2, the respective values were 2.13×10 −3  mm 2 /s and 2.06×10 −3  mm 2 /s. Neither statistically significant interobserver differences nor correlation between ADC values, GFR, and creatinine serum level were observed. Conclusion: The reference ADC values were established. The measurements show high interobserver consistency. The differences in ADC values reported in the literature suggest dependence on the equipment and methodology and point to the necessity of obtaining ADC norms for each MRI unit. -- Highlights: •Magnetic resonance diffusion-weighted imaging of kidneys. •Apparent diffusion coefficient in healthy individuals. •Monoexponential model of diffusion

  14. Acute effects of acrolein in human volunteers during controlled exposure.

    Science.gov (United States)

    Dwivedi, Aishwarya M; Johanson, Gunnar; Lorentzen, Johnny C; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. The aim of the study was to determine thresholds for acute irritation for acrolein. Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p acrolein alone but not during any of the other five exposure conditions. Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein.

  15. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

    Science.gov (United States)

    Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

    2013-01-01

    Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

  16. Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Hanif, Muhammad; Bushra, Rabia; Naz, Asia; Khursheed, Raheela

    2016-09-01

    This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test (F4) tablet formulation with reference product (Caflam). Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 µg.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test (F4) and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using KineticaTM 4.4.1 (Thermo Electron Corp. USA). Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for Cmaxcalc, Tmaxcalc, AUC0-∞, AUCtot and AUClast using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC0-∞ (0.997-1.024), AUCtot (1.004-1.031), AUClast (0.997 -1.024), Cmaxcalc (0.994-1.007) and Tmaxcalc (0.996-1.013) for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated.

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

    Science.gov (United States)

    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.

  18. Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers.

    Science.gov (United States)

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

    2010-01-01

    Valsartan (CAS 137862-53-4) is an antihypertensive drug belonging to the family of angiotensin II receptor antagonists acting at the AT1 receptor, which mediates all known effects of angiotensin II on the cardiovascular system. In the present study, the pharmacokinetic parameters of two oral formulations of valsartan tablets were compared in a randomized, single oral dose, two-treatment crossover design in 24 healthy male volunteers under fasting conditions. After an overnight fast, the volunteers received 80 mg valsartan. Blood samples were collected up to 48 h and drug concentrations were determined by a reverse-phase HPLC method with fluorescence detection. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The obtained values for test and reference products were 3067.7 +/- 1,281.7 and 3,304.3 +/- 1,196.4 ng/ml for Cmax; 17,834.4 +/- 7,083.8 and 18,319.1 +/- 7,800.7 ng x h/ml for AUC0-48; 18,825.7 +/- 7,553.2 and 19,172.2 +/- 8,307.2 ng x h/ml for AUC0-infinity, respectively. The 90% confidence intervals obtained by analysis of variance were 86.84-100.87% for Cmax and 93.43-115.54% for AUC0-t, which are within the acceptance range of 80-125%. Therefore it can be concluded that both products are bioequivalent in terms of rate and extent of drug absorption and therefore interchangeable.

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

    Science.gov (United States)

    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 (pDT2) -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.

  20. Comparison of the effects of dopamine, dobutamine, and dopexamine upon renal blood flow: a study in normal healthy volunteers.

    OpenAIRE

    Mousdale, S; Clyburn, P A; Mackie, A M; Groves, N D; Rosen, M

    1988-01-01

    1. We compared the effects of dopexamine, dopamine and dobutamine on the heart rate, blood pressure and renal blood flow of six healthy volunteers in an open triple crossover trial. 2. The results suggest that at the dose ranges investigated dopamine was the most effective agent for increasing renal blood flow.

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

    NARCIS (Netherlands)

    McMorrow, R. C. N.; Windsor, J. S.; Hart, N. D.; Richards, P.; Rodway, G. W.; Ahuja, V. Y.; O'Dwyer, M. J.; Mythen, M. G.; Grocott, M. P. W.; Ahuja, V.; Aref-Adib, G.; Burnham, R.; Chisholm, A.; Clarke, K.; Coates, D.; Coates, M.; Cook, D.; Cox, M.; Dhillon, S.; Dougall, C.; Doyle, P.; Duncan, P.; Edsell, M.; Edwards, L.; Evans, L.; Gardiner, P.; Grocott, M.; Gunning, P.; Hart, N.; Harrington, J.; Harvey, J.; Holloway, C.; Howard, D.; Hurlbut, D.; Imray, C.; Ince, C.; Jonas, M.; van der Kaaij, J.; Khosravi, M.; Kolfschoten, N.; Levett, D.; Luery, H.; Luks, A.; Martin, D.; McMorrow, R.; Meale, P.; Mitchell, K.; Montgomery, H.; Morgan, G.; Morgan, J.

    2012-01-01

    We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen

  2. Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers

    NARCIS (Netherlands)

    Verhagen, M. A.; Samsom, M.; Maes, B.; Geypens, B. J.; Ghoos, Y. F.; Smout, A. J.

    1997-01-01

    BACKGROUND: ABT-229 is a recently developed derivative of erythromycin, devoid of antibiotic activity. We studied the effect of ABT-229 on gastric emptying and postprandial antroduodenal motility in healthy volunteers. METHODS: Placebo, 4 and 16 mg ABT-229 were given as a single oral dose to nine

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

    Science.gov (United States)

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

    2016-02-01

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

  4. Pharmacokinetics of sugammadex 16 mg/kg in healthy Chinese volunteers.

    Science.gov (United States)

    de Kam, Pieter-Jan; Hou, Jie; Wang, Zaiqi; Lin, Wen Hong; van den Heuvel, Michiel

    2015-06-01

    Elimination of sugammadex occurs predominantly via the kidneys, with the majority of the drug excreted unchanged in the urine. To date, most studies with sugammadex have been performed in non-Asian populations. The objectives of this open-label study were to determine the pharmacokinetics (PK) and safety of single-dose sugammadex (16 mg/kg) in healthy Chinese adult volunteers. 12 Chinese subjects (6 male; 6 female) received intravenous sugammadex (16 mg/kg) as a 10-second bolus infusion. Blood samples were collected pre-sugammadex and at regular intervals up to 24 hours post-sugammadex for PK assessment. Safety was assessed via AEs, vital signs, electrocardiogram, and laboratory parameters. Following sugammadex 16 mg/kg infusion, peak sugammadex concentration was 197 μg/mL, clearance was 99.7 mL/min, and apparent volume of distribution at equilibrium was 10.5 L. Plasma sugammadex concentrations showed a polyexponential decline over time, with an overall geometric mean (CV%) terminal half-life of 145 minutes (17.9%) (139 minutes (17.7%) for males; 152 minutes (18.6%) for females). No influence of gender on the PK of sugammadex was observed. Three subjects experienced an adverse events (AE) (dysgeusia of mild intensity), which was considered possibly or probably related to sugammadex. There were no clinically significant changes in vital signs, electrocardiography or laboratory parameters. PK of sugammadex (16 mg/kg) was characterized in healthy Chinese subjects. Overall between-subject variability on clearance and apparent volume of distribution was ~ 10%. Sugammadex was generally well tolerated.

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

    Directory of Open Access Journals (Sweden)

    Metta S.S. Wiria

    2007-09-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

    Science.gov (United States)

    Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

    2013-01-01

    Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; pdisintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Naoko Ikuta

    2016-06-01

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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Di Donato Michele

    2009-12-01

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

  13. Ocular dynamics of Garcinia cola (Heckel on healthy volunteers following bolus ingestion

    Directory of Open Access Journals (Sweden)

    S. A. Igwe

    2007-12-01

    Full Text Available Garcinia cola Heckel, an angiospermae belonging to the  family Guttiferae, is known in commerce as bitter cola. It is a plant found in the West African subregion, mostly in moist conditions, and often in association with Cola acuminata. The seeds are highly valued ingredients in African ethonomedicine. The seeds have several social uses and applications in folk medicine. These seeds are ordinarily chewed by the local people without prescription or restriction. In an in vivo case control study, the effects of Garcinia cola on some visual functions: pupil diameter, near point of convergence (NPC, amplitude of accommodation (AA, intraocular pressure (IOP, visual acuity (VA and habitual phoria; following bolus ingestion of 20 g was undertaken using healthy visually active volunteers. Results showed that bolus ingestion of Garcinia cola constricted the pupil by 68%, reduced the NPC by 28%, increased the AA by 17.8% at peak effect and decreased the intraocular pressure by 31% without affecting the distance and near VA. The lateral phoria at far and near tended towards esophoria. Possibly the miotic effect and reduction in IOP could be of benefit to patients with raised IOP where conventional drugs may not be effective. Also it is possible that the effects on phoria could be exploited in oculomotor function in combination with visual training.

  14. [Genetic polymorphism in sparteine oxidation--occurrence in healthy volunteers in Slovakia].

    Science.gov (United States)

    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.)

  15. Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

    Science.gov (United States)

    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

  16. Tolerance and biochemical effects from intravenous injection of ioxaglate in healthy volunteers

    International Nuclear Information System (INIS)

    Nilsson, P.E.; Aspelin, P.; Nyman, U.; Hedner, U.; Malmoe Allmaenna Sjukhus

    1984-01-01

    The influence of intravenous injection of ioxaglate (Hexabrix, 320 mg I/ml) on various biochemical, coagulation and fibrinolytic parameters, fractionated plasma proteins, precordial ECG and blood pressure was prospectively and sequentially studied in 9 healthy volunteers. One ml/kg body weight of the contrast medium was injected within one minute into an antecubital vein. Small, but statistically significant, changes in some of the biochemical parameters were found during the observation period, 2 to 4 days. All values of the biochemical parameters were, however, within the normal reference range for each parameter. No significant alterations were seen in the coagulation parameters. Increased fibrinolysis was recorded in some subjects both before and after the injection. No fibrinolytic degradation products were found indicating that the fibrinolysis was nominal. No significant changes were observed in the fractionated plasma proteins. The heart rate decreased significantly 15 seconds after commencing the injection. No significant changes in blood pressure were recorded. Two participants became nauseated and one of them vomited during the injection. Apart from this, no adverse effects were noted. No clinically significant changes following the injections were found. (orig.)

  17. Novel ultrasound-guided inter-semispinal plane block: a comparative pilot study in healthy volunteers.

    Science.gov (United States)

    Ohgoshi, Yuichi; Nishizakura, Ryo; Takahashi, Yuki; Takeda, Keisuke; Nakayama, Hirosuke; Kawamata, Mariko; Kurahashi, Kiyoyasu

    2018-02-01

    We previously reported that a novel multifidus cervicis plane (MCP) block could anesthetize the dorsal rami of the cervical spinal nerves. While MCP sonoanatomy is easily detectable in most patients, it is sometimes difficult to recognize the MCP injection plane, especially in elderly patients. Thus, we proposed the inter-semispinal plane (ISP) block as an alternative for the MCP block. The aim of this study was to evaluate the utility of the ISP block by evaluating the area and duration of anesthesia, compared with that of the MCP block in eight healthy volunteers. Each participant underwent unilateral ultrasound-guided MCP block and ISP block. For each block, 20 ml of ropivacaine 0.2% was injected, and the area of anesthesia was determined using the pinprick test. The anesthetic area ranged from C4 to T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (3/8; 37.5%) in the MCP block, and from C4 to T1 (1/8; 12.5%), T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (1/8; 12.5%) in the ISP block. The mean (standard deviation) duration of sensory loss following MCP and ISP blocks was 329 (77) min and 349 (70) min, respectively. Thus, the ISP block may be a reliable alternative to the MCP block.

  18. Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers.

    Science.gov (United States)

    Partyla, Tomasz; Hacker, Henriette; Edinger, Hardy; Leutzow, Bianca; Lange, Joern; Usichenko, Taras

    2017-03-01

    The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT). Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50-75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers' blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators. Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35-3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05-2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions. We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.

  19. Effects of midazolam on cerebral blood flow in human volunteers

    International Nuclear Information System (INIS)

    Forster, A.; Juge, O.; Morel, D.

    1982-01-01

    The effects of intravenously administered midazolam on cerebral blood flow were evaluated in eight healthy volunteers using the 133 Xe inhalation technique. Six minutes after an intravenous dose of 0.15 mg/kg midazolam, the cerebral blood flow decreased significantly (P less than 0.001) from a value of 40.6 +/- 3.3 to a value of 27.0 +/- 5.0 ml . 100 g-1 . min-1. Cerebrovascular resistance (CVR) increased from 2.8 +/- 0.2 to 3.9 to 0.6 mmHg/(ml . 100 g-1 . min-1)(P less than 0.001). Mean arterial blood pressure decreased significantly (P less than 0.05) from 117 +/- 8 to 109 +/- 9 mmHg and arterial carbon dioxide tension increased from 33.9 +/- 2.3 to 38.6 +/- 3.2 mmHg (P less than 0.05). Arterial oxygen tension remained stable throughout the study, 484 +/- 95 mmHg before the administration of midazolam and 453 +/- 76 mmHg after. All the subjects slept after the injection of the drug and had anterograde amnesia of 24.5 +/- 5 min. The decrease in mean arterial blood pressure was probably not important since it remained in the physiologic range for cerebral blood flow autoregulation. The increase in arterial carbon dioxide tension observed after the midazolam injection may have partially counteracted the effect of this new benzodiazepine on cerebral blood flow. Our data suggest that midazolam might be a safe agent to use for the induction of anethesia in neurosurgical patients with intracranial hypertension

  20. Reproducibility of urodynamic filling sensation at weekly interval in healthy volunteers and in women with detrusor overactivity.

    Science.gov (United States)

    Van Meel, Tom David; Wyndaele, Jean-Jacques

    2011-11-01

    To evaluate the reproducibility of bladder sensation during standardized filling cystometry in female volunteers and overactive bladder (OAB) patients, repeated with weekly interval. We recruited 13 female nulliparous volunteers (age 21-47) and 17 female patients with OAB between (age 18-72). They participated in three investigation periods, each separated by 7 days to assess reproducibility of sensation related to standardized cystometry. Subjects were asked to report all sensations they felt during bladder filling. The previously described pattern of sensation was reported during bladder filling in all. Consecutive sensations corresponded to statistically higher bladder volumes. Volumes, at which different sensations of bladder filling were reported, were significantly higher in controls than in OAB patients [first sensation of filling (FSF) P = 0.003, first desire to void (FDV) P sensation/volume ratios were significantly higher in patients with OAB than in the healthy volunteers: FSF occurred at mean 46% and FDV at mean 73% of SDV in OAB patients, compared to 36% and 64% in healthy volunteers. Sensations proved highly reproducible when determined with weekly interval. Our data demonstrate that cystometric filling sensation determined in a standardized way with weekly interval is highly reproducible in healthy and in OAB patients. This finding has, in our opinion, clinical importance as it shows that the technique is reliable both for a sensory evaluation of the LUT as to study influence of treatment aimed at changing this sensation. Copyright © 2011 Wiley Periodicals, Inc.

  1. Enhanced Chromatographic Determination of Nicotine in Human Plasma: Applied to Human Volunteers.

    Science.gov (United States)

    Ayoub, Bassam M; Mohamady, Samy; Hendy, Moataz S; Elmazar, Mohamed M

    2015-12-01

    Development of enhanced UPLC-UV method for determination of nicotine in human plasma was achieved on a Symmetry(®) C18 column (100 mm × 2.1 mm, 2.2 μm) applying isocratic elution based on Methanol: Acetonitrile: Phosphate Buffer (pH: 2.7) with the ratio (20:30:50, v/v/v) as a mobile phase. The ultraviolet detector was operated at 260 nm. The mobile phase was pumped through the column at a flow rate of 0.2 mL min(-1). The column temperature was adjusted to 50ºC and the injection volume was 2 μL. Quinine was selected as an internal standard (IS) due to its structure similarity to nicotine having basic pyridine ring to optimize the liquid liquid extraction procedure using diethyl ether coupled with vacuum evaporation at 40°C. Validation parameters for nicotine were found to be acceptable over the concentration range of 2.5-50 ng ml(-1). The application of the proposed method on four healthy human volunteers was approved by the ethical committee. The study was carried out under fasting conditions and the concerned subjects were informed about the objectives and possible risks involved in the study. The proposed method proved to be simple and fast which is a major advantage to analyze large number of samples per day using the accelerated vacuum evaporation technique. The method showed satisfactory data for all the parameters tested within the limits for bioanalytical assays. The lower limit of quantification (LLOQ) permits the application of the method for further pharmacological and clinical studies.

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

    Science.gov (United States)

    Pongsuthana, Surapun; Tivatunsakul, Naris

    2016-02-01

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

  3. Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers.

    Science.gov (United States)

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

    2017-01-01

    To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. Fluvoxamine pretreatment increased Cmax and AUC0-∞  of nebivolol (Cmax: 1.67 ± 0.690  vs 2.20 ± 0.970  ng/mL; AUC0-∞: 12.1 ± 11.0  vs 19.3 ± 19.5  ng*h/mL ) and of its active metabolite (Cmax: 0.680  ± 0.220  vs 0.960 ± 0.290  ng/mL; AUC0-∞: 17.6 ±20.1  vs 25.5 ± 29.9  ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For

  4. Effect of Misoprostol on the Pharmacokinetics of Sustained Release Diclofenac in Myanmar Healthy Male Volunteers

    Directory of Open Access Journals (Sweden)

    Htet Htet Aung

    2017-03-01

    Full Text Available Background: Sustained release diclofenac (diclofenac SR is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis. Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR. Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers. Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 μg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC. Pharmacokinetic parameters such as area under concentration-time curve (AUC0-α, peak plasma concentration (Cmax, time to achieve peak plasma concentration (Tmax, absorption half-life (T½(ab, elimination half-life (T1/2(el, absorption rate constant (Kab, and elimination rate constant (Kel were determined. Results: With misoprostol, the mean AUC0-α of diclofenac SR was significantly reduced from 12.11±5.25μg/ mL×hr to 4.17±2.72μg/mL×hr (p0.05. The mean T½(ab was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05. The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05. The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05. Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

  5. Functional magnetic resonance imaging: lateralization and localization of language in healthy volunteers

    International Nuclear Information System (INIS)

    Brinkhoff, C.

