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Human Volunteers (human + volunteer)
Kinds of Human Volunteers Selected AbstractsEFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST-PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Masaki Sanaka SUMMARY 1Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [13C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [13CO2] excretion time () and the time for maximal [13CO2] excretion rate (tlag) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t -test with Bonferroni adjustment. 3The time-course for respiratory [13CO2] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [13CO2] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t -test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t -test). Among the three meals, significant differences were found in (P = 0.002, anova) and tlag (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged (P = 0.007 and P < 0.0001, respectively, Student's t -test) and tlag (P = 0.006 and P = 0.002, respectively, Student's t -test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response. [source] Respiratory Effect of Prolonged Electrical Weapon Application on Human VolunteersACADEMIC EMERGENCY MEDICINE, Issue 3 2007Jeffrey D. Ho MD Background: Conducted electrical weapons (CEWs) are used by law enforcement to subdue combative subjects. Occasionally, subjects will die after a CEW has been used on them. It is theorized that CEWs may contribute to these deaths by impairing respiration. Objectives: To examine the respiratory effects of CEWs. Methods: Human volunteers received a 15-second application of electrical current from a CEW while wearing a respiratory measurement device. Common respiratory parameters were collected before, during, and after exposure. Health histories and demographic information were also collected. Results: Fifty-two subjects were analyzed. Thirty-four underwent a 15-second continuous exposure, and 18 underwent three 5-second burst exposures. In the continuous application group, the baseline mean tidal volume of 1.1 L increased to 1.8 L during application, the baseline end-tidal CO2 level went from 40.5 mm Hg to 37.3 mm Hg after exposure, the baseline end-tidal oxygen level went from 118.7 mm Hg to 121.3 mm Hg after exposure, and the baseline respiratory rate went from 15.9 breaths/min to 16.4 breaths/min after exposure. In the 5-second burst group, the baseline mean tidal volume increased to 1.85 L during application, the baseline end-tidal CO2 level went from 40.9 mm Hg to 39.1 mm Hg after exposure, the baseline end-tidal oxygen level went from 123.1 mm Hg to 127.0 mm Hg after exposure, and the baseline respiratory rate went from 13.8 breaths/min to 14.6 breaths/min after exposure. Conclusions: Prolonged CEW application did not impair respiratory parameters in this population of volunteers. Further study is recommended to validate these findings in other populations. [source] Echocardiographic Evaluation of a TASER-X26 Application in the Ideal Human Cardiac AxisACADEMIC EMERGENCY MEDICINE, Issue 9 2008Jeffrey D. Ho MD Abstract Objectives:, TASER electronic control devices (ECDs) are used by law enforcement to subdue aggressive persons. Some deaths temporally proximate to their use have occurred. There is speculation that these devices can cause dangerous cardiac rhythms. Swine research supports this hypothesis and has reported significant tachyarrhythmias. It is not known if this occurs in humans. The objective of this study was to determine the occurrence of tachyarrhythmias in human subjects subjected to an ECD application. Methods:, This was a prospective, nonblinded study. Human volunteers underwent limited echocardiography before, during, and after a 10-second TASER X26 ECD application with preplaced thoracic electrodes positioned in the upper right sternal border and the cardiac apex. Images were analyzed using M-mode through the anterior leaflet of the mitral valve for evidence of arrhythmia. Heart rate (HR) and the presence of sinus rhythm were determined. Data were analyzed using descriptive statistics. Results:, A total of 34 subjects were enrolled. There were no adverse events reported. The mean HR prior to starting the event was 108.7 beats/min (range 65 to 146 beats/min, 95% CI = 101.0 to 116.4 beats/min). During the ECD exposure, the mean HR was 120.1 beats/min (range 70 to 158 beats/min, 95% CI = 112.2 to 128.0 beats/min) and a mean of 94.1 beats/min (range 55 to 121 beats/min, 95% CI = 88.4 to 99.7 beats/min) at 1 minute after ECD exposure. Sinus rhythm was clearly demonstrated in 21 (61.7%) subjects during ECD exposure (mean HR 121.4 beats/min; range 75 to 158 