Science.gov

Sample records for age-matched healthy subjects

  1. Cardiovascular function is better in veteran football players than age-matched untrained elderly healthy men.

    PubMed

    Schmidt, J F; Andersen, T R; Andersen, L J; Randers, M B; Hornstrup, T; Hansen, P R; Bangsbo, J; Krustrup, P

    2015-02-01

    The aim of the study was to determine whether lifelong football training may improve cardiovascular function, physical fitness, and body composition. Our subjects were 17 male veteran football players (VPG; 68.1 ± 2.1 years) and 26 healthy age-matched untrained men who served as a control group (CG; 68.2 ± 3.2 years). Examinations included measurements of cardiac function, microvascular endothelial function [reactive hyperemic index (RHI)], maximum oxygen uptake (VO2max), and body composition. In VPG, left ventricular (LV) end-diastolic volume was 20% larger (P < 0.01) and LV ejection fraction was higher (P < 0.001). Tissue Doppler imaging revealed an augmented LV longitudinal displacement, i.e., LV shortening of 21% (P < 0.001) and longitudinal 2D strain was 12% higher (P < 0.05), in VPG. In VPG, resting heart rate was lower (6 bpm, P < 0.05), and VO2max was higher (18%, P < 0.05). In addition, RHI was 21% higher (P < 0.05) in VPG. VPG also had lower body mass index (P < 0.05), body fat percentage, total body fat mass, android fat percentage, and gynoid fat percentage (all P < 0.01). Lifelong participation in football training is associated with better LV systolic function, physical fitness, microvascular function, and a healthier body composition. Overall, VPG have better cardiovascular function compared with CG, which may reduce their cardiovascular morbidity and mortality.

  2. Postural finger tremor exhibited by Parkinson patients and age-matched subjects.

    PubMed

    Palmer, S S; Hutton, J T

    1995-09-01

    Physiological correlates of postural tremor of the finger seen in Parkinson's disease patients are different from those seen in age-matched control subjects. A significant correlation between the spectral peak of acceleration and the spectral peak of rectified electromyographic activity from the muscle responsible for finger extension was found in Parkinson's disease patients. This correlation was not seen in age-matched control subjects. Any neural drive imposed on the motoneuron pool from supraspinal levels would enhance the electromyographic activity. Likewise, any feedback effects via spinal stretch reflexes or supraspinal stretch responses would be mediated through the motoneuron pool and electromyographic activity. The results of this research support the theory that Parkinson tremor is a centrally driven rhythm that may be influenced by feedback effects, whereas physiological tremor is due to a complex interaction of central, feedback, and mechanical effects.

  3. Impact of Limiting Visual Input on Gait: Individuals with Parkinson Disease, Age-matched Controls and Healthy Young Participants

    PubMed Central

    Pilgram, Laura M.; Earhart, Gammon M.; Pickett, Kristen A.

    2016-01-01

    Normal and limited vision gait was investigated in individuals with Parkinson disease (PD), healthy older and healthy young individuals. Participants walked a GAITRite mat with normal vision or vision of lower limbs occluded. Results indicate individuals with PD walked more slowly, with shorter and wider steps and spent more time in double support with limited vision as compared to full vision. Healthy young and old individuals took shorter steps but were otherwise unchanged between conditions. PMID:26987577

  4. The Long-Term Effect of Radical Prostatectomy on Erectile Function, Urinary Continence, and Lower Urinary Tract Symptoms: A Comparison to Age-Matched Healthy Controls

    PubMed Central

    Ponholzer, Anton; Augustin, Herbert; Madersbacher, Stephan; Pummer, Karl

    2017-01-01

    Introduction. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. Materials and Methods. Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). Results. Patients after RPE were included (n = 363). Age-matched healthy men (n = 363) were included. The mean IIEF-5 of patients aged 61–70 yrs after RPE was 10.4 ± 6.6 versus 18.8 ± 5.3 in the control cohort; the respective values for men aged 71–80 yrs after RPE were 7.2 ± 6.5 versus 13.6 ± 7.7 in the control cohort. Urinary incontinence after RPE was reported in 41.9% (61–70 years) and 37.7% (71–80) versus 7.5% and 15.1% in the control cohort. The mean IPSS of patients after RPE aged 61–70 yrs was 5.0 ± 4.4 versus 5.5 ± 4.9 in the control cohort; the respective values for men aged 71–80 yrs were 6.0 ± 4.9 versus 7.5 ± 5.7 in the healthy cohort. Conclusions. The negative effect of radical prostatectomy on erectile and urinary incontinence remains substantial. The physiologically declining erectile and lower urinary tract function with ageing reduces the difference between healthy men and those after surgery. Healthy men have a higher IPSS presumably due to the presence of bladder outlet obstruction. PMID:28261619

  5. Hypoconnectivity of Resting-State Networks in Persons with Aphasia Compared with Healthy Age-Matched Adults

    PubMed Central

    Sandberg, Chaleece W.

    2017-01-01

    Aphasia is a language disorder affecting more than one million people in the US. While language function has traditionally been the focus of neuroimaging research, other cognitive functions are affected in this population, which has implications not only for those specific processes but also for the interaction of language and other cognitive functions. Resting state fMRI (rs-fMRI) is a practical and informative way to explore and characterize general cognitive engagement and/or health in this population, but it is currently underutilized. The aim of this study was to explore the functional connectivity in resting state networks (RSNs) and in the semantic network in seven persons with aphasia (PWA) who were at least 6 months post onset compared with 11 neurologically healthy adults (NHA) in order to gain a more comprehensive understanding of general cognitive engagement in aphasia. These preliminary results show that PWA exhibit hypoconnectivity in the semantic network and all RSNs except the visual network. Compared with NHA, PWA appear to have fewer cross- and left-hemispheric connections. However, PWA exhibit some stronger connections than NHA within the semantic network, which could indicate compensatory mechanisms. Importantly, connectivity for RSNs appear to increase with decreasing aphasia severity and decrease with increasing lesion size. This knowledge has the potential to improve aphasia therapy by furthering the understanding of lesion effects on the cognitive system as a whole, which can guide treatment target selection and promotion of favorable neural reorganization for optimal recovery of function. PMID:28293185

  6. Nocturnal bruxing events in healthy geriatric subjects.

    PubMed

    Okeson, J P; Phillips, B A; Berry, D T; Cook, Y; Paesani, D; Galante, J

    1990-09-01

    Thirty healthy geriatric subjects were studied during a single night of sleep in a sleep laboratory. Unilateral masseter muscle activity was recorded in addition to the standard polysomnographic study. The geriatric subjects in this study exhibited fewer bruxing events than other subjects reported in the literature. Certain conditions that have not been previously investigated, such as sleep position, type of bruxing event, and relationship to the state of the dentition, are reported.

  7. Peripapillary choroidal thickness in healthy Turkish subjects

    PubMed Central

    Erbagci, Hulya; Oren, Burak; Okumus, Seydi; Kenan, Serhat; Celemler, Pelin; Erbagci, Ibrahim

    2015-01-01

    Aim The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT), measured by enhanced depth imaging optical coherence tomography (EDI-OCT), in healthy Turkish volunteers. Materials and methods In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. Results The mean age of the 25 female and 32 male patients in the study was 30.9±10.6 years (range, 18–56 years). The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225±57, 183±47, 220±57, and 233±59 μm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all), whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. Conclusion The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. PMID:26257510

  8. Mechanisms of dyspnea in healthy subjects.

    PubMed

    Gigliotti, Francesco

    2010-06-30

    Dyspnea is a general term used to characterize a range of different descriptors; it varies in intensity, and is influenced by a wide variety of factors such as cultural expectations and the patient's experiences. Healthy subjects can experience dyspnea in different situations, e.g. at high altitude, after breath-holding, during stressful situations that cause anxiety or panic, and more commonly during strenuous exercise. Discussing the mechanisms of dyspnea we need to briefly take into account the physiological mechanisms underlying the sensation of dyspnea: the functional status of the respiratory muscles, the role of chemoreceptors and mechanoreceptors, and how the sense of respiratory motor output reaches a level of conscious awareness. We also need to take into account theories on the pathophysiological mechanisms of the sensation of dyspnea and the possibility that each pathophysiological mechanism produces a distinct quality of breathing discomfort. The terms used by subjects to identify different characteristics of breathing discomfort - dyspnea descriptors - may contribute to understanding the mechanisms of dyspnea and providing the rationale for a specific diagnosis.

  9. Ventilatory efficiency during exercise in healthy subjects.

    PubMed

    Sun, Xing-Guo; Hansen, James E; Garatachea, Nuria; Storer, Thomas W; Wasserman, Karlman

    2002-12-01

    When evaluating dyspnea in patients with heart or lung disease it is useful to measure the quantity of ventilation needed to eliminate metabolically produced CO2 (i.e., the ventilatory efficiency). Mathematically, the relationship between ventilation (VE) and CO2 output is determined by the arterial CO2 pressure and the physiologic dead space-tidal volume ratio. We decided to determine how age, sex, size, fitness, and the type of ergometer influenced ventilatory efficiency in normal subjects. Three methods were compared for expressing this relationship: (1) the VE versus CO2 output slope below the ventilatory compensation point, commonly used by cardiologists for estimating the severity of heart failure; (2) the VE/CO2 output ratio at the anaerobic threshold, commonly used by pulmonologists; and (3) the lowest VE/CO2 output ratio during exercise, the latter parameter not previously reported. We studied 474 healthy adults, between 17 and 78 years of age during incremental cycle and treadmill cardiopulmonary exercise tests at three test sites, correcting the total VE for the equipment dead space. The lowest VE/CO2 output ratio was insignificantly different from the ratio at the anaerobic threshold, less variable than that for the slope relationship, and unaffected by the site, ergometer, and gas exchange measurement systems. The regression equation for the lowest VE/CO2 output ratio was 27.94 + 0.108 x age + (0.97 = F, 0.0 = M) - 0.0376 x height, where age is in years and height is in centimeters. We conclude that the lowest VE/CO2 output ratio is the preferred noninvasive method to estimate ventilatory inefficiency.

  10. Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

    PubMed

    Savage, Mary J; Holder, Daniel J; Wu, Guoxin; Kaplow, June; Siuciak, Judith A; Potter, William Z

    2015-01-01

    β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ₄₂ and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals.

  11. On the imitation of CP gait patterns by healthy subjects.

    PubMed

    Rezgui, Taysir; Megrot, Fabrice; Fradet, Laetitia; Marin, Frédéric

    2013-09-01

    The comparison of gait imitated by healthy subjects with real pathological CP gaits is expected to contribute to a better distinction between primary deviations directly induced by neurological troubles and secondary compensatory deviations in relation with the biomechanics of the pathological gait. However, the ability of healthy subjects for imitating typical CP gaits such as "jump" or "crouch" gaits still remains to be determined. The present study proposes to investigate healthy subjects imitating these typical CP gait patterns. 10 healthy adult subjects performed three types of gait: one "normal" and two imitated "jump" and "crouch" gaits. Kinematics and kinetics of the hip, knee and ankle were computed in the sagittal plane. Rectified normalized EMG was also analysed. Our data were compared with reference data. For the statistical analysis, the coefficient of multicorrelation has been used. It has been demonstrated that healthy subjects were able to voluntarily modify their gait pattern with a high level of intra-session and inter-subject reproducibility as quantified by a CMC values higher than 0.76 for all parameters. The comparison with literature reference data showed that healthy subjects not could perfectly reproduce a CP gait, however could only simulate the main characteristics of "crouch" and "jump" gaits pattern. As a perspective, pathological gaits imitated by healthy subjects could be used as valuable additional material to analyse the relationship between a voluntarily modified posture and the altered muscle activation to explore a new paradigm on pathological gait pattern analysis and musculoskeletal modelling.

  12. Peripapillary choroidal thickness in healthy Chinese subjects

    PubMed Central

    2013-01-01

    Background To evaluate the peripapillary choroidal thickness of a healthy Chinese population, and to determine its influencing factors. Methods A total of 76 healthy volunteers (76 eyes) without ophthalmic or systemic symptoms were enrolled. Choroidal scans (360-degree 3.4 mm diameter peripapillary circle scans) were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Choroid thickness was measured at the temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal segments. Results The average peripapillary choroidal thicknesses were 165.03 ± 40.37 μm. Inferonasal, inferior, and inferotemporal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, nasal thicknesses (p < 0.05). No statistically significant difference was found among inferonasal, inferior, and inferotemporal thicknesses. The average peripapillary choroidal thickness decreased linearly with age (β = −1.33, 95% CI −1.98, -0.68, P < 0.001). No correlation was noted between average choroidal thickness and other factors (gender, refractive error, axial length, average retinal nerve fiber layer thickness, intraocular pressure, diastolic blood pressure, systolic blood pressure, mean blood pressure, diastolic ocular perfusion pressure, systolic ocular perfusion pressure, and mean ocular perfusion pressure). Conclusions The inferonasal, inferior, inferotemporal peripapillary choroidal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, and nasal thicknesses. A thinner peripapillary choroid is associated with increasing age. PMID:23758729

  13. Pharmacokinetics of terazosin enantiomers in healthy Chinese male subjects.

    PubMed

    Liu, Man; Zhang, Dan; Yang, Man; Zhao, Ting; Wang, Xiaolin; Zhang, Yanan; Han, Jing; Liu, Huichen

    2012-12-01

    The purpose of this study was to elucidate the pharmacokinetics of terazosin enantiomers in healthy Chinese male subjects. After a single oral dose of 2-mg terazosin, the plasma concentrations of terazosin enantiomers were measured over the course of 48 h in 12 healthy subjects. The plasma concentrations of (+)-(R)-terazosin at all time points were higher than those of (-)-(S)-terazosin. The area under the plasma concentration-time curve (AUC(0-∞) ) and maximum plasma concentration of (+)-(R)-terazosin were significantly greater than those of the (-)-(S)-terazosin (P < 0.01, respectively). The R/S ratio of AUC(0-∞) of terazosin was 1.68. For the first time, it was proven that the pharmacokinetics of terazosin was stereoselective in healthy Chinese male subjects.

  14. Comparison of upper extremity function, pain, and tactile sense between the uneffected side of hemiparetic patients and healthy subjects

    PubMed Central

    Balcı, Nilay Comuk; Dogru, Esra; Aytar, Aydan; Gokmen, Ozge; Depreli, Ozde

    2016-01-01

    [Purpose] The aim of this study was to compare the unaffected upper extremity of patients with hemiparesis with that of healthy subjects in terms of function, pain, and tactile sense. [Subjects and Methods] Upper extremity evaluation parameters of 20 patients with hemiparesis were compared with an age-matched control group of 20 healthy subjects. A shorter version of the Disability of Arm and Shoulder Questionnaire, Upper Extremity Functional Index, and Simple Shoulder Test were used to evaluate the upper extremity functionality. The Visual Analog Scale was used to measure pain severity at rest, at night, and during activity. Tactile sensation levels were assessed by Semmes-Weinstein monofilaments at four palmar areas. [Results] A statistically significant difference was found in the upper extremity functionality between the groups. Pain severity at rest was significantly higher in the hemiparetic group. There was no significant difference in night and activity pain severities or tactile sensation levels between the groups. [Conclusion] According to our results, the unaffected side of patients with hemiparesis differs in functionality and pain at rest compared with that of healthy persons. Studies with larger sample size and various evaluation tests are needed to further investigate the unaffected side of patients with hemiparesis. PMID:27512250

  15. [Muscle post-effects and upright standing in healthy subjects and patients with sensory-motor integration disorders].

    PubMed

    Talis, V L; Kapitonov, M A; Maksimova, E V

    2011-01-01

    We compared the upright standing in 7 patients with sensory-motor disorders and 7 healthy subjects (control) before and after 30-s involuntary neck muscle contraction. A trajectory of the center of pressure was recorded during 30-s standing with the eyes open, eyes closed and standing on a foam-rubber with the eyes open. As compared to healthy subjects, patients exhibited an increased body sway area during standing with the eyes open on both the firm surface and foam-rubber and a backward shift of the center of pressure during standing with the eyes both open and closed. Closing the eyes affected the upright standing of patients to a lesser extent than standing of healthy subjects. Involuntary neck muscle contraction within 30 s elicited a backward shift of the center of pressure in healthy subjects, especially during standing with the eyes closed, and a decrease in the length of the center-of-pressure trajectory, especially of its frontal component during standing on the foam-rubber. In patients, a post-effect of the neck muscle contraction manifested itself as a decrease in the body sway area during standing on the foam-rubber and relative increase in the frontal component of the center-of-pressure trajectory during standing with the eyes closed. The results suggest that the upright standing of patients with sensory-motor disorders is more sensitive to somatosensory than visual input, and 30-s neck muscle contraction approach their postural stability to the age-matched control.

  16. The ratio of the alveolar ventilations of SF6 and He in patients with lung emphysema and in healthy subjects.

    PubMed

    Luijendijk, S C M; van der Grinten, C P M

    2002-03-01

    This study assess the possible impact of changes in the morphometry of acinar airways and air spaces on the efficacy of intrapulmonary gas mixing for sulphur hexafluoride (SF6) relative to that for helium (He). To that end the alveolar ventilations of He and SF6 were determined in patients with macroscopic lung emphysema and in healthy subjects. He-SF6 washout tests were performed in 17 patients (15 emphysema, 2 chronic bronchitis) and 21 healthy subjects. Using a three-compartment model, the data obtained were used to estimate the overall, effective, alveolar ventilations of SF6 and He, and their ratio VAASF6/VAHe. Mean VAASF6/VAHe (+/- S.D.) for patients (0.80 +/- 0.06) was significantly smaller (P < 0.001) than the value for the group of age-matched healthy subjects (0.90 +/- 0.05) which was non-significantly smaller than the result for the group of young, healthy subjects (0.93 +/- 0.03). In our patients, we also determined a score for emphysema using high resolution computed tomography, and this score correlated inversely with VAASF6/VAHe (r = -0.56, P = 0.018). We have interpreted our observations to mean that in patients with lung emphysema, the efficacy of intrapulmonary gas mixing for SF6 as compared with that for He reflected by VAASF6/VAHe is diminished due to increased diffusive path-lengths within the enlarged air spaces of their lungs which impair diffusive gas mixing for SF6 more than for He.

  17. Comparison of Subjective and Objective Sleep Estimations in Patients with Bipolar Disorder and Healthy Control Subjects

    PubMed Central

    Sauer, Cathrin; Pfeiffer, Steffi; Bauer, Michael; Pfennig, Andrea

    2016-01-01

    Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5–7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable. PMID:27891255

  18. Cytokine Levels in the Serum of Healthy Subjects

    PubMed Central

    Kleiner, Giulio; Marcuzzi, Annalisa; Zanin, Valentina; Monasta, Lorenzo; Zauli, Giorgio

    2013-01-01

    Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1–6 and 7–17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging. PMID:23533306

  19. Cytokine levels in the serum of healthy subjects.

    PubMed

    Kleiner, Giulio; Marcuzzi, Annalisa; Zanin, Valentina; Monasta, Lorenzo; Zauli, Giorgio

    2013-01-01

    Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1-6 and 7-17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.

  20. Velopharyngeal mucosal surface topography in healthy subjects and subjects with obstructive sleep apnea.

    PubMed

    Lambeth, Christopher; Amatoury, Jason; Wang, Ziyu; Foster, Sheryl; Amis, Terence; Kairaitis, Kristina

    2017-03-01

    Macroscopic pharyngeal anatomical abnormalities are thought to contribute to the pathogenesis of upper airway (UA) obstruction in obstructive sleep apnea (OSA). Microscopic changes in the UA mucosal lining of OSA subjects are reported; however, the impact of these changes on UA mucosal surface topography is unknown. This study aimed to 1) develop methodology to measure UA mucosal surface topography, and 2) compare findings from healthy and OSA subjects. Ten healthy and eleven OSA subjects were studied. Awake, gated (end expiration), head and neck position controlled magnetic resonance images (MRIs) of the velopharynx (VP) were obtained. VP mucosal surfaces were segmented from axial images, and three-dimensional VP mucosal surface models were constructed. Curvature analysis of the models was used to study the VP mucosal surface topography. Principal, mean, and Gaussian curvatures were used to define surface shape composition and surface roughness of the VP mucosal surface models. Significant differences were found in the surface shape composition, with more saddle/spherical and less flat/cylindrical shapes in OSA than healthy VP mucosal surface models (P < 0.01). OSA VP mucosal surface models were also found to have more mucosal surface roughness (P < 0.0001) than healthy VP mucosal surface models. Our novel methodology was utilized to model the VP mucosal surface of OSA and healthy subjects. OSA subjects were found to have different VP mucosal surface topography, composed of increased irregular shapes and increased roughness. We speculate increased irregularity in VP mucosal surface may increase pharyngeal collapsibility as a consequence of friction-related pressure loss.NEW & NOTEWORTHY A new methodology was used to model the upper airway mucosal surface topography from magnetic resonance images of patients with obstructive sleep apnea and healthy adults. Curvature analysis was used to analyze the topography of the models, and a new metric was derived to describe

  1. [Indicators of dynamic work tolerability in healthy subjects].

    PubMed

    Capodaglio, E M; Capodaglio, P

    1997-01-01

    This paper reports a study on the dynamics of tolerability in performing dynamic cycling in healthy subjects. Data on individually tolerable levels (power x duration) was obtained from 9 subjects by means of three submaximal tests on an ergometric bicycle lasting < or = 40 minutes, with constant load (50%, 65% and 80% of maximum VO2 reached during a previous test of increasing difficulty within the limits of the symptoms). During performance of the test we monitored heart rate and subjective perception of fatigue (Borg's 10-point scale). We then defined the individual functions of "isoperception", which expressed the individual trend of the product "power x duration" at identical subjective perception score. On the basis of the metabolic parameters monitored, the individual isoperceptive functions at a "moderate" level of fatigue (3 on the Borg scale) were defined as "tolerability) threshold" for prolonged dynamic cycling. The product "power x duration" defined by the isoperceptive curves at a "moderate" level of fatigue does in fact reflect the individual aerobic capacity that can be sustained for prolonged dynamic activity (under 60 minutes). In order to validate the hypothesis of tolerability of the functions identified, three further short tests were performed (duration < or = 8.5 minutes) on an ergometric bicycle, with measurement of ventilatory and metabolic parameters.

  2. Variability in Hoffmann and tendon reflexes in healthy male subjects

    NASA Technical Reports Server (NTRS)

    Good, E.; Do, S.; Jaweed, M.

    1992-01-01

    There is a time dependent decrease in amplitude of H- and T-reflexes during Zero-G exposure and subsequently an increase in the amplitude of the H-reflex 2-4 hours after return to a 1-G environment. These alterations have been attributed to the adaptation of the human neurosensory system to gravity. The Hoffman reflex (H-reflex) is an acknowledged method to determine the integrity of the monosynaptic reflex arc. However deep tendon reflexes (DTR's or T-reflexes), elicited by striking the tendon also utilize the entire reflex arc. The objective of this study was to compare the variability in latency and amplitude of the two reflexes in healthy subjects. Methods: Nine healthy male subjects, 27-43 years in age, 161-175 cm in height plus 60-86 Kg in weight, underwent weekly testing for four weeks with a Dan-Tec EMG counterpoint EMG system. Subjects were studied prone and surface EMG electrodes were placed on the right and left soleus muscles. The H-reflex was obtained by stimulating the tibial nerve in the politeal fossa with a 0.2 msec square wave pulse delivered at 2 Hz until the maximum H-reflex was obtained. The T-reflex was invoked by tapping the achilles tendon with a self triggering reflex hammer connected to the EMG system. The latencies and amplitudes for the H- and T-reflexes were measured. Results: These data indicate that the amplitudes of these reflexes varied considerably. However, latencies to invoked responses were consistent. The latency of the T-reflex was approximately 3-5 msec longer than the H-reflex. Conclusion: The T-reflex is easily obtained, requires less time, and is more comfortable to perform. Qualitative data can be obtained by deploying self triggering, force plated reflex hammers both in the 1-G and Zero-G environment.

  3. ABO Blood Type and Personality Traits in Healthy Japanese Subjects.

    PubMed

    Tsuchimine, Shoko; Saruwatari, Junji; Kaneda, Ayako; Yasui-Furukori, Norio

    2015-01-01

    There is no scientific consensus that a relationship exists between the ABO blood group and personality traits. However, a recent study hypothesized that the dopamine beta-hydroxylase (DBH) gene is in linkage with the ABO gene. The sample population consisted of 1,427 healthy Japanese subjects who completed the Temperament and Character Inventory (TCI). Each subject's ABO blood type was determined by genotyping the rs8176719 and rs8176746 ABO gene single-nucleotide polymorphisms (SNPs) using a TaqMan genotyping assay. The relationships between the six ABO genotypes or four ABO phenotypes and personality traits were examined using a multivariate analysis of covariance (MANCOVA), controlling for age and sex. The MANCOVA data showed a significant difference in TCI scores among the ABO genotype groups (F [7, 1393] = 3.354, p = 0.001). A subsequent univariate analysis showed a significant difference in the mean scores for Persistence among the genotype groups (F = 2.680, partial η2 = 0.010, p = 0.020). Similarly, dividing the ABO blood type into four phenotypes revealed a significant difference among the phenotype groups (F [7, 1397] = 2.529, p = 0.014). A subsequent univariate analysis showed a significant difference among the phenotype groups in the mean scores for Persistence (F = 2.952, partial η2= 0.006, p = 0.032). We observed a significant association between ABO blood group genotypes and personality traits in a large number of healthy Japanese subjects. However, these results should be regarded as preliminary and should be interpreted with caution because it is possible that the association between ABO blood group genotype and the Persistence trait is relatively weak.

  4. Sonoelastography of Plantar Fascia: Reproducibility and Pattern Description in Healthy Subjects and Symptomatic Subjects.