    2000-08-01

    Purpose: The purpose of this study was to determine the localization and hemispheric dominance of language in 21 right-handed and 21 left-handed healthy volunteers by functional magnetic resonance imaging (fMRI). Method: For language stimulation two tasks were used: phonological word generation, where subjects were asked to generate words starting with a given input letter (s, t, k), and a language perception and comprehension task requiring subjects to listen closely to the paragraph recall section of the Rivermead Behavioral Memory Test (RBMT) (1). In both tasks, 3 periods of activation were alternated with 3 rest periods of equal length. Activation were measured simultaneously in 15 horizontal slices using echoplanar imaging on a 1.5 T magnetic resonance scanner. Activated pixels were counted and anatomical localization was determined by using the Talairach Atlas of the brain (2). The pixel count in defined regions of the cortex in each hemisphere was taken as indicating the degree of language activation and was correlated with three conventional neuropsychological lateralization tasks: handedness was determined by Edinburgh Handedness Questionnaire (EHI) (3), manual dexterity was assessed by a pegboard test measuring the time to place all pegs for the right and left hand separately. A well-standardized dichotic listening paradigm using paired presentations of CV syllables was employed (4) in a non-forced condition to assess the (right or left ear) advantage indicating left or right hemisphere speech dominance. Results: Activation patterns differed significantly in both paradigms. Language comprehension caused maximum responses in temporal regions of both hemispheres, especially in the superior and the middle temporal gyrus. Independent from handedness, the language perception and comprehension paradigm exhibited bilateral activation predominantly. 52.4 % of right-handed subjects showed a bilateral activation pattern, whereas 33.3 % showed fMRI changes

  6. Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

    Science.gov (United States)

    Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

    2001-04-01

    Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

  7. The feasibility of susceptibility weighted imaging for assessing renal difference of healthy volunteers after water loading

    International Nuclear Information System (INIS)

    Ding Jiule; Xing Wei; Chen Jie; Yu Shengnan; Qiu Jianguo; Xing Shijun; Sun Jun

    2013-01-01

    Objective: To probe the feasibility of susceptibility weighted imaging (SWI) for evaluation of renal blood oxygenation level of healthy volunteers after water loading. Methods: SWI of 11 healthy volunteers, acquired before (group 1) and after water loading (group 2), were assessed retrospectively by two radiologists with more than 10 years abdominal work experience independently. In those images of the same section plane derived from two groups, the phase values in cortex (φ cor ) and medulla (φ med ), difference between the same vein and surrounding tissue on phase map (△ φ ) were measured using SPIN software package, and the oxygen extraction fraction changes (△OEF) was calculated. The φ cor , φ med and △ φ between two groups were compared by paired t test. And the intraclass correlation coefficient (ICC) was used to evaluate the consistency between two radiologists. Results: For the radiologist 1, the φ cor , φ med and △ φ were (0.046 ± 0.019), (-0.014 ± 0.003) and (1.3 ± 0.4) rad in group 1, and were (0.047 ± 0.014), (-0.012 ± 0.005) and (1.1 ± 0.4) rad in group 2 respectively, and no significant change was found in φ cor and φ med after water loading (t = -0.589 and-0.206, P > 0.05 in all), except of in △ φ (t = 2.400, P < 0.01). For the radiologist 2, the φ cor , φ med and △ φ were (0.049 ± 0.011), (-0.012 ± 0.004) and (1.5 ±0.4) rad in Group 1, and were (0.046 ± 0.017), (-0.011 ± 0.003) and (1.3 ± 0.2) rad in group 2 respectively, there was no significant change in φ cor and φ med after water loading (t = 0.590 and -0.974, P > 0.05 in all), except of in △ φ (t = 2.760, P < 0.05). Between two radiologists, the ICC of φ cor , φ med and △ φ were 0.623, 0.472 and 0.328 in group 1 and 0.599, 0.442 and 0.445 in group 2 respectively. △OEF decreased about (-4.2 ± 2.3)% and (-4.3 ± 2.8)% measured by two radiologists respectively, and the consistency is good between two radiologists (ICC = 0.784). Conclusion: SWI

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

    International Nuclear Information System (INIS)

    Pollock, Sean; Keall, Paul; Keall, Robyn

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Heart rate asymmetry follows the inspiration/expiration ratio in healthy volunteers

    International Nuclear Information System (INIS)

    Klintworth, Anne; Ajtay, Zénó; Paljunite, Alina; Szabados, Sándor; Hejjel, László

    2012-01-01

    Heart rate asymmetry (HRA) quantifies the uneven distribution of points above and below the identity-line in a Poincaré plot of RR-intervals. The authors investigated if HRA could be influenced by the inspiration/expiration ratio. Healthy volunteers (n = 18) were studied in the supine position at 4.5 s metronome breathing. ECG and breathing signals were recorded for 360 s at each breathing pattern: inspiration controlled, inspiration/expiration controlled (1:2, 1:1, 2:1 ratio), inspiration controlled again. Time domain, frequency domain and Poincaré plot heart rate variability (HRV) analysis with Porta's and Guzik's indices were performed on 300 s tachograms. There were no statistically significant differences in time domain, frequency domain and standard Poincaré plot parameters during the various breathing patterns, whereas Porta's and Guzik's indices significantly rose at 1:1 and 2:1 compared to physiological 1:2 breathing. There were no significant differences in the HRA parameters between the first and the last runs. In our population the inspiration/expiration ratio significantly influenced HRA, but not standard HRV parameters. Positive correlation of Guzik's and Porta's index reflects reciprocal changes of the number of points and their dispersion in the accelerating and decelerating sets of RR-intervals. HRA-analysis can be a promising method for investigating cardiovascular regulation/health particularly with further spreading of wearable monitors. (paper)

  11. Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

    Science.gov (United States)

    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.

  12. Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers.

    Science.gov (United States)

    Zimmermann, Torsten; Höchel, Joachim; Becka, Michael; Boettger, Michael K; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S; Donath, Frank

    2018-05-01

    Regorafenib is a multikinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. This was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30 mg ml -1 , 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Thirty-six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600-700-fold lower than after multiple oral administration of 160 mg day -1 , the dose approved in cancer indications. These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml -1 tid for use in clinical studies. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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

    Directory of Open Access Journals (Sweden)

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

    2013-10-01

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

  14. Release and Decay Kinetics of Copeptin vs AVP in Response to Osmotic Alterations in Healthy Volunteers.

    Science.gov (United States)

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

    2018-02-01

    Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. To characterize the physiology of osmotically regulated copeptin release and its half-life in direct comparison with plasma AVP. Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison with AVP. Copyright © 2017 Endocrine Society

  15. Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

    Science.gov (United States)

    Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

    2017-03-28

    Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

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

    Science.gov (United States)

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

    2008-02-01

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

  19. Thoracodorsal artery examination with doppler ultrasound in healthy volunteers in a level three hospital

    International Nuclear Information System (INIS)

    Vasquez Rangel, Wolfgang Ignacio; Daza, Gabriel Fernando; Escobar Rojas, William

    2011-01-01

    Introduction: The thoracodorsal artery is a branch of the subscapular artery, which in turn is a branch of the axillary artery. The importance of this artery is that it supplies the latissimus dorsi muscle, used as a muscle-skin flap for breast reconstruction after mastectomy, mainly in patients with poor local tissues, in particular after receiving radiotherapy. Objective: to describe the physical characteristics of the thoracodorsal artery using Doppler ultrasound evaluation in healthy volunteers at Hospital Universitario del Valle. Materials and methods: We conducted a descriptive pilot study, because, after reviewing the medical literature, we did not find any reports assessing the thoracodorsal artery with the use of Doppler ultrasound. Results: we evaluated 51 patients, 50.9% female. The average age of the patients was 28.78 years. the axillary, subscapular and thoracodorsal arteries were identified in all patients. The characteristics of the thoracodorsal artery were as follows: Diameter 1.88 mm, peak systolic velocity 28.45 cm/s, peak diastolic velocity 2.03 cm/s, resistance index 0.94, pulsatility index 4.02. Although the study did not include anthropometric measurements, we found that the artery was more conspicuous in patients with developed muscle mass and in patients with low adiposity. Conclusions: The thoracodorsal artery was identified in all patients, and ultrasound localization is a procedure that is easy to perform and provides vital information about the presence of the vascular pedicle required to perform a latissimus dorsi muscle-skin flap. Additional studies in post mastectomy patients are required in order to assess postoperative changes associated with the presence and physical characteristics of the thoracodorsal artery.

  20. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Ryszard M Pluta

    Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

  1. White matter correlates of impaired attention control in major depressive disorder and healthy volunteers.

    Science.gov (United States)

    Rizk, Mina M; Rubin-Falcone, Harry; Keilp, John; Miller, Jeffrey M; Sublette, M Elizabeth; Burke, Ainsley; Oquendo, Maria A; Kamal, Ahmed M; Abdelhameed, Mohamed A; Mann, J John

    2017-11-01

    Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18-65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses. ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = -0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F (1,41) = 8.87, p = 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level. The modest sample size limits the generalizability of the findings. Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Werner, Mads U; Lacouture, Peter G

    2002-01-01

    BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were...... randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection...... curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence...

  3. Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers.

    Science.gov (United States)

    Ravn-Haren, Gitte; Dragsted, Lars O; Buch-Andersen, Tine; Jensen, Eva N; Jensen, Runa I; Németh-Balogh, Mária; Paulovicsová, Brigita; Bergström, Anders; Wilcks, Andrea; Licht, Tine R; Markowski, Jarosław; Bügel, Susanne

    2013-12-01

    Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the '5 or more a day' campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors of CVD. Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood pressure in a group of 23 healthy volunteers. The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7%), pomace (7.9%) and cloudy juice (2.2%) intake. On the other hand, LDL-cholesterol concentrations increased by 6.9% with clear juice compared to whole apples and pomace. There was no effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, inflammation (hs-CRP), composition of the gut microbiota or markers of glucose metabolism (insulin, IGF1 and IGFBP3). Apples are rich in polyphenols and pectin, two potentially bioactive constituents; however, these constituents segregate differently during processing into juice products and clear juice is free of pectin and other cell wall components. We conclude that the fibre component is necessary for the cholesterol-lowering effect of apples in healthy humans and that clear apple juice may not be a suitable surrogate for the whole fruit in nutritional recommendations.

  4. A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study.

    Directory of Open Access Journals (Sweden)

    Rudie Kortekaas

    Full Text Available UNLABELLED: The 'complex neural pulse'(TM (CNP is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF. A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. TRIAL REGISTRATION: Dutch Cochrane Centre NTR1093.

  5. Effects of sulpiride on true and false memories of thematically related pictures and associated words in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Regina V Guarnieri

    2016-03-01

    Full Text Available 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 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, placebo-controlled trial. The sulpiride group made 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 blockade in healthy volunteers can specifically increase the rate of false recognitions.

  6. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans....... METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

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

    Science.gov (United States)

    Lees, J; Michalopoulou, P G; Lewis, S W; Preston, S; Bamford, C; Collier, T; Kalpakidou, A; Wykes, T; Emsley, R; Pandina, G; Kapur, S; Drake, R J

    2017-10-01

    Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

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

    OpenAIRE

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

    2009-01-01

    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), ...

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

    Science.gov (United States)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

  10. The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility.

    Directory of Open Access Journals (Sweden)

    Morten Sejer Hansen

    Full Text Available Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min in healthy volunteers.Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min., and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied.For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006.We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers.clinicaltrials.gov NCT02166164.

  11. Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers

    OpenAIRE

    Dewland, Peter M; Reader, Sandie; Berry, Phillip

    2009-01-01

    Background The aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets. Methods Twenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate table...

  12. Congruent strain specific intestinal persistence of Lactobacillus plantarum in an intestine-mimicking in vitro system and in human volunteers.

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    Hermien van Bokhorst-van de Veen

    Full Text Available BACKGROUND: An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. METHODOLOGY/PRINCIPAL FINDINGS: The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. CONCLUSION: The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro

  13. Frequency of inflammatory-like MR imaging findings in asymptomatic fingers of healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Agten, Christoph A.; Rosskopf, Andrea B.; Jonczy, Maciej; Pfirrmann, Christian W.A.; Buck, Florian M. [University Hospital Balgrist, Radiology, Zurich (Switzerland); University of Zurich, Faculty of Medicine, Zurich (Switzerland); Brunner, Florian [University of Zurich, Faculty of Medicine, Zurich (Switzerland); University Hospital Balgrist, Department of Physical Medicine and Rheumatology, Zurich (Switzerland)

    2018-02-15

    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. (orig.)

  14. Frequency of inflammatory-like MR imaging findings in asymptomatic fingers of healthy volunteers

    International Nuclear Information System (INIS)

    Agten, Christoph A.; Rosskopf, Andrea B.; Jonczy, Maciej; Pfirrmann, Christian W.A.; Buck, Florian M.; Brunner, Florian

    2018-01-01

    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. (orig.)

  15. Hospital volunteerism as human resource solution: Motivation for both volunteers and the public health sector

    Directory of Open Access Journals (Sweden)

    Guinevere M. Lourens

    2017-08-01

    Full Text Available Background: A volunteer programme with 50 registered volunteers was established in 2007 at a secondary-level public, semi-rural regional hospital in the Cape Winelands, South Africa. This was a rapid response to the extensive renovations and system changes brought about by the hospital revitalisation initiated in 2006 and the resultant expanded services, which required additional human resources. This study describes the hospital volunteer programme and provides hospital administrators with practical planning guidance for hospital volunteer programme implementation. Purpose: The purpose of this study is to (1 describe the outcomes of the hospital volunteer programme implementation intervention and (2 to make sound recommendations for volunteer programme implementation. Methodology and approach: A qualitative case-study methodology was employed using purposive sampling as a technique. Participants were recruited from a public hospital in the Western Cape. A case-study design was applied to explore the hospital volunteer programme implementation. In-depth interviews and a focus group discussion with thematic content analysis of transcripts as well as document reviews were conducted to conclude the study during 2015. The key participants were individually interviewed and included two members of the hospital management, two volunteers and one volunteer coordinator. A focus group discussion consisting of three volunteers was also conducted. Findings: The findings of this study indicate that a volunteer programme can meet needs and be a motivational force for both the individual volunteer and the organisation. However, it requires co-ordination and some secure funding to remain sustainable. Such a programme holds huge benefits in terms of human resource supplementation, organisational development, as well as the possibility of gainful employment for the previously unemployed. Practical implications: In practice, a health service contemplating a

  16. Prevalence of Oral Human Papilloma Virus in Healthy Individuals in East Azerbaijan Province of Iran

    OpenAIRE

    SEIFI, Sharareh; ASVADI KERMANI, Iraj; DOLATKHAH, Roya; ASVADI KERMANI, Atabak; SAKHINIA, Ebrahim; ASGARZADEH, Mohammad; DASTGIRI, Saeed; EBRAHIMI, Ayoub; ASGHARI HAGGI, Arezou; NADRI, Mahsa; ASVADI KERMANI, Touraj

    2013-01-01

    Background: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. Methods: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers compl...

  17. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    David Monteith

    2017-10-01

    Full Text Available Background: Calcitonin gene-related peptide (CGRP is pivotal in the pathophysiology of migraine headaches and represents a promising target for migraine treatment. The humanized monoclonal antibody galcanezumab (LY2951742 binds to CGRP and may be effective in migraine prophylaxis.Objectives: The primary objective was to evaluate the safety and tolerability of single and multiple doses of galcanezumab in humans. Secondary objectives included assessing the pharmacokinetics and evaluating target engagement.Methods: A double-blind, randomized, placebo-controlled study (NCT 01337596 with single escalating and multiple subcutaneous (SC doses of galcanezumab was performed in healthy male volunteers. Single doses of 1, 5, 25, 75, 200, and 600 mg of galcanezumab (n = 7/dose or placebo (n = 2/dose were injected SC in six consecutive cohorts of nine subjects each. One cohort of nine subjects received multiple (4 150 mg doses of galcanezumab or placebo every other week. Target engagement was evaluated by measuring inhibition of capsaicin-induced increase in dermal blood flow (DBF.Findings: Sixty-three subjects were randomized and included in the safety analyses. Galcanezumab was well tolerated in single doses (1–600 mg SC and consecutive doses (150 mg SC. There was no dose-dependent difference in type or frequency of treatment-emergent adverse events, and no clinically meaningful difference when compared with placebo. Pharmacokinetics were linear. Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients.

  18. Insulin-Sensitizer Effects of Fenugreek Seeds in Parallel with Changes in Plasma MCH Levels in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Rita Kiss

    2018-03-01

    Full Text Available In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis. Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease or alleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacy and minimal toxicity of such preparations, along with generally lower per-patient costs, in comparison to many modern pharmaceuticals. A particularly attractive candidate in this respect, is fenugreek, a plant that has been used as a flavouring in human diet through recorded history. The present study assessed the insulin-sensitizing effect of fenugreek seeds in a cohort of human volunteers, and tested a hypothesis that melanin-concentrating hormone (MCH acts as a critical determinant of this effect. A test of the hypothesis was undertaken using a hyperinsulinemic euglycemic glucose clamp approach to assess insulin sensitivity in response to oral administration of a fenugreek seed preparation to healthy subjects. Outcomes of these evaluations demonstrated significant improvement in glucose tolerance, especially in patients with impaired glucose responses. Outcome data further suggested that fenugreek seed intake-mediated improvement in insulin sensitivity correlated with reduction in MCH

  19. Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

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    Werawath Mahatthanatrakul

    2008-05-01

    Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

  20. Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A; Fraunhofer, A; Tetzloff, W

    2000-12-01

    Two open-label, two-way, crossover studies were performed to assess any pharmacokinetic interaction of telmisartan with either acetaminophen or ibuprofen. Healthy male adult volunteers (n = 12) received a single oral dose of acetaminophen 1 g alone and with oral telmisartan 120 mg in one study. Oral ibuprofen 400 mg three times daily with and without oral once-daily telmisartan 120 mg was given for 7 days in the other study conducted in 6 males and 6 females. In both studies, there was a washout period of > or = 13 days between single and combination medication administration. The primary end points Cmax and AUC were compared between combination (acetaminophen or ibuprofen + telmisartan) and single-agent medication (acetaminophen or ibuprofen). Pharmacokinetic drug interaction was assessed by analysis of variance (ANOVA) and calculation of 90% confidence intervals (CI) for treatment ratios using log-transformed parameters. Bioequivalence (i.e., lack of interaction) was concluded if the 90% CI of the ratios for both Cmax and AUC were within the acceptance limit of 0.80 to 1.25. Geometric mean Cmax values for acetaminophen and R-(-)- and S-(+)-ibuprofen enantiomers were similar with and without telmisartan coadministration (12.6 micrograms/mL vs. 14.1 micrograms/mL; 17.3 micrograms/mL vs. 16.7 micrograms/mL; 19.4 micrograms/mL vs. 19.5 micrograms/mL, respectively), and values for R-(-)- as well as S-(+)-ibuprofen were bioequivalent. Geometric mean AUC values for acetaminophen and R-(-)- and S-(+)-ibuprofen were also bioequivalent with and without telmisartan. The distribution and elimination parameters of both acetaminophen and ibuprofen were comparable in the presence or absence of telmisartan. The concomitant and single-agent medications were all well tolerated. In conclusion, the long half-life and excellent safety profile of telmisartan were unaffected by concurrent acetaminophen or ibuprofen medication; thus, once-daily dosing of telmisartan can be maintained

  1. Doppler ultrasonography measurement of hepatic hemodynamics during Valsalva maneuver: healthy volunteer study

    Directory of Open Access Journals (Sweden)

    Dong-Ho Bang

    2015-01-01

    Full Text Available Purpose: The aim of our study was to assess the hemodynamic change of liver during the Valsalva maneuver using Doppler ultrasonography. Methods: Thirty healthy men volunteers were enrolled (mean age, 25.5±3.64 years. The diameter, minimal and maximal velocities, and volume flow of intrahepatic inferior vena cava (IVC, middle hepatic vein (MHV, and right main portal vein (RMPV was measured during both rest and Valsalva maneuver. These changes were compared using paired t-test. Results: The mean diameters (cm of the intrahepatic IVC at rest and Valsalva maneuver were 1.94±0.40 versus 0.56±0.66 (P<0.001. The mean diameter (cm, minimal velocity (cm/sec, maximal velocity (cm/sec, and volume flow (mL/min of MHV at rest and Valsalva maneuver were 0.60±0.15 versus 0.38±0.20 (P<0.001, -7.98±5.47 versus 25.74±13.13 (P<0.001, 21.34±6.89 versus 35.12±19.95 (P=0.002, and 106.94±97.65 versus 153.90±151.80 (P=0.014, respectively. Those of RMPV at rest and Valsalva maneuver were 0.78±0.21 versus 0.76±0.20 (P=0.485, 20.21±8.22 versus 18.73±7.43 (P=0.351, 26.79±8.85 versus 24.93±9.91 (P=0.275, and 391.52±265.63 versus 378.43±239.36 (P=0.315, respectively. Conclusion: The blood flow velocity and volume flow of MHV increased significantly during Valsalva maneuver. These findings suggest that hepatic vein might play an important role to maintain venous return to the heart during the maneuver.