beats/min, 95% CI = 111.5 to 131.4). Sinus rhythm was not clearly demonstrated in 12 subjects due to movement artifact (mean HR 117.8 beats/min, range 70 to 152 beats/min, 95% CI = 102.8 to 132.8 beats/min). Conclusions:, A 10-second ECD exposure in an ideal cardiac axis application did not demonstrate concerning tachyarrhythmias using human models. The swine model may have limitations when evaluating ECD technology. [source] Respiratory Effect of Prolonged Electrical Weapon Application on Human VolunteersACADEMIC EMERGENCY MEDICINE, Issue 3 2007Jeffrey D. Ho MD Background: Conducted electrical weapons (CEWs) are used by law enforcement to subdue combative subjects. Occasionally, subjects will die after a CEW has been used on them. It is theorized that CEWs may contribute to these deaths by impairing respiration. Objectives: To examine the respiratory effects of CEWs. Methods: Human volunteers received a 15-second application of electrical current from a CEW while wearing a respiratory measurement device. Common respiratory parameters were collected before, during, and after exposure. Health histories and demographic information were also collected. Results: Fifty-two subjects were analyzed. Thirty-four underwent a 15-second continuous exposure, and 18 underwent three 5-second burst exposures. In the continuous application group, the baseline mean tidal volume of 1.1 L increased to 1.8 L during application, the baseline end-tidal CO2 level went from 40.5 mm Hg to 37.3 mm Hg after exposure, the baseline end-tidal oxygen level went from 118.7 mm Hg to 121.3 mm Hg after exposure, and the baseline respiratory rate went from 15.9 breaths/min to 16.4 breaths/min after exposure. In the 5-second burst group, the baseline mean tidal volume increased to 1.85 L during application, the baseline end-tidal CO2 level went from 40.9 mm Hg to 39.1 mm Hg after exposure, the baseline end-tidal oxygen level went from 123.1 mm Hg to 127.0 mm Hg after exposure, and the baseline respiratory rate went from 13.8 breaths/min to 14.6 breaths/min after exposure. Conclusions: Prolonged CEW application did not impair respiratory parameters in this population of volunteers. Further study is recommended to validate these findings in other populations. [source] Method for reduced SAR T1, -weighted MRIMAGNETIC RESONANCE IN MEDICINE, Issue 6 2004Andrew J. Wheaton Abstract A reduced specific absorption rate (SAR) version of the T1, -weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k -space acquisition approach in which a full power spin-lock pulse is applied to only the central phase-encode lines of k -space, while the remainder of k -space receives a low-power spin-lock pulse. Acquisition of high- and low-power phase-encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k -space receives full T1, -weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T1, maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T1, differed by only 2%. The reduced SAR sequence enables T1, -weighted MRI in a clinical setting, even at high field strengths. Magn Reson Med 51:1096,1102, 2004. © 2004 Wiley-Liss, Inc. [source] Functional map and age-related differences in the human face: nonimmunologic contact urticaria induced by hexyl nicotinateCONTACT DERMATITIS, Issue 1 2006Slaheddine Marrakchi Variation in human skin reactivity to various irritants in association with age and body region has been reported. Hexyl nicotinate (HN), a lipophilic nicotinate ester, was used to induce nonimmunologic contact urticaria in human volunteers of 2 age groups: 10 young subjects [24,34 years, mean ± standard deviation (SD) 29.8 ± 3.9 years] and 10 older volunteers (66,83 years, mean ± SD 73.6 ± 17.4 years); and to define skin function and potential age-related differences in various facial areas. About 5 mM of HN in ethanol was applied to 8 locations on the face, neck, and volar forearm. A laser Doppler flowmeter was used to determine baseline blood flow and to monitor the skin blood flow changes after HN application. In the contralateral areas, stratum corneum turnover was determined using 5% dansyl chloride in petrolatum. In the young group, the perioral area exhibited the strongest reaction to HN. In the older group, the chin was the most sensitive site. In both the groups, the forearm was the least responsive. The older group demonstrated a stronger reaction than the younger group in 3 sites (forehead, cheek, and nasolabial area). Stratum corneum turnover was slower in the nasolabial area and in the forearm in both age groups, whereas the fastest was in the perioral area and the chin in the younger group and in the chin and the forehead in the older group. Compared to