    PubMed

    Ríos-Díaz, José; Martínez-Payá, Jacinto J; del Baño-Aledo, María Elena; de Groot-Ferrando, Ana; Botía-Castillo, Paloma; Fernández-Rodríguez, David

    2015-10-01

    The purpose of the work reported here was to describe the sonoelastographic appearance of the plantar fascia of healthy volunteers and patients with fasciitis. Twenty-three healthy subjects and 21 patients with plantar fasciitis were examined using B-mode and real-time sonoelastography (RTSR) scanning. B-Mode examination included fascia thickness and echotexture. Echogenicity and echovariation of the color histogram were analyzed. Fasciae were classified into type 1, blue (more elastic); type 2, blue/green (intermediate); or type 3, green (less elastic). RTSE revealed 72.7% of fasciae as type 2, with no significant association with fasciitis (χ(2) = 3.6, df = 2, p = 0.17). Quantitative analysis of the color histogram revealed a significantly greater intensity of green (mean = 77.8, 95% confidence interval [CI] = 71.9-83.6) and blue (mean = 74.2, 95% CI = 69.7-78.8) in healthy subjects. Echovariation of the color red was 33.4% higher in the fasciitis group than in the healthy group (95% CI = 16.7-50.1). Sonoelastography with quantitative analysis of echovariation can be a useful tool for evaluation of plantar fascia pathology.

  5. Cardio-ventilatory coupling in young healthy resting subjects

    PubMed Central

    Dick, Thomas E.; Jacono, Frank J.; Loparo, Kenneth A.; Yeganeh, Amir; Fishman, Mikkel; Wilson, Christopher G.; Strohl, Kingman P.

    2012-01-01

    In this work, cardio-ventilatory coupling (CVC) refers to the statistical relationship between the onset of either inspiration (I) or expiration (E) and the timing of heartbeats (R-waves) before and after these respiratory events. CVC was assessed in healthy, young (<45 yr), resting, supine subjects (n = 19). Four intervals were analyzed: time from I-onset to both the prior R-wave (R-to-I) and the following R-wave (I-to-R), as well as time from E-onset to both the prior R-wave (R-to-E) and following R-wave (E-to-R). The degree of coupling was quantified in terms of transformed relative Shannon entropy (tRSE), and χ2 tests based on histograms of interval times from 200 breaths. Subjects were studied twice, from 5 to 27 days apart, and the test-retest reliability of CVC measures was computed. Several factors pointed to the relative importance of the R-to-I interval compared with other intervals. Coupling was significantly stronger for the R-to-I interval, coupling reliability was largest for the R-to-I interval, and only tRSE for the R-to-I interval was correlated with height, weight, and body surface area. The high test-retest reliability for CVC in the R-to-I interval provides support for the hypothesis that CVC strength is a subject trait. Across subjects, a peak ∼138 ms prior to I-onset was characteristic of CVC in the R-to-I interval, although individual subjects also had earlier peaks (longer R-to-I intervals). CVC for the R-to-I interval was unrelated to two separate measures of respiratory sinus arrhythmia (RSA), suggesting that these two forms of coupling (CVC and RSA) are independent. PMID:22267392

  6. Low-salt diet increases insulin resistance in healthy subjects.

    PubMed

    Garg, Rajesh; Williams, Gordon H; Hurwitz, Shelley; Brown, Nancy J; Hopkins, Paul N; Adler, Gail K

    2011-07-01

    Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium <20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium >150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 ± 12.5 years (range, 18-65) and with body mass index of 25.3 ± 4.0 kg/m(2), were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 ± 1.6 vs 2.4 ± 1.7, P < .01). Serum aldosterone (21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL, P < .001), 24-hour urine aldosterone (63.0 ± 34.0 vs 9.5 ± 6.5 μg/d, P < .001), and 24-hour urine norepinephrine excretion (78.0 ± 36.7 vs 67.9 ± 39.8 μg/d, P < .05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation.

  7. Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment.

    PubMed

    Güntekin, Bahar; Emek-Savaş, Derya Durusu; Kurt, Pınar; Yener, Görsev Gülmen; Başar, Erol

    2013-01-01

    The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersen's criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15-20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes.

  8. Population pharmacokinetics of darbepoetin alfa in healthy subjects

    PubMed Central

    Agoram, Balaji; Sutjandra, Liviawati; Sullivan, John T

    2007-01-01

    Aim To develop and evaluate a population pharmacokinetic (PK) model of the long-acting erythropoiesis-stimulating protein, darbepoetin alfa in healthy subjects. Methods PK profiles were obtained from 140 healthy subjects receiving single intravenous and/or single or multiple subcutaneous doses of darbepoetin alfa (0.75–8.0 µg kg−1, or either 80 or 500 µg). Data were analysed by a nonlinear mixed-effects modelling approach using NONMEM software. Influential covariates were identified by covariate analysis emphasizing parameter estimates and their confidence intervals, rather than stepwise hypothesis testing. The model was evaluated by comparing simulated profiles (obtained using the covariate model) to the observed profiles in a test dataset. Results The population PK model, including first-order absorption, two-compartment disposition and first-order elimination, provided a good description of data. Modelling indicated that for a 70-kg human, the observed nearly twofold disproportionate dose–exposure relationship at the 8.0 µg kg−1-dose relative to the 0.75 µg kg−1-dose may reflect changing relative bioavailability, which increased from ∼48% at 0.75 µg kg−1 to 78% at 8.0 µg kg−1. The covariate analysis showed that increasing body weight may be related to increasing clearance and central compartment volume, and that the absorption rate constant decreased with increasing age. The full covariate model performed adequately in a fixed-effects prediction test against an external dataset. Conclusion The developed population PK model describes the inter- and intraindividual variability in darbepoetin alfa PK. The model is a suitable tool for predicting the PK response of darbepoetin alfa using clinically untested dosing regimens. PMID:16939525

  9. ABO Blood Type and Personality Traits in Healthy Japanese Subjects

    PubMed Central

    Tsuchimine, Shoko; Saruwatari, Junji; Kaneda, Ayako; Yasui-Furukori, Norio

    2015-01-01

    There is no scientific consensus that a relationship exists between the ABO blood group and personality traits. However, a recent study hypothesized that the dopamine beta-hydroxylase (DBH) gene is in linkage with the ABO gene. The sample population consisted of 1,427 healthy Japanese subjects who completed the Temperament and Character Inventory (TCI). Each subject’s ABO blood type was determined by genotyping the rs8176719 and rs8176746 ABO gene single-nucleotide polymorphisms (SNPs) using a TaqMan genotyping assay. The relationships between the six ABO genotypes or four ABO phenotypes and personality traits were examined using a multivariate analysis of covariance (MANCOVA), controlling for age and sex. The MANCOVA data showed a significant difference in TCI scores among the ABO genotype groups (F [7, 1393] = 3.354, p = 0.001). A subsequent univariate analysis showed a significant difference in the mean scores for Persistence among the genotype groups (F = 2.680, partial η2 = 0.010, p = 0.020). Similarly, dividing the ABO blood type into four phenotypes revealed a significant difference among the phenotype groups (F [7, 1397] = 2.529, p = 0.014). A subsequent univariate analysis showed a significant difference among the phenotype groups in the mean scores for Persistence (F = 2.952, partial η2= 0.006, p = 0.032). We observed a significant association between ABO blood group genotypes and personality traits in a large number of healthy Japanese subjects. However, these results should be regarded as preliminary and should be interpreted with caution because it is possible that the association between ABO blood group genotype and the Persistence trait is relatively weak. PMID:25978647

  10. Dispositional Mindfulness and Subjective Time in Healthy Individuals

    PubMed Central

    Weiner, Luisa; Wittmann, Marc; Bertschy, Gilles; Giersch, Anne

    2016-01-01

    How a human observer perceives duration depends on the amount of events taking place during the timed interval, but also on psychological dimensions, such as emotional-wellbeing, mindfulness, impulsivity, and rumination. Here we aimed at exploring these influences on duration estimation and passage of time judgments. One hundred and seventeen healthy individuals filled out mindfulness (FFMQ), impulsivity (BIS-11), rumination (RRS), and depression (BDI-sf) questionnaires. Participants also conducted verbal estimation and production tasks in the multiple seconds range. During these timing tasks, subjects were asked to read digits aloud that were presented on a computer screen. Each condition of the timing tasks differed in terms of the interval between the presentation of the digits, i.e., either short (4-s) or long (16-s). Our findings suggest that long empty intervals (16-s) are associated with a relative underestimation of duration, and to a feeling that the time passes slowly, a seemingly paradoxical result. Also, regarding more mindful individuals, such a dissociation between duration estimation and passage of time judgments was found, but only when empty intervals were short (4-s). Relatively speaking, more mindful subjects showed an increased overestimation of durations, but felt that time passed more quickly. These results provide further evidence for the dissociation between duration estimation and the feeling of the passage of time. We discuss these results in terms of an alerting effect when empty intervals are short and events are more numerous, which could mediate the effect of dispositional mindfulness. PMID:27303344

  11. Effect of Cabotegravir on Cardiac Repolarization in Healthy Subjects

    PubMed Central

    Lou, Yu; Buchanan, Ann M.; Chen, Shuguang; Ford, Susan L.; Gould, Elizabeth; Margolis, David; Spreen, William R.

    2016-01-01

    Abstract A randomized, partial‐blind, repeat‐dose, 3‐period crossover study (NCT02027454) assessed the effect of cabotegravir on QT interval in healthy subjects. To achieve a supratherapeutic dose, each subject received cabotegravir 150 mg (30 mg × 5 tablets) every 12 hours for a total of 3 doses over 2 days, matching placebo (every 12 hours) over 2 days, or a single open‐label 400‐mg dose of the positive control moxifloxacin, with a 21‐day washout between treatments. Blood samples for pharmacokinetic analyses were collected up to 24 hours after the third dose on day 2. QT interval data were obtained by continuous Holter monitoring for approximately 24 hours at baseline (day ‐1) and from 2 hours before to 24 hours after the third dose on day 2. Plasma cabotegravir exposure was approximately 3‐fold above clinically relevant doses. After 3 doses of 150 mg of cabotegravir administered every 12 hours, all upper limits of 2‐sided 90% confidence intervals for ΔΔQTcF (difference in time‐matched change from baseline for QTcF between cabotegravir and placebo) were <10 milliseconds. There was no relationship between cabotegravir plasma concentrations and ΔΔQTcF. No subject receiving cabotegravir had a QTcF value > 450 milliseconds. There were no serious or grade 3 or 4 adverse events or clinically significant changes in laboratory values, vital signs, or electrocardiogram results. These data demonstrate that cabotegravir at a supratherapeutic dose had no effect on cardiac repolarization. PMID:27162089

  12. Subjective Visual Vertical during Caloric Stimulation in Healthy Subjects: Implications to Research and Neurorehabilitation

    PubMed Central

    Funabashi, Martha; Flores, Aline I.; Vicentino, Amanda; Barros, Camila G. C.; Pontes-Neto, Octavio M.; Leite, João P.; Santos-Pontelli, Taiza E. G.

    2015-01-01

    Background. The subjective visual vertical (SVV) is a perception often impaired in patients with neurologic disorders and is considered a sensitive tool to detect otolithic dysfunctions. However, it remains unclear whether the semicircular canals (SCCs) are also involved in the visual vertical perception. Objective. The aim of this study was to analyze the influence of horizontal SCCs on SVV by caloric stimulation in healthy subjects. Methods. SVV was performed before and during the ice-cold caloric stimulation (4°C, right ear) in 30 healthy subjects. Results. The mean SVV tilts before and during the caloric stimulation were 0.31° ± 0.39 and −0.28° ± 0.40, respectively. There was no significant difference between the mean SVV tilts before and during stimulation (p = 0.113). Conclusion. These results suggest that horizontal SCCs do not influence SVV. Therefore, investigations and rehabilitation approaches for SVV misperceptions should be focused on otolithic and cognitive strategies. PMID:26161271

  13. Acute effects of coffee on QT interval in healthy subjects

    PubMed Central

    2011-01-01

    The coronary endothelial function is recognized to have an important role in the physiology of the diastolic ventricular relaxation, a phase of the heart cycle that influences the electrocardiographic QT interval. Endothelial function is investigated in vivo by flow mediated dilation (FMD) in the brachial artery and has proven to be a strong predictor of both coronary endothelial function and cardiovascular events. It has been reported that coffee acutely induces FMD changes. In particular, the brachial artery FMD seems to decrease after caffeinated coffee (CC) and to increase after decaffeinated coffee (DC) ingestion. Since the cardiovascular effects of coffee are still a debated matter, this study aimed at investigating with a randomized, double-blind crossover design, if the QT interval of adult healthy subjects (19 males and 21 females) changes in the hour following CC or DC ingestion. Both systolic and diastolic blood pressure were higher in the hour following the ingestion of CC; the heart rate significantly increased 30 minutes after CC ingestion. A significant increase of the QT duration was observed one hour after DC ingestion (398.9 ± 3.8 vs 405.3 ± 3.7 msec; P < 0.05), not after CC. The QT interval corrected for heart rate did not significantly change following CC or DC ingestion. In conclusion, despite CC and DC previously demonstrated to influence the FMD they do not seem to induce a significant unfavourable acute change of the left ventricular repolarization. Further investigations are required to elucidate the effects of coffee in subjects with cardiovascular diseases. PMID:21288364

  14. Transcutaneous Electrical Nerve Stimulation Improves Exercise Tolerance in Healthy Subjects.

    PubMed

    Tomasi, F P; Chiappa, G; Maldaner da Silva, V; Lucena da Silva, M; Lima, A S C G B; Arena, R; Bottaro, M; Cipriano, G

    2015-07-01

    Transcutaneous electrical nerve stimulation (TENS) increases peripheral blood flow by attenuation of the muscle metaboreflex, improving oxygen supply to working muscles. We tested the hypothesis that application of TENS at ganglion improves exercise performance. 11 subjects underwent constant-work rate tests (CWR) to the limit of tolerance (Tlim) while receiving TENS or placebo. Oxygen uptake (V.O2), carbon dioxide (V.CO2), minute ventilation (V.E), ventilatory equivalent (V.E/V.CO2), heart rate (HR) and oxygen pulse (V.O2/HR) were analyzed at isotime separated by percentile and Tlim. V.O2 was lower and V.CO2 was higher at 100% of isotime during TENS, while there were no differences in V.E and V.E/V.CO2. HR was lower during exercise with TENS, and V.O2/HR increased at peak exercise (17.96±1.9 vs. 20.38±1 ml/min/bpm, P<0.05). TENS increased mechanical efficiency at isotime and Tlim (4.10±0.50 vs. 3.39±0.52%, P<0.05 and 3.95±0.67 vs. 3.77±0.45%, P<0.05) and exercise tolerance compared to P-TENS (390±41 vs. 321±41 s; P<0.05). Our data shows that the application of TENS can potentially increase exercise tolerance and oxygen supply in healthy subjects.

  15. Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects

    PubMed Central

    Jochemsen, Roeline; Wesselman, J. G. J.; van Boxtel, C. J.; Hermans, J.; Breimer, D. D.

    1983-01-01

    1 Pharmacokinetics of oral brotizolam (0.50 mg) and triazolam (0.50 mg) were studied in healthy young volunteers. 2 The plasma concentration profile of brotizolam can be described as a one compartmental open model with first-order absorption. The absorption of triazolam was less regular and in half of the subjects was not consistent with first-order kinetics. Inter-individual variability in absorption rate (peak times) was larger for brotizolam. 3 Mean peak times were 1.1 ± 1.0 h for brotizolam and 1.2 ± 0.5 h for triazolam. Mean peak concentrations were 7.3 ± 3.1 ng/ml and 5.0 ± 3.9 ng/ml respectively. 4 The elimination half-life of brotizolam was twice that of triazolam with mean values of 5.0 ± 1.1 h and 2.6 ± 0.7 h respectively. There was no correlation between the half-lives of the two drugs. 5 Protein unbound fraction was similar for triazolam and brotizolam with mean values of 9.9 ± 1.5% and 8.4 ± 0.7% respectively. PMID:6140948

  16. Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

    PubMed

    Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

    2010-01-01

    Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

  17. Comparative analysis of actigraphy performance in healthy young subjects.

    PubMed

    Bellone, Giannina J; Plano, Santiago A; Cardinali, Daniel P; Chada, Daniel Pérez; Vigo, Daniel E; Golombek, Diego A

    2016-01-01

    Sleep-related health disorders are increasing worldwide; diagnosis and treatment of such sleep diseases are commonly invasive and sometimes unpractical or expensive. Actigraphy has been recently introduced as a tool for the study of sleep and circadian disorders; however, there are several devices that claim to be useful for research and have not been thoroughly tested. This comparative study provides activity, sleep and temperature information regarding several of the most commonly used actigraphers: Micro-Mini Motion Logger; Act Trust; Misfit Flash; Fitbit Flex & Thermochron. Twenty-two healthy young subjects were assessed with five different commercial actigraphs (Micro-Mini Motionlogger Watch, Condor Act Trust, MisFit Flash and Fitbit Flex) and a temperature recorder (Thermochron), and also completed a sleep diary for a week. There were not significant differences in the analysis of rest-activity pattern between devices. Temperature rhythm comparison between the Act Trust and the Thermochron showed significant differences in rhythm percentage (p<0.05) and mesor (p<0.0563) but not in amplitude or acrophase. Although data accessibility and ease of use was very different for the diverse devices, there were no significant differences for sleep onset, total sleep time and sleep efficiency recordings, where applicable. In conclusion, depending on the type of study and analysis desired (as well as cost and compliance of use), we propose some relative advantages for the different actigraphy/temperature recording devices.

  18. Interactions of manganese, iron, and copper in healthy human subjects

    SciTech Connect

    Lin, Paohwa.

    1989-01-01

    In study I, plasma levels of manganese and iron were measured after an oral load was ingested. Four hourly samples of plasma were collected postdose. The ingestion of a dose of 40 mg Mn alone produced a typical response in plasma manganese, which peaked at either the first or second hour postdose. When a combined dose of 40 mg inorganic Fe plus 40 mg Mn was given, the plasma uptake of manganese was substantially inhibited when compared to a dose of 40 mg Mn alone. When the same quantity of heme Fe was substituted for the inorganic Fe in the load of inorganic Fe plus Mn, no depression in plasma manganese was observed. In study II, eight healthy female subjects were fed a baseline Mn-adequate diet of conventional foods for 18 days, followed by a Mn-deficient semi-purified diet for 41 days. Dietary levels of iron and copper averaged 17.7 mg and 4.3 mg/day, respectively, for both diets. Mean iron balance increased significantly from initial levels of 2.20 {plus minus} 1.07 mg/d to 5.02 {plus minus} 1.14 mg/d at the end of the Mn-deficient period. Parameters of iron status were not influenced by the variations of dietary manganese. In contrast, mean copper balance decreased from 2.61 {plus minus} 0.1 mg/d to 0.91 {plus minus} 0.4 mg/d at the end of the Mn-deficient period. Correspondingly, plasma copper and serum ceruloplasmin decreased from 18.57 {plus minus} 1.1 {mu}mol/L to 15.27 {plus minus} 0.94 {mu}mol/L and 269.1 {plus minus} 14.6 mg/L to 205.6 {plus minus} 17.8 mg/L., respectively.

  19. ULTRAFINE PARTICLE DEPOSITION IN HEALTHY SUBJECTS VS. PATIENTS WTH COPD

    EPA Science Inventory

    Individuals affected with chronic obstructive pulmonary disease (COPD) have increased susceptibility to adverse health effects from exposure to particulate air pollution. The dosimetry of ultrafine aerosols (diameter # 0.1 :m) is not well characterized in the healthy or diseas...

  20. Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects

    PubMed Central

    Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A.; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

    2017-01-01

    Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m−2) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO2), continuously adjusted to reach arterial oxygen saturations (SpO2) of 70–80% for 1 h. IH sessions consisted of 5 min with reduced FiO2 (SpO2 = 70–80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results: Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min−1) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (−8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH −6 ± 5%, IH −3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (−13 ± 3% vs. −6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in

  1. Spontaneous Swallowing during All-Night Sleep in Patients with Parkinson Disease in Comparison with Healthy Control Subjects

    PubMed Central

    Uludag, Irem Fatma; Tiftikcioglu, Bedile Irem; Ertekin, Cumhur

    2016-01-01

    Study Objectives: Spontaneous saliva swallows (SS) appear especially during sleep. The rate of SS was rarely investigated in all-night sleep in patients with Parkinson disease (PD). Dysphagia is a frequent symptom in PD, but the rate of SS was never studied with an all-night sleep electroencephalogram (EEG). Methods: A total of 21 patients with PD and 18 age-matched healthy controls were included in the study. Frequencies of SS and coughing were studied in all-night sleep recordings of patients with PD and controls. During all-night sleep, video-EEG 12-channel recording was used including the electromyography (EMG) of the swallowing muscles, nasal airflow, and recording of vertical laryngeal movement using a pair of EEG electrodes over the thyroid cartilage. Results: The total number of SS was increased while the mean duration of sleep was decreased in PD when compared to controls. Sialorrhea and clinical dysphagia, assessed by proper questionnaires, had no effect in any patient group. The new finding was the so-called salvo type of consecutive SS in one set of swallowing. The amount of coughing was significantly increased just after the salvo SS. Conclusions: In PD, the rate of SS was not sufficient to demonstrate the swallowing disorder, such as oropharyngeal dysphagia, but the salvo type of SS was quite frequent. This is a novel finding and may contribute to the understanding of swallowing problems in patients with dysphagic or nondysphagic PD. Citation: Uludag IF, Tiftikcioglu BI, Ertekin C. Spontaneous swallowing during all-night sleep in patients with Parkinson disease in comparison with healthy control subjects. SLEEP 2016;39(4):847–854. PMID:26943467

  2. Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects.

    PubMed

    Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D; Calhoun, Vince D

    2014-01-01

    Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI) data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA) but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs) in cohorts of healthy controls (HCs) and age matched SZ and BP patients. Subsequently, we investigated difference in functional network connectivity, defined as pairwise correlations among the timecourses of ICNs, between HCs and patients. We quantified differences in both static (average) and dynamic (windowed) connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Notably, results suggest that patients make fewer transitions to some states (states 1, 2, and 4) compared to HCs, with most such differences confined to a single state. SZ patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3). Also group differences between SZ and bipolar patients were identified in patterns (states) of connectivity involving the frontal (dynamic state 1) and frontal-parietal regions (dynamic state 3). Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups.

  3. Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects

    PubMed Central

    Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D.; Calhoun, Vince D.

    2014-01-01

    Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI) data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA) but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs) in cohorts of healthy controls (HCs) and age matched SZ and BP patients. Subsequently, we investigated difference in functional network connectivity, defined as pairwise correlations among the timecourses of ICNs, between HCs and patients. We quantified differences in both static (average) and dynamic (windowed) connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Notably, results suggest that patients make fewer transitions to some states (states 1, 2, and 4) compared to HCs, with most such differences confined to a single state. SZ patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3). Also group differences between SZ and bipolar patients were identified in patterns (states) of connectivity involving the frontal (dynamic state 1) and frontal-parietal regions (dynamic state 3). Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups. PMID:25426048

  4. Dynamic characteristics of laser Doppler flowmetry signals obtained in response to a local and progressive pressure applied on diabetic and healthy subjects

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Koitka, Audrey; Abraham, Pierre; Saumet, Jean-Louis; L'Huillier, Jean-Pierre

    2004-09-01

    In the biomedical field, the laser Doppler flowmetry (LDF) technique is a non-invasive method to monitor skin perfusion. On the skin of healthy humans, LDF signals present a significant transient increase in response to a local and progressive pressure application. This vasodilatory reflex response may have important implications for cutaneous pathologies involved in various neurological diseases and in the pathophysiology of decubitus ulcers. The present work analyses the dynamic characteristics of these signals on young type 1 diabetic patients, and on healthy age-matched subjects. To obtain accurate dynamic characteristic values, a de-noising wavelet-based algorithm is first applied to LDF signals. All the de-noised signals are then normalised to the same value. The blood flow peak and the time to reach this peak are then calculated on each computed signal. The results show that a large vasodilation is present on signals of healthy subjects. The mean peak occurs at a pressure of 3.2 kPa approximately. However, a vasodilation of limited amplitude appears on type 1 diabetic patients. The maximum value is visualised, on the average, when the pressure is 1.1 kPa. The inability for diabetic patients to increase largely their cutaneous blood flow may bring explanations to foot ulcers.

  5. Comparative gait analysis between children with autism and age-matched controls: analysis with temporal-spatial and foot pressure variables.

    PubMed

    Lim, Bee-Oh; O'Sullivan, David; Choi, Bum-Gwon; Kim, Mi-Young

    2016-01-01

    [Purpose] The purpose of this study was to investigate the gait pattern of children with autism by using a gait analysis system. [Subjects] Thirty children were selected for this study: 15 with autism (age, 11.2 ± 2.8 years; weight, 48.1 ± 14.1 kg; height, 1.51 ± 0.11 m) and 15 healthy age-matched controls (age, 11.0 ± 2.9 years; weight, 43.6 ± 10 kg; height, 1.51 ± 0.011 m). [Methods] All participants walked three times on the GAITRite(®) system while their plantar pressure was being recorded. [Results] The results showed a reduction in cadence, gait velocity, and step length, and an increase in step width in children with autism. Plantar pressure variables highlight the differences between the active pressure areas, especially in the hindfoot of children with autism. [Conclusion] The results suggest that children with autism have an abnormal gait compared with that of age-matched controls, and thus they need extra attention to correct these abnormal gait patterns.

  6. Linear and angular control of circular walking in healthy older adults and subjects with cerebellar ataxia.

    PubMed

    Goodworth, Adam D; Paquette, Caroline; Jones, Geoffrey Melvill; Block, Edward W; Fletcher, William A; Hu, Bin; Horak, Fay B

    2012-05-01

    Linear and angular control of trunk and leg motion during curvilinear navigation was investigated in subjects with cerebellar ataxia and age-matched control subjects. Subjects walked with eyes open around a 1.2-m circle. The relationship of linear to angular motion was quantified by determining the ratios of trunk linear velocity to trunk angular velocity and foot linear position to foot angular position. Errors in walking radius (the ratio of linear to angular motion) also were quantified continuously during the circular walk. Relative variability of linear and angular measures was compared using coefficients of variation (CoV). Patterns of variability were compared using power spectral analysis for the trunk and auto-covariance analysis for the feet. Errors in radius were significantly increased in patients with cerebellar damage as compared to controls. Cerebellar subjects had significantly larger CoV of feet and trunk in angular, but not linear, motion. Control subjects also showed larger CoV in angular compared to linear motion of the feet and trunk. Angular and linear components of stepping differed in that angular, but not linear, foot placement had a negative correlation from one stride to the next. Thus, walking in a circle was associated with more, and a different type of, variability in angular compared to linear motion. Results are consistent with increased difficulty of, and role of the cerebellum in, control of angular trunk and foot motion for curvilinear locomotion.