  2. Doppler ultrasonography measuement of hepatic hemodynamics during Valsalva maneuver: healthy volunteers study

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Dong Ho; Son, Young Jin; Lee, Young Hwan; Yoon, Kwon Ha [Dept. of Radiology, Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2015-01-15

    The aim of our study was to assess the hemodynamic change of liver during the Valsalva maneuver using Doppler ultrasonography. Thirty healthy men volunteers were enrolled (mean age, 25.5±3.64 years). The diameter, minimal and maximal velocities, and volume flow of intrahepatic inferior vena cava (IVC), middle hepatic vein (MHV), and right main portal vein (RMPV) was measured during both rest and Valsalva maneuver. These changes were compared using paired t-test. The mean diameters (cm) of the intrahepatic IVC at rest and Valsalva maneuver were 1.94±0.40 versus 0.56±0.66 (P<0.001). The mean diameter (cm), minimal velocity (cm/sec), maximal velocity (cm/sec), and volume flow (mL/min) of MHV at rest and Valsalva maneuver were 0.60±0.15 versus 0.38±0.20 (P<0.001), -7.98±5.47 versus 25.74±13.13 (P<0.001), 21.34±6.89 versus 35.12±19.95 (P=0.002), and 106.94±97.65 versus 153.90±151.80 (P=0.014), respectively. Those of RMPV at rest and Valsalva maneuver were 0.78±0.21 versus 0.76±0.20 (P=0.485), 20.21±8.22 versus 18.73±7.43 (P=0.351), 26.79±8.85 versus 24.93±9.91 (P=0.275), and 391.52±265.63 versus 378.43±239.36 (P=0.315), respectively. The blood flow velocity and volume flow of MHV increased significantly during Valsalva maneuver. These findings suggest that hepatic vein might play an important role to maintain venous return to the heart during the maneuver.

  3. 36 CFR 261.3 - Interfering with a Forest officer, volunteer, or human resource program enrollee or giving false...

    Science.gov (United States)

    2010-07-01

    ... officer, volunteer, or human resource program enrollee or giving false report to a Forest officer. 261.3... General Prohibitions § 261.3 Interfering with a Forest officer, volunteer, or human resource program..., intimidating, or intentionally interfering with any Forest officer, volunteer, or human resource program...

  4. A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers.

    Directory of Open Access Journals (Sweden)

    Chris Martini

    Full Text Available Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids.On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet, morphine (40 mg immediate release tablet or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9% at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2% at 120-150 min after drug intake (p = 0.001. No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6% at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9% at 120-150 min after drug intake (p = 0.60.Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol's main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic stimulation on descending controls

  5. Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers

    International Nuclear Information System (INIS)

    Silva, Mario; Nemec, Stefan F.; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H.; Bankier, Alexander A.; Chamberlain, Ryan

    2016-01-01

    Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and Vol Exp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. (orig.)

  6. Effect of two-linked mutations of the FMO3 gene on itopride metabolism in Chinese healthy volunteers.

    Science.gov (United States)

    Zhou, Li-Ping; Tan, Zhi-Rong; Chen, Hao; Guo, Dong; Chen, Yao; Huang, Wei-Hua; Wang, Lian-Sheng; Zhang, Guo-Gang

    2014-11-01

    Itopride is an effective gastroprokinetic agent mainly used for the treatment of functional dyspepsia. Flavin-containing monooxygenase 3 (FMO3) has been confirmed to be the key enzyme involved in the main itopride metabolic pathway. We investigated whether the FMO3 genotypes can affect itopride metabolism in Chinese healthy volunteers. Twelve healthy volunteers who had been genotyped for FMO3 gene were selected to participate in our study. Volunteers were given 50 mg itopride orally and then blood samples were collected from 0 to 24 h. The plasma concentrations of itopride and itopride N-oxide were determined by HPLC-MS/MS method. Itopride and itopride N-oxide both exhibit FMO3 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of itopride increased by 127.82 ± 41.99 % (P itopride N-oxide decreased by 30.30 ± 25.70 % (P itopride and itopride N-oxide were observed between these two genotypes. The FMO3 allele can significantly affect the metabolism of itopride. The pharmacokinetic parameters of both itopride and itopride N-oxide were significantly different between these two genotypes.

  7. Privacy Impact Assessment for the Medical and Research Study Records of Human Volunteers

    Science.gov (United States)

    The Medical & Research Study Records of Human Volunteers System collects demographic and medical information on subjects who participate in research. Learn how this data is collected, used, access to the data, and the purpose of data collection.

  8. The gut mycobiome of the Human Microbiome Project healthy cohort.

    Science.gov (United States)

    Nash, Andrea K; Auchtung, Thomas A; Wong, Matthew C; Smith, Daniel P; Gesell, Jonathan R; Ross, Matthew C; Stewart, Christopher J; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Ajami, Nadim J; Petrosino, Joseph F

    2017-11-25

    Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that

  9. Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers

    Science.gov (United States)

    Olofsen, Erik; Noppers, Ingeborg; Niesters, Marieke; Kharasch, Evan; Aarts, Leon; Sarton, Elise; Dahan, Albert

    2012-01-01

    Background The N-methyl-D-receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring ketamine-effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. Methods In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine (a 2-h infusion of 20 mg/h)-induced analgesia and cognition was quantified. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. Results S-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment, reduced psychomotor speed, reduced reaction time, reduced cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine-induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectievly, the ketamine contribution to analgesia is −3.8 cm (visual analogue pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect −2.3 cm. The blood-effect-site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min, and averaged across all end-points was 6.1 min. Conclusions This first observation that norketamine produces effects in the opposite direction of ketamine requires further proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions. PMID:22692377

  10. A therapeutic dose of zolpidem reduces thalamic GABA in healthy volunteers: a proton MRS study at 4 T.

    Science.gov (United States)

    Licata, Stephanie C; Jensen, J Eric; Penetar, David M; Prescot, Andrew P; Lukas, Scott E; Renshaw, Perry F

    2009-05-01

    Zolpidem is a nonbenzodiazepine sedative/hypnotic that acts at GABA(A) receptors to influence inhibitory neurotransmission throughout the central nervous system. A great deal is known about the behavioral effects of this drug in humans and laboratory animals, but little is known about zolpidem's specific effects on neurochemistry in vivo. We evaluated how acute administration of zolpidem affected levels of GABA, glutamate, glutamine, and other brain metabolites. Proton magnetic resonance spectroscopy ((1)H MRS) at 4 T was employed to measure the effects of zolpidem on brain chemistry in 19 healthy volunteers. Participants underwent scanning following acute oral administration of a therapeutic dose of zolpidem (10 mg) in a within-subject, single-blind, placebo-controlled, single-visit study. In addition to neurochemical measurements from single voxels within the anterior cingulate (ACC) and thalamus, a series of questionnaires were administered periodically throughout the experimental session to assess subjective mood states. Zolpidem reduced GABA levels in the thalamus, but not the ACC. There were no treatment effects with respect to other metabolite levels. Self-reported ratings of "dizzy," "nauseous," "confused," and "bad effects" were increased relative to placebo, as were ratings on the sedation/intoxication (PCAG) and psychotomimetic/dysphoria (LSD) scales of the Addiction Research Center Inventory. Moreover, there was a significant correlation between the decrease in GABA and "dizzy." Zolpidem engendered primarily dysphoric-like effects and the correlation between reduced thalamic GABA and "dizzy" may be a function of zolpidem's interaction with alpha1GABA(A) receptors in the cerebellum, projecting through the vestibular system to the thalamus.

  11. A therapeutic dose of zolpidem reduces thalamic GABA in healthy volunteers: A proton MRS study at 4 Tesla

    Science.gov (United States)

    Licata, Stephanie C.; Jensen, J. Eric; Penetar, David M.; Prescot, Andrew P.; Lukas, scott E.; Renshaw, Perry F.

    2009-01-01

    Background Zolpidem is a non-benzodiazepine sedative/hypnotic that acts at GABAA receptors to influence inhibitory neurotransmission throughout the central nervous system. A great deal is known about the behavioral effects of this drug in humans and laboratory animals, but little is known about zolpidem’s specific effects on neurochemistry in vivo. Objectives We evaluated how acute administration of zolpidem affected levels of GABA, glutamate, glutamine, and other brain metabolites. Methods Proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla was employed to measure the effects of zolpidem on brain chemistry in 19 healthy volunteers. Participants underwent scanning following acute oral administration of a therapeutic dose of zolpidem (10 mg) in a within-subject, single-blind, placebo-controlled, single-visit study. In addition to neurochemical measurements from single voxels within the anterior cingulate (ACC) and thalamus, a series of questionnaires were administered periodically throughout the experimental session to assess subjective mood states. Results Zolpidem reduced GABA levels in the thalamus, but not the ACC. There were no treatment effects with respect to other metabolite levels. Self-reported ratings of “dizzy”, “nauseous”, “confused”, and “bad effects” were increased relative to placebo, as were ratings on the sedation/intoxication (PCAG) and psychotomimetic/dysphoria (LSD) scales of the Addiction Research Center Inventory. Moreover, there was a significant correlation between the decrease in GABA and “dizzy”. Conclusions Zolpidem engendered primarily dysphoric-like effects and the correlation between reduced thalamic GABA and “dizzy” may be a function of zolpidem’s interaction with α1GABAA receptors in the cerebellum, projecting through the vestibular system to the thalamus. PMID:19125238

  12. Effect of fermented milk containing Lactobacillus rhamnosus SD11 on oral microbiota of healthy volunteers: A randomized clinical trial.

    Science.gov (United States)

    Rungsri, P; Akkarachaneeyakorn, N; Wongsuwanlert, M; Piwat, S; Nantarakchaikul, P; Teanpaisan, R

    2017-10-01

    The aims of this study were to evaluate whether short-term consumption of fermented milk containing Lactobacillus rhamnosus SD11 affected levels of oral microbiota in vivo and whether L. rhamnosus SD11 could colonize in the human mouth. We also monitored for potential side effects of the probiotic. The applicability of using L. rhamnosus SD11 compared with Lactobacillus bulgaricus as a starter culture for fermented milk was evaluated. After informed consent, 43 healthy young adults were recruited and randomly assigned to either the probiotic or control group and received fermented milk containing L. rhamnosus SD11 or L. bulgaricus, respectively, once daily for 4 wk. The numbers of mutans streptococci, lactobacilli, and total bacteria in saliva were counted at baseline and then after 4 and 8 wk. An oral examination was performed at baseline and after 8 wk. The persistence of L. rhamnosus SD11 was investigated by DNA fingerprinting using arbitrary primer-PCR. Results demonstrated that statistically significant reductions in mutans streptococci and total bacteria were observed in the probiotic group compared with the control group, and the number of lactobacilli was significantly increased in both groups after receiving fermented milks. Lactobacillus rhamnosus SD11 could be detected (in >80% of subjects) up to 4 wk following cessation of dosing among subjects in the probiotic group. No side effects were reported. Thus, L. rhamnosus SD11 could be used as a starter culture for fermented milk. Daily consumption of L. rhamnosus SD11-containing fermented milk for 4 wk may have beneficial effects on oral health by reducing salivary levels of mutans streptococci. The probiotic was apparently able to colonize the oral cavity for a longer time than previously reported. However, the potential benefits of probiotic L. rhamnosus SD11 on oral health require further evaluation with a larger group of volunteers in a longer-term study. Copyright © 2017 American Dairy Science

  13. Thickness of the retinal photoreceptor outer segment layer in healthy volunteers and in patients with diabetes mellitus without retinopathy, diabetic retinopathy, or diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Abdullah Ozkaya

    2017-04-01

    Conclusion: The PROS layer at the foveal center was thinner in patients who had diabetic retinopathy or diabetic macular edema than both the healthy volunteers and diabetic patients without retinopathy.

  14. The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers

    DEFF Research Database (Denmark)

    Duthie, GG; Pedersen, M W; PC, Morrice

    1998-01-01

    wine, malt whisky or unmatured 'new make'spirit. Each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Bloodsamples were obtained from the anticubital vein at intervals up to 4h after consumption of the beverages when a urinesample was also obtained....... RESULTS: Within 30 min of consumption of the wine and whisky, there was a similar andsignificant increase in plasma total phenol content and antioxidant capacity as determined by the ferric reducing capacityof plasma (FRAP). No changes were observed following consumption of 'new make' spirit. CONCLUSIONS......OBJECTIVE: To assess whether consumption of 100 ml of whisky or red wine by healthy male subjects increasedplasma total phenol content and antioxidant capacity. DESIGN: A Latin square arrangement to eliminate ordering effectswhereby, after an overnight fast, nine volunteers consumed 100 ml of red...

  15. SPIRONOLACTONE IN BIOFEEDBACK SESSIONS IN THE LOOP OF PACED BREATHING AND HEART RATE VARIABILITY IN HEALTHY VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    E. Nazarenko

    2015-12-01

    Full Text Available In 7 conditionally healthy volunteers, aged from 19 to 21 years (average age is 19,53 ± 1,55 years, influence of spironolactone on alterations of regulatory systems state of the organism combined with biofeedback (BFB sessions in the loop of paced breathing (PB and heart rate variability (HRV parameters was evaluated. All volunteers were conducted 2 series of everyday BFB sessions in analyzed loop for 5 days with a 3 months interval between them, 2nd series of sessions were conducted 6 hours after oral application of 25 mg spironolactone. The data was analyzed using non-parametric statistical methods. Optimization of regulatory systems state under influence of BFB sessions in the loop of PB and HRV parameters was found. Spironolactone in studied dose had no significant effect on optimization of regulatory systems state.

  16. Pharmacokinetics of Perfluorobutane after Intra-Venous Bolus Injection of Sonazoid in Healthy Chinese Volunteers.

    Science.gov (United States)

    Li, Pengfei; Hoppmann, Susan; Du, Ping; Li, Huiling; Evans, Paul M; Moestue, Siver A; Yu, Weiyue; Dong, Fang; Liu, Hongchuan; Liu, Lihong

    2017-05-01

    Sonazoid is an ultrasound contrast agent based on microbubbles (MB) containing perfluorobutane (PFB) gas. Sonazoid is approved in Japan, Korea and Norway for contrast-enhanced ultrasonography of focal liver lesions and focal breast lesions (Japan only). The objective of this study was to determine the pharmacokinetics (PKs) and safety of Sonazoid in Chinese healthy volunteers (HVs) and to evaluate the potential for ethnic differences in PKs between Chinese and Caucasian HVs. Sonazoid was administered as an intra-venous bolus injection at the clinical dose of 0.12 μL or 0.60 μL MB/kg body weight to two groups of eight Chinese HVs. Expired air and blood samples were collected and analyzed using a validated gas chromatographic tandem mass spectrometry method, and the main PK parameters were calculated. The highest PFB concentrations in blood were observed shortly after intra-venous administration of Sonazoid, and elimination of PFB was rapid. In the 0.12 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for only 10 to 15 min post-injection. In the 0.60 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for 60 min post-injection, and the shape of the elimination curve suggested a biphasic elimination profile. The maximum observed concentration (C max ) values of PFB in blood were 2.3 ± 1.1 and 19.1 ± 9.2 ng/g for the 0.12 and 0.60 μL MB/kg body weight dose groups (mean ± standard deviation). Area under the curve values were 10.1 ± 2.7 and 90.1 ± 38.3 ng × min/g for the 0.12 and 0.60 μL MB/kg body weight dose groups. C max values of PFB in exhaled air were 0.35 ± 0.2 and 2.4 ± 0.7 ng/mL for the 0.12 and 0.60 μL MB/kg body weight dose groups. Assessment of laboratory parameters, vital signs, oxygen saturation and electrocardiograms revealed no changes indicative of a concern. The PK profile and safety data generated in the Chinese

  17. An anatomical study of the parasacral block using magnetic resonance imaging of healthy volunteers.

    LENUS (Irish Health Repository)

    O'Connor, Maeve

    2012-01-31

    BACKGROUND: The parasacral approach to sciatic blockade is reported to be easy to learn and perform, with a high success rate and few complications. METHODS: Using magnetic resonance imaging, we evaluated the accuracy of a simulated needle (perpendicular to skin) in contacting the sacral plexus with this approach in 10 volunteers. Intrapelvic structures encountered during the simulated parasacral blocks were also recorded. RESULTS: The sacral plexus was contacted by the simulated needle in 4 of the 10 volunteers, and the sciatic nerve itself in one volunteer. The plexus was accurately located adjacent to a variety of visceral structures, including small bowel, blood vessels, and ovary. In the remaining five volunteers (in whom the plexus was not contacted on first needle pass), small bowel, rectum, blood vessels, seminal vesicles, and bony structures were encountered. Historically, when plexus is not encountered, readjustment of the needle insertion point more caudally has been recommended. We found that such an adjustment resulted in simulated perforation of intrapelvic organs or the perianal fossa. CONCLUSIONS: These findings question the reliability of the anatomical landmarks of the parasacral block and raise the possibility of frequent visceral puncture using this technique.

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

    Science.gov (United States)

    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.

  19. Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial.

    Science.gov (United States)

    Vickers, A J; van Haselen, R; Heger, M

    2001-04-01

    To pilot a method for determining whether homeopathically prepared mercury causes more symptoms (a "drug proving") in healthy volunteers than placebo. One hundred and eighteen (118) healthy volunteers ages 18 to 65 were recruited by local advertising. Subjects unfamiliar with homeopathy undertook a 1-week single-blind placebo run-in, a 1-week of double-blind, randomized treatment on either homeopathically prepared mercury 12C or placebo, and a third week of placebo run-out. Each day, symptoms were recorded on a checklist that included both true mercury symptoms and symptoms not expected to be caused by mercury (false symptoms). Additional symptoms were assessed by open reporting. Outcome was assessed by calculating a score for each day as the number of true symptoms minus the number of false symptoms. The mean score during placebo was then subtracted from the mean score for weeks two and three of the trial. Fourteen (14) subjects dropped out during placebo run-in. The remaining 104 completed the trial. Baseline comparability was good. Mean difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for placebo (p > 0.2). No significant differences between groups were found for the number of subjects meeting predefined criteria for a drug-proving reaction. This pilot study failed to find evidence that mercury 12C causes significantly more symptoms in healthy volunteers than placebo. Questionnaires with a limited number of gross symptoms do not seem to be an appropriate methodological technique in drug proving research. If drug-proving phenomena exist, they appear to be rare.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

    2016-01-01

    Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

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

    Science.gov (United States)

    Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

    2016-04-01

    The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

  3. Palatability, digestibility and emotional pattern in 60 healthy volunteers after ingestion of an iced dessert presented in four different flavours: a subjective evaluation.

    Science.gov (United States)

    Garzaro, M; Raimondo, L; Pecorari, G; Riva, G; Sensini, M; Naqe, N; Giordano, C

    2012-01-01

    Several variables lead to changes in human and animal eating behaviour and food choices. A pivotal role is played by food palatability, represented by food, smell, taste, texture, appearance and temperature. The aim of our study is to assess the potential differences in palatability and digestibility of four different flavoured iced desserts, consumed at the end of a standardized meal, and their impact on the emotional status of 60 healthy volunteers. Sixty healthy volunteers, after ENT and psychological assessment, were asked to fill out a Psycho-Emotional Questionnaire (PEQ) to assess their basal emotional pattern before the consumption of an iced dessert at the end of a standard meal, after which they completed an Organoleptic-Sensory Questionnaire (OSQ), a Dynamic Digestibility Questionnaire (DDQ) and again the PEQ. Four different flavors (lemon, tangerine, pineapple and chocolate) were tested on 4 consecutive days on the same subjects. Most of the 60 subjects, by means of OSQ, found taste, aspect, texture and smell of the 4 flavours pleasant, lemon and tangerine were the freshest and lightest. The DDQ identified pineapple and chocolate dessert as those less digestible. By means of PEQ we recorded an improvement in joy, mood and activation, associated with good data of digestibility and palatability after the consumption of all flavors. Our data showed that all flavors improve joy, mood and activation, after their consumption, without statistically significant differences. However, among the tested flavours, lemon and tangerine appear to be the most pleasant and those which facilitate the digestive process.