the older group, the younger group showed a slower stratum corneum turnover in the nose and the neck. This study demonstrates the regional and the age-related variability of the stratum corneum turnover and the skin reactions to HN. These observations may help explain some aspects of the cutaneous intolerance in skin care of the face. [source] Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] Behavioral and cardiovascular effects of 7.5% CO2 in human volunteersDEPRESSION AND ANXIETY, Issue 1 2005Jayne E. Bailey M.Sc. Abstract The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5,7% CO2 inhaled for 15,20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety. Depression and Anxiety 00:000,000, 2005. © 2005 Wiley-Liss, Inc. [source] CNS response to a thermal stressor in human volunteers and rats may predict the clinical utility of analgesicsDRUG DEVELOPMENT RESEARCH, Issue 1 2007David Borsook Abstract fMRI was used to test the hypothesis that global brain activation following a stressor (a thermal stimulus) that activates multiple brain circuits in healthy subjects can predict which drugs have higher potential for clinical utility for neuropathic pain. The rationale is that a drug will modulate multiple neural circuits that are activated by the system-specific stressor (e.g., pain). In neuropathic pain, some brain circuits have altered function, but most brain systems are "normal." Thus, the manner in which a drug effect on neural circuits is modulated by the stressor may provide insight into the clinical utility based on the readout of brain activation in response to the stimulus. Six drugs with known clinical efficacy (or lack thereof) in treating neuropathic pain were selected and the CNS response to each drug in the presence or absence of a pain stimulus was examined. The present results suggest that it is possible to identify potentially effective drugs based on patterns of brain activation in healthy human subjects and indicate that CNS activity is a more sensitive measure of drug action than standard psychophysical measures of pain intensity. This approach was repeated in rats and showed that a similar fMRI paradigm segregates these drugs in a similar manner suggesting a potential "translational tool" in evaluating drug efficacy for neuropathic pain. The sensitivity of this paradigm using fMRI allows clinical screening in small groups of healthy subjects, suggesting it could become a useful tool for drug development as well as for elucidating the mechanisms of neuropathic disease and therapy. Drug Dev. Res. 68:23,41, 2007. © 2007 Wiley-Liss, Inc. [source] Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009Seyed Jalal Hosseinimehr Abstract The ability of Daflon to protect against genotoxicity induced by gamma irradiation has been investigated in vivo and in vitro in cultured lymphocytes from healthy human volunteers. Peripheral human blood samples were collected predose (10 min before) and 1, 2, and 3 hr after a single oral ingestion of 1000 mg of Daflon. At each time point, whole blood was exposed in vitro to 150 cGy of cobalt-60 gamma rays, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. For each volunteer, the results showed a significant increase in the incidence of micronuclei after exposure to gamma irradiation as compared to control unexposed samples. As early as 1 hr after Daflon administration, a significant decrease in the incidence of micronuclei was observed in comparison with similarly irradiated lymphocytes collected before administration. The maximum protection was reached 1 hr after administration of Daflon with a significant decrease in the frequency of micronuclei of 40%. These findings suggest the possible application of Daflon for the protection of human lymphocytes from the genetic damage and side effects induced by gamma irradiation. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Production and clearance of cyclobutane dipyrimidine dimers in UV-irradiated skin pretreated with 1% pimecrolimus or 0.1% triamcinolone acetonide creams in normal and atopic patientsEXPERIMENTAL DERMATOLOGY, Issue 5 2006Laurence Doelker Background:, Ultraviolet (UV)-induced pyrimidine dimers are an early step in skin carcinogenesis, which is accelerated in the setting of long-term immunosuppression with systemic calcineurin inhibitors. It is not known whether topical application of calcineurin inhibitors exposes to a similar risk. Objective:, To assess the formation and clearance of UV-induced dipyrimidine dimers in human epidermis treated with topical pimecrolimus as compared to topical steroid, vehicle and untreated control. Methods:, Pretreated buttock skin of 20 human volunteers