  7. Pharmacokinetics of oral ciprofloxacin in healthy, young Brazilian subjects.

    PubMed

    Sudo, R T; Melo, P A; Suarez-Kurtz, G

    1990-01-01

    1. The pharmacokinetics of ciprofloxacin were determined in 8 healthy young volunteers (5 men and 3 women) after administration of single oral doses of 250 mg. 2. The peak plasma concentration of ciprofloxacin (Cmax = 1.26 +/- 0.21 mg/l), the time to reach Cmax (Tmax = 1.99 +/- 0.26 h), the area under the time-plasma concentration curve (AUC = 5.52 +/- 0.84 mg h l-1), the terminal phase half-life (T1/2 = 3.05 +/- 0.56 h), the volume of distribution (Vd/F = 195.4 +/- 14.0 l) and total body clearance (CL/F = 46.3 +/- 2.6 l/h), both expressed as functions of the oral bioavailability (F) of ciprofloxacin were within the corresponding values reported in the literature for other healthy population groups. 3. Multiple dose administration (250 mg, po, twice daily for 4 days) did not result in accumulation of ciprofloxacin in plasma. No adverse side effects occurred during the study. 4. The pharmacokinetic data are discussed in relation to the minimum inhibitory concentration (MIC) of ciprofloxacin for a number of common pathogens isolated from human infections in Rio de Janeiro.

  8. [Effects of nifuroxazide on fecal flora in healthy subjects].

    PubMed

    Buisson, Y; Larribaud, J

    1989-01-01

    Effect of nifuroxazide on fecal flora was studied in 12 healthy volunteers receiving, in hazardous order and double-blind procedure, three six-days courses of treatment separated by eight-days spaces of time: the conventional dosage of 400 mg twice a day, a dosage of 1200 mg once a day, and placebo. Among six settled bacteriological index (wealth of the fecal flora, percentage of gram-negative bacteria, numbers of E. coli, Enterococcus, Clostridium and Bacteroides), no significant variation was found by means of statistical study between D0, D2 and D7, nor between the three courses of treatment. Therefore nifuroxazide, even in high dosage, does not injure integrity of microbial intestinal ecosystem under so defined experimental conditions, similar with clinical conditions.

  9. Influence of biperiden and bornaprine on sleep in healthy subjects.

    PubMed

    Hohagen, F; Lis, S; Riemann, D; Krieger, S; Meyer, C; Montero, R F; Grunze, H; Berger, M

    1994-08-01

    Biperiden, 4 mg, an anticholinergic drug that is relatively selective for the M1 receptor subtype, and bornaprine, 4 mg, a nonselective M1 and M2 antagonist, were administered orally in a randomized, double-blind design to twelve healthy volunteers to investigate the effect on polysomnographically recorded sleep. Both drugs suppressed rapid eye movement (REM) sleep as reflected by an increase of REM latency and a decrease in the percentage of REM sleep period time with the effects of biperiden being more pronounced. No significant effect on slow wave sleep was observed. The results of this study support the hypothesis that both the M1 and the M2 receptor subtype are involved in the regulation of REM sleep in humans.

  10. Neurochemical and psychotropic effects of bupropion in healthy male subjects.

    PubMed

    Gobbi, Gabriella; Slater, Susan; Boucher, Nathalie; Debonnel, Guy; Blier, Pierre

    2003-06-01

    Bupropion is a weak inhibitor of noradrenaline (NE) and dopamine (DA) reuptake and has no direct action on serotonin (5-HT) neuronal elements. In the rat brain, bupropion suppresses NE neuron firing activity via the activation of alpha(2)-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons. Twenty-five healthy young male volunteers, with no previous history of psychiatric disorders, were randomized to one of four 7-day regimens: placebo, bupropion (150 mg) once daily, bupropion (150 mg) twice a day, and methylphenidate SR (20 mg daily). To assess the activity of the NE reuptake process, the blood pressure response to intravenous tyramine was determined. A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition. Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration, with a decrease serving as an index of 5-HT reuptake blockade. The Profile of Mood States (POMS) scale was used to assess behavioral and psychological changes. Neither bupropion nor methylphenidate altered the tyramine pressor response, in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors. Neither drug modified 5-HT concentrations. However, POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness, agreeability, and energy, whereas 300 mg/day improved only attention. In contrast, methylphenidate improved only energy. These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans. Presumably it enhances synaptic availability of NE by increasing release. Yet, because its behavioral profile is different from that of methylphenidate, it may not share all the biochemical properties of psychostimulants.

  11. ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

    PubMed Central

    Frankfort, Suzanne V; Doodeman, Valerie D; Bakker, Remco; Tulner, Linda R; van Campen, Jos PCM; Smits, Paul HM; Beijnen, Jos H

    2006-01-01

    Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects. PMID:16999857

  12. A Thorough QT Study of Teduglutide in Healthy Subjects.

    PubMed

    Hartmann, Manfred; Timmer, Wolfgang; Schultz, Armin; Nave, Rüdiger; Luehmann, Reinhold; Krause, Stephan; Lahu, Gezim; Scholpp, Joachim

    2012-04-01

    Teduglutide, an analog of the endogenous hormone glucagon-like peptide-2, is currently being developed for the treatment of short bowel syndrome. This study investigated the potential effects of teduglutide on cardiac conduction and repolarization. Seventy-two healthy volunteers underwent 4 treatment periods in randomized order with a single subcutaneous injection of placebo, 5 and 20 mg teduglutide, and a single oral 400-mg dose of moxifloxacin. The primary variable to investigate the effect on cardiac repolarization was the difference between QTcF after administration versus predose. The observed upper bounds of the 95% one-sided confidence intervals were 3.0 ms (5 mg) and 4.5 ms (20 mg). Arithmetic mean curves of QTcF intervals over time of both doses of teduglutide and of placebo were almost superposable. Assay sensitivity for the positive control moxifloxacin was shown. In conclusion, teduglutide at intended therapeutic and supratherapeutic doses had no effect on cardiac repolarization. No safety concerns were identified. Treatment with teduglutide was well tolerated.

  13. Brivaracetam and carbamazepine interaction in healthy subjects and in vitro.

    PubMed

    Stockis, Armel; Chanteux, Hugues; Rosa, Maria; Rolan, Paul

    2015-07-01

    This phase I, open-label study investigated the effects of steady-state brivaracetam administration on steady-state pharmacokinetics of carbamazepine, and steady-state carbamazepine administration on single-dose and steady-state pharmacokinetics of brivaracetam, in 14 healthy participants who received brivaracetam 200mg single doses on days 1 and 22, and 200mg twice daily (bid) on days 24-35; and were titrated to carbamazepine 300mg bid on days 4-35. Brivaracetam did not significantly alter carbamazepine area under the plasma concentration-time curve (AUC) over a dosing interval, but resulted in a 2.6-fold increase in carbamazepine-epoxide. Carbamazepine decreased brivaracetam AUC by 29%, while hydroxy-brivaracetam metabolite was increased by 17%. Urinary 6β-hydroxycortisol/cortisol ratio was unchanged by brivaracetam, but was increased 3-fold by carbamazepine. In vitro hydrolysis of carbamazepine-epoxide in human hepatocytes was inhibited by brivaracetam, with an IC50 of 8.2μM. Brivaracetam 200mg bid was predicted to increase carbamazepine-epoxide by 2.3-fold, in close agreement with the observed value. In conclusion, brivaracetam did not modify carbamazepine exposure but increased carbamazepine-epoxide. Carbamazepine modestly decreased brivaracetam exposure and increased oxidative metabolism.

  14. Pharmacokinetics of oral cyclosporin A (Sandimmun) in healthy subjects.

    PubMed

    Grevel, J; Nüesch, E; Abisch, E; Kutz, K

    1986-01-01

    Extensive pharmacokinetic (PK) profiles after oral dosing of 300 mg cyclosporin A (CsA) were determined in whole blood by radioimmunoassay (RIA) in 14 healthy male volunteers, using two-compartment models with either first order (M1) or zero order (M0) absorption. According to zero order absorption the mean of the following PK parameters was determined: terminal half-life = 12.1 +/- 5.0 h, apparent volume of distribution at steady-state = 5.6 +/- 2.11 X kg-1, apparent clearance = 0.51 +/- 0.11 l X h-1 X kg-1. The time lag between drug ingestion and first blood level was short, 0.38 +/- 0.11 h. Drug absorption lasted for 2.8 +/- 1.6 h. The end of absorption was indicated in each individual by a sharp drop in blood levels. The observations support the assumption that CsA is absorbed in the upper part of the small intestine with a clear-cut termination (absorption window). This assumption may explain the high degree of variability in the bioavailability of CsA.

  15. Disease-related differences in resting-state networks: a comparison between localized provoked vulvodynia, irritable bowel syndrome, and healthy control subjects.

    PubMed

    Gupta, Arpana; Rapkin, Andrea J; Gill, Zafar; Kilpatrick, Lisa; Fling, Connor; Stains, Jean; Masghati, Salome; Tillisch, Kirsten; Mayer, Emeran A; Labus, Jennifer S

    2015-05-01

    Localized provoked vulvodynia (LPVD) affects approximately 16% of the female population, but biological mechanisms underlying symptoms remain unknown. Like in other often comorbid chronic pain disorders, altered sensory processing and modulation of pain, including central sensitization, dysregulation of endogenous pain modulatory systems, and attentional enhancement of pain perception, have been implicated. The aim of this study was to test whether regions of interest showing differences in LPVD compared to healthy control subjects (HCs) in structural and evoked-pain neuroimaging studies, also show alterations during rest when compared with HCs and a chronic pain control group (irritable bowel syndrome [IBS]). Functional magnetic resonance imaging was performed during resting state in 87 age-matched premenopausal females (29 LPVD, 29 HCs, and 29 IBS). Group-independent component analysis and general linear models were applied to investigate group differences in the intrinsic connectivity of regions comprising sensorimotor, salience, and default mode resting-state networks. Subjects with LPVD showed substantial alterations in the intrinsic connectivity of these networks compared with HCs and IBS. The intrinsic connectivity of many of the regions showing group differences during rest were moderately associated with clinical symptom reports in LPVD. Findings were robust to controlling for affect and medication usage. The current findings indicate that subjects with LPVD have alterations in the intrinsic connectivity of regions comprising the sensorimotor, salience, and default mode networks. Although shared brain mechanisms between different chronic pain disorders have been postulated, the current findings suggest that some alterations in functional connectivity may show disease specificity.

  16. Multivariate morphological brain signatures predict chronic abdominal pain patients from healthy control subjects

    PubMed Central

    Labus, Jennifer S.; Van Horn, John D.; Gupta, Arpana; Alaverdyan, Mher; Torgerson, Carinna; Ashe-McNalley, Cody; Irimia, Andrei; Hong, Jui-Yang; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.

    2015-01-01

    Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood, however evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature which could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical regions was performed using Freesurfer and the Destrieux and Harvard-Oxford atlases. Volume, mean curvature, surface area and cortical thickness were calculated for each region. Sparse partial least squares-discriminant analysis was applied to develop a diagnostic model using a training set of 160 females (80 healthy controls, 80 IBS). Predictive accuracy was assessed in an age matched holdout test set of 52 females (26 health controls, 26 IBS). A two-component classification algorithm comprised of the morphometry of 1) primary somato-sensory and motor regions, and 2) multimodal network regions, explained 36% of the variance. Overall predictive accuracy of the classification algorithm was 70%. Small effect size associations were observed between the somatosensory and motor signature and non-gastrointestinal somatic symptoms. The findings demonstrate the predictive accuracy of a classification algorithm based solely on regional brain morphometry is not sufficient but they do provide support for the utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS. Perspective This article presents the development, optimization, and testing of a classification algorithm for discriminating female IBS patients from healthy controls using only brain morphometry data. The results provide support for utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS. PMID:25906347

  17. Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls.

    PubMed Central

    Gengo, F M; Fagan, S C; Krol, G; Bernhard, H

    1987-01-01

    Six biopsy proven cirrhotics and five age-matched controls (mean 55.3 vs 52.4 years) were randomly given single 60 mg p.o. and 30 mg s.l. doses of nimodipine. Serum concentrations and blood pressure were measured regularly over the subsequent 24 h period. The clearance of nimodipine was reduced in the patients with cirrhosis. Apparent oral clearance of nimodipine in the cirrhotic group was significantly lower than that observed in the normal group (187 +/- 163 l h-1 vs 469.6 +/- 198.4 l h-1, P less than 0.01). There were no significant changes in mean arterial pressure (MAP) in the normal subjects. There were, however, significant reductions in MAP following oral nimodipine in the cirrhotics. These reductions were significantly related to nimodipine concentrations in individual patients (P less than 0.05). PMID:3814462

  18. Characteristics of Vocal Fold Vibrations in Vocally Healthy Subjects: Analysis with Multi-Line Kymography

    ERIC Educational Resources Information Center

    Yamauchi, Akihito; Imagawa, Hiroshi; Sakakibara, Ken-Ichi; Yokonishi, Hisayuki; Nito, Takaharu; Yamasoba, Tatsuya; Tayama, Niro

    2014-01-01

    Purpose: In this study, the authors aimed to analyze longitudinal data from high-speed digital images in normative subjects using multi-line kymography. Method: Vocally healthy subjects were divided into young (9 men and 17 women; M[subscript age] = 27 years) and older groups (8 men and 12 women; M[subscript age] = 73 years). From high-speed…

  19. Are Uric Acid Levels Different from Healthy Subjects in Bipolar Affective Disorder and Schizophrenia?: Relationship Between Clinical Improvement and Episode Severity in Male Patients

    PubMed Central

    GÜLTEKİN, Bülent Kadri; KESEBİR, Sermin; KABAK, Sevgi Gül; ERGÜN, Ferzan Fikret; TATLIDİL YAYLACI, Elif

    2014-01-01

    Introduction Purinergic system dysfunction has been shown both in patients with bipolar disorder (BD) and those with schizophrenia. The aim of this study was to evaluate whether uric acid levels in male BD patients with manic episode and schizophrenia patients with psychotic relapse differ from healthy male subjects. Secondly to assess whether uric acid levels in both patient groups correlate with episode severity and if a decrease in uric acid levels correlate with clinical improvement. Method A total of 55 BD patients with manic episode and 59 schizophrenic patients with psychotic relapse were evaluated at baseline and at weeks 1, 2, 3 using the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS), and their plasma uric acid levels were measured. 60 age-matched healthy males without history of any previous or current psychiatric diagnosis and treatment constituted the control group. In order to determine plasma uric acid levels, blood samples were centrifuged at 3000 × g for 15 minutes, stored at −80°C and measured in milligrams per deciliter. Results Uric acid levels in both patient groups with manic episode and psychotic relapse were found higher than in healthy controls (f=6.122, p=.027). The difference between repeated measurements of uric acid levels in BD patient group was found to be between baseline and first week measurements (after Bonferroni correction) (p<.001). No correlation was found between YMRS and PANSS scores and uric acid levels at 4 assessment times. Conclusion Uric acid levels in male BD and schizophrenia patients with manic episode and psychotic relapse were similar with each other, and higher than in healthy males. No correlation was found between uric acid levels and episode severity in both groups. However, for patients with BD, a decrease in uric acid levels between baseline and first week seems to be correlated with clinical improvement.

  20. Effect of the stringency of conditions on caloric test results in healthy subjects.

    PubMed

    Krstulovic, Claudio; Tulsidas Mahtani, Bharti; Atrache Al Attrache, Nabil; Pérez-Garrigues, Herminio

    The caloric test is widely used to assess vestibular function, but the conditions in which it is performed can vary. Caloric nystagmus obtained in 57 healthy subjects were compared: 24 subjects studied in ideal conditions and 33 subjects in non-ideal conditions. A statistically significant decrease in the slow phase velocity of the 4 irrigations performed on the subjects in non-ideal conditions was observed. This must be considered, especially in subjects with suspected bilateral involvement. Stringent conditions reduce the risk of misdiagnosis with bilateral deficit.

  1. Comparison of static postural balance between healthy subjects and those with low back pain

    PubMed Central

    Braga, Alice Bernardi; Rodrigues, Ana Carolina de Mello Alves; de Lima, Giliane Vanessa Moraes Pereira; de Melo, Larissa Rabello; de Carvalho, Alberito Rodrigo; Bertolini, Gladson Ricardo Flor

    2012-01-01

    Objective To compare the static postural balance between women suffering from chronic low back pain and healthy subjects, by moving the center of pressure. Methods The study included 15 women with low back pain (LBP group) and 15 healthy women (healthy group). They were instructed to remain in standing on the force platform for 30 seconds. We analyzed the area and the speed of displacement of center of pressure of both groups. Data analysis was performed using the Student's t-test, with significance of 5%. Results Individuals with chronic low back pain showed a larger area of displacement of the center of pressure relative to the healthy ones but there was no significant difference in the speed of displacement of the center of pressure. Conclusion Individuals with chronic low back pain had alterations in static balance with respect to healthy ones. Level of Evidence III, Prognostic Studies. PMID:24453604

  2. Variability of the perception of dyspnea in healthy subjects assessed through inspiratory resistive loading*

    PubMed Central

    Ziegler, Bruna; Fernandes, Andréia Kist; Sanches, Paulo Roberto Stefani; Konzen, Glauco Luís; Dalcin, Paulo de Tarso Roth

    2015-01-01

    Objective: Few studies have evaluated the variability of the perception of dyspnea in healthy subjects. The objective of this study was to evaluate the variability of the perception of dyspnea in healthy subjects during breathing against increasing inspiratory resistive loads, as well as to assess the association between the level of perception of dyspnea and the level of physical activity. Methods: This was a cross-sectional study involving healthy individuals 16 years of age or older. Subjects underwent inspiratory resistive loading testing, in which the level of perception of dyspnea was quantified with the modified Borg scale. We also determined body mass indices (BMIs), assessed maximal respiratory pressures, performed pulmonary function tests, applied the international physical activity questionnaire (IPAQ)-long form, and conducted six-minute walk tests (6MWTs). The level of perception of dyspnea was classified as low (Borg score < 2), intermediate (Borg score, 2-5), or high (Borg score > 5). Results: We included 48 healthy subjects in the study. Forty-two subjects completed the test up to a load of 46.7 cmH2O/L/s. The level of perception of dyspnea was classified as low, intermediate, and high in 13, 19, and 10 subjects, respectively. The level of perception of dyspnea was not significantly associated with age, gender, BMI, IPAQ-long form score, maximal respiratory pressures, or pulmonary function test results. Conclusions: The scores for perceived dyspnea induced by inspiratory resistive loading in healthy subjects presented wide variability. The perception of dyspnea was classified as low in 31% of the subjects, intermediate in 45%, and high in 24%. There was no association between the level of perception of dyspnea and the level of physical activity (IPAQ or six-minute walk distance). PMID:25830380

  3. Objective assessment of mastication predominance in healthy dentate subjects and patients with unilateral posterior missing teeth.

    PubMed

    Yamasaki, Y; Kuwatsuru, R; Tsukiyama, Y; Oki, K; Koyano, K

    2016-08-01

    We aimed to investigate mastication predominance in healthy dentate individuals and patients with unilateral posterior missing teeth using objective and subjective methods. The sample comprised 50 healthy dentate individuals (healthy dentate group) and 30 patients with unilateral posterior missing teeth (partially edentulous group). Subjects were asked to freely chew three kinds of test foods (peanuts, beef jerky and chewing gum). Electromyographic activity of the bilateral masseter muscles was recorded. The chewing side (right side or left side) was judged by the level of root mean square electromyographic amplitude. Mastication predominance was then objectively assessed using the mastication predominant score and the mastication predominant index. Self-awareness of mastication predominance was evaluated using a modified visual analogue scale. Mastication predominance scores of the healthy dentate and partially edentulous groups for each test food were analysed. There was a significant difference in the distribution of the mastication predominant index between the two groups (P < 0·05). The mastication predominant score was weakly correlated with self-awareness of mastication predominance in the healthy dentate group, whereas strong correlation was observed in the partially edentulous group (P < 0·05). The results suggest that the individuals with missing unilateral posterior teeth exhibited greater mastication predominance and were more aware of mastication predominance than healthy dentate individuals. Our findings suggest that an objective evaluation of mastication predominance is more precise than a subjective method.

  4. Strategies to minimize risks and exploitation in phase one trials on healthy subjects.

    PubMed

    Shamoo, Adil E; Resnik, David B

    2006-01-01

    Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors.

  5. Strategies to Minimize Risks and Exploitation in Phase One Trials on Healthy Subjects*

    PubMed Central

    Shamoo, Adil E.; Resnik, David B.

    2014-01-01

    Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. PMID:16754430

  6. Reduced postural differences between phobic postural vertigo patients and healthy subjects during a postural threat.

    PubMed

    Holmberg, Johan; Tjernström, Fredrik; Karlberg, Mikael; Fransson, Per Anders; Magnusson, Måns

    2009-08-01

    Phobic postural vertigo is characterized by subjective imbalance and dizziness while standing or walking, despite normal values for clinical balance tests. Patients with phobic postural vertigo exhibit an increased high-frequency sway in posturographic tests. Their postural sway, however, becomes similar to the sway of healthy subjects during difficult balance tasks. Posturographic recordings of 30 s of quiet stance was compared to recordings of 30 s of quiet stance during a postural threat, which consisted of the knowledge of forthcoming vibratory calf muscle stimulation, in 37 consecutive patients with phobic postural vertigo and 24 healthy subjects. During quiet stance without the threat of forthcoming vibratory stimulation, patients with phobic postural vertigo exhibited a postural sway containing significantly more high-frequency sway than the healthy subjects. During the quiet stance with forthcoming vibratory stimulation, i.e., anticipation of a postural threat, the significant differences between groups disappeared for all variables except sagittal high-frequency sway. During postural threat, healthy subjects seemed to adopt a postural strategy that was similar to that exhibited by phobic postural vertigo patients. The lack of additional effects facing a postural threat among phobic postural vertigo patients may be due to an already maximized postural adaptation. Deviant postural reactions among patients with phobic postural vertigo may be considered as an avoidant postural response due to a constant fear of losing postural control.

  7. Sex differences in emotion-related cognitive processes in irritable bowel syndrome and healthy control subjects.

    PubMed

    Labus, Jennifer S; Gupta, Arpana; Coveleskie, Kristen; Tillisch, Kirsten; Kilpatrick, Lisa; Jarcho, Johanna; Feier, Natasha; Bueller, Joshua; Stains, Jean; Smith, Suzanne; Suyenobu, Brandall; Naliboff, Bruce; Mayer, Emeran A

    2013-10-01

    Greater responsiveness of emotional arousal circuits in relation to delivered visceral pain has been implicated as underlying central pain amplification in irritable bowel syndrome (IBS), with female subjects showing greater responses than male subjects. Functional magnetic resonance imaging was used to measure neural responses to an emotion recognition paradigm, using faces expressing negative emotions (fear and anger). Sex and disease differences in the connectivity of affective and modulatory cortical circuits were studied in 47 IBS (27 premenopausal female subjects) and 67 healthy control subjects (HCs; 38 premenopausal female subjects). Male subjects (IBS+HC) showed greater overall brain responses to stimuli than female subjects in prefrontal cortex, insula, and amygdala. Effective connectivity analyses identified major sex- and disease-related differences in the functioning of brain networks related to prefrontal regions, cingulate, insula, and amygdala. Male subjects had stronger connectivity between anterior cingulate subregions, amygdala, and insula, whereas female subjects had stronger connectivity to and from the prefrontal modulatory regions (medial/dorsolateral cortex). Male IBS subjects demonstrate greater engagement of cortical and affect-related brain circuitry compared to male control subjects and female subjects, when viewing faces depicting emotions previously shown to elicit greater behavioral and brain responses in male subjects.