  4. Effect of dairy fat on plasma phytanic acid in healthy volunteers - a randomized controlled study

    Directory of Open Access Journals (Sweden)

    Drachmann Tue

    2011-06-01

    Full Text Available Abstract Background Phytanic acid produced in ruminants from chlorophyll may have preventive effects on the metabolic syndrome, partly due to its reported RXR and PPAR- α agonist activity. Milk from cows fed increased levels of green plant material, contains increased phytanic acid concentrations, but it is unknown to what extent minor increases in phytanic acid content in dairy fat leads to higher circulating levels of phytanic acid in plasma of the consumers. Objective To investigate if cow feeding regimes affects concentration of plasma phytanic acid and risk markers of the metabolic syndrome in human. Design In a double-blind, randomized, 4 wk, parallel intervention study 14 healthy young subjects were given 45 g milk fat/d from test butter and cheese with 0.24 wt% phytanic acid or a control diet with 0.13 wt% phytanic acid. Difference in phytanic acid was obtained by feeding roughage with low or high content of chlorophyll. Results There tended to be a difference in plasma phytanic acid (P = 0.0730 concentration after the dietary intervention. Plasma phytanic acid increased significantly within both groups with the highest increase in control group (24% compared to phytanic acid group (15%. There were no significant effects of phytanic acid on risk markers for the metabolic syndrome. Conclusions The results indicate that increased intake of dairy fat modify the plasma phytanic acid concentration, regardless of cows feeding regime and the minor difference in dietary phytanic acid. Whether the phytanic acid has potential to affects the risk markers of the metabolic syndrome in human still remain to be elucidated. Trial Registration ClinicalTrials.gov: NCT01343576

  5. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

    Science.gov (United States)

    Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

    2012-06-01

    Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Bevans-Fonti, Shannon; Grigoryev, Dmitry N; Punjabi, Naresh M

    2015-01-01

    Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.

  7. Effect of Sildenafil Citrate on Intraocular Pressure and Blood Pressure in Human Volunteers

    Science.gov (United States)

    Gerometta, Rosana; Alvarez, Lawrence J.; Candia, Oscar A.

    2011-01-01

    Anecdotal reports have suggested that the vasodilator, sildenafil citrate, which evokes its effect via a select inhibition of PDE5, has the potential to increase intraocular pressure (IOP) in some individuals. An ocular hypertensive effect by sildenafil was also recently described in a sheep animal model. In contrast, clinical studies have not found a direct association between sildenafil ingestion (commonly consumed as Viagra) and changes in IOP. However, some such studies also reported no effects of sildenafil on systemic blood pressure (BP) at the time of the IOP determination. Given this surprising result, our purpose was to repeat a study in human volunteers in the city of Corrientes, Argentina to corroborate the effects of sildenafil on human IOP and systemic BP. For the present study, 9 healthy volunteers (male and female, 18 to 74 years old) were selected as subjects after ophthalmic and cardiovascular evaluation indicated that they exhibited normal parameters for their age. In a masked, placebo-controlled study, the subjects ingested 100 mg sildenafil citrate (provided as Vorst from Laboratorios Bernabo, Argentina) in one session, and a placebo on a second separate occasion. IOP was measured with a Goldman applanation tonometer by an ophthalmologist, and BP by a second physician, neither of whom witnessed the tablet ingestion by the volunteers, nor provided with information on the nature of the test compounds. A third individual administered the tablets. The average baseline IOP of this group of 9 was 13.1 ± 0.6 mm Hg. Subsequent to sildenafil ingestion, IOP increased by 26% to 16.5 ± 0.8 mm Hg 60 min later (p< 0.005, as paired data), and returned to control values within 2 hrs. Both systolic and diastolic BP were significantly reduced by sildenafil ingestion. At the point of maximal systemic hypotension (90 min), the systolic and diastolic pressures declined by 15% and 13%, respectively. No significant changes in IOP or BP were recorded after ingestion

  8. Effect of sildenafil citrate on intraocular pressure and blood pressure in human volunteers.

    Science.gov (United States)

    Gerometta, Rosana; Alvarez, Lawrence J; Candia, Oscar A

    2011-07-01

    Anecdotal reports have suggested that the vasodilator, sildenafil citrate, which evokes its effect via a select inhibition of PDE5, has the potential to increase intraocular pressure (IOP) in some individuals. An ocular hypertensive effect by sildenafil was also recently described in a sheep animal model. In contrast, clinical studies have not found a direct association between sildenafil ingestion (commonly consumed as Viagra) and changes in IOP. However, some such studies also reported no effects of sildenafil on systemic blood pressure (BP) at the time of the IOP determination. Given this surprising result, our purpose was to repeat a study in human volunteers in the city of Corrientes, Argentina to corroborate the effects of sildenafil on human IOP and systemic BP. For the present study, 9 healthy volunteers (male and female, 18-74 years old) were selected as subjects after ophthalmic and cardiovascular evaluation indicated that they exhibited normal parameters for their age. In a masked, placebo-controlled study, the subjects ingested 100 mg sildenafil citrate (provided as Vorst from Laboratorios Bernabo, Argentina) in one session, and a placebo on a second separate occasion. IOP was measured with a Goldman applanation tonometer by an ophthalmologist, and BP by a second physician, neither of whom witnessed the tablet ingestion by the volunteers, nor provided with information on the nature of the test compounds. A third individual administered the tablets. The average baseline IOP of this group of 9 was 13.1 ± 0.6 mm Hg. Subsequent to sildenafil ingestion, IOP increased by 26% to 16.5 ± 0.8 mm Hg 60 min later (P < 0.005, as paired data), and returned to control values within 2 h. Both systolic and diastolic BP were significantly reduced by sildenafil ingestion. At the point of maximal systemic hypotension (90 min), the systolic and diastolic pressures declined by 15% and 13%, respectively. No significant changes in IOP or BP were recorded after

  9. Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

    OpenAIRE

    Patat, A; Perault, M C; Vandel, B; Ulliac, N; Zieleniuk, I; Rosenzweig, P

    1995-01-01

    1. The possible interaction between a new H1 antihistamine, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval. The interaction of mizolastine, at steady-state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2. Psychomotor performance and cogniti...

  10. [The effect of a single inhalation of mineral water on the blood hormonal status in healthy volunteers].

    Science.gov (United States)

    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.

  11. MR-imaging of the breast at 0.5 Tesla: menstrual-cycle dependency of parenchymal contrast enhancement in healthy volunteers with oral contraceptive use?

    International Nuclear Information System (INIS)

    Lorenzen, J.; Welger, J.; Krupski, G.; Adam, G.; Lisboa, B.W.

    2003-01-01

    Introduction: To evaluate changes of contrast medium enhancement of the breast parenchyma due to menstrual cycle in healthy volunteers with oral contraceptive use in MR-imaging of the breast. Material and Methods: 15 healthy volunteers (age: 22 - 36, mean 28,2) without breast disease were examined two times during one menstrual cycle (days 7 - 14 and days 21 - 2). Two volunteers were examined only in the second part of the cycle (days 21 - 2). All volunteers used oral contraceptives for more than 6 month continuously. Examinations were performed with a 0,5 T magnet (dynamic 3D-gradient echo protocol with subtraction postprocessing). We evaluated the number of enhancing foci and the parenchymal contrast medium enhancement during the different phases of the cycle by region of interest. Results: Only a total of two enhancing foci were found in 2 of 17 volunteers. Time/signal intensity diagrams in these both cases were not suspicious ( [de

  12. Coronative antibody tires in sera of healthy adults and experimentally infected volunteers.

    Science.gov (United States)

    Bradburne, A F; Somerset, B A

    1972-06-01

    Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.

  13. Photoplethysmographic signals and blood oxygen saturation values during artificial hypothermia in healthy volunteers

    International Nuclear Information System (INIS)

    Shafique, M; Kyriacou, P A

    2012-01-01

    Pulse oximetry utilizes the technique of photoplethysmography to estimate arterial oxygen saturation (SpO 2 ) values. During hypothermia, the amplitude of the photoplethysmograph (PPG) is compromised which can lead to inaccurate estimation of SpO 2 . A new mutlimode PPG/pulse oximeter sensor was developed to investigate the behaviour of PPGs during conditions of induced hypothermia (hand immersed in an ice bath). PPG measurements from 20 volunteers were conducted and SpO 2 values were estimated at all stages of the experiment. Good quality PPG signals were observed from the majority of the volunteers at almost all hand temperatures. At low temperature ranges, from 13 to 21 °C, the failure rate to estimate SpO 2 values from the multimode transreflectance PPG sensor was 2.4% as compared to the commercial pulse oximeter with a failure rate of 70%. (paper)

  14. Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers

    Directory of Open Access Journals (Sweden)

    Zwickl Beth W

    2011-09-01

    Full Text Available Abstract Background Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF. A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. Results We constructed 35000HPΔflp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HPΔflp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP. Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU on one arm and three doses of 35000HPΔflp1-3 (ranging from 63 to 961 CFU on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9% and for the mutant was 70.0% (95% CI, 50.5%-89.5% (P = 0.52. Mutant papules were significantly smaller (mean, 11.2 mm2 than were parent papules (21.8 mm2 24 h after inoculation (P = 0.018. The overall pustule formation rates were 46.7% (95% CI 23.7-69.7% at 30 parent sites and 6.7% (95% CI, 0.1-19.1% at 30 mutant sites (P = 0.001. Conclusion These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H

  15. Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers.

    Science.gov (United States)

    Janowicz, Diane M; Cooney, Sean A; Walsh, Jessica; Baker, Beth; Katz, Barry P; Fortney, Kate R; Zwickl, Beth W; Ellinger, Sheila; Munson, Robert S

    2011-09-22

    Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. We constructed 35000HPΔflp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HPΔflp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP). Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU) on one arm and three doses of 35000HPΔflp1-3 (ranging from 63 to 961 CFU) on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0% (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller (mean, 11.2 mm2) than were parent papules (21.8 mm2) 24 h after inoculation (P = 0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30 parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001). These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and progress to

  16. Cefotaxime resistant Escherichia coli collected from a healthy volunteer; characterisation and the effect of plasmid loss.

    Directory of Open Access Journals (Sweden)

    Miranda Kirchner

    Full Text Available In this study 6 CTX-M positive E. coli isolates collected during a clinical study examining the effect of antibiotic use in a human trial were analysed. The aim of the study was to analyse these isolates and assess the effect of full or partial loss of plasmid genes on bacterial fitness and pathogenicity. A DNA array was utilised to assess resistance and virulence gene carriage. Plasmids were characterised by PCR-based replicon typing and addiction system multiplex PCR. A phenotypic array and insect virulence model were utilised to assess the effect of plasmid-loss in E. coli of a large multi-resistance plasmid. All six E. coli carrying bla CTX-M-14 were detected from a single participant and were identical by pulse field gel electrophoresis and MLST. Plasmid profiling and arrays indicated absence of a large multi-drug resistance (MDR F-replicon plasmid carrying blaTEM, aadA4, strA, strB, dfrA17/19, sul1, and tetB from one isolate. Although this isolate partially retained the plasmid it showed altered fitness characteristics e.g. inability to respire in presence of antiseptics, similar to a plasmid-cured strain. However, unlike the plasmid-cured or plasmid harbouring strains, the survival rate for Galleria mellonella infected by the former strain was approximately 5-times lower, indicating other possible changes accompanying partial plasmid loss. In conclusion, our results demonstrated that an apparently healthy individual can harbour bla CTX-M-14 E. coli strains. In one such strain, isolated from the same individual, partial absence of a large MDR plasmid resulted in altered fitness and virulence characteristics, which may have implications in the ability of this strain to infect and any subsequent treatment.

  17. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers

    Directory of Open Access Journals (Sweden)

    Makoto eBannai

    2012-04-01

    Full Text Available Approximately 30% of the general population suffers from insomnia. Given that insomnia causes many problems, amelioration of the symptoms is crucial. Recently, we found that a nonessential amino acid, glycine subjectively and objectively improves sleep quality in humans who have difficulty sleeping. We evaluated the effects of glycine on daytime sleepiness, fatigue and performances in sleep-restricted healthy subjects. Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested, sleepiness and fatigue were evaluated using the visual analogue scale (VAS and a questionnaire, and performance were estimated by personal computer (PC performance test program on the following day. In subjects given glycine, the VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. PC performance test revealed significant improvement in psychomotor vigilance test. We also measured plasma melatonin and the expression of circadian-modulated genes expression in the rat suprachiasmatic nucleus (SCN to evaluate the effects of glycine on circadian rhythms. Glycine did not show significant effects on plasma melatonin concentrations during either the dark or light period. Moreover, the expression levels of clock genes such as Bmal1 and Per2 remained unchanged. However, we observed a glycine-induced increase in the neuropeptides arginine vasopressin and vasoactive intestinal polypeptide in the light period. Although no alterations in the circadian clock itself were observed, our results indicate that glycine modulated SCN function. Thus, glycine modulates certain neuropeptides in the SCN and this phenomenon may indirectly contribute to improving the occasional sleepiness and fatigue induced by sleep

  18. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    Energy Technology Data Exchange (ETDEWEB)

    Fellner, C. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics]|[Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Schlaier, J.; Schwerdtner, J.; Brawanski, A. [Regensburg Univ. (Germany). Dept. of Radiology; Fellner, F. [Regensburg Univ. (Germany). Dept. of Neurosurgery]|[Oberoesterreichische Landesnervenklinik, Linz (Austria). Dept. of Neuroradiology; Held, P. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Blank, M.; Kalender, W.A. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics

    1999-06-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [Deutsch] Das Ziel der vorliegenden Studie war ein Vergleich der funktionellen MR-Bildgebung (fMRI: Functional magnetic resonance imaging) des Motorkortex bei gesunden Probanden und Patienten mit Hirntumor. Die funktionelle MR-Bildgebung wurde bei 14 gesunden Probanden und bei 14 Patienten mit einem Tumor im oder nahe des primaeren Motorkortex durchgefuehrt, wobei beide Kollektive

  19. Pharmacokinetic interaction of telmisartan with s-amlodipine: an open-label, two-period crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Noh, Yook-Hwan; Lim, Hyeong-Seok; Kim, Mi Jo; Kim, Yo Han; Choi, Hee Youn; Sung, Hye Ryoung; Jin, Seok-Joon; Lim, Jonglae; Bae, Kyun-Seop

    2012-07-01

    Telmisartan belongs to a class of orally active angiotensin II receptor blockers (ARBs), and S-amlodipine is an enantiomer of amlodipine. Amlodipine is a racemic mixture and the calcium channel blocking (CCB) effect is confined to S-amlodipine, whereas R-amlodipine has a 1000-fold lower activity and no racemization occurs in vivo in human plasma. Combination therapy of ARBs with CCBs provides advantages for blood pressure control and vascular protection over monotherapy. To investigate the effects of coadministration of telmisartan and S-amlodipine on the steady-state pharmacokinetic properties of each drug as a drug-drug interaction study required before developing the fixed-dose combination agent. This study comprised 2 separate parts, A and B; each was a multiple-dose, open-label, 2-sequence, 2-period, crossover study in healthy male Korean volunteers. In part A, volunteers were administered 80 mg of telmisartan, either alone or with 5 mg of S-amlodipine. In part B, volunteers were administered 5 mg of S-amlodipine, either alone or with 80 mg of telmisartan. Blood samples were taken on days 9 and 37, following the final dose of each treatment, and at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours after administration in part A, and were taken at 0 (predose), 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, and 24 hours after administration in part B. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic properties of each drug after coadministration of telmisartan and S-amlodipine were compared with those of each drug administered alone. Tolerability was assessed using measurements of vital signs, clinical chemistry tests, and interviews. Fifty-six volunteers were enrolled (32 in part A and 24 in part B), and all completed except 4 volunteers (3 withdrawn in part A and 1 withdrawn in part B). The geometric mean ratios (GMRs) (90% CI) for the C(max,ss) and AUC(τ,ss) of telmisartan (with or without S-amlodipine) were 1.039 (0

  20. Neuroprotective impact of a vitamin trace element composition - a randomized, double blind, placebo controlled clinical trial with healthy volunteers.

    Science.gov (United States)

    Muss, Claus; Mosgoeller, Wilhelm; Endler, Thomas

    2015-01-01

    Neurotoxic metabolites and oxidative and nitrosative stress reactions play a crucial role in the pathways leading to neuronal cell death and neurodegeneration. The bioavailability of the many antioxidant ingredients a vitamin and trace element composition was investigated, to reveal the neuroprotective (preventive) potential of the composition. We recruited 159 healthy volunteers, assigned them randomly and double blind to a placebo and verum group. Physicians excluded volunteers with severe chronic diseases or interfeering medications. 142 participants finished the six month trial. Laboratory parameters were determined 1) before participation, and 2) after three and 3) six months. We confirmed the bioavailability of ingredients, and determined metabolic parameters associated with the integrity of the blood brain barrier, mitochondrial deficiency (Q 10), neurodegeneration (homocystein), and antioxidative capacity (e.g. lipidperoxidation), and superoxiddismutase activity. Starting from baseleine, after three months neuroprotective ingredients increased within their physiological borders, folic acid (p<0.003), pyridoxin (p<0.001), cobalamin (p=0.001), and the fat soluble vitamin tocopherol (p<0.001). In parallel, homocytein decreased after 3 and 6 months (p<0.001, and p<0.025, respectively). Other paramters like zinc reacted slower, significant changes were observed only after 6 months. The observed metabolic changes and alteration of the oxidative status after 3 and six month of regular intake underlines the compositions' potential to ameliorate neurodegenerative processes. We conclude that the subsitution of vitamins and trace-elements with natural source in a proper manner may be effective for neuroprotection in healthy population.

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

    Science.gov (United States)

    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.

  2. The effects of Andrographis paniculata (Burm.f. Nees on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa

    2012-11-01

    Full Text Available Andrographis paniculata (Burm.f. Nees has been widely used for centuries in Asia for the treatment of common coldand diarrhea. Although it was previously reported to inhibit cytochrome P450 in vitro, the potential to cause herb-druginteraction has been questioned. The purpose of this study was to evaluate the effects of A. paniculata on the pharmacokineticsand pharmacodynamics of midazolam, a CYP3A4 probe drug, in normal healthy volunteers. The study was anopen-label, randomized, 2-phase crossover design with a 2-weeks washout period. Twelve healthy male volunteers received4 capsules of 250 mg A. paniculata 3 times a day orally for 7 days. Midazolam plasma concentration time profiles werecharacterized after a single oral dose of 7.5 mg midazolam on the day before and after A. paniculata medication. Pharmacodynamicsof midazolam were also evaluated. The results demonstrated that pretreatment with A. paniculata did not changemean pharmacokinetic parameters (Cmax, Tmax, AUC0-12, AUC0-”, T1/2, Cl/F of oral midazolam. Since midazolam is the mostsensitive substrate for CYP3A4, thus, herb-drug interaction caused by CYP3A4 inhibition after A. paniculata in healthyvolunteers was considered not clinically relevant. However, A. paniculata potentiated the effect of midazolam in loweringblood pressure and pulse rate. Therefore, co-administration of A. paniculata with midazolam should be warranted.

  3. Preliminary study of relationships between hypnotic susceptibility and personality disorder functioning styles in healthy volunteers and personality disorder patients

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    He Wei

    2011-07-01

    Full Text Available Abstract Background Hypnotic susceptibility is one of the stable characteristics of individuals, but not closely related to the personality traits such as those measured by the five-factor model in the general population. Whether it is related to the personality disorder functioning styles remains unanswered. Methods In 77 patients with personality disorders and 154 healthy volunteers, we administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSSC and the Parker Personality Measure (PERM tests. Results Patients with personality disorders showed higher passing rates on SHSSC Dream and Posthypnotic Amnesia items. No significant correlation was found in healthy volunteers. In the patients however, SHSSC Taste hallucination (β = 0.26 and Anosmia to Ammonia (β = -0.23 were significantly correlated with the PERM Borderline style; SHSSC Posthypnotic Amnesia was correlated with the PERM Schizoid style (β = 0.25 but negatively the PERM Narcissistic style (β = -0.23. Conclusions Our results provide limited evidence that could help to understand the abnormal cognitions in personality disorders, such as their hallucination and memory distortions.