with (10) or without (10) atopic dermatitis was exposed to two minimal erythema doses (MED) of simulated solar radiation. DNA was extracted from epidermis 1 and 24 h postirradiation. Pyrimidine dimers were visualized by immuno slot blots and quantified by chemoluminescence image analysis. Results:, One-hour postirradiation, pimecrolimus-treated epidermis contains less DNA damage as compared to untreated control, but there were no statistically significant differences between pimecrolimus, triamcinolone acetonide and vehicle. Dimer levels at 24 h postirradiation showed no significant differences between different treatments. Conclusion:, Treatment with pimecrolimus cream, triamcinolone acetonide cream and vehicle is not associated with increased epidermal DNA damage at 1 and 24 h post-UV exposure. [source] In vitro response to Candida albicans in cultures of whole human blood from young and aged donorsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Celia Murciano Abstract Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15,42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1,, IL-6, IL-10, tumour necrosis factor (TNF)-, and IL-12p70] and prostaglandin E2 (PGE2) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti- C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood. [source] Salmonella vaccines for use in humans: present and future perspectivesFEMS MICROBIOLOGY REVIEWS, Issue 4 2002Helen S Garmory Abstract In recent years there has been significant progress in the development of attenuated Salmonella enterica serovar Typhi strains as candidate typhoid fever vaccines. In clinical trials these vaccines have been shown to be well tolerated and immunogenic. For example, the attenuated S. enterica var. Typhi strains CVD 908- htrA (aroC aroD htrA), Ty800 (phoPphoQ) and ,4073 (cya crp cdt) are all promising candidate typhoid vaccines. In addition, clinical trials have demonstrated that S. enterica var. Typhi vaccines expressing heterologous antigens, such as the tetanus toxin fragment C, can induce immunity to the expressed antigens in human volunteers. In many cases, the problems associated with expression of antigens in Salmonella have been successfully addressed and the future of Salmonella vaccine development is very promising. [source] Repellent studies with Aedes aegypti mosquitoes and human olfactory tests on 19 essential oils from Corsica, FranceFLAVOUR AND FRAGRANCE JOURNAL, Issue 4 2009J. Drapeau Abstract In order to reduce the risk of getting infected with any epidemic disease transmitted by mosquitoes, repellent products are often used to protect populations at risk. The repellent potential of 19 essential oils from the island of Corsica, France, was evaluated in a bio-assay with the mosquito Aedes aegypti, in order to assess the ,space repellent' properties of these oils. Lavendula stoechas, Helichrysum italicum (leaves) and Laurus nobilis oils showed a capability of reducing the attractivity of a human finger for yellow fever mosquitoes in a Y-tube olfactometer. In addition to the behavioural studies on mosquitoes, two tests on the olfactory perception of these 19 oils were performed, involving 25 female and 25 male human volunteers. The aspects studied were the ,hedonic dimension' of these oils and their acceptance as a final fragrance for a repellent formulation. The experiments yielded promising results concerning both aspects for three oils, from Calamintha nepeta, Laurus nobilis and Rosmarinus officinalis, with minor differences between male and female participants. Laurus nobilis oil was the only oil tested fulfilling both properties: a spatial repellent effect on Aedes aegypti and acceptance by the volunteers for its integration in a repellent product. Thermogravimetric analysis showed that Calamintha nepeta oil has a slower evaporation rate in comparison to the Laurus nobilis and Rosmarinus officinalis oils. Copyright © 2009 John Wiley & Sons, Ltd. [source] Nest protection in mallards Anas platyrhynchos: untangling the role of crypsis and parental behaviourFUNCTIONAL ECOLOGY, Issue 5 2008J. Kreisinger Summary 1The covering of clutches with nest material is generally considered to improve the thermal environment of developing embryos. Here we tested an alternative hypothesis: that this behaviour reduces the risk of clutch detection by predators and hence, fulfils a cryptic anti-predation function in a ground-nesting non-passerine bird, the mallard. In addition, we assess the anti-predation function of the direct presence of an incubating parent on the nest for the first time in a ground-nesting non-passerine bird. 2We compared predation rates of real mallard nests with two types of artificial clutches: (i) covered with nest material and (ii) uncovered. In addition, the cryptic effectiveness of nest material, female body presence, and uncovered clutch were assessed using a simulated search for nests on photographs by human volunteers. This allowed us to evaluate separately the impact of overall crypsis (covering of the clutch by nest material and colouration of the female feather) and the direct protective capacity of the incubating female. 