  8. Evaluation of the Highly Variable Agomelatine Pharmacokinetics in Chinese Healthy Subjects to Support Bioequivalence Study

    PubMed Central

    Hu, Zhe-Yi; Liu, Shi-Kun; Tan, Hong-Yi; Guo, Cheng-Xian; Zhang, Ran-Ran; Xiang, Yu-Xia; Huang, Jie; Huang, Lu; Yuan, Hong; Yang, Guo-Ping

    2014-01-01

    Objectives We aim to obtain the intra-subject coefficient of variability of a highly variable antidepressant agomelatine in humans, and propose an adjusted bioequivalence assessment strategy. Methods A single-dose, randomized crossover design was conducted in four periods (reference administered thrice, placebo administered once) separated by seven days. A validated LC-MS/MS assay was used to measure drug concentrations in serial blood samples. Results The intra-subject coefficient of variability was calculated using the residual variance of ANOVA analysis, and the results for Cmax and AUC0-t was 78.34% and 43.52%, respectively, in Chinese healthy subjects. The sample size required for standard BE study were 124(192, 340) if the expected deviation between the reference and generic products was set to 0 (5%, 10%). Conclusions Agomelatine meets the criteria for highly variable drug in Chinese healthy male subjects, and the traditional BE criteria for agomelatine needs to be adjusted to alleviate the resource and ethical burden of using a large numbers of subjects in clinical trials. Our clinical data on the intra-subject variability of agomelatine PK in Chinese healthy population enables to adjust bioequivalence (BE) assessment approach for agomelatine based on the RSABE approaches recommended by regulatory agencies. Trial Registration ChiCTR.org ChiCTR-TTRCC-13003835 PMID:25330096

  9. Volumes and Breathing Patterns during Speech in Healthy and Asthmatic Subjects.

    ERIC Educational Resources Information Center

    Loudon, Robert G.; And Others

    1988-01-01

    Lung volumes and ventilatory patterns used by 10 healthy and 14 asthmatic subjects during conversation, monologue, and counting at two loudness levels were studied. Asthmatics were found to favor respiratory over communications needs. They used a greater percentage of their reduced vital capacity, with slower inspiratory and faster expiratory flow…

  10. Molecular Analysis of Malassezia Microflora on the Skin of Atopic Dermatitis Patients and Healthy Subjects

    PubMed Central

    Sugita, Takashi; Suto, Hajime; Unno, Tetsushi; Tsuboi, Ryoji; Ogawa, Hideoki; Shinoda, Takako; Nishikawa, Akemi

    2001-01-01

    Members of the genus Malassezia, lipophilic yeasts, are considered to be one of the exacerbating factors in atopic dermatitis (AD). We examined variation in cutaneous colonization by Malassezia species in AD patients and compared it with variation in healthy subjects. Samples were collected by applying transparent dressings to the skin lesions of AD patients. DNA was extracted directly from the dressings and amplified in a specific nested PCR assay. Malassezia-specific DNA was detected in all samples obtained from 32 AD patients. In particular, Malassezia globosa and M. restricta were detected in approximately 90% of the AD patients and M. furfur and M. sympodialis were detected in approximately 40% of the cases. The detection rate was not dependent on the type of skin lesion. In healthy subjects, Malassezia DNA was detected in 78% of the samples, among which M. globosa, M. restricta, and M. sympodialis were detected at frequencies ranging from 44 to 61%, with M. furfur at 11%. The diversity of Malassezia species found in AD patients was greater (2.7 species detected in each individual) than that found in healthy subjects (1.8 species per individual). Our results suggest that M. furfur, M. globosa, M. restricta, and M. sympodialis are common inhabitants of the skin of both AD patients and healthy subjects, while the skin microflora of AD patients shows more diversity than that of healthy subjects. To our knowledge, this is the first report of the use of a nested PCR as an alternative to fungal culture for analysis of the distribution of cutaneous Malassezia spp. PMID:11574560

  11. Quasispecies analysis of JC virus DNA present in urine of healthy subjects.

    PubMed

    Van Loy, Tom; Thys, Kim; Tritsmans, Luc; Stuyver, Lieven J

    2013-01-01

    JC virus is a human polyomavirus that infects the majority of people without apparent symptoms in healthy subjects and it is the causative agent of progressive multifocal leucoencephalopathy (PML), a disorder following lytic infection of oligodendrocytes that mainly manifests itself under immunosuppressive conditions. A hallmark for JC virus isolated from PML-brain is the presence of rearrangements in the non-coding control region (NCCR) interspersed between the early and late genes on the viral genome. Such rearrangements are believed to originate from the archetype JC virus which is shed in urine by healthy subjects and PML patients. We applied next generation sequencing to explore the non-coding control region variability in urine of healthy subjects in search for JC virus quasispecies and rearrangements reminiscent of PML. For 61 viral shedders (out of a total of 254 healthy subjects) non-coding control region DNA and VP1 (major capsid protein) coding sequences were initially obtained by Sanger sequencing. Deletions between 1 and 28 nucleotides long appeared in ∼24.5% of the NCCR sequences while insertions were only detected in ∼3.3% of the samples. 454 pyrosequencing was applied on a subset of 54 urine samples demonstrating the existence of JC virus quasispecies in four subjects (∼7.4%). Hence, our results indicate that JC virus DNA in urine is not always restricted to one unique virus variant, but can be a mixture of naturally occurring variants (quasispecies) reflecting the susceptibility of the non-coding control region for genomic rearrangements in healthy individuals. Our findings pave the way to explore the presence of viral quasispecies and the altered viral tropism that might go along with it as a potential risk factor for opportunistic secondary infections such as PML.

  12. Test-Retest Reliability of Sudden Ankle Inversion Measurements in Subjects With Healthy Ankle Joints

    PubMed Central

    Eechaute, Christophe; Vaes, Peter; Duquet, William; Van Gheluwe, Bart

    2007-01-01

    Context: Sudden ankle inversion tests have been used to investigate whether the onset of peroneal muscle activity is delayed in patients with chronically unstable ankle joints. Before interpreting test results of latency times in patients with chronic ankle instability and healthy subjects, the reliability of these measures must be first demonstrated. Objective: To investigate the test-retest reliability of variables measured during a sudden ankle inversion movement in standing subjects with healthy ankle joints. Design: Validation study. Setting: Research laboratory. Patients or Other Participants: 15 subjects with healthy ankle joints (30 ankles). Intervention(s): Subjects stood on an ankle inversion platform with both feet tightly fixed to independently moveable trapdoors. An unexpected sudden ankle inversion of 50° was imposed. Main Outcome Measure(s): We measured latency and motor response times and electromechanical delay of the peroneus longus muscle, along with the time and angular position of the first and second decelerating moments, the mean and maximum inversion speed, and the total inversion time. Correlation coefficients and standard error of measurements were calculated. Results: Intraclass correlation coefficients ranged from 0.17 for the electromechanical delay of the peroneus longus muscle (standard error of measurement = 2.7 milliseconds) to 0.89 for the maximum inversion speed (standard error of measurement = 34.8 milliseconds). Conclusions: The reliability of the latency and motor response times of the peroneus longus muscle, the time of the first and second decelerating moments, and the mean and maximum inversion speed was acceptable in subjects with healthy ankle joints and supports the investigation of the reliability of these measures in subjects with chronic ankle instability. The lower reliability of the electromechanical delay of the peroneus longus muscle and the angular positions of both decelerating moments calls the use of these

  13. Effect of hyperhydration on bone mineralization in physically healthy subjects after prolonged restriction of motor activity

    NASA Astrophysics Data System (ADS)

    Zorbas, Yan G.; Federenko, Youri F.; Naexu, Konstantin A.

    The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on bone mineralization in physically healthy male volunteers after exposure to hypokinesia (decreased number of steps taken/day) over a period of 364 days. The studies were performed after exposure to 364 days of hypokinesia (HK) on 18 physically healthy male volunteers who had an average VO2max of 65 ml/kg/min and were aged between 19 and 24 years. For the simulation of the hypokinetic effect the volunteers were kept under an average of 1000 steps/day. The subjects were divided into three equal groups of 6: 6 underwent a normal ambulatory life (control group), 6 were placed under HK (hypokinetic group) and the remaining 6 were subjected to HK and consumed a daily FSS (water 26 ml/kg body wt and NaCl 0.10 mg/kg body wt) (hyperhydrated group). The density of the ulnar, radius, tibia, fibular, lumbar vertebrae and calcenous was measured. Calcium and phosphorus changes, plasma volume, blood pressure and body weight were determined. Calcium content in the examined skeletal bones decreased more in the hypokinetic subjects than in the hyperhydrated subjects. Urinary calcium and phosphorus losses were more pronounced in hypokinetic than hyperhydrated subjects. Plasma volume and body weight increased in hyperhydrated subjects, while it decreased in hypokinetic subjects. It was concluded that a daily intake of FSS may be used to neutralize bone demineralization in physically healthy subjects during prolonged restriction of motor activity.

  14. Neural Mechanisms of Verb Argument Structure Processing in Agrammatic Aphasic and Healthy Age-Matched Listeners

    ERIC Educational Resources Information Center

    Thompson, Cynthia K.; Bonakdarpour, Borna; Fix, Stephen F.

    2010-01-01

    Processing of lexical verbs involves automatic access to argument structure entries entailed within the verb's representation. Recent neuroimaging studies with young normal listeners suggest that this involves bilateral posterior peri-sylvian tissue, with graded activation in these regions on the basis of argument structure complexity. The aim of…

  15. Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects.

    PubMed Central

    Lewis, R V; Ramsay, L E; Jackson, P R; Yeo, W W; Lennard, M S; Tucker, G T

    1991-01-01

    1. The effects of single doses of metoprolol 50 mg, metoprolol 100 mg and atenolol 100 mg on exercise tolerance were compared with placebo in a double-blind random cross-over study in 12 healthy subjects. Nine subjects were extensive metabolisers of debrisoquine, and three were poor metabolisers. 2. Three hours after dosing beta-adrenoceptor blocker treatments significantly reduced exercise heart rate, prolonged time to complete exercise, and increased subjective fatigue measured by visual analogue scale. 3. Scores for subjective fatigue did not correlate with reduction in exercise heart rate or prolongation of exercise time. Exercise time prolongation was weakly but not significantly correlated with exercise heart rate reduction. 4. When compared with placebo, prolongation of exercise time and increased fatigue with metoprolol were not significantly related to debrisoquine oxidation phenotype or to the debrisoquine/4-hydroxydebrisoquine (D/4OH-D) ratio. 5. When metoprolol responses were compared with those for atenolol, changes in exercise time and fatigue scores were significantly related to oxidation phenotype. For metoprolol 100 mg, poor metabolisers required 20.8 s longer to complete exercise (P less than 0.05) and had higher fatigue scores by 78% (P less than 0.05) as compared with extensive metabolisers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2049246

  16. Haemodynamic responses in young and elderly, healthy subjects during ambient and warm head-up tilt.

    PubMed

    Lye, M; Walley, T

    1998-05-01

    1. Postural hypotension is common in elderly people and is usually multifactorial in origin. In young subjects increased ambient temperature is associated with postural symptoms. We hypothesized that such increases in skin temperature due to the use of bed clothes might contribute to nocturnal postural hypotension in the elderly. We therefore studied haemodynamic responses to head-up tilt in healthy elderly and young subjects, with and without passive heating induced by covering with blankets. 2. Nine young (28.7 +/- 1.5 years; mean +/- S.E.M.) and nine elderly (71.9 +/- 1.8 years) subjects were studied. All had been carefully screened to exclude factors likely to affect responses to tilt. All subjects underwent a standard head-up tilt procedure at ambient room temperature while haemodynamic responses were monitored. The subjects were then covered in blankets for 55 min and the tilt repeated. Skin temperature before the second tilt had increased from approximately 32.5 degrees C to approximately 35.2 degrees C (P < 0.001). 3. The elderly subjects maintained higher blood pressures throughout both tilts (P < 0.001) and both groups showed similar qualitative responses to tilt. Supine heart rates were higher in the elderly group (P < 0.01) with a tendency to increase more in the young group in response to tilt, especially while warm (P = 0.370). Stroke volumes and cardiac indices were consistently higher in the young group who showed larger changes during both head-up tilts. In both groups the haemodynamic responses to ambient and warm tilt were essentially the same. 4. Healthy elderly subjects, who are carefully screened to exclude individuals with cardiovascular pathology, respond to head-up tilt in the same qualitative fashion as young subjects. Quantitative responses in older subjects are 'damped'. Short-term natural body warming does not impair the reflexes in young or old subjects.

  17. Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects

    PubMed Central

    Moulier, Virginie; Gaudeau-Bosma, Christian; Isaac, Clémence; Allard, Anne-Camille; Bouaziz, Noomane; Sidhoumi, Djedia; Braha-Zeitoun, Sonia; Benadhira, René; Thomas, Fanny; Januel, Dominique

    2016-01-01

    Background High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. Objective Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. Design In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency) or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs), and the Ekman 60 faces test. Results The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. Conclusion This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life. PMID:26993786

  18. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.

    PubMed

    Ma, Jing; Chang, Jessica; Checklin, Helen L; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2010-09-01

    It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0.9% saline) or control (0.9% saline) at 4 ml/min for 150 min (T = - 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2.5 %), were co-infused intraduodenally (T = 0-120 min; 4.2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P < 0.005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.

  19. Immediate effects of bilateral manipulation of talocrural joints on standing stability in healthy subjects.

    PubMed

    Alburquerque-Sendín, Francisco; Fernández-de-las-Peñas, César; Santos-del-Rey, Miguel; Martín-Vallejo, Francisco Javier

    2009-02-01

    The purpose of this study was to investigate the immediate effects of bilateral talocrural joint manipulation on standing stability in healthy subjects. Sixty-two healthy subjects, 16 males and 46 females, aged from 18 to 32 years old (mean: 21+/-3 years old) participated in the study. Subjects were randomly divided into two groups: an intervention group (n=32), who received manipulation of bilateral talocrural joints and a control group (n=30) which did not receive any intervention. Baropodometric and stabilometric evaluations were assessed pre- and 5 min post-intervention by an assessor blinded to the treatment allocation. Intra-group and inter-group comparisons were analysed using appropriate parametric tests. The results indicated that changes on the X coordinate range, length of motion, and mean speed approximated to statistical significance (P=0.06), and changes on the Y coordinate range reached statistical significance (P=0.02). Average X and Y motions, and anterior-posterior or lateral velocities did not show significant differences. Our results showed that bilateral thrust manipulation of the talocrural joint did not modify standing stability, that is, the behavioural pattern of the projection of the centre of pressure, in healthy subjects.

  20. Pharmacokinetics of orally administered oseltamivir in healthy obese and nonobese Thai subjects.

    PubMed

    Jittamala, Podjanee; Pukrittayakamee, Sasithon; Tarning, Joel; Lindegardh, Niklas; Hanpithakpong, Warunee; Taylor, Walter Robert John; Lawpoolsri, Saranath; Charunwattana, Prakaykaew; Panapipat, Salwaluk; White, Nicholas J; Day, Nicholas P J

    2014-01-01

    Oseltamivir is the most widely used anti-influenza drug. In the 2009 H1N1 pandemic, in which the influenza viruses were oseltamivir sensitive, obesity was identified as a risk factor for severe disease and unfavorable outcomes. The aim of this study was to investigate the pharmacokinetic properties of oseltamivir and its active metabolite, oseltamivir carboxylate, in obese and nonobese healthy subjects. A single-dose, randomized, two-sequence crossover study was conducted in 12 obese and 12 nonobese healthy Thai volunteers. Each volunteer was given 75 mg and 150 mg oseltamivir orally with an intervening washout period of more than 3 days. The pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated using a noncompartmental approach. The median (range) body mass indexes (BMIs) for obese subjects were 33.8 kg/m(2) (30.8 to 43.2) and 22.2 (18.8 to 24.2) for nonobese subjects. The pharmacokinetic parameters of oseltamivir carboxylate, the active metabolite of oseltamivir, were not significantly different between obese and nonobese subjects for both 75-mg and 150-mg doses. Both doses were well tolerated. Despite the lower dose per kilogram body weight in obese subjects, there was no significant difference in the exposure of oseltamivir carboxylate between the obese and nonobese groups. Standard dosing is appropriate for obese subjects. (The study was registered at ClinicalTrials.gov under registration no. NCT 01049763.).

  1. Parietal rTMS distorts the mental number line: simulating 'spatial' neglect in healthy subjects.

    PubMed

    Göbel, Silke M; Calabria, Marco; Farnè, Alessandro; Rossetti, Yves

    2006-01-01

    Patients with left-sided visuospatial neglect, typically after damage to the right parietal lobe, show a systematic bias towards larger numbers when asked to bisect a numerical interval. This has been taken as further evidence for a spatial representation of numbers, perhaps akin to a mental number line with smaller numbers represented to the left and larger numbers to the right. Previously, contralateral neglect-like symptoms in physical line bisection have been induced in healthy subjects with repetitive transcranial magnetic stimulation (rTMS) over right posterior parietal lobe. Here we used rTMS over parietal and occipital sites in healthy subjects to investigate spatial representations in a number bisection task. Subjects were asked to name the midpoint of numerical intervals without calculating. On control trials subjects' behaviour was similar to performance reported in physical line bisection experiments. Subjects underestimated the midpoint of the numerical interval. Repetitive transcranial magnetic stimulation produced representational neglect-like symptoms in number bisection when applied over right posterior parietal cortex (right PPC). Repetitive TMS over right PPC shifted the perceived midpoint of the numerical interval significantly to the right while occipital TMS had no effect on bisection performance. Our study therefore provides further evidence that subjects use spatial representations, perhaps akin to a mental number line, in basic numerical processing tasks. Furthermore, we showed that the right posterior parietal cortex is crucially involved in spatial representation of numbers.

  2. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects

    NASA Technical Reports Server (NTRS)

    Meier-Ewert, H. K.; Ridker, P. M.; Rifai, N.; Price, N.; Dinges, D. F.; Mullington, J. M.

    2001-01-01

    BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation. METHODS: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.

  3. Levels of common salivary protein 1 in healthy subjects and periodontal patients

    PubMed Central

    2016-01-01

    Purpose Human saliva, as a vital part of the immune defense system, contains a number of distinct proteins and peptides. Recently human common salivary protein 1 (CSP1) has been identified as an abundant salivary protein and may play a role in promoting the binding of cariogenic bacteria to salivary pellicles. However, nothing else is known regarding the role of CSP1 in periodontology. The aim of this study was to quantify and compare CSP1 levels between healthy subjects and periodontal patients. Methods This controlled clinical study was conducted in periodontally healthy individuals and patients with chronic periodontitis Chonbuk National University Hospital, with Institutional Review Board approval. Whole saliva samples were collected from 36 healthy subjects and 33 chronic periodontitis patients and analyzed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immune blotting were conducted to ensure that anti-CSP1 monoclonal antibody (mAb) binds to CSP1 in human saliva. A sandwich enzyme-linked immunosorbent assay (ELISA) system was house-fabricated using mAb-hCSP1#14 and mAb-hCSP1#4 as a capture and a detector mAb, respectively. The CSP1 concentrations in saliva from 36 healthy subjects and 33 periodontal patients were quantified using the CSP1 sandwich ELISA system, and the results were analyzed using the Student’s t-test. Results Immunoblot analysis using mAb-hCSP1 as a probe confirmed that CSP1 in human saliva existed as a single band with a molecular weight of approximately 27-kDa. The quantification of CSP1 concentrations by CSP1 ELISA showed that the median values (25th to 75th percentiles) of periodontal patients and healthy subjects were 9,474 ng/mL (range, 8,434–10,139 ng/mL) and 8,598 ng/mL (range, 7,421–9,877 ng/mL), respectively. The Student’s t-test indicated the presence of a statistically significant difference between the 2 groups (P=0.024). Conclusions The presence of a significant difference in CSP1 levels between healthy

  4. Natural Course of Metabolically Healthy Overweight/Obese Subjects and the Impact of Weight Change.

    PubMed

    Zheng, Ruizhi; Liu, Chengguo; Wang, Chunmei; Zhou, Biao; Liu, Yi; Pan, Feixia; Zhang, Ronghua; Zhu, Yimin

    2016-07-15

    Few studies have described the characteristics of metabolically healthy individuals with excess fat in the Chinese population. This study aimed to prospectively investigate the natural course of metabolically healthy overweight/obese (MH-OW/OB) adults, and to assess the impact of weight change on developing metabolic abnormalities. During 2009-2010, 525 subjects without any metabolic abnormalities or other obesity-related diseases were evaluated and reevaluated after 5 years. The subjects were categorized into two groups of overweight/obese and normal weight based on the criteria of BMI by 24.0 at baseline. At follow-up, the MH-OW/OB subjects had a significantly increased risk of developing metabolically abnormalities compared with metabolically healthy normal-weight (MH-NW) individuals (risk ratio: 1.35, 95% confidence interval: 1.17-1.49, p value < 0.001). In the groups of weight gain and weight maintenance, the MH-OW/OB subjects was associated with a larger increase in fasting glucose, triglycerides, systolic blood pressure, diastolic blood pressure and decrease in high-density lipoprotein cholesterol comparing with MH-NW subjects. In the weight loss group, no significant difference of changes of metabolic parameters was observed between MH-OW/OB and MH-NW adults. This study verifies that MH-OW/OB are different from MH-NW subjects. Weight management is needed for all individuals since weight change has a significant effect on metabolic health without considering the impact of weight change according to weight status.

  5. Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects.

    PubMed

    Smith, Matthew J; Cobia, Derin J; Reilly, James L; Gilman, Jodi M; Roberts, Andrea G; Alpert, Kathryn I; Wang, Lei; Breiter, Hans C; Csernansky, John G

    2015-09-01

    Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis.

  6. Outcome over seven years of healthy adults with and without subjective cognitive impairment

    PubMed Central

    Reisberg, Barry; Shulman, Melanie B.; Torossian, Carol; Leng, Ling; Zhu, Wei

    2011-01-01

    Background Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. Methods A consecutive series of healthy subjects, aged ≥40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 ± 9.1 years, was well-educated (mean, 15.5 ± 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 ± 1.2). Results A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 ± 3.4 years, and subjects had a mean of 2.9 ± 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined (P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer’s disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9–10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45–0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects (P = .0003). Conclusions These results indicate that SCI in subjects with normal cognition is a harbinger

  7. Pharmacokinetics and safety of the sesame lignans, sesamin and episesamin, in healthy subjects.

    PubMed

    Tomimori, Namino; Tanaka, Yasuhiro; Kitagawa, Yoshinori; Fujii, Wataru; Sakakibara, Yutaka; Shibata, Hiroshi

    2013-11-01

    A single-blind, placebo-controlled, parallel-group and multiple oral dose study was conducted in 48 healthy subjects to investigate the pharmacokinetics and safety of multiple oral doses of sesame lignans (sesamin and episesamin). Subjects were randomly divided into two groups. Each subject was administered 50 mg of sesame lignans (sesamin/episesamin=1/1) or placebo once daily for 28 days. The pharmacokinetics of the sesame lignans were investigated using 10 of the 24 subjects in the sesame lignans group. No serious adverse events were observed in this study. Sesamin was absorbed with a peak plasma concentration at 5.0 h. The plasma concentration of the main metabolite, SC-1, reached a peak at 5.0 h and decreased rapidly with a terminal half-life of 2.4 h. Episesamin was also absorbed with a peak plasma concentration at 5.0 h and decreased with a terminal half-life of 7.1 h. The plasma concentration of the main metabolite, EC-1, reached a peak at 5.0 h and decreased rapidly with a terminal half-life of 3.4 h. The plasma concentrations of sesamin and episesamin reached a steady state by day 7. Sesame lignans were confirmed to be safe and tolerable in healthy subjects. The results of the pharmacokinetic study demonstrate that no accumulation was observed following multiple 50 mg doses of sesame lignans.

  8. Classification of heart rate signals of healthy and pathological subjects using threshold based symbolic entropy.

    PubMed

    Aziz, Wajid; Rafique, M; Ahmad, I; Arif, M; Habib, Nazneen; Nadeem, M S A

    2014-09-01

    The dynamical fluctuations of biological signals provide a unique window to construe the underlying mechanism of the biological systems in health and disease. Recent research evidences suggest that a wide class of diseases appear to degrade the biological complexity and adaptive capacity of the system. Heart rate signals are one of the most important biological signals that have widely been investigated during the last two and half decades. Recent studies suggested that heart rate signals fluctuate in a complex manner. Various entropy based complexity analysis measures have been developed for quantifying the valuable information that may be helpful for clinical monitoring and for early intervention. This study is focused on determining HRV dynamics to distinguish healthy subjects from patients with certain cardiac problems using symbolic time series analysis technique. For that purpose, we have employed recently developed threshold based symbolic entropy to cardiac inter-beat interval time series of healthy, congestive heart failure and atrial fibrillation subjects. Normalized Corrected Shannon Entropy (NCSE) was used to quantify the dynamics of heart rate signals by continuously varying threshold values. A rule based classifier was implemented for classification of different groups by selecting threshold values for the optimal separation. The findings indicated that there is reduction in the complexity of pathological subjects as compared to healthy ones at wide range of threshold values. The results also demonstrated that complexity decreased with disease severity.

  9. The Traditional Kampo Medicine Tokishakuyakusan Increases Ocular Blood Flow in Healthy Subjects

    PubMed Central

    Takayama, Shin; Shiga, Yukihiro; Kokubun, Taiki; Konno, Hideyuki; Himori, Noriko; Ryu, Morin; Numata, Takehiro; Kaneko, Soichiro; Kuroda, Hitoshi; Tanaka, Junichi; Kanemura, Seiki; Ishii, Tadashi; Yaegashi, Nobuo; Nakazawa, Toru

    2014-01-01

    The aim of this study was to examine the effects of oral administration of kampo medical formulas on ocular blood flow (OBF). A crossover protocol was used to randomly administer five grams of yokukansan, tokishakuyakusan (TSS), keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3 ± 12.3 years). The mean blur rate, a quantitative OBF index obtained with laser speckle flowgraphy, was measured at the optic nerve head before and 30 minutes after administration. Blood pressure (BP) and intraocular pressure (IOP) were also recorded. No significant changes were observed in mean BP or IOP after the administration of any of the kampo medical formulas. There was a significant increase in OBF 30 minutes after administration of TSS (100% to 103.6 ± 6.9%, P < 0.01). Next, TSS was administered to 19 healthy subjects (mean age: 32.0 ± 11.0 years) and OBF was measured before and 15, 30, 45, and 60 minutes after administration. Plain water was used as a control. OBF increased significantly after TSS administration compared to control (P < 0.01) and also increased from 30 to 60 minutes after administration compared to baseline (P < 0.05). These results suggest that TSS can increase OBF without affecting BP or IOP in healthy subjects. PMID:24872835

  10. Advantages of EEG phase patterns for the detection of gait intention in healthy and stroke subjects

    NASA Astrophysics Data System (ADS)

    Ioana Sburlea, Andreea; Montesano, Luis; Minguez, Javier

    2017-06-01

    Objective. One use of EEG-based brain–computer interfaces (BCIs) in rehabilitation is the detection of movement intention. In this paper we investigate for the first time the instantaneous phase of movement related cortical potential (MRCP) and its application to the detection of gait intention. Approach. We demonstrate the utility of MRCP phase in two independent datasets, in which 10 healthy subjects and 9 chronic stroke patients executed a self-initiated gait task in three sessions. Phase features were compared to more conventional amplitude and power features. Main results. The neurophysiology analysis showed that phase features have higher signal-to-noise ratio than the other features. Also, BCI detectors of gait intention based on phase, amplitude, and their combination were evaluated under three conditions: session-specific calibration, intersession transfer, and intersubject transfer. Results show that the phase based detector is the most accurate for session-specific calibration (movement intention was correctly detected in 66.5% of trials in healthy subjects, and in 63.3% in stroke patients). However, in intersession and intersubject transfer, the detector that combines amplitude and phase features is the most accurate one and the only that retains its accuracy (62.5% in healthy subjects and 59% in stroke patients) w.r.t. session-specific calibration. Significance. MRCP phase features improve the detection of gait intention and could be used in practice to remove time-consuming BCI recalibration.