  4. Comparison of Quantitative Cartilage T2 Measurements and Qualitative MR Imaging between Professional Ballet Dancers and Healthy Volunteers.

    Science.gov (United States)

    Cha, Jang Gyu; Yi, Ji Sook; Han, Jong Kyu; Lee, Young Koo

    2015-07-01

    To compare qualitative magnetic resonance (MR) images and quantitative T2 measurements of the tibiotalar cartilage between ballerinas and healthy volunteers. Institutional review board approval for this study and informed consent (from all participants) were obtained. MR examinations were performed by using a 3-T MR imaging system with 21 professional female ballet dancers and 20 healthy female volunteers. Two musculoskeletal radiologists qualitatively measured tibiotalar cartilage T2 values in the anterior zones, middle zones, and posterior zones of cartilage. MR findings were also qualitatively analyzed in both groups. The tibial cartilage T2 values measured in the anterior and posterior zones and the talar cartilage T2 values measured in all three zones were significantly higher in the ballerina group than in the control group (P The posterior zones exhibited the highest T2 values among the three tibiotalar cartilage zones in both groups (P the presence of posterior soft-tissue edema (P = .001) and flexor hallucis longus tenosynovitis (P The findings showed a trend toward increasing cartilage T2 values in ballerinas when compared with control subjects, indicating that quantitative T2 measurement may potentially be used as a noninvasive imaging tool for early detection of cartilage lesions in the tibiotalar joint.

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

    Science.gov (United States)

    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.

  6. Gender Differences in Cerebral Regional Homogeneity of Adult Healthy Volunteers: A Resting-State fMRI Study

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    Chunsheng Xu

    2015-01-01

    Full Text Available Objective. We sought to use the regional homogeneity (ReHo approach as an index in the resting-state functional MRI to investigate the gender differences of spontaneous brain activity within cerebral cortex and resting-state networks (RSNs in young adult healthy volunteers. Methods. One hundred and twelve healthy volunteers (56 males, 56 females participated in the resting-state fMRI scan. The ReHo mappings in the cerebral cortex and twelve RSNs of the male and female groups were compared. Results. We found statistically significant gender differences in the primary visual network (PVN (P<0.004, with Bonferroni correction and left attention network (LAtN, default mode network (DMN, sensorimotor network (SMN, executive network (EN, and dorsal medial prefrontal network (DMPFC as well (P<0.05, uncorrected. The male group showed higher ReHo in the left precuneus, while the female group showed higher ReHo in the right middle cingulate gyrus, fusiform gyrus, left inferior parietal lobule, precentral gyrus, supramarginal gyrus, and postcentral gyrus. Conclusions. Our results suggested that men and women had regional specific differences during the resting-state. The findings may improve our understanding of the gender differences in behavior and cognition from the perspective of resting-state brain function.

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

    Science.gov (United States)

    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.

  8. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers

    International Nuclear Information System (INIS)

    Morrow, Jasper M.; Reilly, Mary M.; Hanna, Michael G.; Sinclair, Christopher D.J.; Yousry, Tarek A.; Thornton, John S.; Fischmann, Arne

    2014-01-01

    Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies. Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T 1 -relaxometry, T 2 -relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. Mean between-muscle fat fraction and T 2 differences were small, but significant (p 2 correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively. Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials. (orig.)

  9. Prevalence of Desloratadine Slow-metabolizer Phenotype and Food-dependent Pharmacokinetics of Desloratadine in Healthy Chinese Volunteers.

    Science.gov (United States)

    Wang, Ting; Zhang, Kun; Li, Tingting; He, Lin; Xie, Huiru; Jiang, Xuehua; Wang, Ling

    2015-12-01

    Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolizer (DSM) phenotype and the effects of food on the pharmacokinetics of desloratadine and its active metabolite 3-OH-desloratadine in healthy Chinese volunteers. A total of 46 healthy Chinese male volunteers were included in this investigation. All subjects received a single dose of a 5-mg desloratadine tablet under fasting or fed conditions and the plasma concentrations of desloratadine and 3-OH-desloratadine were measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. The individuals with a 3-OH-desloratadine-to-desloratadine exposure ratio lower than 10 % or a desloratadine half-life (t 1/2) of ≥50 h were supposed to be DSM. There was only one DSM among the 46 volunteers, with a prevalence of 2.2 %. Moreover, administration in a fed state resulted in 34.07 and 32.06 % decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity for desloratadine and 47.26 and 48.46 % for 3-OH-desloratadine compared with those values under fasting conditions. Taken together, these results indicated that the incidence of the DSM phenotype in the Chinese population was low and that food intake could significantly decrease the absorption rate and extent of desloratadine.

  10. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

    Science.gov (United States)

    Umbricht, D; Schmid, L; Koller, R; Vollenweider, F X; Hell, D; Javitt, D C

    2000-12-01

    In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

  11. Single-Dose pharmacokinetics of sustained-release fampridine (Fampridine-SR) in healthy volunteers and adults with renal impairment.

    Science.gov (United States)

    Smith, William; Swan, Suzanne; Marbury, Thomas; Henney, Herbert

    2010-02-01

    Fampridine-SR is a sustained-release formulation of fampridine (4-aminopyridine), a potassium channel blocker demonstrated to improve walking ability in patients with multiple sclerosis. This study evaluated the pharmacokinetics of fampridine and its metabolites after administration of fampridine-SR 10 mg in healthy volunteers and in subjects with mild, moderate, or severe renal impairment (5 per group). Analysis of variance was used to calculate 90% confidence intervals (CIs) for the ratios (impaired/healthy) of least squares mean in maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC). Clearance was primarily through urinary excretion. In renally impaired subjects, fampridine plasma concentrations were consistently higher than in healthy individuals: ratios for C(max) ranged from 166.5% to 199.9% for mild and severe renal impairment, respectively. AUC(0-infinity) ratios ranged from 175.3% to 398.7%, respectively, for mild and severe renal impairment. Mean terminal disposition half-life was 6.4 hours in healthy individuals, compared with 7.4, 8.1, and 14.3 hours in patients with mild, moderate, and severe renal impairment, respectively. Regression analysis confirmed the significant relationship between creatinine clearance and extent of exposure as quantified by AUC for fampridine and its metabolites, suggesting cautious use in patients with mild renal impairment and avoidance in cases of moderate or severe renal impairment.

  12. Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Schouten Evert G

    2004-07-01

    Full Text Available Abstract Background Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. Methods The response of serum alanine aminotransferase (ALAT and aspartate aminotransferase (ASAT to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol was measured in 18 healthy volunteers. Results After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN. Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25th,75th percentile: 0.09;0.53 for ALAT and 0.06 ULN (25th,75th percentile -0.06;0.22 for ASAT. Conclusions We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee.

  13. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

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    Vance L Albaugh

    Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

  14. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers.

    Science.gov (United States)

    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.

  15. Effects of subanaesthetic and anaesthetic doses of sevoflurane on regional cerebral blood flow in healthy volunteers. A positron emission tomographic study

    DEFF Research Database (Denmark)

    Schlünzen, L; Vafaee, M S; Cold, G E

    2004-01-01

    in the thalamus. At the last level (0.4 MAC vs. 1 MAC) the rCBF was increased in the insula and decreased in the posterior cingulate, the lingual gyrus, precuneus and in the frontal cortex. CONCLUSION: At sevoflurane concentrations at 0.7% and 2.0% a significant decrease in relative rCBF was detected...... escalating doses using 0.4%, 0.7% and 2.0% end-tidal sevoflurane inhalation. During baseline and each of the three levels of anaesthesia one PET scan was performed after injection of . Cardiovascular and respiratory parameters were monitored and electroencephalography and bispectral index (BIS) were......BACKGROUND: We tested the hypothesis that escalating drug concentrations of sevoflurane are associated with a significant decline of cerebral blood flow in regions subserving conscious brain activity, including specifically the thalamus. METHODS: Nine healthy human volunteers received three...

  16. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers

    DEFF Research Database (Denmark)

    Naert, A.L.; Kehlet, H.; Kupers, R.

    2008-01-01

    .2+/-0.4, females scoring higher than men (7.4+/-0.5 vs. 5.2+/-0.5; pstimulation period after which they stabilized. A strong interindividual variability was observed in the time profiles of the pain ratings over the course of the 7-min...... tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6...... stimulation period. The model showed a good test-retest reproducibility. Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable...

  17. Effect of n-3 polyunsaturated fatty acids on the lipidic profile of healthy Mexican volunteers

    Directory of Open Access Journals (Sweden)

    CARVAJAL OCTAVIO

    1997-01-01

    Full Text Available Objective. The effect of n-3 polyunsaturated fatty acids on the serum lipid profile in a Mexican population was evaluated. Material and methods. Three g of salmon oil was the daily intake during four weeks. Total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and erythrocyte fatty acid composition were analyzed. Results. The hypertriglyceridemic group showed a statistically significant (p< 0.05 reduction of triglycerides and significant (p< 0.01 elevation of high density lipoproteins. The hypercholesterolemic group reduced significantly the levels of cholesterol and triglycerides; high density lipoproteins were augmented by 11.6%. Conclusions. The hipolipidemic effect of n-3 polyunsaturated fatty acids was manifest in the Mexican volunteers under the conditions here evaluated.

  18. Esophageal transit scintigraphy in healthy volunteers using TC-99M sulphur colloid semisolid jelly

    International Nuclear Information System (INIS)

    Ashwani Sood; Kumar, U.; Gambhir, S.; Sewatkar, A.B.; Kheruka, S.C.; Dube, V.

    2004-01-01

    Functional symptoms caused by esophageal motor disorders are very common. The esophageal transit scintigraphy has been done using liquid and solid meals to understand pathophysiology of esophageal motor disorders better. The present study was aimed to develop and standardize a stable and easily acceptable radioactive semisolid meal for esophageal transit scintigraphy. Semisolid jelly incorporated with Tc-99m sulphur colloid was prepared from the commercially available edible jelly powder-containing gelatin. The tracer stability was investigated by in-vitro method up to 4 hours to test the affinity of tracer and mechanical stability of semisolid meal. The amount of semisolid meal per bolus was also standardized in relation to ease of swallowing and free passage of it through whole of esophagus. The additional objective was to establish the normal esophageal transit scintigraphic parameters. Materials and methods: A total of 31 normal volunteers were studied. The esophageal transit scintigraphy was performed in supine and sitting positions thrice using single bolus of 2 gm semisolid jelly containing 7.4 MBq (200uCi) of tracer for the acquisition period of 192 seconds. The esophageal emptying time for 50% (T50) and for 90% (T90) were calculated by computer analysis in addition to generation of condensed dynamic images. Results: The 50% and 90% whole esophageal emptying time are given below in the table in sitting and supine positions respectively.(P<0.05). Conclusions: Condensed dynamic images revealed normal transit pattern without delay or stasis and fragmentation of bolus through the esophagus. The stability and homogeneity of tracer in the semisolid meal provided a simple and reliable method for carrying out esophageal transit scintigraphy. It was found that this bolus was well accepted by normal volunteers and values obtained were well within the acceptable range. Thus we established the normal values in our laboratory and also standardized a semisolid meal with

  19. Rule-guided human classification of Volunteered Geographic Information

    Science.gov (United States)

    Ali, Ahmed Loai; Falomir, Zoe; Schmid, Falko; Freksa, Christian

    2017-05-01

    During the last decade, web technologies and location sensing devices have evolved generating a form of crowdsourcing known as Volunteered Geographic Information (VGI). VGI acted as a platform of spatial data collection, in particular, when a group of public participants are involved in collaborative mapping activities: they work together to collect, share, and use information about geographic features. VGI exploits participants' local knowledge to produce rich data sources. However, the resulting data inherits problematic data classification. In VGI projects, the challenges of data classification are due to the following: (i) data is likely prone to subjective classification, (ii) remote contributions and flexible contribution mechanisms in most projects, and (iii) the uncertainty of spatial data and non-strict definitions of geographic features. These factors lead to various forms of problematic classification: inconsistent, incomplete, and imprecise data classification. This research addresses classification appropriateness. Whether the classification of an entity is appropriate or inappropriate is related to quantitative and/or qualitative observations. Small differences between observations may be not recognizable particularly for non-expert participants. Hence, in this paper, the problem is tackled by developing a rule-guided classification approach. This approach exploits data mining techniques of Association Classification (AC) to extract descriptive (qualitative) rules of specific geographic features. The rules are extracted based on the investigation of qualitative topological relations between target features and their context. Afterwards, the extracted rules are used to develop a recommendation system able to guide participants to the most appropriate classification. The approach proposes two scenarios to guide participants towards enhancing the quality of data classification. An empirical study is conducted to investigate the classification of grass

  20. Evaluating automated dynamic contrast enhanced wrist 3T MRI in healthy volunteers

    DEFF Research Database (Denmark)

    Rastogi, Anshul; Kubassova, Olga; Krasnosselskaia, Lada V

    2013-01-01

    Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so...

  1. Quantitative pulmonary perfusion imaging with 3-dimensional, contrast-enhanced MR: regional difference in the perfusion parameters of healthy volunteers

    International Nuclear Information System (INIS)

    Kim, Song Soo; Seo, Joon Beom; Kim, Nam Kuk; Do, Kyung Hyun; Lee, Young Kyung; Song, Jae Woo; Lee, Jin Seong; Kim, Jin Hwan

    2007-01-01

    We wanted to evaluate the regional differences in such perfusion parameters as pulmonary blood flow (PBF), mean transit time (MTT) and pulmonary blood volume (PBV) in the entire lung of healthy volunteers with using three-dimensional, contrast-enhanced MR imaging (3D CEMRI). Six healthy volunteers underwent dynamic 3D CEMRI (TR/TE 2.7/0.6 msec; flip angle 40 .deg. ; matrix 128 x 96; reconstructed matrix 256 x 192; rectangular field of view 450 x 315 mm; coronal 100-150mm-thick x 10 slabs; temporal resolution 1.0 sec; 35 dynamic phases) For all subjects, 2 mL of Gd-DTPA mixed with 3 ml of physiologic saline was administered as a bolus at a rate of 5 mL/sec, and this was followed by 20 mL of physiologic saline flush. From the signal intensity-time curves, the PBF, MTT and PBV maps were generated using indicator dilution theories and the central volume principle on a pixel-by-pixel basis. A total of 54 round, 1-cm sized ROIs were placed in the lung in each subject (6 ROIs per slab x 9 slices except for the most posterior slab). The regional differences of the measured parameters were statistically evaluated in the gravitational direction and in the upper-mid-lower direction by one-way ANOVA tests. The calculated PBF, MTT and PBV in the entire lung were 141.8 ± 53.4 mL/100 mL/min (mean ± SD), 5.35 ± 1.38 sec, and 13.4 ± 6.48 mL/100mL, respectively. In the gravitational direction, there was a significant increase in the PBF and PBV as it goes to the posterior direction (ρ < 0.05). No statistical difference was found in PBF or PBV between the upper, mid and lower lung zone areas. Regional difference in the various perfusion parameters of the lung in healthy volunteers can be quantitatively assessed with performing 3D CEMRI

  2. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Ying G

    2013-01-01

    Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

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

    Directory of Open Access Journals (Sweden)

    Manuela Kobelt

    2018-04-01

    Full Text Available 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

  4. Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

    Science.gov (United States)

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

    2016-01-01

    To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞  were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  5. The role of serotonin in nonnormative risky choice: the effects of tryptophan supplements on the "reflection effect" in healthy adult volunteers.

    Science.gov (United States)

    Murphy, Susannah E; Longhitano, Carlo; Ayres, Rachael E; Cowen, Philip J; Harmer, Catherine J; Rogers, Robert D

    2009-09-01

    Risky decision-making involves weighing good and bad outcomes against their probabilities in order to determine the relative values of candidate actions. Although human decision-making sometimes conforms to rational models of how this weighting is achieved, irrational (or nonnormative) patterns of risky choice, including shifts between risk-averse and risk-seeking choices involving equivalent-value gambles (the "reflection effect"), are frequently observed. In the present experiment, we investigated the role of serotonin in decision-making under conditions of uncertainty. Fifteen healthy adult volunteers received a treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control volunteers received a matched placebo substance. At test, all participants completed a risky decision-making task involving a series of choices between two simultaneously presented gambles, differing in the magnitude of their possible gains, the magnitude of their possible losses, and the probabilities with which these outcomes were delivered. Tryptophan supplements were associated with alterations in the weighting of gains and small losses perhaps reflecting reduced loss-aversion, and a marked and significant diminution of the reflection effect. We conclude that serotonin activity plays a significant role in nonnormative risky decision-making under conditions of uncertainty.

  6. Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers.

    Science.gov (United States)

    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

  7. Randomized, Double-Blind Clinical Trial to Assess the Acute Diuretic Effect of Equisetum arvense (Field Horsetail in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Danilo Maciel Carneiro

    2014-01-01

    Full Text Available In this double-blind, randomized clinical trial, 36 healthy male volunteers were randomly distributed into three groups (n=12 that underwent a three-step treatment. For four consecutive days, we alternately administered a standardized dried extract of Equisetum arvense (EADE, 900 mg/day, placebo (corn starch, 900 mg/day, or hydrochlorothiazide (25 mg/day, separated by a 10-day washout period. Each volunteer served as his own control, and the groups’ results were compared. We repeated the same evaluation after each stage of treatment to evaluate the safety of the drug. The diuretic effect of EADE was assessed by monitoring the volunteers’ water balance over a 24 h period. The E. arvense extract produced a diuretic effect that was stronger than that of the negative control and was equivalent to that of hydrochlorothiazide without causing significant changes in the elimination of electrolytes. There was no significant increase in the urinary elimination of catabolites. Rare minor adverse events were reported. The clinical examinations and laboratory tests showed no changes before or after the experiment, suggesting that the drug is safe for acute use. Further research is needed to better clarify the mechanism of diuretic action and the other possible pharmacological actions of this phytomedicine.

  8. LPS infusion suppresses serum FGF21 levels in healthy adult volunteers

    DEFF Research Database (Denmark)

    Lauritzen, Esben Stistrup; Rittig, Nikolaj; Bach, Ermina

    2017-01-01

    circulating levels of FGF21 after lipopolysaccharide (LPS) infusion. DESIGN: Two randomized, single blinded, placebo-controlled crossover trials were used. SETTING: The studies were performed at a university hospital clinical research center. PATIENTS AND INTERVENTIONS: Study 1 (LPS bolus): Eight young......, healthy, lean males were investigated two times: 1) after isotonic saline injection, and 2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 hours. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: 1) during continuously isotonic saline infusion, and 2......) during continuously LPS infusion (0.06 ng/kg/h). Each study day lasted 4 hours. Circulating FGF21 levels were quantified every second hour by an immunoassay. RESULTS: A LPS bolus resulted in a late suppression (t = 240 minutes) of serum FGF21 (P=0.035). Continuous LPS infusion revealed no significant...

  9. A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers

    DEFF Research Database (Denmark)

    Wienberg, M; Glenthøj, Birte Yding; Jensen, K S

    2009-01-01

    processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally...... administered dose of 15 mg escitalopram (a highly selective serotonin reuptake inhibitor (SSRI)) or placebo, after which their PN, MMN and P300 amplitude were assessed. Similar to our initial study with 10 mg escitalopram, 15 mg escitalopram significantly increased MMN, while it did not affect P300 amplitude....... In contrast to our initial study, however, the currently higher dose of escitalopram did not increase PN. Results support the view that a broad range of increased serotonergic activity enhances MMN, while the relationship between serotonin and PN seems more complex. The current study does not support...

  10. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy

    DEFF Research Database (Denmark)

    Reimer, Christina; Søndergaard, Bo; Hilsted, Linda

    2009-01-01

    -controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid...... dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS: PPI therapy...