3Our data demonstrate that in mallards, concealment of the clutch with nest material reduces the risk of nest predation. Although the incubating female seems to provide less effective crypsis to the nest than nest material alone, the presence of the female on the clutch enhanced nest survival, suggesting a significant anti-predation capacity of the incubating parent in this species. 4Contrary to some previous studies, the relative effects of crypsis and parental anti-predation behaviour on nest survival did not differ with respect to nest concealment by surrounding vegetation. [source] Effects of serotonin and catecholamine depletion on interleukin-6 activation and mood in human volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2002Ben J. Harrison Abstract There is increasing evidence that depression and related neurotic illnesses are associated with alterations in immune function that may contribute to their pathogenesis. For example, clinical and experimental studies have shown that abnormal HPA-axis activation and monoamine neurotransmission may be related to an increased release of proinflammatory cytokines from stimulated lymphocytes in the periphery and brain. In the present investigation, the effects of tryptophan depletion (TD) on unstimulated plasma interleukin-6 (IL-6) concentrations were investigated in order to determine whether acute changes in serotonin (5-HT) neurotransmission would induce a proinflammatory response in healthy individuals. The effects of TD were compared with the analogous procedure of tyrosine depletion (TPD), which reduces catecholamine metabolism in humans. Thirteen female participants completed three experimental sessions: TD, TPD and a balanced-control condition (B). Mood-ratings and blood sampling were performed at baseline and 5,h after the administration of the mixtures. Analyses revealed that TD and TPD markedly reduced tryptophan and tyrosine/phenylalanine levels, respectively. No changes in plasma IL-6 production or ratings of lowered mood were observed, however, subjects did report feeling more fatigued after TD. These findings indicate that a transient disruption in global monoamine function does not stimulate a proinflammatory response of IL-6 in normal volunteers. Copyright © 2002 John Wiley & Sons, Ltd. [source] Which neuroreceptors mediate the subjective effects of MDMA in humans?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001A summary of mechanistic studies Abstract In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd. [source] A miniaturized assay for influenza neuraminidase-inhibiting antibodies utilizing reverse genetics-derived antigensINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5 2009Matthew R. Sandbulte Background, Antibodies to neuraminidase (NA) contribute to protection during influenza virus infection, but NA inhibition (NI) titers are not routinely analyzed in vaccine trials. One reason is the cumbersome nature of the conventional thiobarbituric acid (TBA) NI assay, which uses chemical methods to quantify free sialic acid following incubation of NA with substrate in the presence of serum. In addition, the assay is complicated by the need to use virus of a hemagglutinin (HA) subtype novel to the host to detect NA-specific antibodies only. Objectives, Our primary objectives were to miniaturize the colorimetric NI assay to a format suitable for quantitative analysis of large numbers of samples, and validate the specificity and sensitivity of the miniaturized format with ferret and human sera. An additional aim was to use reverse genetics to construct HA-mismatched viral reagents bearing NA of recent influenza A vaccine strains and H6 HA. Results, Analysis of ferret antisera by the miniaturized assay demonstrated sensitivity and specificity comparable with the conventional assay. Similar increases in the NI titers in sera from vaccinated human volunteers were measured in miniaturized and conventional assays. Inactivated and live-attenuated vaccines increased NI titers against a given subtype at approximately the same rate. Conclusions, The reagents and miniaturized format of the TBA method described here provide a platform for practical serological monitoring