  11. Differentiation of Schizophrenia Patients from Healthy Subjects by Mismatch Negativity and Neuropsychological Tests

    PubMed Central

    Lin, Yi-Ting; Liu, Chih-Min; Chiu, Ming-Jang; Liu, Chen-Chung; Chien, Yi-Ling; Hwang, Tzung-Jeng; Jaw, Fu-Shan; Shan, Jia-Chi; Hsieh, Ming H.; Hwu, Hai-Gwo

    2012-01-01

    Background Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. Methodology/Principal Findings 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%). Conclusions/Significance MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility. PMID:22496807

  12. Relationship Between Retinal Perfusion and Retinal Thickness in Healthy Subjects: An Optical Coherence Tomography Angiography Study

    PubMed Central

    Yu, Jian; Gu, Ruiping; Zong, Yuan; Xu, Huan; Wang, Xiaolei; Sun, Xinghuai; Jiang, Chunhui; Xie, Bing; Jia, Yali; Huang, David

    2016-01-01

    Purpose To investigate the relationship between retinal perfusion and retinal thickness in the peripapillary and macular areas of healthy subjects. Methods Using spectral-domain optic coherence tomography and split-spectrum amplitude decorrelation angiography (SSADA) algorithm, retinal perfusion and retinal thicknesses in the macular and peripapillary areas were measured in healthy volunteers, and correlations among these variables were analyzed. Results Overall, 64 subjects (121 eyes) including 28 males and 36 females with a mean ± SD age of 38 ± 13 years participated. Linear mixed-models showed that vessel area density was significantly correlated with the inner retinal thickness (from the inner limiting membrane to the outer border of the inner nucleus layer; P < 0.05), but not with the thickness of the full retina (P > 0.05) in the parafoveal area. The area of the foveal capillary-free zone was negatively correlated with the inner and full foveal thicknesses (all P < 0.001). In the peripapillary area, the vessel area density was positively correlated with the thickness of the retinal nerve fiber layer (P < 0.001). Conclusions In healthy subjects, retinal perfusion in small vessels was closely correlated with the thickness of the inner retinal layers in both the macular and peripapillary areas. PMID:27409474

  13. Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

    PubMed

    Derosa, G; D'Angelo, A; Salvadeo, S A T; Ferrari, I; Fogari, E; Gravina, A; Mereu, R; Palumbo, I; Maffioli, P; Randazzo, S; Cicero, A F G

    2010-01-01

    The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

  14. Aggression, Suicidality, and Intermittent Explosive Disorder: Serotonergic Correlates in Personality Disorder and Healthy Control Subjects

    PubMed Central

    Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J

    2010-01-01

    Central serotonergic (5-HT) activity has long been implicated in the regulation of impulsive aggressive behavior. This study was performed to use a highly selective agent for 5-HT (d-Fenfluramine, d-FEN) in a large group of human subjects to further explore this relationship dimensionally and categorically. One hundred and fifty healthy subjects (100 with personality disorder, PD and 50 healthy volunteer controls, HV) underwent d-FEN challenge studies. Residual peak delta prolactin (ΔPRL[d-FEN]-R; ie, after the removal of potentially confounding variables) was used as the primary 5-HT response variable. Composite measures of aggression and impulsivity were used as dimensional measures, and history of suicidal/self-injurious behavior as well as the presence of intermittent explosive disorder (IED) were used as categorical variables. ΔPRL[d-FEN]-R responses correlated inversely with composite aggression, but not composite impulsivity, in all subjects and in males and females examined separately. The correlation with composite aggression was strongest in male PD subjects. ΔPRL[d-FEN]-R values were reduced in PD subjects with a history of suicidal behavior but not, self-injurious behavior. ΔPRL[d-FEN]-R values were also reduced in patients meeting Research Criteria for IED. Physiologic responses to 5-HT stimulation are reduced as a function of aggression (but not generalized impulsivity) in human subjects. The same is true for personality disordered subjects with a history of suicidal, but not self-injurious, behavior and for subjects with a diagnosis of IED by research criteria. These data have particular relevance to the notion of impulsive aggression and the biological validity of IED. PMID:19776731

  15. Which oropharyngeal factors are significant risk factors for obstructive sleep apnea? An age-matched study and dentist perspectives

    PubMed Central

    Ruangsri, Supanigar; Jorns, Teekayu Plangkoon; Puasiri, Subin; Luecha, Thitisan; Chaithap, Chariya; Sawanyawisuth, Kittisak

    2016-01-01

    Objective Obstructive sleep apnea (OSA) is a common sleep breathing disorder. Untreated OSA may lead to a number of cardiovascular complications. Dentists may play an important role in OSA detection by conducting careful oral examinations. This study focused on the correlation of oral anatomical features in Thai patients who presented with OSA. Methods We conducted a prospective comparative study at a sleep/hypertension clinic and a dental clinic at Khon Kaen University in Thailand. Patients with OSA were enrolled in the study, along with age-matched patients with non-OSA (controls). Baseline characteristics, clinical data, and oropharyngeal data of all patients were compared between the two groups. Oropharyngeal measurements included tongue size, torus mandibularis, Mallampati classification, palatal space, and lateral pharyngeal wall area. Multivariate logistic regression analysis was used to identify the factors associated with OSA. Results During the study period, there were 156 patients who met the study criteria; 78 were patients with OSA and the other 78 were healthy control subjects. In the OSA group, there were 43 males with a mean age of 53 (standard deviation 12.29) years and a mean BMI of 30.86 kg/mm2. There were 37 males in the control group with a mean age of 50 (standard deviation 12.04) years and a mean BMI of 24.03 kg/mm2. According to multivariate logistic analysis, three factors were perfectly associated with OSA, including torus mandibularis class 6, narrow lateral pharyngeal wall, and Mallampati class 4. There were two other significant factors associated with having OSA, namely, BMI and Mallampati classification. The adjusted odds ratios (95% confidence interval) of these two factors were 1.445 (1.017, 2.052) and 5.040 (1.655, 15.358), respectively. Conclusion Dentists may play an important role in the detection of OSA in patients with high BMI through careful oropharyngeal examination in routine dental treatment. A large torus mandibularis

  16. Cognitive functions related to interpersonal problem-solving skills in schizophrenic patients compared with healthy subjects.

    PubMed

    Zanello, Adriano; Perrig, Lisa; Huguelet, Philippe

    2006-05-30

    Subjects with schizophrenia have cognitive alterations. The functional consequences of these deficits need to be fully determined, in order to implement more effective rehabilitation programs for patients with schizophrenia. This research explores the relationships between cognitive functioning and social problem-solving skills in a group of 20 chronic schizophrenic patients compared with those found in a group of 20 healthy subjects. The following cognitive domains were evaluated: verbal memory (Rey Auditory-Verbal Test; RAVLT), visuo-spatial organization and visuo-spatial memory (Rey-Osterrieth complex figure test; RF), executive functioning (semantic verbal fluency test; VF, design fluency task; DF and Wisconsin Card Sorting Test; WCST), attention (d 2 cancellation test) and general intellectual ability (Standard Progressive Matrices of Raven; SPM). Social problem-solving skills were assessed with a video-based test; the Assessment of Interpersonal Problem-Solving Skills (AIPSS). As a group, patients performed significantly worse than control subjects on every cognitive variable and on AIPSS receiving, processing and sending constructs. Among schizophrenic patients, correlations between AIPSS constructs and neuropsychological tests were observed for VF, DF, d2 and SPM whilst these associations were not replicated in healthy subjects. However, in the whole sample, after adjusting for age, gender and education, SPM displayed significant associations with all three AIPSS constructs. Moreover, after taking SPM into account, neither diagnostic groups (patients versus control) nor cognitive variables, except d2, provided an additional contribution to AIPSS performance. Cognitive impaired performances, mainly frontal, have a deleterious effect on social problem-solving skills in the schizophrenic group. It is suggested that alterations in social problem-solving skills may reflect social anxiety and/or " theory of mind " impairment. These factors may explain the lack of

  17. Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects.

    PubMed

    Pandya, Jayesh M; Lundell, Anna-Carin; Hallström, Magnus; Andersson, Kerstin; Nordström, Inger; Rudin, Anna

    2016-10-01

    The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25(+) CD127(low) and also FOXP3 CXCR5(+) cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4(+)CXCR3(-) (Th2 and Th17), CTLA4(+) and FOXP3(+) subsets were present in significantly higher frequencies, whereas CCR4(-) (Th1/Th17, CCR6(+)CCR4(-)CXCR3(-), and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3(+)/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4(+)CXCR3(-) T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of

  18. Subjective, Psychomotor, and Physiological Effects of Pregabalin Alone and in Combination With Oxycodone in Healthy Volunteers

    PubMed Central

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

    2011-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substance Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers. PMID:22085697

  19. Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers.

    PubMed

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

    2012-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers.

  20. Characterizing the Subjective and Psychomotor Effects of Carisoprodol in Healthy Volunteers

    PubMed Central

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

    2011-01-01

    Carisoprodol is a centrally acting drug used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. There is evidence from different sources that this oral muscle relaxant is abused and that it is associated with impairment leading to arrests for “driving under the influence” as well as increased risk of automobile accidents. Its subjective and psychomotor effects in healthy volunteers at therapeutic and supratherapeutic doses have not been well-characterized, and form the basis of this report. Fifteen healthy volunteers (8 males, 7 females) were administered 0, 350, and 700 mg of carisoprodol in separate sessions and for 6 h afterwards they completed a battery of tests at fixed time intervals so as to assess the subjective and psychomotor effects of the drug. The supratherapeutic dose, 700 mg, increased visual analog scale ratings of terms that were more reflective of sedation (e.g., “sleepy,” “heavy, sluggish feeling”) than those of abuse liability, and produced impaired performance on several psychomotor tests. The therapeutic dose, 350 mg, while producing few and mild subjective effects, still produced psychomotor impairment. The fact that the therapeutic dose of carisoprodol produced minimal subjective effects while adversely affecting performance is of concern in that patients prescribed this drug may feel relatively normal and engage in tasks (driving) that could put themselves and others at risk. PMID:21884720

  1. Effect of chronic intermittent hypoxia on exercise adaptations in healthy subjects.

    PubMed

    Tonini, Julia; Michallet, Anne-Sophie; Flore, Patrice; Nespoulet, Hugo; Pepin, Jean-Louis; Wuyam, Bernard; Levy, Patrick; Tamisier, Renaud

    2011-12-15

    Reduced exercise tolerance has been reported in obstructive sleep apnea syndrome (OSAS) patients, although the associated hypertension, obesity and/or metabolic disorder may underlie this reduction. Therefore, we evaluated the effects of chronic intermittent hypoxia (CIH) in 12 healthy subjects on exercise capacity, cardio-respiratory responses, and substrate oxidation during maximal and sub-maximal exercise. Subjects were exposed to 30 cycles of hypoxia-reoxygenation per hour for 14 nights. Although exercise capacity was unaltered PETCO(2) was reduced and V˙E/V˙CO(2) increased during both maximal and submaximal exercise tests, indicating a hyperventilatory response. Maximal heart rate was lower and diastolic arterial blood pressure (DBP) was higher in the 1st min of recovery after submaximal exercise. Subjects reached maximal lipid oxidation at a higher power output and had decreased blood lactate for a given power output. This suggests that although the metabolic adaptations to CIH in healthy subjects may improve exercise performance, the cardio-pulmonary modifications are similar to those observed in OSAS patients and could limit exercise capacity.

  2. Evaluation of Salivary Leptin Levels in Healthy Subjects and Patients with Advanced Periodontitis

    PubMed Central

    Khorsand, Afshin; Bayani, Mojtaba; Torabi, Sepehr; Kharrazifard, Mohammad Javad; Mohammadnejhad, Fatemeh

    2016-01-01

    Objectives: Leptin is a hormone-like protein produced by the adipose tissue. It plays an important role in protection of host against inflammation and infection. Some studies have reported changes in leptin levels in the gingival crevicular fluid (GCF), saliva and blood serum of patients with periodontal disease compared to healthy individuals. The aim of the present study was to compare the salivary leptin levels in patients with advanced periodontitis and healthy individuals. Materials and Methods: In this case-control study, the salivary samples of healthy individuals and patients with advanced periodontitis with clinical attachment loss >5mm were obtained using a standardized method and the leptin levels were measured in the salivary samples by means of ELISA. The effects of the periodontal status and sex on the salivary leptin levels of both groups were statistically analyzed by two-way ANOVA. Results: The means ± standard deviation (SD) of salivary leptin levels in healthy subjects and patients with advanced periodontitis were 34.27±6.88 and 17.87±5.89 pg/mL, respectively. Statistical analysis showed that the effect of sex on the salivary leptin levels was not significant (P=0.91), while the effect of advanced periodontitis on the salivary leptin levels was significant compared to healthy individuals (P<0.0001). Conclusions: In patients with advanced periodontitis, the salivary leptin levels were significantly lower compared to healthy individuals. Thus, assessment of salivary leptin can be done as a non-invasive and simple method to determine the susceptibility of patients to advanced periodontitis. PMID:27536322

  3. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    PubMed

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation.

  4. Circadian rhythm in plasma noradrenaline of healthy sleep-deprived subjects.

    PubMed

    Candito, M; Pringuey, D; Jacomet, Y; Souêtre, E; Salvati, E; Ardisson, J L; Chambon, P; Darcourt, G

    1992-12-01

    Under normal sleep-wake conditions, noradrenaline (NA) secretions in supine subjects exhibit a weak circadian variation with a peak that occurs around noon; the sleep span is characterized by reduced NA secretion. Some investigators have reported that the circadian NA rhythm is completely obliterated during sleep deprivation. In our laboratory, plasma NA was assayed every hour for 24 h in nine healthy men 20-23 years of age. All men were deprived of sleep and were required to eat and walk around every hour to prevent sleep. However, subjects remained supine for 20 min before blood samples were collected to eliminate the effect of activity. Persistence of a slight decrease in the night concentration in several subjects, despite sleep deprivation, suggests that NA secretion may be influenced by a biological clock whose activity becomes visible when the influence of posture is removed.

  5. Centenarians' offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview.

    PubMed

    Bucci, Laura; Ostan, Rita; Cevenini, Elisa; Pini, Elisa; Scurti, Maria; Vitale, Giovanni; Mari, Daniela; Caruso, Calogero; Sansoni, Paolo; Fanelli, Flaminia; Pasquali, Renato; Gueresi, Paola; Franceschi, Claudio; Monti, Daniela

    2016-03-01

    Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis-hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible.

  6. Centenarians’ offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview

    PubMed Central

    Cevenini, Elisa; Pini, Elisa; Scurti, Maria; Vitale, Giovanni; Mari, Daniela; Caruso, Calogero; Sansoni, Paolo; Fanelli, Flaminia; Pasquali, Renato; Gueresi, Paola; Franceschi, Claudio; Monti, Daniela

    2016-01-01

    Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis-hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible. PMID:26979133

  7. Tidal breathing patterns derived from structured light plethysmography in COPD patients compared with healthy subjects

    PubMed Central

    Motamedi-Fakhr, Shayan; Wilson, Rachel C; Iles, Richard

    2017-01-01

    Purpose Differences in tidal breathing patterns have been reported between patients with chronic obstructive pulmonary disease (COPD) and healthy individuals using traditional measurement techniques. This feasibility study examined whether structured light plethysmography (SLP) – a noncontact, light-based technique – could also detect differences in tidal breathing patterns between patients with COPD and healthy subjects. Patients and methods A 5 min period of tidal (quiet) breathing was recorded in each patient with COPD (n=31) and each healthy subject (n=31), matched for age, body mass index, and sex. For every participant, the median and interquartile range (IQR; denoting within-subject variability) of 12 tidal breathing parameters were calculated. Individual data were then combined by cohort and summarized by its median and IQR. Results After correction for multiple comparisons, inspiratory time (median tI) and its variability (IQR of tI) were lower in patients with COPD (p<0.001 and p<0.01, respectively) as were ratios derived from tI (tI/tE and tI/tTot, both p<0.01) and their variability (p<0.01 and p<0.05, respectively). IE50SLP (the ratio of inspiratory to expiratory flow at 50% tidal volume calculated from the SLP signal) was higher (p<0.001) in COPD while SLP-derived time to reach peak tidal expiratory flow over expiratory time (median tPTEFSLP/tE) was shorter (p<0.01) and considerably less variable (p<0.001). Thoraco–abdominal asynchrony was increased (p<0.05) in COPD. Conclusion These early observations suggest that, like traditional techniques, SLP is able to detect different breathing patterns in COPD patients compared with subjects with no respiratory disease. This provides support for further investigation into the potential uses of SLP in assessing clinical conditions and interventions. PMID:28096696

  8. Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects

    PubMed Central

    Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S.; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

    2016-01-01

    Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18–65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses. PMID:26731525

  9. Baroreflex sensitivity is higher during acute psychological stress in healthy subjects under β-adrenergic blockade

    PubMed Central

    Truijen, Jasper; Davis, Shyrin C.A.T.; Stok, Wim J.; Kim, Yu-Sok; van Westerloo, David J.; Levi, Marcel; van der Poll, Tom; Westerhof, Berend E.; Karemaker, John M.; van Lieshout, Johannes J.

    2010-01-01

    Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). β-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under β-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24–42) compared with 17 (16–28) ms·mmHg−1, P<0.05; BRSFD: 27 (20–34) compared with 14 (9–19) ms·mmHg−1, P<0.05; values are medians (interquartile range)]. BP declined after the jump in both groups, and post-jump BRS did not differ between the groups. In conclusion, during acute psychological stress, BRS is higher in healthy subjects treated with non-selective β-adrenergic blockade with significantly lower HR but comparable BP. PMID:20828371

  10. Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects.

    PubMed

    Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

    2016-01-01

    Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18-65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses.

  11. Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

    PubMed

    Noguchi, Katsuhiko; Matsuzaki, Toshihiro; Sakanashi, Mayuko; Hamadate, Naobumi; Uchida, Taro; Kina-Tanada, Mika; Kubota, Haruaki; Nakasone, Junko; Sakanashi, Matao; Ueda, Shinichiro; Masuzaki, Hiroaki; Ishiuchi, Shogo; Ohya, Yusuke; Tsutsui, Masato

    2015-02-01

    Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals.

  12. Relationship between jaw opening force and hyoid bone dynamics in healthy elderly subjects

    PubMed Central

    Shinozaki, Hiromichi; Tohara, Haruka; Matsubara, Mariko; Inokuchi, Nobuhiro; Yamazaki, Yasuhiro; Nakane, Ayako; Wakasugi, Yoko; Minakuchi, Shunsuke

    2017-01-01

    Purpose This study aimed to examine the relationship between jaw opening force and hyoid bone dynamics and resting position in elderly individuals based on gender. Subjects and methods Subjects were 36 healthy elderly individuals aged ≥65 years without dysphagia (16 men and 20 women; mean age 75.5 years, range 65–88 years). Videofluorographic images during the swallowing of 10 mL of 40% (w/v) barium sulfate were obtained and the degrees of anterior, superior, and hypotenuse displacements of the hyoid bone and maximum/resting hyoid position were evaluated. Jaw opening force was measured three times using a jaw opening force sthenometer; the mean of these three measurements was used for analysis. Results In men, there was a positive correlation between jaw opening force and resting hyoid position and negative correlations among all the degrees of anterior, superior, and hypotenuse displacements of the hyoid bone. In women, there was no statistically significant correlation between jaw opening force and any of the measurement items. There was no statistically significant correlation between jaw opening force and maximum hyoid position in either men or women. Conclusion Our findings suggest that low jaw opening force leads to low resting hyoid position only in elderly men, and a lower hyoid position in healthy elderly men results in a larger total amount of hyoid displacement during swallowing. Moreover, a maximum hyoid position in healthy individuals of either gender does not differ depending on their jaw opening force.

  13. What is healthy food? Objective nutrient profile scores and subjective lay evaluations in comparison.

    PubMed

    Bucher, T; Müller, B; Siegrist, M

    2015-12-01

    To date, it is unclear how consumers evaluate the healthiness of individual foods and meals and how consumers' perceptions are related to expert opinions. This knowledge is essential for efficient communication of nutrition information with the goal of promoting healthy eating. This study used the fake food buffet method to investigate health perceptions of selected meals and of 54 individual foods and beverages. Lay consumers' subjective healthiness evaluations of meals and foods were compared to objective nutrient profile scores, which were previously shown to correlate highly with expert opinions. The results show that nutrition profile scores and lay evaluations were highly correlated, which indicates that lay people used similar criteria as experts to evaluate the healthiness of foods. However, lay consumers tended to neglect the amount of saturated fat, protein and sodium for their judgments. Also, it was found that while lay consumers were quite able to evaluate single food products, they had difficulties in evaluating entire meals. Future interventions should focus particularly on educating the consumer about the negative effects of diets high in salt and saturated fat and they should improve the consumer's abilities to evaluate entire meals.

  14. Influence of nopal intake upon fasting glycemia in type II diabetics and healthy subjects.

    PubMed

    Frati, A C; Gordillo, B E; Altamirano, P; Ariza, C R; Cortés-Franco, R; Chávez-Negrete, A; Islas-Andrade, S

    1991-01-01

    To assess if the acute hypoglycemic effect of nopal which occurs in diabetic patients also appears in healthy individuals, 500 g of nopal stems (O. streptacantha Lem.) were given orally to 14 healthy volunteers and to 14 patients with NIDDM. Serum glucose and insulin levels were measured at 0, 60, 120 and 180 minutes after nopal ingestion. A control test was performed with the intake of 400 ml of water. The intake of nopal by the NIDDM group was followed by a significant reduction of serum glucose and insulin concentration reaching 40.8 + 4.6 mg/dl (n = 14) (mean+SEM) and 7.8 + 1.5 uU/ml (n = 7) less than basal value, respectively, at 180 minutes. (P less than 0.001 vs control test). No significant changes were noticed in the healthy group as compared with the control test (P greater than 0.05). Acute hypoglycemic effect of nopal was observed in patients with NIDDM but not in healthy subjects, thus the mechanisms of this effect differs from current hypoglycemic agents.

  15. Breakfast high in whey protein or carbohydrates improves coping with workload in healthy subjects.

    PubMed

    Sihvola, Nora; Korpela, Riitta; Henelius, Andreas; Holm, Anu; Huotilainen, Minna; Müller, Kiti; Poussa, Tuija; Pettersson, Kati; Turpeinen, Anu; Peuhkuri, Katri

    2013-11-14

    Dietary components may affect brain function and influence behaviour by inducing the synthesis of neurotransmitters. The aim of the present study was to examine the influence of consumption of a whey protein-containing breakfast drink v. a carbohydrate drink v. control on subjective and physiological responses to mental workload in simulated work. In a randomised cross-over design, ten healthy subjects (seven women, median age 26 years, median BMI 23 kg/m(2)) participated in a single-blinded, placebo-controlled study. The subjects performed demanding work-like tasks after having a breakfast drink high in protein (HP) or high in carbohydrate (HC) or a control drink on separate sessions. Subjective states were assessed using the NASA Task Load Index (NASA-TLX), the Karolinska sleepiness scale (KSS) and the modified Profile of Mood States. Heart rate was recorded during task performance. The ratio of plasma tryptophan (Trp) to the sum of the other large neutral amino acids (LNAA) and salivary cortisol were also analysed. The plasma Trp:LNAA ratio was 30 % higher after the test drinks HP (median 0·13 (μmol/l)/(μmol/l)) and HC (median 0·13 (μmol/l)/(μmol/l)) than after the control drink (median 0·10 (μmol/l)/(μmol/l)). The increase in heart rate was smaller after the HP (median 2·7 beats/min) and HC (median 1·9 beats/min) drinks when compared with the control drink (median 7·2 beats/min) during task performance. Subjective sleepiness was reduced more after the HC drink (median KSS - 1·5) than after the control drink (median KSS - 0·5). There were no significant differences between the breakfast types in the NASA-TLX index, cortisol levels or task performance. We conclude that a breakfast drink high in whey protein or carbohydrates may improve coping with mental tasks in healthy subjects.

  16. Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial.

    PubMed

    Ahmed, Amir I A; van den Elsen, Geke A H; Colbers, Angela; van der Marck, Marjolein A; Burger, David M; Feuth, Ton B; Rikkert, Marcel G M Olde; Kramers, Cornelis

    2014-09-01

    There is a great concern about the safety of THC-based drugs in older people (≥65 years), as most of THC-trials did not include such group. In this phase 1, randomized, double-blind, double-dummy, placebo-controlled, cross-over trial, we evaluated the safety and pharmacokinetics of three oral doses of Namisol(®), a novel THC in tablet form, in older subjects. Twelve healthy older subjects (6 male; mean age 72±5 years) randomly received a single oral dose of 3mg, 5mg, or 6.5mg of THC or matching placebo, in a crossover manner, on each intervention day. The data for 11 subjects were included in the analysis. The data of 1 subject were excluded due to non-compliance to study medication. THC was safe and well tolerated. The most frequently reported adverse events (AEs) were drowsiness (27%) and dry mouth (11%). Subjects reported more AEs with THC 6.5mg than with 3mg (p=0.048), 5mg (p=0.034) and placebo (p=0.013). There was a wide inter-individual variability in plasma concentrations of THC. Subjects for whom the Cmax fell within the sampling period (over 2h), Cmax was 1.42-4.57ng/mL and Tmax was 67-92min. The AUC0-2h (n=11) was 1.67-3.51ng/mL. Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC.