  11. Safety of a New Compact Male Intermittent Catheter: Randomized, Cross-Over, Single-Blind Study in Healthy Male Volunteers

    DEFF Research Database (Denmark)

    Bagi, Per; Hannibalsen, Jane; Permild, Rikke

    2011-01-01

    in hematuria (p = 0.54) or discomfort/stinging/pain at first micturition (p = 0.56). During insertion, handling was easier (p = 0.0001) and touching the coating was necessary less often (2.2 vs. 81.3% of catheterizations; p catheter; it was preferred by nurses for 20 of 23......Introduction: A new compact male intermittent catheter was compared with a regular intermittent male catheter in terms of safety and acceptability. Methods: In this randomized, single-blind, cross-over study, healthy male volunteers were catheterized twice with a compact catheter and twice...... with a regular catheter. Results: 28 participants were enrolled. Mean ± SD discomfort (visual analogue scale; primary objective) was 2.25 ± 1.5 and 2.52 ± 1.8 for the compact and regular catheters, respectively (difference -0.27; 95% confidence interval -0.73 to 0.19); there was no significant difference...

  12. Short echo time proton spectroscopy of the brain in healthy volunteers using an insert gradient head coil

    DEFF Research Database (Denmark)

    Gideon, P; Danielsen, E R; Schneider, M

    1995-01-01

    An insert gradient head coil with built-in X, Y, and Z gradients was used for localized proton spectroscopy in the brain of healthy volunteers, using short echo time stimulated echo acquisition mode (STEAM) sequences. Volume of interest size was 3.4 ml, repetition time was 6.0 s, and echo times...... were 10 and 20 ms, respectively. Good quality proton spectra with practically no eddy current artefacts were acquired allowing observation of strongly coupled compounds, and compounds with short T2 relaxation times. The gradient head coil thus permits further studies of compounds such as glutamine....../glutamate and myo-inositols. These compounds were more prominent within grey matter than within white matter. Rough estimations of metabolite concentrations using water as an internal standard were in good agreement with previous reports....

  13. Study on Yang-Xu Using Body Constitution Questionnaire and Blood Variables in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Hong-Jhang Chen

    2016-01-01

    Full Text Available Traditional Chinese medicine (TCM formulates treatment according to body constitution (BC differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%, while subjects of the other group, named as the sub-healthy group, had three BCs (32%. Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC.

  14. Gender Difference of Gastric Emptying in Healthy Volunteers and Patients with Functional Dyspepsia.

    Science.gov (United States)

    Mori, Hideki; Suzuki, Hidekazu; Matsuzaki, Juntaro; Taniguchi, Kanami; Shimizu, Toshiyuki; Yamane, Tsuyoshi; Masaoka, Tatsuhiro; Kanai, Takanori

    2017-01-01

    Delayed gastric emptying is one of the reasons why functional dyspepsia (FD) occurs. The 13C-acetate breath test is widely used to evaluate gastric emptying. Nevertheless, the standard value of 13C-acetate breath test has not taken into account the gender difference of gastric emptying among healthy individuals. The main aim of this study was to readjust the standard value of 13C-acetate breath test in the light of gender differences. In addition, we clarified the prevalence and clinical characteristics of delayed gastric emptying in patients with FD using the modified standard values of 13C-acetate breath test. Fifty-two healthy individuals and 126 patients with patients with FD were enrolled. Gastric emptying was evaluated by the 13C-acetate breath test. The cut-off points of Tmax for the diagnosis of delayed gastric emptying were determined on the basis of results from healthy individuals making a distinction of genders. Gastroesophageal reflux symptoms, dyspeptic symptoms, scores of anxiety and depression, age, body mass index (BMI), smoking and alcohol consumption were compared between the delayed gastric emptying group and the non-delayed gastric emptying group. Since gastric emptying was delayed in healthy women compared with that in healthy men (Tmax, 53.6 ± 19.3 vs. 42.7 ± 16.9 min, p = 0.04), we set the cut-off points of Tmax at 60 min in men and at 75 min in women. In patients with FD, the prevalence of delayed gastric emptying was not different between men and women with the modified standard values of 13C-acetate breath test. (31.0 vs. 27.4%, p = 0.68). BMI was lower in the delayed gastric emptying group than in the non-delayed group among the male patients. Reflux symptoms were more severe in delayed gastric emptying group than in the non-delayed group among the female patients. The standard values of 13C-acetate breath test should be modified bearing the gender difference in mind. It provides us more appropriate information to understand the

  15. Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Parag R Gajendragadkar

    Full Text Available AIMS: The mechanisms by which a 'Mediterranean diet' reduces cardiovascular disease (CVD burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV. METHODS AND RESULTS: We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV, sodium nitroprusside (endothelium-independent vasodilatation; EIDV, and NG-monomethyl-L-arginine (basal nitric oxide (NO synthase activity were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: -45% to -10%, P = 0.008, despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: -1.6 to -0.9 mmol/L, P<0.001. Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: -30% to +30%, P = 0.85, also suggesting lycopene improved endothelial function. CONCLUSIONS: Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01100385.

  16. Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers.

    Science.gov (United States)

    Berteau, Cecile; Schwarzenbach, Florence; Donazzolo, Yves; Latreille, Mathilde; Berube, Julie; Abry, Herve; Cotten, Joël; Feger, Celine; Laurent, Philippe E

    2010-10-05

    A disposable autoinjector was developed for subcutaneous (SC) self-injection by patients with chronic diseases. To verify its performance and evaluate its acceptance, a clinical study was conducted in healthy volunteers, comparing SC injections performed by subjects using the autoinjector with SC injections performed by nurses using a syringe. This was a randomized, single-center, crossover study comparing SC self-injection using an autoinjector with SC nurse-administered injection using a syringe. Two volumes (0.2 mL and 1 mL) were injected into healthy volunteers. Study objectives included assessment of the accuracy and consistency of the volume injected by the injection systems, and skin reaction and pain associated with the injection. The fluid depot in the SC tissue layer was evaluated by ultrasound. Subject acceptance was evaluated using questionnaires on attitudes and emotions towards the injection technique, and challenged by seeking the subjects' preferred system for a final study injection or future treatment. A total of 960 injections (480 with autoinjector, 480 with syringe) were performed in 40 subjects. There were no significant differences in mean fluid leakage and injected volumes between the systems. Pain associated with the injection was significantly lower with the auto-injector than with the syringe. Local skin reaction at the injection site was overall satisfactory. Injections were appropriately performed by all subjects. At study end, all 40 subjects preferred the autoinjector for a final study injection and for future treatment. This study indicated that the autoinjector used by the subject was similar to a syringe used by a nurse in terms of performance and safety in administering the injections, and better in terms of pain, overall acceptance, and preference.

  17. Feasibility of navigator setting on the left diaphragm for whole-heart coronary MRA. A study in healthy volunteers

    International Nuclear Information System (INIS)

    Watanabe, Kunihiro; Suzuki, Takayoshi; Maruyama, Kazuhiro; Noda, Mayumi; Fujita, Mitsuo; Morita, Satoru; Ohnishi, Takahiro

    2009-01-01

    We prospectively compared the quality of images obtained by navigator setting on the left and right diaphragm on whole-heart coronary magnetic resonance angiography (WHCMRA). In 10 healthy volunteers, we performed free-breathing, 3-dimensional segmented true fast imaging with steady-state precession (trueFISP) WHCMRA by setting the navigator on the left and right diaphragm in random order. For the left diaphragm, we set the navigator outside the scope of the heart to avoid the influence on coronary arteries. We compared image acquisition time and visible length of coronary arteries using paired t-test and subjective image quality on a 4-point scale (1, poor; 4, excellent) using Wilcoxon signed-rank test. Mean overall subjective image quality was significantly better in the left diaphragm than the right (3.3±0.7 versus 2.9±0.9, P=0.02). Mean overall visible length of the coronary arteries was significantly better in the left diaphragm than the right (115.4±31.1 vs. 112.6±29.9 mm, P=0.02). Mean acquisition time between the left and right diaphragm was not significantly different (15.6±5.0 versus 16.0±5.7 min, P=0.79). In this small group of healthy volunteers, navigator setting for WHCMRA was superior on the left diaphragm than the right; however, feasibility of the technique requires additional consideration in a larger group of actual patients. (author)

  18. A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers.

    Science.gov (United States)

    Mendes, Gustavo D; dos Santos Filho, Hilton Oliveira; dos Santos Pereira, Alberto; Mendes, Fabiana D; Ilha, Jaime O; Alkharfy, Khalid M; De Nucci, Gilberto

    2012-12-01

    Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). The study was an open label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for tmax and t1/2 were 1.6 ( ± 0.4) h and 3.3 ( ± 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.

  19. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    International Nuclear Information System (INIS)

    Galtier, F.; Mura, T.; Raynaud de Mauverger, E.; Chevassus, H.; Farret, A.; Gagnol, J.-P.; Costa, F.; Dupuy, A.

    2012-01-01

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca 2+ homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca 2+ spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P 2+ sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca 2+ spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca 2+ spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK increase was associated with alterations in Ca2+ sparks and mitochondrial function.

  20. Effects of Oral Lycopene Supplementation on Vascular Function in Patients with Cardiovascular Disease and Healthy Volunteers: A Randomised Controlled Trial

    Science.gov (United States)

    Gajendragadkar, Parag R.; Hubsch, Annette; Mäki-Petäjä, Kaisa M.; Serg, Martin; Wilkinson, Ian B.; Cheriyan, Joseph

    2014-01-01

    Aims The mechanisms by which a ‘Mediterranean diet’ reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV). Methods and Results We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine (basal nitric oxide (NO) synthase activity) were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: −45% to −10%, P = 0.008), despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: −1.6 to −0.9 mmol/L, Plycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: −30% to +30%, P = 0.85), also suggesting lycopene improved endothelial function. Conclusions Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. Trial Registration ClinicalTrials.gov NCT01100385 PMID:24911964

  1. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, Jasper M.; Reilly, Mary M.; Hanna, Michael G. [UCL Institute of Neurology, Medical Research Council Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, London (United Kingdom); Sinclair, Christopher D.J.; Yousry, Tarek A.; Thornton, John S. [UCL Institute of Neurology, Medical Research Council Centre for Neuromuscular Diseases, Department of Molecular Neuroscience, London (United Kingdom); UCL Institute of Neurology, Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, London (United Kingdom); Fischmann, Arne [University of Basel Hospital, Department of Radiology, Division of Diagnostic and Interventional Neuroradiology, Basel (Switzerland)

    2014-07-15

    Quantitative magnetic resonance imaging (MRI) can potentially meet the pressing need for objective, sensitive, reproducible outcome measures in neuromuscular disease trials. We tested, in healthy volunteers, the consistency, reliability and sensitivity to normal inter-subject variation of MRI methods targeted to lower limb muscle pathology to inform the design of practical but comprehensive MRI outcome measure protocols for use in imminent patient studies. Forty-seven healthy volunteers, age 21-81 years, were subject at 3T to three-point Dixon fat-fraction measurement, T{sub 1}-relaxometry, T{sub 2}-relaxometry and magnetisation transfer ratio (MTR) imaging at mid-thigh and mid-calf level bilaterally. Fifteen subjects underwent repeat imaging at 2 weeks. Mean between-muscle fat fraction and T{sub 2} differences were small, but significant (p < 0.001). Fat fraction and T{sub 2} correlated positively, and MTR negatively with subject age in both the thigh and calf, with similar significant correlations with weight at thigh level only (p < 0.001 to p < 0.05). Scan-rescan and inter-observer intra-class correlation coefficients ranged between 0.62-0.84 and 0.79-0.99 respectively. Quantitative lower-limb muscle MRI using readily implementable methods was sensitive enough to demonstrate inter-muscle differences (small in health), and correlations with subject age and weight. In combination with high reliability, this strongly supports the suitability of these methods to provide longitudinal outcome measures in neuromuscular disease treatment trials. (orig.)

  2. Jerusalem artichoke and chicory inulin in bakery products affect faecal microbiota of healthy volunteers.

    Science.gov (United States)

    Kleessen, Brigitta; Schwarz, Sandra; Boehm, Anke; Fuhrmann, H; Richter, A; Henle, T; Krueger, Monika

    2007-09-01

    A study was conducted to test the effects of Jerusalem artichoke inulin (JA) or chicory inulin (CH) in snack bars on composition of faecal microbiota, concentration of faecal SCFA, bowel habit and gastrointestinal symptoms. Forty-five volunteers participated in a double-blind, randomized, placebo-controlled, parallel-group study. At the end of a 7 d run-in period, subjects were randomly assigned to three groups of fifteen subjects each, consuming either snack bars with CH or JA, or snack bars without fructans (placebo); for 7 d (adaptation period), they ingested one snack bar per day (7.7 g fructan/d) and continued for 14 d with two snack bars per day. The composition of the microbiota was monitored weekly. The consumption of CH or JA increased counts of bifidobacteria (+1.2 log10 in 21 d) and reduced Bacteroides/Prevotella in number and the Clostridium histolyticum/C. lituseburense group in frequency at the end of intervention (P bakery products stimulates the growth of bifidobacteria and may contribute to the suppression of potential pathogenic bacteria.

  3. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers.

    Science.gov (United States)

    Naert, Arne L G; Kehlet, Henrik; Kupers, Ron

    2008-08-15

    The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6.2+/-0.4, females scoring higher than men (7.4+/-0.5 vs. 5.2+/-0.5; pPain ratings showed a steady increase during the first half of the stimulation period after which they stabilized. A strong interindividual variability was observed in the time profiles of the pain ratings over the course of the 7-min stimulation period. The model showed a good test-retest reproducibility. Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable model that can be applied without excessive discomfort in the majority of subjects and offers a valuable addition to the armamentarium of experimental pain models. The model can be particularly suitable for brain imaging receptor binding studies which require long stimulation periods.

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

    Directory of Open Access Journals (Sweden)

    von Eisenhart-Rothe Ruediger

    2012-11-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions Significant changes in tibiofemoral and patellofemoral joint kinematics occur in patients with isolated PCL

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

    Science.gov (United States)

    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

  6. Evaluating automated dynamic contrast enhanced wrist 3 T MRI in healthy volunteers: One-year longitudinal observational study

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Anshul, E-mail: anshul.rastogi@bartshealth.nhs.uk [Kennedy Institute of Rheumatology, Imperial College London (United Kingdom); Kubassova, Olga, E-mail: olga@imageanalysis.org.uk [Image Analysis, Leeds (United Kingdom); Krasnosselskaia, Lada V., E-mail: solaguz@yahoo.com [Imaging Sciences Department, Imperial College London (United Kingdom); Lim, Adrian K.P., E-mail: a.lim@imperial.ac.uk [Department of Radiology, Imperial College Healthcare NHS Trust, London (United Kingdom); Satchithananda, Keshthra, E-mail: keshthra.satchithananda@imperial.nhs.uk [Department of Radiology, Imperial College Healthcare NHS Trust, London (United Kingdom); Boesen, Mikael, E-mail: mikael.boesen@gmail.com [Department of Radiology and the Parker Institute, Frederiksberg and Bispebjerg Hospitals (Denmark); Binks, Michael, E-mail: michael.h.binks@gsk.com [GlaxoSmithKline, Stevenage, SG1 2NY (United Kingdom); Hajnal, Joseph V., E-mail: jo.hajnal@kcl.ac.uk [Imaging Sciences Department, Imperial College London (United Kingdom); Taylor, Peter C., E-mail: peter.taylor@kennedy.ox.ac.uk [Kennedy Institute of Rheumatology, Imperial College London (United Kingdom)

    2013-08-15

    Rational and Objective: Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so as to differentiate changes induced by treatment from the inherent variability of perfusion measures. The objective of this study was to test a pixel-by-pixel parametric map based approach for analysis of DCE-MRI (Dynamika) and to investigate the variability in signal characteristics over time in healthy controls using longitudinally acquired images. Materials and Methods: 10 healthy volunteers enrolled, dominant wrists were imaged with contrast enhanced 3T MRI at baseline, week 12, 24 and 52 and scored with RAMRIS, DCE-MRI was analysed using a novel quantification parametric map based approach. Radiographs were obtained at baseline and week 52 and scored using modified Sharp van der Heidje method. RAMRIS scores and dynamic MRI measures were correlated. Results: No erosions were seen on radiographs, whereas MRI showed erosion-like changes, low grade bone marrow oedema and low-moderate synovial enhancement. The DCE-MRI parameters were stable (baseline scores, variability) (mean ± st.dev); in whole wrist analysis, ME{sub mean} (1.3 ± 0.07, −0.08 ± 0.1 at week 24) and IRE{sub mean} (0.008 ± 0.004, −0.002 ± 0.005 at week 12 and 24). In the rough wrist ROI, ME{sub mean} (1.2 ± 0.07, 0.04 ± 0.02 at week 52) and IRE{sub mean} (0.001 ± 0.0008, 0.0006 ± 0.0009 at week 52) and precise wrist ROI, ME{sub mean} (1.2 ± 0.09, 0.04 ± 0.04 at week 52) and IRE{sub mean} (0.001 ± 0.0008, 0.0008 ± 0.001 at week 24 and 52). The Dynamic parameters obtained using fully automated analysis demonstrated strong, statistically significant correlations with RAMRIS synovitis scores. Conclusion: The study demonstrated that contrast enhancement does occur in

  7. Measuring tongue volumes and visualizing the chewing and swallowing process using real-time TrueFISP imaging - initial clinical experience in healthy volunteers and patients with acromegaly

    International Nuclear Information System (INIS)

    Ajaj, W.; Goyen, M.; Herrmann, B.; Massing, S.; Goehde, S.; Lauenstein, T.; Ruehm, S.G.

    2005-01-01

    This study assessed both two-dimensional (2D) TrueFISP imaging for quantifying tongue volume and real-time TrueFISP imaging for evaluating chewing and swallowing in healthy volunteers and patients with acromegaly. In 50 healthy volunteers, tongue volumes were measured using a 2D TrueFISP sequence. Chewing and swallowing were visualized using a real-time TrueFISP sequence. Ten patients with acromegaly were examined twice with the same magnetic resonance imaging protocol: once prior to therapy and a second time 6 months after therapy. Prior to therapy, healthy volunteers had an average tongue volume of 140 ml for men and 90 ml for women, and patients with acromegaly had an average tongue volume of 180 ml for men and 145 ml for women. However, 6 months after therapy the mean tongue volumes in patients with acromegaly had decreased to 154 ml in the men and to 125 ml in the women. The chewing and swallowing process was normal in all volunteers. Prior to therapy, just two patients showed a chewing and swallowing pathology, which disappeared after therapy. Patients with acromegaly had larger tongue volumes than healthy volunteers, and TrueFISP imaging proved feasible for visualizing chewing and swallowing in real time and is capable of detecting possible pathologies. Furthermore, TrueFISP imaging can be used to monitor therapeutic approaches in patients with acromegaly. (orig.)

  8. Measuring tongue volumes and visualizing the chewing and swallowing process using real-time TrueFISP imaging - initial clinical experience in healthy volunteers and patients with acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Ajaj, W.; Goyen, M.; Herrmann, B.; Massing, S.; Goehde, S.; Lauenstein, T.; Ruehm, S.G. [University Hospital, Department of Diagnostic and Interventional Radiology, Essen (Germany)

    2005-05-01

    This study assessed both two-dimensional (2D) TrueFISP imaging for quantifying tongue volume and real-time TrueFISP imaging for evaluating chewing and swallowing in healthy volunteers and patients with acromegaly. In 50 healthy volunteers, tongue volumes were measured using a 2D TrueFISP sequence. Chewing and swallowing were visualized using a real-time TrueFISP sequence. Ten patients with acromegaly were examined twice with the same magnetic resonance imaging protocol: once prior to therapy and a second time 6 months after therapy. Prior to therapy, healthy volunteers had an average tongue volume of 140 ml for men and 90 ml for women, and patients with acromegaly had an average tongue volume of 180 ml for men and 145 ml for women. However, 6 months after therapy the mean tongue volumes in patients with acromegaly had decreased to 154 ml in the men and to 125 ml in the women. The chewing and swallowing process was normal in all volunteers. Prior to therapy, just two patients showed a chewing and swallowing pathology, which disappeared after therapy. Patients with acromegaly had larger tongue volumes than healthy volunteers, and TrueFISP imaging proved feasible for visualizing chewing and swallowing in real time and is capable of detecting possible pathologies. Furthermore, TrueFISP imaging can be used to monitor therapeutic approaches in patients with acromegaly. (orig.)