of functional antibodies against NA. [source] Ethics of studies involving human volunteers I. Historical backgroundINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2007P. A. Carson The evaluation of personal products using panels of human volunteers is crucial to the continued development of the industry. Nowadays, however, it is increasingly important to ensure that such studies are both safe for the participants and are ethical. As a means of defining general rules for judging and justifying the ethics of human testing, historical milestones in the development of human experimentation are given. While most experience originates from biomedical research, findings help establish standards of ethical review of non-therapeutic human testing used in the cosmetics industry. [source] Ethics of studies involving human volunteers.INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2007The importance to the personal products industry of testing novel products in healthy human volunteers and the need to ensure the trials were both safe and ethical were addressed in part I. The historical development of ethical standards for human testing was also summarized. The present paper highlights the ethical principles to be considered when testing novel non-medicinal products on human volunteers, and it describes how they can be implemented in a pragmatic manner to avoid delay to the sponsor's research program. The structure and function of ethics committees is discussed. [source] Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PETACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010L. SCHLÜNZEN Background: Arterial carbon dioxide tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H215O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO2 was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia. [source] A colony immunoblotting method for quantitative detection of a Bifidobacterium animalis probiotic strain in human faecesJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2000H. Duez A colony immunoblotting method has been developed to allow detection of the probiotic Bifidobacterium animalis strain DN-173 010 in human faecal samples. Rabbits were immunized with heat-killed DN-173 010 bacteria resulting in the production of an antiserum highly specific for bacteria belonging to Bif. animalis species. Of the 89 strains representative of 29 different bifidobacterial species tested, only the 15 strains of the Bif. animalis species could be detected with the antiserum. In Western immunoblotting the serum reacts with a protein of 45-kDa apparent molecular weight. None of the bacteria classically encountered in human faecal samples and able to grow on non-selective Columbia blood agar (enterobacteria, Bacteroides or Lactobacillus for instance) reacted with the antiserum. Taking advantage of the high specificity of the antiserum and of the absence of Bif. animalis bacteria in faeces samples of five human volunteers, we demonstrated that strain DN-173 010 survives the intestinal transit. Being based on a combination of semiselective cultivation and colony immunoblotting techniques, the method allowed detection of the Bif. animalis strain even when it represented only one thousandth of the total bifidobacterial population. [source] Pralidoxime and l -lactate effects in vitro on the inhibition of acetylcholinesterase by paraoxon: pralidoxime does not confer superior protectionJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2001Georg Petroianu Abstract Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l -lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL,baseline (or untreated plasma); sample a,after addition of POX to plasma (pl + POX); sample b,after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c,after addition of oxime to plasma (pl + PRX); sample d,after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e,after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme ,pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted. Copyright © 2001 John Wiley & Sons, Ltd. [source] Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteersJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005W. Ridtitid MD FCFPT Summary Background:, Antimalarial mefloquine has a structure related to quinine. The major metabolite of quinine is 3-hydroxyquinine formed by cytochrome P450 3A4 (CYP3A4). Ketoconazole, a potent inhibitor of CYP3A4, is known to markedly increase plasma concentrations of various co-administered drugs including quinine. Objective:, To assess the effect of ketoconazole on plasma concentrations of mefloquine in healthy Thai male volunteers. Methods:, In an open, randomized two-phase