  17. Study of Repetitive Movements Induced Oscillatory Activities in Healthy Subjects and Chronic Stroke Patients

    PubMed Central

    Hsu, Chuan-Chih; Lee, Wai-Keung; Shyu, Kuo-Kai; Chang, Hsiao-Huang; Yeh, Ting-Kuang; Hsu, Hao-Teng; Chang, Chun-Yen; Lan, Gong-Yau; Lee, Po-Lei

    2016-01-01

    Repetitive movements at a constant rate require the integration of internal time counting and motor neural networks. Previous studies have proved that humans can follow short durations automatically (automatic timing) but require more cognitive efforts to track or estimate long durations. In this study, we studied sensorimotor oscillatory activities in healthy subjects and chronic stroke patients when subjects were performing repetitive finger movements. We found the movement-modulated changes in alpha and beta oscillatory activities were decreased with the increase of movement rates in finger lifting of healthy subjects and the non-paretic hands in stroke patients, whereas no difference was found in the paretic-hand movements at different movement rates in stroke patients. The significant difference in oscillatory activities between movements of non-paretic hands and paretic hands could imply the requirement of higher cognitive efforts to perform fast repetitive movements in paretic hands. The sensorimotor oscillatory response in fast repetitive movements could be a possible indicator to probe the recovery of motor function in stroke patients. PMID:27976723

  18. Motor potentials evoked by navigated transcranial magnetic stimulation in healthy subjects.

    PubMed

    Säisänen, Laura; Julkunen, Petro; Niskanen, Eini; Danner, Nils; Hukkanen, Taina; Lohioja, Tarja; Nurkkala, Jouko; Mervaala, Esa; Karhu, Jari; Könönen, Mervi

    2008-12-01

    Navigated transcranial magnetic stimulation (TMS) is a tool for targeted, noninvasive stimulation of cerebral cortex. Transcranial stimuli can depolarize neurons and evoke measurable effects which are unique in two ways: the effects are caused directly and without a consciousness of the subject, and, the responses from peripheral muscles provide a direct measure for the integrity of the whole motor pathway. The clinical relevance of the method has not always been fully exposed because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders it has been uncertain, whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. We characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. We delivered focal TMS pulses on the primary motor area (M1) and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects' height is provided. In conclusion, we provide a modified baseline of TMS-related parameters for healthy subjects. Earlier such large-scale baseline material has not been available.

  19. Systemic and renal effects of an ETA receptor subtype-specific antagonist in healthy subjects

    PubMed Central

    Schmetterer, Leopold; Dallinger, Susanne; Bobr, Barbara; Selenko, Nicole; Eichler, Hans-Georg; Wolzt, Michael

    1998-01-01

    Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ETA receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1.The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way cross-over design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg−1 min−1 for 120 min) or placebo and BQ-123 (15 μg min−1 for 60 min and subsequently 60 μg min−1 for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively.BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (−24%, P<0.001) and GFR (−12%, P=0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020).BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ETA receptor subtype. PMID:9692778

  20. Effects of Incentive Spirometry on Respiratory Motion in Healthy Subjects Using Cine Breathing Magnetic Resonance Imaging

    PubMed Central

    Akazawa, Tsutomu; Sakuma, Tsuyoshi; Nagaya, Shigeyuki; Sonoda, Masaru; Tanaka, Yuji; Katogi, Takehide; Nemoto, Tetsuharu; Minami, Shohei

    2015-01-01

    Objective To investigate the effectiveness of incentive spirometry on respiratory motion in healthy subjects using cine breathing magnetic resonance imaging (MRI). Methods Ten non-smoking healthy subjects without any history of respiratory disease were studied. Subjects were asked to perform pulmonary training using incentive spirometry every day for two weeks. To assess the effectiveness of this training, pulmonary function tests and cine breathing MRI were performed before starting pulmonary training and two weeks after its completion. Results After training, there were significant improvements in vital capacity (VC) from 3.58±0.8 L to 3.74±0.8 L and in %VC from 107.4±10.8 to 112.1±8.2. Significant changes were observed in the right diaphragm motion, right chest wall motion, and left chest wall motion, which were increased from 55.7±9.6 mm to 63.4±10.2 mm, from 15.6±6.1 mm to 23.4±10.4 mm, and from 16.3±7.6 mm to 22.0±9.8 mm, respectively. Conclusion Two weeks of training using incentive spirometry provided improvements in pulmonary function and respiratory motion, which suggested that incentive spirometry may be a useful preoperative modality for improving pulmonary function during the perioperative period. PMID:26161341

  1. Assessing the Relationship between Central Corneal Thickness and Retinal Nerve Fiber Layer Thickness in Healthy Subjects

    PubMed Central

    Mumcuoglu, Tarkan; Townsend, Kelly A; Wollstein, Gadi; Ishikawa, Hiroshi; Bilonick, Richard A; Sung, Kyung Rim; Kagemann, Larry; Schuman, Joel S

    2008-01-01

    Purpose To determine the relationship between central corneal thickness (CCT) and retinal nerve fiber layer (RNFL) thickness obtained by scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Dublin, CA) confocal scanning laser ophthalmoscopy (HRT II; Heidelberg Engineering, Heidelberg, Germany) and optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Dublin, CA). Design Multi-center clinical trial, retrospective cross-sectional study. Methods One hundred and nine healthy subjects from the Advanced Imaging in Glaucoma Study were enrolled in this study. All subjects had a standard clinical examination, including visual field and good quality scans from all three imaging devices. Central corneal thickness was measured using an ultrasonic pachymeter. A linear mixed effects model was used to assess the relationship between RNFL thickness and CCT, accounting for clustering of eyes within subjects, testing site, ethnicity, family history of glaucoma, axial length intraocular pressure and visual field global indices. Results For OCT and GDx, there was a slight non-statistically significant positive relationship between CCT and RNFL thickness. For HRT, there was a slight non-statistically significant negative relationship between CCT and RNFL thickness. Relationships for each device were found to differ between sites. Conclusions CCT was not statistically significantly related to RNFL thickness in healthy eyes. PMID:18657796

  2. Diurnal and seasonal variation of the brain serotonin system in healthy male subjects.

    PubMed

    Matheson, Granville J; Schain, Martin; Almeida, Rita; Lundberg, Johan; Cselényi, Zsolt; Borg, Jacqueline; Varrone, Andrea; Farde, Lars; Cervenka, Simon

    2015-05-15

    The mammalian circadian clock underlies both diurnal and seasonal changes in physiology, and its function is thought to be disturbed in both seasonal and non-seasonal depression. In humans, molecular imaging studies have reported seasonal changes in the serotonin system. Despite the role of the circadian clock in generating seasonal physiological changes, however, diurnal variation of serotonin receptors and transporters has never been directly studied in humans. We used positron emission tomography to examine diurnal and seasonal changes in the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of healthy male subjects, employing a cross-sectional design. In 56 subjects measured with [(11)C]WAY-100635, we observed diurnal increases in the availability of 5-HT1A receptors in the cortex. In 40 subjects measured with [(11)C]MADAM, a decrease in 5-HTT was observed in the midbrain across the day. We also found seasonal changes in the 5-HT1A receptor in serotonin projection regions, with higher availability on days with a longer duration of daylight. Our observation that serotonin receptor and transporter levels may change across the day in humans is corroborated by experimental research in rodents. These findings have important implications for understanding the relationship between the circadian and serotonin systems in both the healthy brain and in affective disorders, as well as for the design of future molecular imaging studies.

  3. The Effect of Sampling and Storage on the Fecal Microbiota Composition in Healthy and Diseased Subjects

    PubMed Central

    Tedjo, Danyta I.; Jonkers, Daisy M. A. E.; Savelkoul, Paul H.; Masclee, Ad A.; van Best, Niels; Pierik, Marieke J.; Penders, John

    2015-01-01

    Large-scale cohort studies are currently being designed to investigate the human microbiome in health and disease. Adequate sampling strategies are required to limit bias due to shifts in microbial communities during sampling and storage. Therefore, we examined the impact of different sampling and storage conditions on the stability of fecal microbial communities in healthy and diseased subjects. Fecal samples from 10 healthy controls, 10 irritable bowel syndrome and 8 inflammatory bowel disease patients were collected on site, aliquoted immediately after defecation and stored at -80°C, -20°C for 1 week, at +4°C or room temperature for 24 hours. Fecal transport swabs (FecalSwab, Copan) were collected and stored for 48-72 hours at room temperature. We used pyrosequencing of the 16S gene to investigate the stability of microbial communities. Alpha diversity did not differ between all storage methods and -80°C, except for the fecal swabs. UPGMA clustering and principal coordinate analysis showed significant clustering by test subject (p<0.001) but not by storage method. Bray-Curtis dissimilarity and (un)weighted UniFrac showed a significant higher distance between fecal swabs and -80°C versus the other methods and -80°C samples (p<0.009). The relative abundance of Ruminococcus and Enterobacteriaceae did not differ between the storage methods versus -80°C, but was higher in fecal swabs (p<0.05). Storage up to 24 hours (at +4°C or room temperature) or freezing at -20°C did not significantly alter the fecal microbial community structure compared to direct freezing of samples from healthy subjects and patients with gastrointestinal disorders. PMID:26024217

  4. Feasibility of intercostal blood flow measurement by echo-Doppler technique in healthy subjects.

    PubMed

    de Bisschop, Claire; Montaudon, Michel; Glénet, Stéphane; Guénard, Hervé

    2015-10-02

    Intercostal artery blood flow supplies the external and internal intercostal muscles, which are inspiratory and expiratory muscles. Intercostal blood flow measured by the echo-Doppler (ED) technique has not previously been reported in humans. This study describes the feasibility of this measurement during free and loaded breathing in healthy subjects. Systolic, diastolic and mean blood flows were measured in the eighth dorsal intercostal space during free and loaded breathing using the ED technique. Flows were calculated as the product of the artery intraluminal surface and blood velocity. Ten healthy subjects (42 ± 13·6 years) were included. Integrated electromyogram (iEMG), arterial pressure, cardiac frequency and breathing pattern were also recorded. Mean blood flows were 3·5 ± 1·2 ml min(-1) at rest, 6 ± 2·6 ml min(-1) while breathing through a combined inspiratory and expiratory resistance and 4·0 ± 1·3 ml min(-1) 1 min after unloading. Diastolic blood flow was about one-third the systolic blood flow. The changes in blood flows were consistent with those in iEMG. No change in mean blood flow was observed between inspiration and expiration, suggesting a balance in the perfusion of external and internal muscles during breathing. In conclusion, ED is a feasible technique for non-invasive, real-time measurement of intercostal blood flow in humans. In healthy subjects, mean blood flow appeared tightly matched to iEMG activity. This technique may provide a way to assess the vascular adaptations induced by diseases in which respiratory work is increased or cardiac blood flow altered.

  5. Macular retinal sensitivity using MP-1 in healthy Malaysian subjects of different ages

    PubMed Central

    Ismail, Siti Aishah; Sharanjeet-Kaur; Mutalib, Haliza Abdul; Ngah, Nor Fariza

    2015-01-01

    Purpose To determine the influence of age and gender on macular sensitivity to light in healthy subjects of 4 age groups using the MP-1 microperimeter. Methods A prospective study was carried out on 50 healthy subjects (age range: 18–60 years) divided into 4 age groups; 18–30 years, 31–40 years, 41–50 years and 51–60 years. Full-threshold microperimetry of the central 10° of retina was performed utilizing 32 points with the MP-1. Macula area was divided into four quadrants, which were superior nasal (SN), inferior nasal (IN), inferior temporal (IT) and superior temporal (ST). Results Total mean sensitivity at 10° for age groups 18–30 years, 31–40 years, 41–50 years and 51–60 years were 19.46 ± 0.30, 19.40 ± 0.39, 19.47 ± 0.35 and 18.73 ± 0.75 (dB), respectively. There was a significant difference in total mean retinal sensitivity at 10° and at the four quadrants with age but not for gender. The retinal sensitivity was highest in the IT quadrant and lowest in the SN quadrant for all age groups. The linear regression analysis revealed that there was a 0.019 dB, 0.016 dB, 0.022 dB, 0.029 dB and 0.029 dB per year age-related decline in mean macular sensitivity within the central 10° diameter in the SN, IN, IT and ST quadrants respectively. Conclusion Among normal healthy subjects, there was a linear decline in retinal light sensitivity with increasing age with the highest reduction in the superior nasal quadrant and lowest in the inferior temporal quadrant. PMID:26025808

  6. In vivo knee laxity in flexion and extension: a radiographic study in 30 older healthy subjects.

    PubMed

    Heesterbeek, P J C; Verdonschot, N; Wymenga, A B

    2008-01-01

    In order to determine how "tight" a total knee prosthesis should be implanted, it is important to know the amount of laxity in a healthy knee. The objective of this study was to determine knee laxity in extension and flexion in healthy, non-arthritic knees of subjects similar in age to patients undergoing a total knee arthroplasty and to provide guidelines for the orthopaedic surgeon in his attempt to restore the stability of an osteoarthritic knee to normal. Thirty healthy subjects (15 male, 15 female), mean age 62 (SD 6.4) years, were included in the study. For each subject one, randomly selected, knee was stressed in extension and in 70 degrees flexion (15 Nm). Varus and valgus laxity were measured on radiographs. The passive range of motion and active flexion was assessed. Mean valgus laxity in extension was 2.3 degrees (SD 0.9, range 0.2 degrees -4.1 degrees ). In extension mean varus laxity was 2.8 degrees (SD 1.3, range 0.6 degrees -5.4 degrees ). In flexion, mean valgus laxity was 2.5 degrees (SD 1.5, range 0.0 degrees -6.0 degrees ) and mean varus laxity was 3.1 degrees (SD 2.0, range 0.1 degrees -7.0 degrees ). Varus and valgus knee laxity in extension and in flexion were comparable. This study shows that the normal knee in this age group has an inherent degree of varus-valgus laxity. Whether the results of the present study can be used to optimise the total knee arthroplasty implantation technique requires further investigation.

  7. [Individual responses of arterial pressure to geomagnetic activity in practically healthy subjects].

    PubMed

    Zenchenko, T A; Dimitrova, S; Stoilova, I; Breus, T K

    2009-01-01

    Dynamic analysis of arterial blood pressure in relation to the Earth's magnetic field perturbations was performed in 77 practically healthy volunteers (staff of Bulgarian Academy of Sciences). Almost half of them proved magneto-sensitive, i.e. experienced AP elevation with increased geomagnetic activity. The probability of development of magnetic sensitivity was independent of age and gender but increased in volunteers having even mild cardiovascular pathology. These subjects complained of worsened health condition upon a rise in geomagnetic activity. However, some volunteers reported deteriorated well-being without AD elevation. It means that AD measurement may be insufficient for reliable monitoring magnetic sensitivity.

  8. Oxygen desaturation in healthy subjects undergoing the incremental shuttle walk test*

    PubMed Central

    Seixas, Daniel Machado; Seixas, Daniela Miti Tsukumo; Pereira, Monica Corso; Moreira, Marcos Mello; Paschoal, Ilma Aparecida

    2013-01-01

    OBJECTIVE: To determine the probability of oxygen desaturation in healthy individuals undergoing the incremental shuttle walk test (ISWT). METHODS: We enrolled 83 healthy subjects: 55 males (including 1 smoker) and 28 females. We determined pre-ISWT FEV1, FEV6, HR and SpO2, as well as post-ISWT HR and SpO2. RESULTS: Mean values overall were as follows: age, 35.05 ± 12.53 years; body mass index, 24.30 ± 3.47 kg/m2; resting HR, 75.12 ± 12.48 bpm; resting SpO2, 97.96 ± 1.02%; FEV1, 3.75 ± 0.81 L; FEV6, 4.45 ± 0.87 L; FEV1/FEV6 ratio, 0.83 ± 0.08 (no restriction or obstruction); incremental shuttle walk distance, 958.30 ± 146.32 m; post-ISWT HR, 162.41 ± 18.24 bpm; and post-ISWT SpO2, 96.27 ± 2.21%. In 11 subjects, post-ISWT SpO2 was higher than was pre-ISWT SpO2. In 17 subjects, there was a 4% decrease in SpO2 after the ISWT. There were no statistically significant differences between the groups with and without post-ISWT oxygen desaturation in terms of age, gender, FEV1, FEV6, FEV1/FEV6, pre-ISWT SpO2, incremental shuttle walk distance, HR, or percentage of maximal HR. In the individuals with post-ISWT oxygen desaturation, the body mass index was higher (p = 0.01) and post-ISWT SpO2 was lower (p = 0.0001). CONCLUSIONS: Healthy individuals can present oxygen desaturation after the ISWT. Using the ISWT to predict subtle respiratory abnormalities can be misleading. In healthy subjects, oxygen desaturation is common after the ISWT, as it is during any intense physical activity. PMID:24068265

  9. Effects of extreme endurance running on cardiac autonomic nervous modulation in healthy trained subjects.

    PubMed

    Sztajzel, Juan; Atchou, Guillaume; Adamec, Richard; Bayes de Luna, Antonio

    2006-01-15

    This study examined spectral components of heart rate variability (HRV) during endurance mountain running in 8 healthy trained subjects. The data showed that during this type of mountain running, all spectral components of HRV may severely decrease, particularly very-low-frequency and low-frequency (LF) power, suggesting extreme activation of the sympathetic nervous system. The physiologic response of the heart in this situation was the downregulation of the beta-adrenergic receptors to protect myocardial function, with a subsequent increase in parasympathetic tone, reflected by an increase in high-frequency (HF) power and a decrease in the LF/HF ratio.

  10. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

    PubMed

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; da Rosa, Eduarda Dias; de Lucena, David; Macêdo, Danielle; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Gama, Clarissa Severino

    2016-07-01

    Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

  11. Effects of manual lymph drainage on cardiac autonomic tone in healthy subjects.

    PubMed

    Kim, Sung-Joong; Kwon, Oh-Yun; Yi, Chung-Hwi

    2009-01-01

    This study was designed to investigate the effects of manual lymph drainage on the cardiac autonomic tone. Thirty-two healthy male subjects were randomly assigned to manual lymph drainage (MLD) (experimental) and rest (control) groups. Electrocardiogram (ECG) parameters were recorded with bipolar electrocardiography using standard limb lead positions. The pressure-pain threshold (PPT) was quantitatively measured using an algometer. Heart rate variability differed significantly between the experimental and control groups (p < 0.05), but the PPT in the upper trapezius muscle did not (p > 0.05). These findings indicate that the application of MLD was effective in reducing the activity of the sympathetic nervous system.

  12. Voluntary control of corticomuscular coherence through neurofeedback: a proof-of-principle study in healthy subjects.

    PubMed

    von Carlowitz-Ghori, K; Bayraktaroglu, Z; Waterstraat, G; Curio, G; Nikulin, V V

    2015-04-02

    Corticomuscular coherence (CMC) relates to synchronization between activity in the motor cortex and the muscle activity. The strength of CMC can be affected by motor behavior. In a proof-of-principle study, we examined whether independent of motor output parameters, healthy subjects are able to voluntarily modulate CMC in a neurofeedback paradigm. Subjects received visual online feedback of their instantaneous CMC strength, which was calculated between an optimized spatial projection of multichannel electroencephalography (EEG) and electromyography (EMG) in an individually defined target frequency range. The neurofeedback training consisted of either increasing or decreasing CMC strength using a self-chosen mental strategy while performing a simple motor task. Evaluation of instantaneous coherence showed that CMC strength was significantly larger when subjects had to increase than when to decrease CMC; this difference between the two task conditions did not depend on motor performance. The exclusion of confounding factors such as motor performance, attention and task complexity in study design provides evidence that subjects were able to voluntarily modify CMC independent of motor output parameters. Additional analysis further strengthened the assumption that the subjects' response was specifically shaped by the neurofeedback. In perspective, we suggest that CMC-based neurofeedback could provide a therapeutic approach in clinical conditions, such as motor stroke, where CMC is altered.

  13. Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects

    PubMed Central

    Doberer, D; Haschemi, A; Andreas, M; Zapf, T-C; Clive, B; Jeitler, M; Heinzl, H; Wagner, O; Wolzt, M; Bilban, M

    2010-01-01

    BACKGROUND AND PURPOSE Haem oxygenase 1 (HO-1) is an inducible protein that plays a major protective role in conditions such as ischaemia-reperfusion injury and inflammation. In this study, we have investigated the role of haem arginate (HA) in human male subjects in the modulation of HO-1 expression and its correlation with the GT length polymorphism (GTn) in the promoter of the HO-1 gene. EXPERIMENTAL APPROACH In a dose-escalation, randomized, placebo-controlled trial, seven healthy male subjects with a homozygous short (S/S) and eight with a long (L/L) GTn genotype received intravenous HA. HO-1 protein expression and mRNA levels in peripheral blood monocytes, bilirubin, haptoglobin, haemopexin and haem levels were analysed over a 48 h observation period. KEY RESULTS We found that the baseline mRNA levels of HO-1 were higher in L/L subjects, while protein levels were higher in S/S subjects. HA induced a dose-dependent increase in the baseline corrected area under the curve values of HO-1 mRNA and protein over 48 h. The response of HO-1 mRNA was more pronounced in L/L subjects but the protein level was similar across the groups. CONCLUSIONS AND IMPLICATION HA is an effective inducer of HO-1 in humans irrespective of the GTn genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials. PMID:20718734

  14. The effects of horse riding simulation exercise with blindfolding on healthy subjects' balance and gait.

    PubMed

    Cha, Hyun Gyu; Lee, Byung Joon; Lee, Wan Hee

    2016-11-01

    [Purpose] The study was conducted to determine the effect of horse riding simulation combined with blindfolding on healthy individuals' balance and gait. [Subjects and Methods] Thirty subjects were randomly divided into an experimental group (n=15) and a control group (n=15). The subjects in the experimental group covered their eyes using a blindfold, climbed onto a horse riding simulator, and performed the horse riding simulation exercise. The control group took part in the horse riding exercises without a blindfold. All of the subjects performed the 20 minutes long exercise once a day, five times a week, over a four-week period. [Results] The experimental group showed significant improvement in static balance, dynamic balance, velocity, and cadence compared to pre-intervention measurements. In addition, the control group showed significant improvement in static balance, dynamic balance, single support, and cadence compared to pre-intervention measurements. Significant differences in post-training gains in static balance, dynamic balance, and cadence were observed between the experimental group and the control group. [Conclusion] Subjects that performed horse riding simulation exercise after blindfolding showed significant improvements in balance and cadence compared to the control group.

  15. Stable Schizophrenia Patients Learn Equally Well as Age-Matched Controls and Better than Elderly Controls in Two Sensorimotor Rotary Pursuit Tasks

    PubMed Central

    De Picker, Livia J.; Cornelis, Claudia; Hulstijn, Wouter; Dumont, Glenn; Fransen, Erik; Timmers, Maarten; Janssens, Luc; Morrens, Manuel; Sabbe, Bernard G. C.

    2014-01-01

    Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. Results: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls. Conclusion: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study. PMID:25505425

  16. Pharmacokinetics and safety study of posaconazole intravenous solution administered peripherally to healthy subjects.

    PubMed

    Kersemaekers, Wendy M; van Iersel, Thijs; Nassander, Ulla; O'Mara, Edward; Waskin, Hetty; Caceres, Maria; van Iersel, Marlou L P S

    2015-02-01

    This study evaluated the safety, tolerability, and pharmacokinetics of a posaconazole i.v. (intravenous) solution. This was a single-center, 2-part, randomized, rising single- and multiple-dose study in healthy adults. In part 1, subjects received 0 (vehicle), 50, 100, 200, 250, or 300 mg posaconazole in a single dose i.v. by 30-min peripheral infusion (6 cohorts of 12 subjects each [9 active and 3 placebo], making a total of 72 subjects). Blood samples were collected until 168 h postdose. In part 2, subjects were to receive 2 peripheral infusions at a 12-h interval on day 1 followed by once-daily infusion for 9 days. However, part 2 was terminated early because of high rates of infusion site reactions with multiple dosing at the same infusion site. The pharmacokinetics results for part 1 (n=45 subjects) showed that the mean posaconazole exposure (area under the concentration-time curve from time zero to infinity [AUC0-∞]) ranged from 4,890 to 46,400 ng · h/ml (range of coefficient of variation values, 26 to 50). The dose-proportionality slope estimate (90% confidence interval) for AUC0-∞ was 1.30 (1.19 to 1.41), indicating a greater-than-dose-proportional increase. The data for safety in part 1 show that 29/72 subjects had ≥1 adverse event. Infusion site reactions were reported in 2/9 vehicle subjects, 0/18 placebo subjects, and 7/45 i.v. posaconazole subjects. The data for safety in part 2 show that infusion site reactions were reported in 1/4 (25%) placebo subjects, 3/9 (33%) vehicle control subjects, and 4/5 (80%) i.v. posaconazole (100 mg) subjects (3 posaconazole recipients subsequently developed thrombophlebitis and were discontinued from treatment). In conclusion, the posaconazole i.v. solution showed a greater-than-dose-proportional increase in exposure, primarily at doses below 200 mg. When administered peripherally at the same infusion site, multiple dosing of i.v. posaconazole led to unacceptably high rates of infusion site reactions. Intravenous

  17. Immediate effects of acupuncture on biceps brachii muscle function in healthy and post-stroke subjects

    PubMed Central

    2012-01-01

    Background The effects of acupuncture on muscle function in healthy subjects are contradictory and cannot be extrapolated to post-stroke patients. This study evaluated the immediate effects of manual acupuncture on myoelectric activity and isometric force in healthy and post-stroke patients. Methods A randomized clinical trial, with parallel groups, single-blinded study design, was conducted with 32 healthy subjects and 15 post-stroke patients with chronic hemiparesis. Surface electromyography from biceps brachii during maximal isometric voluntary tests was performed before and after 20-min intermittent, and manual stimulation of acupoints Quchi (LI11) or Tianquan (PC2). Pattern differentiation was performed by an automated method based on logistic regression equations. Results Healthy subjects showed a decrease in the root mean-squared (RMS) values after the stimulation of LI11 (pre: 1.392 ± 0.826 V; post: 0.612 ± 0.0.320 V; P = 0.002) and PC2 (pre: 1.494 ± 0.826 V; post: 0.623 ± 0.320 V; P = 0.001). Elbow flexion maximal isometric voluntary contraction (MIVC) was not significantly different after acupuncture stimulation of LI11 (pre: 22.2 ± 10.7 kg; post: 21.7 ± 9.5 kg; P = 0.288) or PC2 (pre: 18.8 ± 4.6 kg; post: 18.7 ± 6.0 kg; P = 0.468). Post-stroke patients did not exhibit any significant decrease in the RMS values after the stimulation of LI11 (pre: 0.627 ± 0.335 V; post: 0.530 ± 0.272 V; P = 0.187) and PC2 (pre: 0.601 ± 0.258 V; post: 0.591 ± 0.326 V; P = 0.398). Also, no significant decrease in the MIVC value was observed after the stimulation of LI11 (pre: 9.6 ± 3.9 kg; post: 9.6 ± 4.7 kg; P = 0.499) or PC2 (pre: 10.7 ± 5.6 kg; post: 10.2 ± 5.3 kg; P = 0.251). Different frequency of patterns was observed among healthy subjects and post-stroke patients groups (χ2 = 9.759; P = 0.021). Conclusion Manual acupuncture provides sufficient neuromuscular stimuli to promote immediate changes in motor unit gross recruitment without repercussion in

  18. Contralateral neglect induced by right posterior parietal rTMS in healthy subjects.

    PubMed

    Fierro, B; Brighina, F; Oliveri, M; Piazza, A; La Bua, V; Buffa, D; Bisiach, E

    2000-05-15

    We applied repetitive transcranial magnetic stimulation (rTMS) in order to induce interference on visuo-spatial perception in 11 healthy subjects. Subjects performed a visuo-spatial task requiring judgements about the symmetry of prebisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 50 ms on a computer-monitor. Performance was examined in basal condition and during rTMS trains of 10 stimuli at 25 Hz, delivered through a focal coil over right or left posterior parietal cortex (P5 and P6 sites) and triggered synchronously with visual stimulus. Randomly intermixed sham rTMS trains were employed to control for non-specific effects. Right parietal rTMS induced a significant rightward bias in symmetry judgements as compared with basal and sham rTMS conditions. No differences emerged between other conditions.