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

    Science.gov (United States)

    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.

  10. Wood smoke in a controlled exposure experiment with human volunteers

    DEFF Research Database (Denmark)

    Riddervold, Ingunn Skogstad; Bønløkke, Jakob Hjort; Mølhave, Lars

    2011-01-01

    Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung...... function and normal bronchial reactivity were randomly exposed for 3h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions.......0007), “irritative body perceptions” (p = 0.0127), “psychological/neurological effects” (p = 0.0075) and “weak inflammatory responses” (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating...

  11. Evaluation of Pulmonary Hypertension with CMR: Pulmonary Hypertension 
Patients and Healthy Volunteers Control Study

    Directory of Open Access Journals (Sweden)

    Meng WANG

    2016-05-01

    Full Text Available Background and objective The clinical course of pulmonary hypertension (PH is one of progressive deterioration interspersed with episodes of acute decompensation. It is difficult to predict when patients will die because death may come either suddenly or slowly due to progressive heart failure. The aim of this study is to investigate morphology, function and hemodynamics in PH, compared with healthy people, and to investigate the clinical value of detection of PH by use of cardiac magnetic resonance (CMR parameters. Methods CMR was performed in 56 PH patients collected from Tianjin Medical University General Hospital from January 2012 to December 2014 and 22 healthy controls. The following parameters were calculated: right ventricle (RV end-diastolic volume (EDV, end-systolic volume (ESV, ejection fraction (EF, myocardial mass (MM, RV fractional area change (RVFAC, interventricular septal curvature (CIVS, left ventricular free wall curvature (CFW, and CIVS/CFW, main pulmonary artery (MPA positive peak velocity, maximal area, minimal area and distensibility. Comparisons of CMR measurements between PH patients and controls were analyzed by using the student t-tests. Receiver operating characteristic (ROC curve analysis was used to compare the PH diagnostic abilities for four parameters (MPA positive peak velocity, distensibility, curvature ratio, and RVFAC and combined CMR parameter. P<0.05 was considered significant. Results Compared with healthy controls, RV morphology, function and hemodynamics of PH group declined and deteriorate obviously. The ROC curve analysis showed that among the four parameters distensibility of MPA had the highest AUC value (AUC=0.95. Additionally, combined CMR parameter (positive peak velocity+distensibility+curvature ratio+RVFAC had even higher AUC (AUC=0.988. Conclusion Comprehensive CMR parameters is conducive to accurately reflect the overall state RV-pulmonary circulation in patients with PH.

  12. Day-night variation in heart rate variability changes induced by endotoxaemia in healthy volunteers

    DEFF Research Database (Denmark)

    Alamili, M.; Rosenberg, J; Gögenur, I

    2015-01-01

    /night variation in endotoxaemia-induced changes in HRV. METHODS: A randomized, crossover study with 12 healthy men (age 18-31) was conducted. Endotoxaemia were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg b.w. in two visits (day visit and night visit). At the day visit, endotoxaemia were induced at 12...... at both night and day resulted in a significant depression in HRV parameters high-frequency power (HF), low-frequency power (LF), standard deviation of normal-to-normal (NN) intervals, root mean square of successive differences and proportion of NN50 divided by total number of NNs (P

  13. Nutrition studies with human volunteers, designs and compliance to good clinical practice

    NARCIS (Netherlands)

    Schaafsma, G.

    2002-01-01

    In vitro experiments with cell cultures, studies with the TNO gastrointestinal model, animal experiments, and studies with human volunteers are used in nutrition research on the assessment of efficacy and safety of ingredients that can be used as bio actives in functional foods, functional drinks

  14. The Human Volunteer in Military Biomedical Research (Military Medical Ethics. Volume 2, Chapter 19)

    Science.gov (United States)

    2002-10-01

    justice have long been associated with social practices such as punishment, taxation and political The Human Volunteer in Military Biomedical Research...suspension of eligibility to receive research funding, to use investigational interventions, or to practise medicine. Unless there are persuasive reasons to do

  15. Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers.

    Science.gov (United States)

    Liu, Alex H; Bondonno, Catherine P; Croft, Kevin D; Puddey, Ian B; Woodman, Richard J; Rich, Lisa; Ward, Natalie C; Vita, Joseph A; Hodgson, Jonathan M

    2013-11-30

    An increase in nitrate intake can augment circulating nitrite and nitric oxide. This may lead to lower blood pressure and improved vascular function. Green leafy vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women. Twenty-six participants aged 38-69years were recruited to a randomized controlled cross-over trial. The acute effects of two energy-matched (2000kJ) meals, administered in random order, were compared. The meals were either high nitrate (220mg of nitrate derived from spinach [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal and at specific time points up to 210min post meal. Spinach resulted in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal (Pnitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women. If sustained, these effects could contribute to better cardiovascular health. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Corneal clarity measurements in healthy volunteers across different age groups: Observational study.

    Science.gov (United States)

    Alzahrani, Khaled; Carley, Fiona; Brahma, Arun; Morley, Debbie; Hillarby, M Chantal

    2017-11-01

    The aim of this study was to standardize and investigate the changes in corneal clarity with age. Densitometry software for the Oculus Pentacam was used to examine corneal clarity at different age groups.A total of 192 eyes from 97 healthy participants were included in this cohort comparative nonrandomized, cross-sectional study. An Oculus Pentcam was used to image the cornea of healthy participants grouped by age (between 10 and 70 years old). Data from the densitometry output have been used to determine clarity in concentric zones and different depths of the cornea.Corneal densitometry (CD) across all ages showed significant differences between groups when divided into the following layers: anterior, central, and posterior or divided into 0 to 2, 2 to 6, and 6 to 10 mm concentric zones (P age in all 3 layers of the periphery (6-10 mm) (P age group had lower clarity than the 20 to 30-age group (P age is differed when the cornea is divided into layers and zones. This study suggests that there are other factors that may play an essential role in corneal clarity as well as age.

  17. Recognition of visual stimuli and memory for spatial context in schizophrenic patients and healthy volunteers.

    Science.gov (United States)

    Brébion, Gildas; David, Anthony S; Pilowsky, Lyn S; Jones, Hugh

    2004-11-01

    Verbal and visual recognition tasks were administered to 40 patients with schizophrenia and 40 healthy comparison subjects. The verbal recognition task consisted of discriminating between 16 target words and 16 new words. The visual recognition task consisted of discriminating between 16 target pictures (8 black-and-white and 8 color) and 16 new pictures (8 black-and-white and 8 color). Visual recognition was followed by a spatial context discrimination task in which subjects were required to remember the spatial location of the target pictures at encoding. Results showed that recognition deficit in patients was similar for verbal and visual material. In both schizophrenic and healthy groups, men, but not women, obtained better recognition scores for the colored than for the black-and-white pictures. However, men and women similarly benefited from color to reduce spatial context discrimination errors. Patients showed a significant deficit in remembering the spatial location of the pictures, independently of accuracy in remembering the pictures themselves. These data suggest that patients are impaired in the amount of visual information that they can encode. With regards to the perceptual attributes of the stimuli, memory for spatial information appears to be affected, but not processing of color information.

  18. Volunteer feedback and perceptions after participation in a phase I, first-in-human Ebola vaccine trial: An anonymous survey.

    Directory of Open Access Journals (Sweden)

    Julie-Anne Dayer

    Full Text Available The continued participation of volunteers in clinical trials is crucial to advances in healthcare. Few data are available regarding the satisfaction and impressions of healthy volunteers after participation in phase I trials, many of which lead to unexpected adverse events. We report feedback from over 100 adult volunteers who took part in a first-in-human trial conducted in a high-income country testing an experimental Ebola vaccine causing significant reactogenicity, as well as unexpected arthritis in one fifth of participants. The anonymous, internet-based satisfaction survey was sent by email to all participants upon their completion of this one-year trial; it asked 24 questions concerning volunteers' motivations, impressions of the trial experience, and overall satisfaction. Answers were summarized using descriptive statistics. Of the 115 trial participants, 103 (90% filled out the survey. Fifty-five respondents (53% were male. Thirty-five respondents (34% were healthcare workers, many of whom would deploy to Ebola-affected countries. All respondents cited scientific advancement as their chief motivation for participation, while 100/103 (97% and 61/103 (59% reported additional "humanitarian reasons" and potential protection from Ebolavirus, respectively. Although investigators had documented adverse events in 97% of trial participants, only 74 of 103 respondents (72% recalled experiencing an adverse event. All reported an overall positive experience, and 93/103 (90% a willingness to participate in future trials. Given the high level of satisfaction, no significant associations could be detected between trial experiences and satisfaction, even among respondents reporting adverse events lasting weeks or months. Despite considerable reactogenicity and unexpected vaccine-related arthritis, all survey respondents reported overall satisfaction. While this trial's context was unique, the positive feedback is likely due at least in part to the

  19. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  20. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers : A Double-Blind Sham-Controlled Crossover Study

    NARCIS (Netherlands)

    Kortekaas, R.; van Nierop, L.E.; Baas, V.G.; Konopka, K.H.; Harbers, M.; van der Hoeven, J.H.; van Wijhe, M.; Aleman, A.; Maurits, N.M.

    2013-01-01

    The 'complex neural pulse'(TM) (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a

  1. Activation of coagulation and inhibition of fibrinolysis in the lung after inhalation of lipopolysaccharide by healthy volunteers

    NARCIS (Netherlands)

    Maris, Nico A.; de Vos, Alex F.; Bresser, Paul; van der Zee, Jaring S.; Meijers, Joost C.; Lijnen, H. Roger; Levi, Marcel; Jansen, Henk M.; van der Poll, Tom

    2005-01-01

    Pneumonia is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. To determine the effect of lipopolysaccharide (LPS) on the hemostatic balance in the human lung, six healthy subjects inhaled nebulized LPS or saline in a randomized cross-over study and

  2. Presence of human papillomavirus in semen of healthy men is firmly associated with HPV infections of the penile epithelium

    NARCIS (Netherlands)

    Luttmer, Roosmarijn; Dijkstra, Maaike G.; Snijders, Peter J. F.; Jordanova, Ekaterina S.; King, Audrey J.; Pronk, Divera T. M.; Foresta, Carlo; Garolla, Andrea; Hompes, Peter G. A.; Berkhof, Johannes; Bleeker, Maaike C. G.; Doorbar, John; Heideman, Daniëlle A. M.; Meijer, Chris J. L. M.

    2015-01-01

    To study the source of human papillomavirus (HPV) in semen. Observational study (CCMO-NL3248800010). Academic hospital-based laboratory. Healthy male volunteers (n = 213). One penile scrape and three semen samples were obtained per participant for HPV-DNA testing by both GP5+/6+ polymerase chain

  3. Modafinil improves attentional performance in healthy, non-sleep deprived humans at doses not inducing hyperarousal across species

    NARCIS (Netherlands)

    Cope, Zackary A; Minassian, Arpi; Kreitner, Dustin; MacQueen, David A; Milienne-Petiot, Morgane; Geyer, Mark A; Perry, William; Young, Jared W

    2017-01-01

    The wake-promoting drug modafinil is frequently used off-label to improve cognition in psychiatric and academic populations alike. The domain-specific attentional benefits of modafinil have yet to be quantified objectively in healthy human volunteers using tasks validated for comparison across

  4. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Directory of Open Access Journals (Sweden)

    Neelkamal Chaudhary

    2010-02-01

    Full Text Available Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H1-T(H17 and destructive allergic (T(H2 immunity. How Aspergillus allergens (Asp f proteins participate in the development of allergic sensitization is unknown.To determine whether Asp f proteins are strictly associated with T(H2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17 to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H1-responses to Asp f3 (a putative peroxismal membrane protein, Asp f9/16 (cell wall glucanase, Asp f11 (cyclophilin type peptidyl-prolyl isomerase and Asp f22 (enolase. Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals.Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  5. Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking.

    Science.gov (United States)

    Parente, Alexandre C B V; Garcia-Leal, Cybele; Del-Ben, Cristina M; Guimarães, Francisco S; Graeff, Frederico G

    2005-12-01

    Drug-free symptomatic panic patients, drug-treated nonsymptomatic patients and healthy controls were submitted to simulated public speaking. Subjective anxiety, cognitive impairment and discomfort measured by the visual analog mood scale as well as skin conductance level were higher in symptomatic patients than in controls at the beginning of the experimental session, nonsymptomatic patients lying in between. Subjective sedation, spontaneous fluctuations of skin conductance, heart rate and blood pressure were similar in the three groups. Preparation and performance of speech decreased sedation while increasing anxiety, cognitive impairment, level and fluctuations of skin conductance, heart rate and blood pressure. Anxiety, cognitive impairment and conductance level were less increased in symptomatic patients than in controls. Electrodermal activity, but not cardiovascular measures of sympathetic arousal correlated with anticipatory anxiety. Chronic treatment with serotonin uptake inhibitors attenuated the differences between panic patients and controls, supporting the participation of serotonin in panic disorder.

  6. Lack of effect of norepinephrine on cranial haemodynamics and headache in healthy volunteers

    DEFF Research Database (Denmark)

    Lindholt, M; Petersen, K A; Tvedskov, J F

    2009-01-01

    Stress is a provoking factor for both tension-type headache and migraine attacks. In the present single-blind study, we investigated if stress induced by norepinephrine (NE) could elicit delayed headache in 10 healthy subjects and recorded the cranial arterial responses. NE at a dose of 0...... no changes in these arterial parameters after NE. In both treatment groups three subjects developed delayed headaches. Thus, stress by NE infusion did not result in delayed headache........025 microg kg(-1) min(-1) or placebo was infused for 90 min and the headache was followed for 14 h. Blood flow velocity in the middle cerebral artery (measured with transcranial Doppler) and diameters of the temporal artery and the radial artery (measured with ultrasound) were followed for 2 h. There were...

  7. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants

    Science.gov (United States)

    Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-01-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP. PMID:23685775

  8. Seroprevalence of Hepatitis B and C Infections among Healthy Volunteer Blood Donors in the Central California Valley.

    Science.gov (United States)

    Sheikh, Muhammad Y; Atla, Pradeep R; Ameer, Adnan; Sadiq, Humaira; Sadler, Patrick C

    2013-01-01

    The Central California Valley has a diverse population with significant proportions of Hispanics and Asians. This cross-sectional study was conducted to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in healthy blood donors in the Valley. A total of 217,738 voluntary blood donors were identified between 2006 and 2010 (36,795 first-time donors; 180,943 repeat donors). Among the first-time donors, the HBV and HCV prevalence was 0.28% and 0.52%, respectively. Higher HBV prevalence seen in Asians (3%) followed by Caucasians (0.05%), African Americans (0.15%), and Hispanics (0.05%). Hmong had a HBV prevalence of 7.63% with a peak prevalence of 8.76% among the 16- to 35-year-old age group. Highest HCV prevalence in Native Americans (2.8) followed by Caucasians (0.59%), Hispanics (0.45%), African Americans (0.38%), and Asians (0.2%). Ethnic disparities persist with regard to the prevalence of HBV and HCV in the Central California Valley. The reported prevalence may be an underestimate because our study enrolled healthy volunteer blood donors only. The development of aggressive public health measures to evaluate the true prevalence of HBV and HCV and to identify those in need of HBV and HCV prevention measures and therapy is critically important.

  9. Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers.

    Science.gov (United States)

    Del Bó, Cristian; Simonetti, Paolo; Gardana, Claudio; Riso, Patrizia; Lucchini, Giorgio; Ciappellano, Salvatore

    2013-03-01

    This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly (p ≤ 0.05) reduced serum levels of total and low-density lipoprotein cholesterol ( - 6.2% and - 9.1%, respectively) and transferrin ( - 4.6%). Total n - 3, long chain polyunsaturated fatty acids n - 3 and docosahexeanoic acid content in erythrocytes increased (p ≤ 0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n - 3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects.

  10. The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Fariborz Mobarrez

    Full Text Available BACKGROUND: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs and circulating microparticles (MPs following the smoking of one cigarette by young, healthy intermittent smokers. MATERIALS AND METHODS: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. RESULTS: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin. CD144 (VE-cadherin or HMGB1 release did not significantly change during active smoking. CONCLUSION: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

  11. Effects of experimental insoles on body posture, mandibular kinematics and masticatory muscles activity. A pilot study in healthy volunteers.

    Science.gov (United States)

    Marini, Ida; Alessandri Bonetti, Giulio; Bortolotti, Francesco; Bartolucci, Maria Lavinia; Gatto, Maria Rosaria; Michelotti, Ambra

    2015-06-01

    It has been hypothesized that different plantar sensory inputs could influence the whole body posture and dental occlusion but there is a lack of evidence on this possible association. To investigate the effects of experimental insoles redistributing plantar pressure on body posture, mandibular kinematics and electromyographic (EMG) activity of masticatory muscles on healthy subjects. A pilot study was conducted on 19 healthy volunteers that wore custom-made insoles normalizing the plantar pressure distribution for 2 weeks. Body posture parameters were measured by means of an optoelectronic stereophotogrammetric analysis; mandibular kinematics was analyzed by means of gothic arch tracings; superficial EMG activity of head and neck muscles was performed. Measurements were carried out 10 days before the insertion of the insoles, immediately before the insertion, the day after, 7 and 14 days after, in four different exteroceptive conditions. The outcomes of the present study show that insoles do not modify significantly over time the parameters of body posture, SEMG activity of head and neck muscles and mandibular kinematics. In this pilot study the experimental insoles did not significantly influence the body posture, the mandibular kinematics and the activity of masticatory muscles during a 14-day follow up period. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants.

    Science.gov (United States)

    Ibáñez, Agustín; Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-07-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers.

    Science.gov (United States)

    Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Okada, Hiroki; Watari, Jiro; Miwa, Hiroto

    2015-07-01

    We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men. We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay. Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P heartburn and esophageal levels of PGE2 (r = 0.53; P heartburn vs PGE2). Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Assessing the Metabolic Effects of Aromatherapy in Human Volunteers

    Directory of Open Access Journals (Sweden)

    Yinan Zhang

    2013-01-01

    Full Text Available Aromatherapy, a form of complementary and alternative medicine (CAM that uses essential oils through inhalation, is believed to enhance physical and spiritual conditions. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of aromatherapy in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive metabolomics study that reveals metabolic changes in people after exposed to aroma inhalation for 10 continuous days. In this study, the metabolic alterations in urine of 31 females with mild anxiety symptoms exposed to aerial diffusion of aromas were measured by GC-TOF-MS and UPLC-Q-TOF-MS analyses. A significant alteration of metabolic profile in subjects responsive to essential oil was found, which is characterized by the increased levels of arginine, homocysteine, and betaine, as well as decreased levels of alcohols, carbohydrates, and organic acids in urine. Notably, the metabolites from tricarboxylic acid (TCA cycle and gut microbial metabolism were significantly altered. This study demonstrates that the metabolomics approach can capture the subtle metabolic changes resulting from exposure to essential oils, which may lead to an improved mechanistic understanding of aromatherapy.