crossover study separated by a 1-month period, eight healthy Thai male volunteers received a single oral dose of 500 mg mefloquine alone or co-administration with 400 mg/day ketoconazole orally for 10 days. Serial blood samples were collected at specific time points for a 56-day period. Plasma mefloquine and mefloquine carboxylic metabolite concentrations during 56 days were measured by a modified and validated high-performance liquid chromatographic method with UV detection. Results:, Co-administration with ketoconazole markedly increased the mean values of mefloquine AUC0,t, t1/2, and Cmax when compared with mefloquine alone by 79% (P < 0·001), 39% (P < 0·05) and 64% (P < 0·001) respectively. The AUC0,t,, and Cmax of mefloquine carboxylic acid metabolite were decreased by 28% (P < 0·05) and 31% (P < 0·05), respectively when compared with mefloquine alone. Conclusions:, Co-administration with ketoconazole increased plasma mefloquine concentrations in healthy human volunteers. One of possible mechanisms of the increase in plasma mefloquine concentrations may be the result of the inhibition of CYP3A4 by ketoconazole. In case of mefloquine is co-administered with ketoconazole, drug,drug interactions should be recognized and the dose of mefloquine should be adjusted to maximize the therapeutic efficacy and to reduce the cost of therapy. [source] Muscle mitochondrial activity increases rapidly after an endotoxin challenge in human volunteersACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009K. FREDRIKSSON Background: Mitochondrial derangements in muscle of patients suffering from sepsis have been established in several studies and have been related to muscle dysfunction and organ failure. It is not possible to study the early phase of sepsis in patients; therefore, we used a human endotoxaemia model to study the effect of early sepsis on muscle mitochondria. Methods: Seven healthy male volunteers received a standardised endotoxin challenge. Muscle biopsies were obtained immediately before the challenge, and at 2 and 4 h following the endotoxin challenge. The muscle biopsies were analysed for maximal activities of citrate synthase and complexes I and IV of the respiratory chain. In addition, total and mitochondrial superoxide dismutase (SOD) activities were analysed. The concentrations of ATP, creatine phosphate and lactate were analysed to assess the cellular energy status. Total and phosphorylated AMP-activated protein kinase (AMPK-P), a key regulator in intracellular energy metabolism, was measured. Results: Activities of citrate synthase and complex I were significantly increased 2 h after the endotoxin challenge. SOD activities were unaffected by the endotoxin challenge. No changes in ATP, creatine phosphate or lactate were observed. Neither total nor AMPK-P changed. Conclusions: An endotoxin challenge given to healthy volunteers rapidly increases mitochondrial enzyme activity in skeletal muscle. The results of this human model indicate that possibly early during sepsis, mitochondrial activity might be increased in contrast to what has been shown in the later phases of sepsis. It is possible that this early activation leads to exhaustion of the mitochondria and a decreased function later during sepsis. [source] 1H spectroscopic imaging of human brain at 3 Tesla: Comparison of fast three-dimensional magnetic resonance spectroscopic imaging techniquesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2009Matthew L. Zierhut PhD Abstract Purpose To investigate the signal-to-noise-ratio (SNR) and data quality of time-reduced three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H MRSI) techniques in the human brain at 3 Tesla. Materials and Methods Techniques that were investigated included ellipsoidal k -space sampling, parallel imaging, and echo-planar spectroscopic imaging (EPSI). The SNR values for N-acetyl aspartate, choline, creatine, and lactate or lipid peaks were compared after correcting for effective spatial resolution and acquisition time in a phantom and in the brains of human volunteers. Other factors considered were linewidths, metabolite ratios, partial volume effects, and subcutaneous lipid contamination. Results In volunteers, the median normalized SNR for parallel imaging data decreased by 34,42%, but could be significantly improved using regularization. The normalized signal to noise loss in flyback EPSI data was 11,18%. The effective spatial resolutions of the traditional, ellipsoidal, sensitivity encoding (SENSE) sampling scheme, and EPSI data were 1.02, 2.43, 1.03, and 1.01 cm3, respectively. As expected, lipid contamination was variable between subjects but was highest