  19. A comparison of the cardiovascular effects and subjective tolerability of binedaline and amitriptylene in healthy volunteers.

    PubMed

    Joubert, P H; Starke, D D; Van Reenen, O; Venter, C P

    1985-01-01

    Binedaline is a new antidepressant drug which is not a tricyclic compound. In animal investigations it showed a greater therapeutic index than imipramine and amitriptylene and a smaller ED50. It also showed less anticholinergic and antihistaminic activity. In this study the effects of 100 mg (females) and 150 mg (males) of binedaline was compared with 50 mg and 75 mg of amitriptylene and placebo in healthy volunteers. Binedaline was better tolerated than amitriptylene and produced less sedation and fewer instances of dry mouth. Binedaline was devoid of the marked postural hypotension produced by amitriptylene but caused the same degree of tachycardia as amitriptylene at rest, when subjects were tilted and when subjected to ergometry. It was concluded that binedaline causes less alpha-adrenergic blockade than amitriptylene but that the sympathomimetic effects were similar. At the doses employed no major changes in electrocardiogram or systolic time intervals occurred.

  20. Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking.

    PubMed

    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.

  1. Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.

    PubMed

    Lötsch, Jörn; Dimova, Violeta; Hermens, Hanneke; Zimmermann, Michael; Geisslinger, Gerd; Oertel, Bruno G; Ultsch, Alfred

    2015-03-01

    Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. Z-transformed QST-parameter values obtained at the test site were compared with corresponding values published from 1236 patients with neuropathic pain using Bayesian statistics. Subjects were clustered for the resemblance of their QST pattern to neuropathic pain. Although QST parameter values from the untreated site agreed with reference values, several QST parameters acquired at the test site treated with topical capsaicin deviated from normal. These deviations resembled in 0 to 7 parameters of the QST pattern observed in patients with neuropathic pain. Higher degrees (50%-60%) of resemblance to neuropathic QST pattern were obtained in 18% of the subjects. Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.

  2. AMP deaminase deficiency is associated with lower sprint cycling performance in healthy subjects.

    PubMed

    Fischer, Heléne; Esbjörnsson, Mona; Sabina, Richard L; Strömberg, Anna; Peyrard-Janvid, Myriam; Norman, Barbara

    2007-07-01

    AMP deaminase (AMPD) deficiency is an inherited disorder of skeletal muscle found in approximately 2% of the Caucasian population. Although most AMPD-deficient individuals are asymptomatic, a small subset has exercise-related cramping and pain without any other identifiable neuromuscular complications. This heterogeneity has raised doubts about the physiological significance of AMPD in skeletal muscle, despite evidence for disrupted adenine nucleotide catabolism during exercise in deficient individuals. Previous studies have evaluated the effect of AMPD deficiency on exercise performance with mixed results. This study was designed to circumvent the perceived limitations in previous reports by measuring exercise performance during a 30-s Wingate test in 139 healthy, physically active subjects of both sexes, with different AMPD1 genotypes, including 12 AMPD-deficient subjects. Three of the deficient subjects were compound heterozygotes characterized by the common c.34C>T mutation in one allele and a newly discovered AMPD1 mutation, c.404delT, in the other. While there was no significant difference in peak power across AMPD1 genotypes, statistical analysis revealed a faster power decrease in the AMPD-deficient group and a difference in mean power across the genotypes (P = 0.0035). This divergence was most striking at 15 s of the 30-s cycling. Assessed by the fatigue index, the decrease in power output at 15 s of exercise was significantly greater in the deficient group compared with the other genotypes (P = 0.0006). The approximate 10% lower mean power in healthy AMPD-deficient subjects during a 30-s Wingate cycling test reveals a functional role for the AMPD1 enzyme in sprint exercise.

  3. Confirmatory and Exploratory Factor Analysis for Validating the Phlegm Pattern Questionnaire for Healthy Subjects

    PubMed Central

    Kim, Hyunho; Ku, Boncho; Kim, Jong Yeol; Park, Young-Jae

    2016-01-01

    Background. Phlegm pattern questionnaire (PPQ) was developed to evaluate and diagnose phlegm pattern in Korean Medicine and Traditional Chinese Medicine, but it was based on a dataset from patients who visited the hospital to consult with a clinician regarding their health without any strict exclusion or inclusion. In this study, we reinvestigated the construct validity of PPQ with a new dataset and confirmed the feasibility of applying it to a healthy population. Methods. 286 healthy subjects were finally included and their responses to PPQ were acquired. Confirmatory factor analysis (CFA) was conducted and the model fit was discussed. We extracted a new factor structure by exploratory factor analysis (EFA) and compared the two factor structures. Results. In CFA results, the model fit indices are acceptable (RMSEA = 0.074) or slightly less than the good fit values (CFI = 0.839, TLI = 0.860). Many average variances extracted were smaller than the correlation coefficients of the factors, which shows the somewhat insufficient discriminant validity. Conclusions. Through the results from CFA and EFA, this study shows clinically acceptable model fits and suggests the feasibility of applying PPQ to a healthy population with relatively good construct validity and internal consistency. PMID:27051447

  4. Assessment of lifestyle effects on the overall antioxidant capacity of healthy subjects.

    PubMed

    Lesgards, Jean-François; Durand, Philippe; Lassarre, Magali; Stocker, Pierre; Lesgards, Guy; Lanteaume, André; Prost, Michel; Lehucher-Michel, Marie-Pascale

    2002-05-01

    Oxidative damage is increasingly recognized as playing an important role in the pathogenesis of several diseases such as cancer and cardiovascular diseases. Using a biologic test based on whole blood resistance to free-radical aggression, we sought to evaluate lifestyle factors that may contribute to the normal variability of the overall antioxidant status. We assessed this global antiradical defense capacity in 88 men and 96 women in relation to information on lifestyle obtained by questionnaire. In our relatively young, healthy population, we found a weak negative relation between male sex or aging and the resistance to oxidant stress. Among the factors studied, nonsmoking, vitamin and/or mineral supplementation, and regular physical activity were closely associated with an increased overall antioxidant capacity. Conversely, the antioxidant potential was negatively related to tobacco smoking; psychologic stress; alcohol consumption; moderate vegetable, low fruit, and low fish consumption; and, to a lesser extent, high natural ultraviolet light exposure. Thus, we were able to determine "unhealthy" and "healthy" lifestyle patterns that truly contributed to the variation of individual antioxidant capacity. We conclude that lifestyle determinants of cancer and cardiovascular risks were associated with a decreased overall antioxidant status as dynamically measured by means of a biologic test. Thus, the evaluation of the total human resistance against free-radical aggression, taking into account nutritional habits, lifestyle, and environmental factors, may be useful in preventive medicine as a precocious diagnosis to identify healthy subjects who are at risk for free-radical-mediated diseases.

  5. Arm path fragmentation and spatiotemporal features of hand reaching in healthy subjects and stroke patients.

    PubMed

    Liebermann, Dario G; Levin, Mindy F; McIntyre, Joseph; Weiss, Patrice L; Berman, Sigal

    2010-01-01

    Arm motion in healthy humans is characterized by smooth and relatively short paths. The current study focused on 3D reaching in stroke patients. Sixteen right-hemiparetic stroke patients and 8 healthy adults performed 42 reaching movements towards 3 visual targets located at an extended arm distance. Performance was assessed in terms of spatial and temporal features of the movement; i.e., hand path, arm posture and smoothness. Differences between groups and within subjects were hypothesized for spatial and temporal aspects of reaching under the assumption that both are independent. As expected, upper limb motion of patients was characterized by longer and jerkier hand paths and slower speeds. Assessment of the number of sub-movements within each movement did not clearly discriminate between groups. Principal component analyses revealed specific clusters of either spatial or temporal measures, which accounted for a large proportion of the variance in patients but not in healthy controls. These findings support the notion of a separation between spatial and temporal features of movement. Stroke patients may fail to integrate the two aspects when executing reaching movements towards visual targets.

  6. Assessment of lifestyle effects on the overall antioxidant capacity of healthy subjects.

    PubMed Central

    Lesgards, Jean-François; Durand, Philippe; Lassarre, Magali; Stocker, Pierre; Lesgards, Guy; Lanteaume, André; Prost, Michel; Lehucher-Michel, Marie-Pascale

    2002-01-01

    Oxidative damage is increasingly recognized as playing an important role in the pathogenesis of several diseases such as cancer and cardiovascular diseases. Using a biologic test based on whole blood resistance to free-radical aggression, we sought to evaluate lifestyle factors that may contribute to the normal variability of the overall antioxidant status. We assessed this global antiradical defense capacity in 88 men and 96 women in relation to information on lifestyle obtained by questionnaire. In our relatively young, healthy population, we found a weak negative relation between male sex or aging and the resistance to oxidant stress. Among the factors studied, nonsmoking, vitamin and/or mineral supplementation, and regular physical activity were closely associated with an increased overall antioxidant capacity. Conversely, the antioxidant potential was negatively related to tobacco smoking; psychologic stress; alcohol consumption; moderate vegetable, low fruit, and low fish consumption; and, to a lesser extent, high natural ultraviolet light exposure. Thus, we were able to determine "unhealthy" and "healthy" lifestyle patterns that truly contributed to the variation of individual antioxidant capacity. We conclude that lifestyle determinants of cancer and cardiovascular risks were associated with a decreased overall antioxidant status as dynamically measured by means of a biologic test. Thus, the evaluation of the total human resistance against free-radical aggression, taking into account nutritional habits, lifestyle, and environmental factors, may be useful in preventive medicine as a precocious diagnosis to identify healthy subjects who are at risk for free-radical-mediated diseases. PMID:12003751

  7. Single-dose pharmacokinetics of intravenous ampicillin plus sulbactam in healthy elderly and young adult subjects.

    PubMed

    Rho, J P; Jones, A; Woo, M; Castle, S; Smith, K; Bawdon, R E; Norman, D C

    1989-10-01

    The pharmacokinetics of intravenous ampicillin and sulbactam, a beta-lactamase inhibitor, were evaluated in two different age groups. Twelve healthy elderly subjects (age 65-93 years) and 12 healthy young adult subjects (age 20-35 years) received both a dose of ampicillin 1 g plus sulbactam 0.5 g and a higher dose of ampicillin 2 g plus sulbactam 1 g after a one-week period between doses. A reverse-phase high-pressure liquid chromatography method was used for the quantitation of ampicillin and sulbactam in serum and urine. The pharmacokinetic parameters for both ampicillin and sulbactam were calculated by computer-based two-compartment nonlinear model. After a 30-min infusion, serum concentrations of both drugs declined in a biexponential manner for both doses. Elderly subjects demonstrated significantly lower total clearances (Clt) than young adult subjects of ampicillin 1 g (220.0 +/- 104.2 vs 360.0 +/- 95.8 ml/min/1.73 m2), ampicillin 2 g (72.6 +/- 36.6 vs 306.8 +/- 109.77 ml/min/1.73 m2), sulbactam 0.5 g (122.3 +/- 47.8 vs 263.9 +/- 93.7 ml/min/1.73 m2), and sulbactam 1 g (171.2 +/- 85.8 vs 391.7 +/- 70.8 ml/min/1.73 m2), respectively. Significance was defined as P less than 0.05. Renal clearance was also significantly reduced in the elderly subjects. Area under the curve was found to be significantly increased in the elderly subjects compared to the young subjects for both ampicillin and sulbactam as were the beta elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P greater than 0.95) or ampicillin (P greater than 0.95) between the two groups. Linear regression analysis revealed that age was significantly correlated with the Clt of ampicillin 1 g (r = 0.85, P less than 0.001), ampicillin 2 g (r = 0.90, P less than 0.001), sulbactam 0.5 g (r = 0.80, P less than 0.001), and sulbactam 1 g (r = 0.93, P less than 0.001). A multivariate analysis showed a slight

  8. Nifedipine does not impair the hormonal responses to graded exercise in healthy subjects.

    PubMed

    Joffe, B I; Shires, R; Lamprey, J M; Kalk, W J; Botha, A; Haitas, B; Seftel, H C

    1985-01-01

    The aim of this study was to assess whether the potent calcium antagonist nifedipine was capable of modifying the hormonal response to graded exercise in 7 healthy young men. After fasting overnight, each subject came to the laboratory on 2 consecutive mornings. On one day he was given 10 mg of nifedipine sublingually and on the other an identical placebo capsule; the order was randomised in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive short treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. While significantly blunting the rise in mean systolic blood pressure and inducing a greater fall in diastolic blood pressure during and after exercise compared with the placebo, nifedipine did not impair the brisk response to pituitary-adrenal hormones (ACTH, cortisol and total catecholamines). Nifedipine also did not modify the effects of short-term exercise in raising mean plasma glucose levels, stimulating pancreatic glucagon secretion and producing a delayed increase in plasma insulin concentrations. Nor did the drug blunt the significant rise of growth hormone and prolactin levels occurring during and after the treadmill run. It was concluded that, apart from inducing significant changes in blood pressure, a single dose of nifedipine does not appear to suppress the counterregulatory hormonal responses to short-term physical activity in healthy men.

  9. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects.

    PubMed

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C

    2001-05-01

    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  10. Brainstem auditory evoked potentials--a review and modified studies in healthy subjects.

    PubMed

    Stone, James L; Calderon-Arnulphi, Mateo; Watson, Karriem S; Patel, Ketan; Mander, Navneet S; Suss, Nichole; Fino, John; Hughes, John R

    2009-06-01

    The authors review the brainstem auditory evoked potential (BAEP), and present studies on 40 healthy subjects. In addition to the conventional click evoked BAEP, three modified BAEP examinations were performed. The modified BAEP tests include a 1,000 Hz tone-burst BAEP, and more rapid rate binaural click and 1,000 Hz tone-burst BAEPs-each of the last two studies performed at four diminishing moderate intensities. In addition to the usual parameters, the authors examined the Wave V to Vn interpeak latency, and stimulus intensity versus Wave V latency and amplitude functions in the rapid rate binaural studies. Studies were also repeated on healthy subjects in a dependant head position in an attempt to increase intracranial pressure. Discussion centers on the BAEP, its current utility in medicine, unique neurophysiology, and literature support that the above modifications could increase the practicality of the test in patients at risk with intracranial lesions and perhaps improve the feasibility for real-time continuous or frequent monitoring in the future.

  11. Neuroticism and serotonin 5-HT1A receptors in healthy subjects.

    PubMed

    Hirvonen, Jussi; Tuominen, Lauri; Någren, Kjell; Hietala, Jarmo

    2015-10-30

    Neuroticism is a personality trait associated with vulnerability for mood and anxiety disorders. Serotonergic mechanisms likely contribute to neuroticism. Serotonin 5-HT1A receptors are altered in mood and anxiety disorders, but whether 5-HT1A receptors are associated with neuroticism in healthy subjects is unclear. We measured brain serotonin 5-HT1A receptor in 34 healthy subjects in vivo using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635. Binding potential (BPP) was determined using the golden standard of kinetic compartmental modeling using arterial blood samples and radiometabolite determination. Personality traits were assessed using the Karolinska Scales of Personality. We found a strong negative association between serotonin 5-HT1A receptor BPP and neuroticism. That is, individuals with high neuroticism tended to have lower 5-HT1A receptor binding than individuals with low neuroticism. This finding was confirmed with an independent voxel-based whole-brain analysis. Other personality traits did not correlate with 5-HT1A receptor BPP. Previous observations have reported lower serotonin 5-HT1A receptor density in major depression. This neurobiological finding may be a trait-like phenomenon and partly explained by higher neuroticism in patients with affective disorders. The link between personality traits and 5-HT1A receptors should be studied in patients with major depression.

  12. Lack of habituation of evoked visual potentials in analytic information processing style: evidence in healthy subjects.

    PubMed

    Buonfiglio, Marzia; Toscano, M; Puledda, F; Avanzini, G; Di Clemente, L; Di Sabato, F; Di Piero, V

    2015-03-01

    Habituation is considered one of the most basic mechanisms of learning. Habituation deficit to several sensory stimulations has been defined as a trait of migraine brain and also observed in other disorders. On the other hand, analytic information processing style is characterized by the habit of continually evaluating stimuli and it has been associated with migraine. We investigated a possible correlation between lack of habituation of evoked visual potentials and analytic cognitive style in healthy subjects. According to Sternberg-Wagner self-assessment inventory, 15 healthy volunteers (HV) with high analytic score and 15 HV with high global score were recruited. Both groups underwent visual evoked potentials recordings after psychological evaluation. We observed significant lack of habituation in analytical individuals compared to global group. In conclusion, a reduced habituation of visual evoked potentials has been observed in analytic subjects. Our results suggest that further research should be undertaken regarding the relationship between analytic cognitive style and lack of habituation in both physiological and pathophysiological conditions.

  13. Cerebral oxygenation and haemodynamic effects induced by nimodipine in healthy subjects

    PubMed Central

    Canova, Daniela; Roatta, Silvestro; Micieli, Giuseppe; Bosone, Daniele

    2012-01-01

    Summary The cerebrovascular effects of nimodipine are still poorly understood even in the healthy condition; in particular, its effects on tissue oxygenation have never been investigated. The aim of the present study was to investigate changes in cerebral oxygenation and blood volume upon oral administration of nimodipine (90 mg) in the healthy condition. In eight subjects, changes in cerebral tissue oxygenation and blood volume were determined simultaneously with changes in blood velocity of the middle cerebral artery (VMCA) by using, respectively, near infrared spectroscopy (NIRS) and transcranial Doppler ultrasonography (TCD). The subjects also underwent non-invasive assessment of arterial blood pressure (ABP) and end-tidal CO2. TCD and NIRS CO2 reactivity indices were also extracted. Nimodipine significantly reduced ABP (11±13%) and increased heart rate, as well as NIRS oxygenation (6.0±4.8%) and blood volume indices (9.4±10.1%), while VMCA was not significantly decreased (2.0±3.5%). Nimodipine slightly but significantly reduced the VMCA response to changes in pCO2 whereas the CO2 reactivity of NIRS parameters was improved. The observed changes in cerebral tissue oxygenation and blood volume indicate nimodipine-induced cerebrovascular dilation and increased perfusion, while the effect on VMCA possibly results from dilation of the insonated artery. The present results cast doubt on the putative nimodipine-induced impairment of CO2 reactivity. PMID:23402678

  14. Cerebral oxygenation and haemodynamic effects induced by nimodipine in healthy subjects.

    PubMed

    Canova, Daniela; Roatta, Silvestro; Micieli, Giuseppe; Bosone, Daniele

    2012-01-01

    The cerebrovascular effects of nimodipine are still poorly understood even in the healthy condition; in particular, its effects on tissue oxygenation have never been investigated. The aim of the present study was to investigate changes in cerebral oxygenation and blood volume upon oral administration of nimodipine (90 mg) in the healthy condition. In eight subjects, changes in cerebral tissue oxygenation and blood volume were determined simultaneously with changes in blood velocity of the middle cerebral artery (VMCA) by using, respectively, near infrared spectroscopy (NIRS) and transcranial Doppler ultrasonography (TCD). The subjects also underwent noninvasive assessment of arterial blood pressure (ABP) and end-tidal CO2. TCD and NIRS CO2 reactivity indices were al-so extracted. Nimodipine significantly reduced ABP (11±13%) and increased heart rate, as well as NIRS oxygenation(6.0±4.8%) and blood volume indices (9.4±10.1%), while V(MCA) was not significantly decreased (2.0±3.5%). Nimodipine slightly but significantly reduced the V(MCA) response to changes in pCO2 whereas the CO2 reactivity of NIRS parameters was improved. The observed changes in cerebral tissue oxygenation and blood volume indicate nimodipine-induced cerebrovascular dilation and increased perfusion, while the effect on V(MCA)possibly results from dilation of the insonated artery. The present results cast doubt on the putative nimodipine-induced impairment of CO2 reactivity.

  15. Effects of Visual Cortex Activation on the Nociceptive Blink Reflex in Healthy Subjects

    PubMed Central

    Sava, Simona L.; de Pasqua, Victor; Magis, Delphine; Schoenen, Jean

    2014-01-01

    Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not known. To address this issue in healthy human subjects we modulated differentially visual cortex activity by repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation, and studied the effect on supraorbital pain thresholds and the nociceptive-specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi- and contralaterally and potentiated habituation contralaterally. After high frequency or sham rTMS over the visual cortex, and rMS over the right greater occipital nerve we found no significant change. By contrast, excitatory flash light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi- and contralaterally and increased habituation contralaterally. Our data demonstrate in healthy subjects a functional relation between the visual cortex and the trigeminal nociceptive system, as assessed by the nociceptive blink reflex. The results argue in favour of a top-down inhibitory pathway from the visual areas to trigemino-cervical nociceptors. We postulate that in normal conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of vision by too frequent blinking and that hypoactivity of the visual cortex for pathological reasons may promote headache and photophobia. PMID:24936654

  16. Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

    PubMed

    Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

    2017-02-01

    Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

  17. Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans.

    PubMed

    Toplak, N; Avcin, T

    2009-11-01

    Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

  18. Validation of a semi-physiological model for caffeine in healthy subjects and cirrhotic patients.

    PubMed

    Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

    2015-06-20

    The objective of this paper was to validate a previously developed semi physiological model to simulate bioequivalence trials of drug products. The aim of the model was to ascertain whether the measurement of the metabolite concentration-time profiles would provide any additional information in bioequivalence studies (Fernandez-Teruel et al., 2009a,b; Navarro-Fontestad et al., 2010). The semi-physiological model implemented in NONMEM VI was used to simulate caffeine and its main metabolite plasma levels using caffeine parameters from bibliography. Data from 3 bioequivalence studies in healthy subjects at 3 different doses (100, 175 and 400mg of caffeine) and one study in cirrhotic patients (200 or 250mg) were used. The first aim was to adapt the previous semi-physiological model for caffeine, showing the hepatic metabolism with one main metabolite, paraxanthine. The second aim was to validate the model by comparison of the simulated plasma levels of parent drug and metabolite to the experimental data. The simulations have shown that the proposed semi-physiological model was able to reproduce adequately the pharmacokinetic behavior of caffeine and paraxanthine in both healthy subjects and cirrhotic patients at all the assayed doses. Therefore, the model could be used to simulate plasma concentrations vs. time of drugs with the same pharmacokinetic scheme as caffeine, as long as their population parameters are known, and it could be useful for bioequivalence trial simulation of drugs that undergo hepatic metabolism with a single main metabolite.

  19. Pharmacokinetics, pharmacodynamics and safety of CKD-519, a CETP inhibitor, in healthy subjects

    PubMed Central

    Kim, Choon Ok; Oh, Eun Sil; Choi, Chungam; Kim, Yeonjoo; Lee, Sera; Kim, Semi; Park, Min Soo

    2016-01-01

    CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of dyslipidemia to raise high-density lipoprotein cholesterol. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy adult subjects. A randomized, double-blinded, placebo-controlled, single ascending dose study was performed. Eight healthy subjects were enrolled in each CKD-519 dose group (25, 50, 100, 200, or 400 mg) and randomized to CKD-519 (n=6) or matching placebo (n=2). CKD-519 reached the maximum plasma concentration (Cmax) at 5–6 h post-dose, and had a long terminal half-life ranging between 40–70 h. The area under the plasma concentration–time curve (AUC) and Cmax increased with the dose, however, Cmax and AUC normalized by dose decreased with each incremental dose. CETP activity decreased with dose, and the maximum decrease (63%–83%) was observed at 6–8 h post-dose. A sigmoid Emax model best described the relationship between CKD-519 plasma concentrations and CETP activity with an EC50 of 17.3 ng/mL. Overall, 11 adverse events (AEs) were observed. All AEs were mild or moderate in intensity, and resolved without any complications. There were no clinically significant effects on blood pressure. In conclusion, single doses of CKD-519 up to 400 mg were well tolerated and showed potent inhibition of CETP activity. PMID:27895466

  20. Multifractal spectra of laser Doppler flowmetry signals in healthy and sleep apnea syndrome subjects

    NASA Astrophysics Data System (ADS)

    Buard, Benjamin; Trzepizur, Wojciech; Mahe, Guillaume; Chapeau-Blondeau, François; Rousseau, David; Gagnadoux, Frédéric; Abraham, Pierre; Humeau, Anne

    2009-07-01

    Laser Doppler flowmetry (LDF) signals give a peripheral view of the cardiovascular system. To better understand the possible modifications brought by sleep apnea syndrome (SAS) in LDF signals, we herein propose to analyze the complexity of such signals in obstructive SAS subjects, and to compare the results with those obtained in healthy subjects. SAS is a pathology that leads to a drop in the parasympathetic tone associated with an increase in the sympathetic tone in awakens SAS patients. Nine men with obstructive SAS and nine healthy men participated awaken in our study and LDF signals were recorded in the forearm. In our work, complexity of LDF signals is analyzed through the computation and analysis of their multifractal spectra. The multifractal spectra are estimated by first estimating the discrete partition function of the signals, then by determining their Renyi exponents with a linear regression, and finally by computing their Legendre transform. The results show that, at rest, obstructive SAS has no or little impact on the multifractal spectra of LDF signals recorded in the forearm. This study shows that the physiological modifications brought by obstructive SAS do not modify the complexity of LDF signals when recorded in the forearm.