  15. Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers

    Science.gov (United States)

    Riba, Jordi; Anderer, Peter; Morte, Adelaida; Urbano, Gloria; Jané, Francesc; Saletu, Bernd; Barbanoj, Manel J

    2002-01-01

    Aims Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and β-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity. Methods Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg−1 body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Results Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were −20.20±15.23 µV2 and −2.70±2.21 µV2 for total power and theta power, respectively. Relative power decreased in the delta (−1.20±1.31% after 120 min at P3) and theta (−3.30±2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00±0.88% after 90 min at P

  16. The oral bioavailability of nitrate from vegetables investigated in healthy volunteers

    NARCIS (Netherlands)

    Lambers AC; Kortboyer JM; Schothorst RC; Sips AJAM; Cleven RFMJ; Meulenbelt J; VIC; LBM; ARO; LAC

    2000-01-01

    The major source of human nitrate exposure comes from vegetables. Several studies were performed to estimate the total daily dietary nitrate intake based on the nitrate contents of food and drinking water. However, only nitrate that is absorbed from the gastro-intestinal tract may contribute to

  17. Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Beck-Nielsen, Henning; Højlund, Kurt

    2011-01-01

    Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective...

  18. Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers

    NARCIS (Netherlands)

    Vissers, M.N.; Zock, P.L.; Wiseman, S.A.; Meyboom, S.; Katan, M.B.

    2001-01-01

    Objective: We studied whether consumption of phenol-rich extra virgin olive oil affects the susceptibility of low density lipoproteins (LDL) to oxidation and other markers of oxidation in humans. Design: Randomized cross-over intervention trial, stratified according to sex, age and energy intake.

  19. Human volunteer studies with non-pharmaceutical chemicals: metabolism and pharmacokinetic studies.

    Science.gov (United States)

    Wilks, M F; Woollen, B H

    1994-06-01

    1. Human volunteer studies are an essential part of drug development but their use in the area of non-pharmaceutical chemicals has so far been very limited. Such studies can have considerable value in the assessment and improvement of the safe use of chemicals. 2. Once metabolic pathways and target metabolites have been identified in volunteers this information can be used in studies in the workplace or in the general population. Studies should be performed selectively only if there is both a toxic hazard and a significant exposure potential. In addition, they should only be carried out if the required information cannot be obtained in any other way. 3. Volunteer studies with non-pharmaceuticals have become increasingly acceptable in the light of established international guidelines, no-fault compensation, improvements in study design and technical developments which allow the use of very low dose levels. The final decision on whether to carry out a study must always rest with an independent ethical committee. 4. The practical aspects of the study should be specified in a detailed protocol conforming with the principles of good clinical practice. The safety of volunteers must be of paramount concern throughout. Depending on the nature of the chemical and the study, it may be advisable to carry out studies in a clinical facility where equipment is available for the treatment of any emergencies that might occur. 5. Numerous investigators have now shown that human volunteer studies are ethically acceptable, practicable and yield important information. The risk to volunteers is minimal and this approach can lead to an improved foundation for occupational hygiene standards, more accurate risk assessment and thus better protection of the workforce and the general population.

  20. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

    Science.gov (United States)

    Hanley, Michael J; Masse, Gina; Harmatz, Jerold S; Cancalon, Paul F; Dolnikowski, Gregory G; Court, Michael H; Greenblatt, David J

    2013-01-01

    Aim The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9). Methods A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ. Results BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03). Conclusion The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9. PMID:22943633

  1. A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

    Science.gov (United States)

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

    2016-07-01

    Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  4. Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers.

    Science.gov (United States)

    Schantz, Daryl I; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B; Seed, Mike; Grosse-Wortmann, Lars

    2016-10-01

    Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (PHydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a "variable" that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient.

  5. Effects of Mangifera indica (Careless) on Microcirculation and Glucose Metabolism in Healthy Volunteers.

    Science.gov (United States)

    Buchwald-Werner, Sybille; Schön, Christiane; Frank, Sonja; Reule, Claudia

    2017-07-01

    A commercial Mangifera indica fruit powder (Careless) showed beneficial acute effects on microcirculation in a randomized, double-blind, crossover pilot study. Here, long-term effects on microcirculation and glucose metabolism were investigated in a double-blind, randomized, placebo-controlled, 3-arm parallel-design study in healthy individuals. A daily dose of 100 mg or 300 mg of the fruit powder was compared to placebo after supplementation for 4 weeks. Microcirculation and endothelial function were assessed by the Oxygen-to-see System and pulse amplitude tonometry, respectively. Glucose metabolism was assessed under fasting and postprandial conditions by capillary glucose and HbA1c values.Microcirculatory reactive hyperemia flow increased, especially in the 100 mg group (p = 0.025). The 300 mg of the M. indica fruit preparation reduced postprandial glucose levels by trend if compared to placebo (p = 0.0535) accompanied by significantly lower HbA1c values compared to baseline. Furthermore, 300 mg intake significantly improved postprandial endothelial function in individuals with decreased endothelial function after high-dose glucose intake (p = 0.0408; n = 11).In conclusion, the study suggests moderate beneficial effects of M. indica fruit preparation on microcirculation, endothelial function, and glucose metabolism. Georg Thieme Verlag KG Stuttgart · New York.

  6. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 ± 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning

  7. Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.

    Science.gov (United States)

    Luiking, Yvette C; Engelen, Mariëlle P K J; Soeters, Peter B; Boirie, Yves; Deutz, Nicolaas E P

    2011-02-01

    Dietary protein intake is known to affect whole body and interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate casein and soy meals have a different effect on skeletal muscle protein and amino acid kinetics in healthy young subjects. Muscle protein and amino acid kinetics were measured in the postabsorptive state and during 4-h enteral intake of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope and muscle biopsy techniques were used to study metabolic effects. The net uptake of glutamate, serine, histidine, and lysine across the leg was larger during CAPM than during SOPM intake. Muscle concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA changed differently after CAPM and SOPM (P CAPM and SOPM, but differences in their (net) breakdown rates were not significant. Muscle protein synthesis was not different between CAPM and SOPM. Moderate-nitrogen casein and soy protein meals differently alter leg amino acid uptake without a significant difference in influencing acute muscle protein metabolism. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sarker, Shafiqul Alam, E-mail: sasarker@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); McCallin, Shawna; Barretto, Caroline [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Berger, Bernard, E-mail: bernard.berger@rdls.nestle.com [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Pittet, Anne-Cecile [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Sultana, Shamima, E-mail: shamima@icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Krause, Lutz, E-mail: ltz.krause@gmail.com [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Huq, Sayeda, E-mail: sayeeda@mail.icddrb.org [International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212 (Bangladesh); Bibiloni, Rodrigo, E-mail: Rodrigo.Bibiloni@agresearch.co.nz [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bruttin, Anne, E-mail: anne.bruttin@rdls.nestle.com [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Reuteler, Gloria, E-mail: gloria.reuteler@rdls.nestle.com [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Bruessow, Harald, E-mail: harald.bruessow@rdls.nestle.com [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

    2012-12-20

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

  9. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 {+-} 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning.

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

    Science.gov (United States)

    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

  11. The oral bioavailability of nitrate from vegetables investigated in healthy volunteers

    OpenAIRE

    Lambers AC; Kortboyer JM; Schothorst RC; Sips AJAM; Cleven RFMJ; Meulenbelt J; VIC; LBM; ARO; LAC

    2000-01-01

    The major source of human nitrate exposure comes from vegetables. Several studies were performed to estimate the total daily dietary nitrate intake based on the nitrate contents of food and drinking water. However, only nitrate that is absorbed from the gastro-intestinal tract may contribute to the toxicity of nitrate in the body. At present no data are available on the bioavailability of nitrate from vegetables. Therefore the present study was performed to evaluate the oral bioavailability o...

  12. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers

    OpenAIRE

    Louis, Mariam; Punjabi, Naresh M.

    2009-01-01

    Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize th...

  13. Whole-body magnetic resonance imaging of healthy volunteers. Pilot study results from the population-based SHIP study

    Energy Technology Data Exchange (ETDEWEB)

    Hegenscheid, K.; Kuehn, J.P.; Hosten, N.; Puls, R. [Inst. fuer Diagnostische Radiologie und Neuroradiologie, Universitaetsklinikum der Ernst-Moritz-Arndt-Univ. Greifswald (Germany); Voelzke, H. [Inst. fuer Community Medicine, Universitaetsklinikum der Ernst-Moritz-Arndt-Univ. Greifswald (Germany); Biffar, R. [Zentrum fuer Zahn-, Mund- und Kieferheilkunde, Universitaetsklinikum der Ernst-Moritz-Arndt-Univ. Greifswald (Germany)

    2009-08-15

    Purpose: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. Materials and Methods: The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MR1 and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. Results: One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (K = 0.799) (orig.)

  14. Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.

    Science.gov (United States)

    Gilleen, J; Michalopoulou, P G; Reichenberg, A; Drake, R; Wykes, T; Lewis, S W; Kapur, S

    2014-04-01

    Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  15. Sex differences in itch perception and modulation by distraction--an FMRI pilot study in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Astrid Stumpf

    Full Text Available BACKGROUND: Even though itch is a common syndrome of many diseases there is only little knowledge about sex and gender differences in pruritus, especially in central itch perception and modulation. To our knowledge, this is the first fMRI study examining sex differences in perception and its modulation by distraction. METHODS: Experimental itch was induced by application of histamine (0.1 mM via microdialysis fibers twice at the left forearm and twice at the left lower leg in 33 healthy volunteers (17 females, 16 males. The brain activation patterns were assessed by fMRI during itch without and with distraction (Stroop task. Between the various conditions, subjects were asked to rate itch intensity, desire to scratch and pain intensity. In a second experiment in 10 of the 33 volunteers histamine was replaced by saline solution to serve as control for the 'Stroop' condition. RESULTS: Women generally presented higher itch intensities compared to men during itch over the course of the experiment. A more specific analysis revealed higher itch intensities and desire to scratch in women during experimental induced itch that can be reduced by distraction at the lower legs when itch is followed by 'Stroop'. In contrast, men depicted significant reduction of 'itch' by 'Stroop' at the forearms. Women depicted higher brain activation of structures responsible for integration of sensory, affective information and motor integration/planning during 'itch' and 'Stroop' condition when compared to men. No sex differences were seen in the saline control condition. CONCLUSION: Women and men exhibited localisation dependent differences in their itch perception with women presenting higher itch intensities and desire to scratch. Our findings parallel clinical observations of women reporting higher itch intensities depending on itch localisation and suffering more from itch as compared to men.

  16. Whole-body magnetic resonance imaging of healthy volunteers. Pilot study results from the population-based SHIP study

    International Nuclear Information System (INIS)

    Hegenscheid, K.; Kuehn, J.P.; Hosten, N.; Puls, R.; Voelzke, H.; Biffar, R.

    2009-01-01

    Purpose: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. Materials and Methods: The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MR1 and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. Results: One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (K = 0.799) (orig.)

  17. Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Schantz, Daryl I. [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); University of Manitoba, Variety Children' s Heart Centre, Winnipeg, MB (Canada); Dragulescu, Andreea [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); Memauri, Brett [University of Manitoba, Department of Radiology, St. Boniface General Hospital, Winnipeg, MB (Canada); Grotenhuis, Heynric B. [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); Wilhelmina Children' s Hospital, Utrecht (Netherlands); Seed, Mike; Grosse-Wortmann, Lars [The Hospital for Sick Children, The Labatt Family Heart Centre in the Department of Paediatrics, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

    2016-10-15

    Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a ''variable'' that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient. (orig.)

  18. Day-night variation in heart rate variability changes induced by endotoxaemia in healthy volunteers.

    Science.gov (United States)

    Alamili, M; Rosenberg, J; Gögenur, I

    2015-04-01

    Morbidity and mortality in response to sepsis may be dependent on clock time for the initiation of sepsis. Endotoxaemia, an experimental model for systemic inflammation, induces alterations in sympatico-vagal balance in the autonomic nervous system (ANS). The activity of sympathetic and parasympathetic activity can be estimated by measuring heart rate variability (HRV). Based on the intimate link between ANS and the inflammatory response, we hypothesized, that HRV changes seen during endotoxaemia would be different based on time of the day the endotoxaemia is initiated. We investigated day/night variation in endotoxaemia-induced changes in HRV. A randomized, crossover study with 12 healthy men (age 18-31) was conducted. Endotoxaemia were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg b.w. in two visits (day visit and night visit). At the day visit, endotoxaemia were induced at 12:00 h, and at the night visit it was induced at 24:00 h. Holter recordings were started 1 h before administration of LPS, and continued for 10 h. Time-domain and frequency-domain parameters of HRV were analysed. A total of nine persons finished the study with valid recordings. Endotoxaemia at both night and day resulted in a significant depression in HRV parameters high-frequency power (HF), low-frequency power (LF), standard deviation of normal-to-normal (NN) intervals, root mean square of successive differences and proportion of NN50 divided by total number of NNs (Pnight-time endotoxaemia, a more pronounced depression of LF, HF and SDNN (Pday-time endotoxaemia. Endotoxaemia induced changes in HRV exhibit a day-night difference. This difference may have clinical consequences in patients with sepsis. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers

    Science.gov (United States)

    Lee, Jieon; Lee, Howard; Jang, Kyungho; Lim, Kyoung Soo; Shin, Dongseong; Yu, Kyung-Sang

    2014-01-01

    Purpose Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug–drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. Patients and methods Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. Results A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUClast for cilnidipine with and without valsartan was 1.04 (0.98–1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUClast for valsartan with and without cilnidipine was 0.94 (0.83–1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. Conclusion Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated. PMID:25336921

  20. Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers

    International Nuclear Information System (INIS)

    Schantz, Daryl I.; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B.; Seed, Mike; Grosse-Wortmann, Lars

    2016-01-01

    Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a ''variable'' that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient. (orig.)

  1. Experimental orofacial pain and sensory deprivation lead to perceptual distortion of the face in healthy volunteers.

    Science.gov (United States)

    Dagsdóttir, Lilja Kristín; Skyt, Ina; Vase, Lene; Baad-Hansen, Lene; Castrillon, Eduardo; Svensson, Peter

    2015-09-01

    Patients suffering from persistent orofacial pain may sporadically report that the painful area feels "swollen" or "differently," a phenomenon that may be conceptualized as a perceptual distortion because there are no clinical signs of swelling present. Our aim was to investigate whether standardized experimental pain and sensory deprivation of specific orofacial test sites would lead to changes in the size perception of these face areas. Twenty-four healthy participants received either 0.2 mL hypertonic saline (HS) or local anesthetics (LA) into six regions (buccal, mental, lingual, masseter muscle, infraorbital and auriculotemporal nerve regions). Participants estimated the perceived size changes in percentage (0 % = no change, -100 % = half the size or +100 % = double the size), and somatosensory function was checked with tactile stimuli. The pain intensity was rated on a 0-10 Verbal Numerical Rating Scale (VNRS), and sets of psychological questionnaires were completed. HS and LA were associated with significant self-reported perceptual distortions as indicated by consistent increases in perceived size of the adjacent face areas (P ≤ 0.050). Perceptual distortion was most pronounced in the buccal region, and the smallest increase was observed in the auriculotemporal region. HS was associated with moderate levels of pain VNRS = 7.3 ± 0.6. Weak correlations were found between HS-evoked perceptual distortion and level of dissociation in two regions (P pain and transient sensory deprivation evoked perceptual distortions in all face regions and overall demonstrated the importance of afferent inputs for the perception of the face. We propose that perceptual distortion may be an important phenomenon to consider in persistent orofacial pain conditions.

  2. Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.

    Science.gov (United States)

    Gelal, Ayse; Guven, Hulya; Balkan, Dilara; Artok, Levent; Benowitz, Neal L

    2003-09-01

    The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study. Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments. We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

  3. Occupant kinematics in low-speed frontal sled tests: Human volunteers, Hybrid III ATD, and PMHS.

    Science.gov (United States)

    Beeman, Stephanie M; Kemper, Andrew R; Madigan, Michael L; Franck, Christopher T; Loftus, Stephen C

    2012-07-01

    A total of 34 dynamic matched frontal sled tests were performed, 17 low (2.5g, Δv=4.8kph) and 17 medium (5.0g, Δv=9.7kph), with five male human volunteers of approximately 50th percentile height and weight, a Hybrid III 50th percentile male ATD, and three male PMHS. Each volunteer was exposed to two impulses at each severity, one relaxed and one braced prior to the impulse. A total of four tests were performed at each severity with the ATD and one trial was performed at each severity with each PMHS. A Vicon motion analysis system, 12 MX-T20 2 megapixel cameras, was used to quantify subject 3D kinematics (±1mm) (1kHz). Excursions of select anatomical regions were normalized to their respective initial positions and compared by test condition and between subject types. The forward excursions of the select anatomical regions generally increased with increasing severity. The forward excursions of relaxed human volunteers were significantly larger than those of the ATD for nearly every region at both severities. The forward excursions of the upper body regions of the braced volunteers were generally significantly smaller than those of the ATD at both severities. Forward excursions of the relaxed human volunteers and PMHSs were fairly similar except the head CG response at both severities and the right knee and C7 at the medium severity. The forward excursions of the upper body of the PMHS were generally significantly larger than those of the braced volunteers at both severities. Forward excursions of the PMHSs exceeded those of the ATD for all regions at both severities with significant differences within the upper body regions. Overall human volunteers, ATD, and PMHSs do not have identical biomechanical responses in low-speed frontal sled tests but all contribute valuable data that can be used to refine and validate computational models and ATDs used to assess injury risk in automotive collisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Inter-individual variation, seasonal variation and close correlation of OGG1 and ERCC1 mRNA levels in full blood from healthy volunteers

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Møller, Peter; Dragsted, Lars

    2002-01-01

    The mRNA levels of the nucleotide excision DNA repair gene ERCC1 and the base excision DNA repair gene OGG1 were quantified in 43 healthy volunteers in a dietary intervention trial as markers for the DNA repair capacity. Nine samples were collected from each subject over a period of 52 days. Samp...

  5. Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers

    NARCIS (Netherlands)

    Doorn, M. van; Vogels, J.; Tas, A.; Hoogdalem, E.J. van; Burggraaf, J.; Cohen, A.; Greef, J. van der

    2007-01-01

    Aims: To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the

  6. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Moore, K. T.; Castillejos, C. F.; Kubitza, D.; Berkowitz, S. D.; Goldhaber, S. Z.; Raghoebar, M.; Patel, M. R.; Weitz, J. I.; Levy, J. H.

    2014-01-01

    Four-factor prothrombin complex concentrates (PCCs), which contain factor II, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The purpose of this study was to determine whether a three-factor PCC, which contains little FVII, has a

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

    NARCIS (Netherlands)

    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.

    2013-01-01

    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

  8. Right-sided cardiac function in healthy volunteers measured by first-pass radionuclide ventriculography and gated blood-pool SPECT: comparison with cine MRI

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette; Hesse, Birger

    2005-01-01

    for evaluation of right-sided cardiac function. The aim of our study was to compare the agreement between these methods when measuring right-sided cardiac function. METHODS: Twenty-four healthy volunteers were included. Mean age was 44 years (range: 25-60) and 29% were females. All participants had FP, GBPS...

  9. Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers.

    Science.gov (United States)

    Gibbs, Ayana A; Bautista, Carla E; Mowlem, Florence D; Naudts, Kris H; Duka, Theodora

    2013-10-23

    Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

  10. Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.

    Science.gov (United States)

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen; Asghar, Mohammad Sohail; Dahl, Jørgen Berg

    2016-05-31

    Several factors are believed to influence the development and experience of pain. Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R(2) heat stimulation, and thus may be a biomarker of an individual's pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in humans is still incomplete. We therefore find it interesting to investigate if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitization Clinicaltrials

  11. Pharmacokinetic bioequivalence studies of a fixed-dose combination of tamsulosin and dutasteride in healthy volunteers.

    Science.gov (United States)

    Fossler, Michael J; Collins, David A; Thompson, Meg M; Nino, Antonio; Bianco, Joseph J; Chetty, Dushen

    2014-05-01

    The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0