for the SENSE data. Patient data obtained using the flyback EPSI method were of excellent quality. Conclusion Data from all 1H 3D-MRSI techniques were qualitatively acceptable, based upon SNR, linewidths, and metabolite ratios. The larger field of view obtained with the EPSI methods showed negligible lipid aliasing with acceptable SNR values in less than 9.5 min without compromising the point-spread function. J. Magn. Reson. Imaging 2009;30:473,480. © 2009 Wiley-Liss, Inc. [source] Comparison of TCA and ICA techniques in fMRI data processingJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2004Xia Zhao MS Abstract Purpose To make a quantitative comparison of temporal cluster analysis (TCA) and independent component analysis (ICA) techniques in detecting brain activation by using simulated data and in vivo event-related functional MRI (fMRI) experiments. Materials and Methods A single-slice MRI image was replicated 150 times to simulate an fMRI time series. An event-related brain activation pattern with five different levels of intensity and Gaussian noise was superimposed on these images. Maximum contrast-to-noise ratio (CNR) of the signal change ranged from 1.0 to 2.0 by 0.25 increments. In vivo visual stimulation fMRI experiments were performed on a 1.9 T magnet. Six human volunteers participated in this study. All imaging data were analyzed using both TCA and ICA methods. Results Both simulated and in vivo data have shown that no statistically significant difference exists in the activation areas detected by both ICA and TCA techniques when CNR of fMRI signal is larger than 1.75. Conclusion TCA and ICA techniques are comparable in generating functional brain maps in event-related fMRI experiments. Although ICA has richer features in exploring the spatial and temporal information of the functional images, the TCA method has advantages in its computational efficiency, repeatability, and readiness to average data from group subjects. J. Magn. Reson. Imaging 2004;19:397,402. © 2004 Wiley-Liss, Inc. [source] Experimental infection of Macaca nemestrina with a Toronto Norwalk-like virus of epidemic viral gastroenteritisJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002D.S. Subekti Abstract Norwalk virus (NV) and Norwalk-like viruses (NLVs) are common etiologic agents of viral gastroenteritis. Viral gastroenteritis is a common disease that is highly transmissible, spreading rapidly through families, institutions, and communities. Because methods for in vitro cultivation of Norwalk etiologic agents are not available, information regarding this syndrome has come largely from studies in human volunteers. Sequential passaging of an NLV through an immunoincompetent newborn pigtail macaque (Macaca nemestrina) may allow for the adaptation of a human NLV to a primate host, thus providing an animal model for investigating this disease. A fecal filtrate of human origin containing NLV, Toronto virus P2-A, was obtained from a patient during an epidemic of viral gastroenteritis. The filtrate was administered via nasogastric tube to three newborn pigtailed macaques. Clinical illness, which was characterized by diarrhea, dehydration, and vomiting, occurred in three monkeys. Reverse transcription-polymerase chain reaction (RT-PCR) and oligonucleotide probe analysis of RNA extracted from the stool samples following infection revealed viral RNA in all inoculated monkeys. Infection was also transmitted experimentally by feeding two additional newborn macaques a fecal filtrate prepared from the three previously infected animals. Detection of viral RNA in the stools of animals that received the fecal filtrate indicates that viral replication occurred in association with clinical illness. The susceptibility of Macaca nemestrina to infection with a Norwalk-like agent will facilitate the study of the mechanisms of the pathogenesis of NLV. This system may also have the potential to serve as a vaccine test model for human epidemic viral gastroenteritis. J. Med. Virol. 66:400-406, 2002. © 2002 Wiley-Liss, Inc. [source] Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutineJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2002Yoshimi Hashimoto The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1,2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method. [source] In-vitro Antioxidant and In-vivo Photoprotective Effect of Three Lyophilized Extracts of Sedum telephium L. LeavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000FRANCESCO BONINA Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13 000 and 13 500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage. [source] | |||||||||||||||||||||||||||||||||||||