  1. Similar and contrasting dimensions of social cognition in schizophrenia and healthy subjects.

    PubMed

    Mehta, Urvakhsh Meherwan; Thirthalli, Jagadisha; Bhagyavathi, H D; Keshav Kumar, J; Subbakrishna, D K; Gangadhar, Bangalore N; Eack, Shaun M; Keshavan, Matcheri S

    2014-08-01

    Schizophrenia patients experience substantial impairments in social cognition (SC) and these deficits are associated with their poor functional outcome. Though SC is consistently shown to emerge as a cognitive dimension distinct from neurocognition, the dimensionality of SC is poorly understood. Moreover, comparing the components of SC between schizophrenia patients and healthy comparison subjects would provide specific insights on the construct validity of SC. We conducted principal component analyses of eight SC test scores (representing four domains of SC, namely, theory of mind, emotion processing, social perception and attributional bias) independently in 170 remitted schizophrenia patients and 111 matched healthy comparison subjects. We also conducted regression analyses to evaluate the relative contribution of individual SC components to other symptom dimensions, which are important clinical determinants of functional outcome (i.e., neurocognition, negative symptoms, motivational deficits and insight) in schizophrenia. A three-factor solution representing socio-emotional processing, social-inferential ability and external attribution components emerged in the patient group that accounted for 64.43% of the variance. In contrast, a two-factor solution representing socio-emotional processing and social-inferential ability was derived in the healthy comparison group that explained 56.5% of the variance. In the patient group, the social-inferential component predicted negative symptoms and motivational deficits. Our results suggest the presence of a multidimensional SC construct. The dimensionality of SC observed across the two groups, though not identical, displayed important parallels. Individual components also demonstrated distinct patterns of association with other symptom dimensions, thus supporting their external validity.

  2. Effect of blood donation-mediated volume reduction on regional right ventricular deformation in healthy subjects.

    PubMed

    Açar, Göksel; Alizade, Elnur; Avci, Anıl; Cakir, Hakan; Efe, Suleyman Cagan; Kalkan, Mehmet Emin; Tabakci, Mehmet Mustafa; Toprak, Cuneyt; Tanboğa, Ibrahim Halil; Esen, Ali Metin

    2014-03-01

    Strain (S) and strain rate (SR) are known to be altered in diseases associated with right ventricular (RV) pressure/volume overload and RV myocardial dysfunction; however determinants of S/SR are incompletely understood. The aim of this study was to examine the effect of blood donation-mediated volume reduction on regional RV deformation in healthy young adults. Study population was composed of 61 consecutive healthy subjects who were volunteers for blood donation. All underwent standard echocardiography and two-dimensional S and SR imaging by speckle tracking before and after 450 mL blood donation. We found no change in RV lateral wall SR in all three segments. However, the S in the apical and mid segments of the RV lateral wall immediately decreased after blood donation [-26.2 ± 3.3 vs. -23.2 ± 3.3 % (p < 0.0001) and -28.2 ± 3.4 vs. -27.1 ± 3.2 % (p = 0.009), respectively], whereas no change was observed in the basal segment. Moreover, changes in systolic S on the apical segment of the RV lateral wall before and after blood donation were significantly correlated with the changes in the RV size [end-diastolic area index, r = - 0.369 (p = 0.003) and end-systolic area index, r = - 0.319 (p = 0.012)] and changes in the stroke volume index [r = - 0.436 (p < 0.001)]. Blood donation-mediated volume reduction in healthy subjects caused a regional difference in RV longitudinal deformation with the lower mid and apical S that was related to parameters of volume load severity. However, RV systolic SR was found to be resistant to the effects of volume depletion.

  3. Validity and Reliability of the Persian Version of Baecke Habitual Physical Activity Questionnaire in Healthy Subjects

    PubMed Central

    Sadeghisani, Meissam; Dehghan Manshadi, Farideh; Azimi, Hadi; Montazeri, Ali

    2016-01-01

    Background Baecke Habitual Physical Activity Questionnaire (BHPAQ) has widely been employed in clinical and laboratorial studies as a tool for measuring subjects' physical activities. But, the reliability and validity of this questionnaire have not been investigated among Persian speakers. Objectives Therefore, the aim of the current study was examining the reliability and validity of the Persian version of the BHPAQ in healthy Persian adults. Materials and Methods After following the process of forward-backward translation, 32 subjects were invited to fill out the Persian version of the questionnaire in two independent sessions (3 - 7 days after the first session) in order to determine the reliability index. Also, the validity of the questionnaire was assessed through concurrent validity by 126 subjects (66 males and 60 females) answering both the Baecke and the International Physical Activity Questionnaire (IPAQ). Results An acceptable level of intraclass correlation coefficient (ICC of work score = 0.95, sport score = 0.93, and leisure score = 0.77) was achieved for the Persian Baecke questionnaire. Correlations between Persian Baecke and IPAQ with and without the score for sitting position were found to be 0.19 and 0.36, respectively. Conclusions The Persian version of the BHPAQ is a reliable and valid instrument that can be used to measure the level of habitual functional activities in Persian-speaking subjects. PMID:27826396

  4. Chronic periodic fluid redistribution effect on muscle calcium in healthy subjects during prolonged hypokinesia.

    PubMed

    Zorbas, Yan G; Deogenov, Victor A; Merkov, Pavel L; Federenko, Yuri F

    2012-05-01

    Studies have shown that chronic periodic fluid shifting upwards is not sensed as excessive fluid volume and excretion mechanisms are not activated. To determine if chronic periodic fluid and volume shifting upwards can affect muscle calcium (Ca(2+)) during hypokinesia (HK) we measured muscle Ca(2+) content, plasma Ca(2+) concentration, and Ca(2+) losses in urine and feces. Studies were conducted on 40 healthy male volunteers. They were divided into four equal groups: active control subjects (ACS), hypokinetic subjects (HKS), periodic fluid redistribution control subjects (PFRCS), and periodic fluid redistribution hypokinetic subjects (PFRHS). Plasma Ca(2+) level decreased (p < 0.05) in Ca(2+) repleted muscle, muscle Ca(2+) level increased (p < 0.05), and Ca(2+) losses in urine and feces decreased (p < 0.05) in the PFRHS group compared with the HKS group. Plasma Ca(2+) level increased (p < 0.05) in Ca(2+) deficient muscle, muscle Ca(2+) level decreased (p < 0.05), and Ca(2+) losses in urine and feces increased (p < 0.05) in the HKS group compared with their pre-experimental levels and the values in their respective control groups (ACS and PFRCS). This study shows that the muscle Ca(2+) content increases and Ca(2+) excretion decreases, suggesting the clinical potential of chronic periodic fluid and volume redistribution in treatment of muscle Ca(2+) deficiency.

  5. Measurement of neural respiratory drive via parasternal intercostal electromyography in healthy adult subjects.

    PubMed

    MacBean, V; Hughes, C; Nicol, G; Reilly, C C; Rafferty, G F

    2016-11-01

    Neural respiratory drive, quantified by the parasternal intercostal muscle electromyogram (EMGpara), provides a sensitive measure of respiratory system load-capacity balance. Reference values for EMGpara-based measures are lacking and the influence of individual anthropometric characteristics is not known. EMGpara is conventionally expressed as a percentage of that obtained during a maximal inspiratory effort (EMGpara%max), leading to difficulty in applying the technique in subjects unable to reliably perform such manoeuvres. To measure EMGpara in a large, unselected cohort of healthy adult subjects in order to evaluate relevant technical and anthropometric factors. Surface second intercostal space EMGpara was measured during resting breathing and maximal inspiratory efforts in 63 healthy adult subjects, median (IQR) age 31.0 (25.0-47.0) years, 28 males. Detailed anthropometry, spirometry and respiratory muscle strength were also recorded. Median (IQR EMGpara was 4.95 (3.35-6.93) µV, EMGpara%max 4.95 (3.39-8.65)% and neural respiratory drive index (NRDI, the product of EMGpara%max and respiratory rate) was 73.62 (46.41-143.92) %.breath/min. EMGpara increased significantly to 6.28 (4.26-9.93) µV (p  <  0.001) with a mouthpiece, noseclip and pneumotachograph in situ. Median (IQR) EMGpara was higher in female subjects (5.79 (4.42-7.98) µV versus 3.56 (2.81-5.35) µV, p  =  0.003); after controlling for sex neither EMGpara, EMGpara%max or NRDI were significantly related to anthropometrics, age or respiratory muscle strength. In subjects undergoing repeat measurements within the same testing session (n  =  48) or on a separate occasion (n  =  19) similar repeatability was observed for both EMGpara and EMGpara%max. EMGpara is higher in female subjects than males, without influence of other anthropometric characteristics. Reference values are provided for EMGpara-derived measures. Expressing EMGpara as a percentage of maximum confers no

  6. Pharmacokinetics and electrocardiographic effect of ebastine in young versus elderly healthy subjects.

    PubMed

    Huang, M Y; Argenti, D; Wilson, J; Garcia, J; Heald, D

    1998-05-01

    The objective of this study was to compare the single- and multiple-dose pharmacokinetics and electrocardiographic effect of a 10-mg oral dose of ebastine in elderly (ages, 65-85 years) and young (ages, 18-35 years) healthy volunteers. Thirty-seven subjects completed this randomized, double-blind, multiple-dose, placebo-controlled, parallel group study. The elderly group consisted of 18 subjects, with 13 subjects receiving 10 mg ebastine and 5 receiving matching placebo. The young group consisted of 19 subjects, with 13 subjects receiving 10 mg ebastine and 6 receiving matching placebo. On study days 1 and 3 through 10, each subject received a single 10-mg dose of ebastine or matching placebo in the morning with a standard breakfast. No drug was administered on study day 2 because of pharmacokinetic sampling. Blood samples were collected at selected times postdose on study days 1, 2, and 10. Plasma samples were analyzed for ebastine and its active metabolite, carebastine, using a validated high-performance liquid chromatography method. No plasma ebastine concentrations were detected, suggesting essentially complete metabolic conversion of ebastine to its metabolites. Analysis of variance showed no statistically significant differences between young and elderly single- and multiple-dose carebastine pharmacokinetics with respect to area under the plasma concentration-time curve, maximum concentration (Cmax ), terminal elimination rate constant, apparent oral clearance, or apparent volume of distribution. The mean time of maximum concentration value for young subjects was 1 hour longer than that for elderly subjects after single-dose administration but was comparable after multiple-dose administration. Within-group comparisons of both the young and elderly showed that pharmacokinetics between single dose and steady state were not statistically different. However, the mean steady-state carebastine Cmax values were approximately twofold greater than the mean Cmax values

  7. Ocular Blood Flow Measurements in Healthy White Subjects Using Laser Speckle Flowgraphy

    PubMed Central

    Luft, Nikolaus; Wozniak, Piotr A.; Aschinger, Gerold C.; Fondi, Klemens; Bata, Ahmed M.; Werkmeister, René M.; Schmidl, Doreen; Witkowska, Katarzyna J.; Bolz, Matthias; Garhöfer, Gerhard; Schmetterer, Leopold

    2016-01-01

    Purpose To assess the feasibility and reliability of Laser Speckle Flowgraphy (LSFG) to measure ocular perfusion in a sample of healthy white subjects and to elucidate the age-dependence of the parameters obtained. Methods This cross-sectional study included 80 eyes of 80 healthy, non-smoking white subjects of Western European descent between 19 and 79 years of age. A commercial LSFG instrument was applied to measure ocular blood flow at the optic nerve head (ONH) three successive times before and after pharmacological pupil dilation. The mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for different regions of the ONH. Eight parameters of ocular perfusion derived from the pulse-waveform analysis of MBR including blowout time (BOT) and falling rate (FR) were also recorded. Results Artifact-free LSFG images meeting the quality criteria for automated image analysis were obtainable in 93.8% without pupil dilation and in 98.8% with pharmacological pupil dilation. Measurements of MBR showed excellent repeatability with intraclass correlation coefficients ≥ 0.937 and were barely affected by pupil dilation. The majority of pulse-waveform derived variables exhibited equally high repeatability. MBR-related blood flow indices exhibited significant age dependence (p<0.001). FR (r = 0.747, p<0.001) and BOT (r = -0.714, p<0.001) most strongly correlated with age. Conclusions LSFG represents a reliable method for the quantitative assessment of ocular blood flow in white subjects. Our data affirms that the LSFG-derived variables FR and BOT may be useful biomarkers for age-related changes in ocular perfusion. PMID:27959905

  8. Dynamic soft tissue mobilisation increases hamstring flexibility in healthy male subjects

    PubMed Central

    Hopper, D; Deacon, S; Das, S; Jain, A; Riddell, D; Hall, T; Briffa, K; Vicenzino, B.

    2005-01-01

    Objectives: The purpose of this study was to investigate the effect of dynamic soft tissue mobilisation (STM) on hamstring flexibility in healthy male subjects. Methods: Forty five males volunteered to participate in a randomised, controlled single blind design study. Volunteers were randomised to either control, classic STM, or dynamic STM intervention. The control group was positioned prone for 5 min. The classic STM group received standard STM techniques performed in a neutral prone position for 5 min. The dynamic STM group received all elements of classic STM followed by distal to proximal longitudinal strokes performed during passive, active, and eccentric loading of the hamstring. Only specific areas of tissue tightness were treated during the dynamic phase. Hamstring flexibility was quantified as hip flexion angle (HFA) which was the difference between the total range of straight leg raise and the range of pelvic rotation. Pre- and post-testing was conducted for the subjects in each group. A one-way ANCOVA followed by pairwise post-hoc comparisons was used to determine whether change in HFA differed between groups. The α level was set at 0.05. Results: Increase in hamstring flexibility was significantly greater in the dynamic STM group than either the control or classic STM groups with mean (standard deviation) increase in degrees in the HFA measures of 4.7 (4.8), –0.04 (4.8), and 1.3 (3.8), respectively. Conclusions: Dynamic soft tissue mobilisation (STM) significantly increased hamstring flexibility in healthy male subjects. PMID:16118294

  9. Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects.

    PubMed

    Zhang, Dan; Yang, Man; Liu, Man; Zhang, Yanan; Wang, Xiaolin; Xiao, Xue; Liu, Huichen

    2012-11-01

    The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v. doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration-time curve (AUC(0-t)) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg · L(-1) and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg · h · L(-1), respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15-60 mg. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

  10. Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects.

    PubMed

    Acalovschi, Monica; Dumitrascu, Dan L.; Hagiu, Claudia

    2002-03-01

    Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.

  11. Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure

    PubMed Central

    Orlando, Rocco; De Martin, Sara; Andrighetto, Laura; Floreani, Maura; Palatini, Pietro

    2010-01-01

    AIMS To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine. METHODS A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h. RESULTS With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 ± 19 vs. 15 ± 9 ng ml−1; difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration–time curve was almost three times higher [885 ± 560 vs. 304 ± 84 ng h ml−1; difference (95% CI) 581 (205, 957), P < 0.05]; half-life was prolonged by 63% [21.1 ± 6.2 vs. 12.9 ± 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 ± 0.77 vs. 2.25 ± 0.66 l h−1 kg−1; difference (95% CI) −1.13 (−1.80, −0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=−0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects. CONCLUSIONS Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF. PMID:20233199

  12. Stair dimension affects knee kinematics and kinetics in patients with good outcome after TKA similarly as in healthy subjects.

    PubMed

    Trinler, Ursula K; Baty, Florent; Mündermann, Annegret; Fenner, Verena; Behrend, Henrik; Jost, Bernhard; Wegener, Regina

    2016-10-01

    Joint biomechanics during stair walking may contain important information on functional deficits in patients with orthopaedic conditions but depend on the stair dimension. The goal of this study was to compare knee kinematics and kinetics between patients with good outcome 2 years after total knee arthroplasty (TKA) and age-matched controls during stair ascent and descent at two different stair heights. Principal component analysis was used to detect differences in gait mechanics between 15 patients and 15 controls at different stair conditions. Linear mixed models showed differences in knee kinematic and kinetic patterns (in flexion/extension and abduction/adduction) between stair heights. The knee adduction angle was more affected by stair heights in stair ascending whereas knee adduction moment and knee power were more affected during stair descent. Some stair by height and subject effects were small but not significant. Overall, good outcome after TKA is reflected in close-to-normal knee biomechanics during stair walking. Specific stair configuration must be considered when comparing joint biomechanics between subject groups and studies. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1753-1761, 2016.

  13. Retinal vessel oxygen saturation in healthy subjects and early branch retinal vein occlusion

    PubMed Central

    Yang, Jing-Yan; You, Bing; Wang, Qian; Chan, Szy Yann; Jonas, Jost B.; Wei, Wen-Bin

    2017-01-01

    AIM To measure the retinal oxygen saturation in healthy subjects and early branch retinal vein occlusion (BRVO) in Chinese population. METHODS The retinal vessel oxygen saturation of the healthy subjects and BRVO patients were measured by a noninvasive retinal oximeter (Oxymap ehf., Reykjavik, Iceland). RESULTS The study included 22 patients with unilateral BRVO (mean age: 55.1±8.8y) in the study group and 91 healthy participants (mean age: 37.5±14.0y) in the control group. In the healthy individuals, mean arterial and venous oxygen saturation were significantly (P<0.001) higher in the superior nasal quadrant (98.5%±10.1% and 57.3%±8.7%, respectively) than in the inferior nasal quadrant (94.2%±9.0% and 54.1%±9.6%, respectively), followed by the superior temporal quadrant (89.1%±10.1% and 51.9%±8.9%, respectively) and the inferior temporal quadrant (86.4%±9.4% and 46.6%±9.6%, respectively). In patients with ischemic BRVO, arterial oxymetric values were significantly higher and venous measurements significantly lower for the affected vessel (107.5%±9.7% and 46.4%±14.2%, respectively) than the unaffected vessel in the same eye (99.2%±12.2% and 55.5%±7.9%, respectively) and as compared to the vessel in the unaffected fellow eye (93.1%±6.9% and 55.7%±6.8%) (P=0.005 and P=0.02, respectively). In the patients with non-ischemic BRVO, mean venous oxygen saturation was lower in the affected vein (39.8%±12.2%) than in the unaffected vessels of the same eye (50.8%±10.5%) and in the fellow eye (58.21%±5.7%) (P=0.03). Mean arterial oxygen saturation did not differ significantly (P=0.42) between all three groups. CONCLUSION In patients with BRVO, the venous oxygen saturation in the affected vessels is decreased potentially due to decreased blood velocity and flow. Interestingly, the arterial oxygen saturation in eyes with ischemic BRVO is increased in the affected arteries. PMID:28251087

  14. Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects

    PubMed Central

    Dumont, G J H; de Visser, S J; Cohen, A F; van Gerven, J M A

    2005-01-01

    Aims Studies of novel centrally acting drugs in healthy volunteers are traditionally concerned with kinetics and tolerability, but useful information may also be obtained from biomarkers of clinical endpoints. This paper provides a systematic overview of CNS-tests used with SSRIs in healthy subjects. A useful biomarker should meet the following requirements: a consistent response across studies and drugs; a clear response of the biomarker to a therapeutic dose; a dose–response relationship; a plausible relationship between biomarker, pharmacology and pathogenesis. Methods These criteria were applied to all individual tests found in studies of selective serotonin reuptake inhibitors (SSRIs), performed in healthy subjects since 1966, identified with a systematic MedLine search. Separate databases were created to evaluate the effects of single or multiple dose SSRI-studies, and for amitriptyline whenever the original report included this antidepressant as a positive control. Doses of the antidepressant were divided into high- and low-dose ranges, relative to a medium range of therapeutic doses. For each test, the drug effects were scored as statistically significant impairment/decrease (−), improvement/increase (+) or no change (=) relative to placebo. Results 56 single dose studies and 22 multiple dose studies were identified, investigating the effects of 13 different SSRIs on 171 variants of neuropsychological tests, which could be clustered into seven neuropsychological domains. Low single doses of SSRIs generally stimulated tests of attention and memory. High doses tended to impair visual/auditory and visuomotor systems and subjective performance, while showing an acceleration in motor function. The most pronounced effects were observed using tests that measure flicker discrimination (improvement at low doses: 75%, medium doses: 40%, high doses: 43% of studies); REM sleep (inconsistent decrease after medium doses, decrease in 83% of studies after high doses

  15. ECG parameters and exposure to carbon ultrafine particles in young healthy subjects.

    PubMed

    Zareba, Wojciech; Couderc, Jean Philippe; Oberdörster, Günter; Chalupa, David; Cox, Christopher; Huang, Li-Shan; Peters, Annette; Utell, Mark J; Frampton, Mark W

    2009-02-01

    The mechanisms underlying the association between air pollution and cardiovascular morbidity and mortality are unknown. This study aimed to determine whether controlled exposure to elemental carbon ultrafine particles (UFP) affects electrocardiogram (ECG) parameters describing heart rate variability; repolarization duration, morphology, and variability; and changes in the ST segment. Two separate controlled studies (12 subjects each) were performed using a crossover design, in which each subject was exposed to filtered air and carbon UFP for 2 hours. The first protocol involved 2 exposures to air and 10 microg/m(3) (approximately 2 x 10(6) particles/cm(3), count median diameter approximately 25 nm, geometric standard deviation approximately 1.6), at rest. The second protocol included 3 exposures to air, 10, and 25 microg/m(3) UFP (approximately 7 x 10(6) particles/cm(3)), with repeated exercise. Each subject underwent a continuous digital 12-lead ECG Holter recording to analyze the above ECG parameters. Repeated measures analysis of variance (ANOVA) was used to compare tested parameters between exposures. The observed responses to UFP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFP in comparison to air exposure. In conclusion, transient exposure to 10-25 microg/m(3) ultrafine carbon particles does not cause marked changes in ECG-derived parameters in young healthy subjects. However, trends are observed indicating that some subjects might be susceptible to air pollution, with a response involving autonomic modulation of the heart and repolarization of the ventricular myocardium.

  16. Magnetic resonance imaging and ultrasound evaluation of "healthy" joints in young subjects with severe haemophilia A.

    PubMed

    Di Minno, M N D; Iervolino, S; Soscia, E; Tosetto, A; Coppola, A; Schiavulli, M; Marrone, E; Ruosi, C; Salvatore, M; Di Minno, G

    2013-05-01

    Magnetic resonance imaging (MRI) and ultrasonography (US) are increasingly used in haemophilia A (HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events ["healthy joints" (HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 ± 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non-haemophilic (no-HA) subjects (mean age 23.90 ± 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P-MRI) and additive (A-MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no-HA subjects (3.40 ± 1.72 vs. 0.80 ± 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no-HA joints (P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no-HA joints; cartilage erosion was found in 30% of HA and in none of no-HA joints. MRI examinations confirmed these findings and the US score correlated with the A-MRI (r = 0.732, P < 0.001) and with the P-MRI (r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion (r = 0.819, P = 0.002), synovial hypertrophy (r = 0.633, P = 0.036) and cartilage erosion (r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA.

  17. Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety.

    PubMed

    Paillard, A C; Quarck, G; Paolino, F; Denise, P; Paolino, M; Golding, J F; Ghulyan-Bedikian, V

    2013-01-01

    Several studies have suggested that anxiety may play a role in motion sickness susceptibility (MSS) variability. This study aimed to assess motion sickness susceptibility in healthy subjects and chronic vestibular patients and to investigate its relationship to gender, age and trait-anxiety. Healthy subjects (n=167) and chronic dizzy patients with various vestibulopathies (n=94), aged from 20 to 92 years old, were asked to complete Motion Sickness Susceptibility questionnaire (MSSQ) and trait-anxiety questionnaire (STAI-B). When patients were divided into those who had vestibular loss (n=51) vs. patients without vestibular loss (n=43), the MSSQ scores (mean ± SD) for patients with vestibular loss (18.8 ± 30.9) were lower than healthy subjects (36.4 ± 34.8), who were lower than vestibular patients without vestibular loss (59.0 ± 39.7). These significant differences could not be explained by gender, age, trait-anxiety, or interaction. Women had higher MSS than men, and MSS declined with age for healthy subjects and vestibular patients. The overall relationship between anxiety and MSS scores was weak and only reached significance in healthy subjects. These results support the conclusion that the vestibular system is heavily involved in MSS and that trait-anxiety may play a role in MSS but only in healthy subjects.

  18. Negative correlation between leftward bias in line bisection and schizotypal features in healthy subjects

    PubMed Central

    Ribolsi, Michele; Lisi, Giulia; Di Lorenzo, Giorgio; Rociola, Giuseppe; Niolu, Cinzia; Siracusano, Alberto

    2013-01-01

    Introduction: Recent studies have found a lack of normal pseudoneglect in schizophrenia patients and in their first degree relatives. Similarly, several contributions have reported that measures of schizotypy in the healthy population may be related to signs of right-sided lateralization, but most of these studies differ greatly in methodology (sample size, choice of schizotypy scales, and laterality tasks) and, consequently, the results cannot be compared and so definitive conclusion cannot be drawn. In this study, our purpose is to investigate whether some tasks of spatial attention may be related to different dimensions of schizotypy not only in a larger sample of healthy subjects (HS), but testing the same people with several supposedly related measures several times. Materials and Methods: In the first part of the study (Part I), the performance on “paper and pencil” line bisection (LB) tasks in 205 HS was investigated. Each task was repeated three times. In the second part of the study (Part II), a subgroup of 80 subjects performed a computerized version of the LB test and of the mental number line bisection (MNL) test. In both parts of the study, every subject completed the 74-item version of the Schizotypal Personality Questionnaire (SPQ) and the Edinburgh Handedness Inventory (EHI). Results: In both parts of the study, high scores on the subscale “magical thinking” of SPQ have resulted in being closely linked to a decreased pseudoneglect as assessed by the LB task. On the contrary, right handedness is related to an increased leftward bias at the same task. No association was found between MNL and the other variables. Discussion: The main finding of this study is that a decreased spatial leftward bias at the LB task correlates with positive schizotypy in the healthy population. This finding supports the hypothesis that a deviation from leftward hemispatial visual preference may be related to the degree of psychosis-like schizotypal signs in non

  19. Effects of biological variations on platelet count in healthy subjects in China.

    PubMed

    Peng, Liming; Yang, Jing; Lu, Xiaojun; Okada, Tokuhiro; Kondo, Tamiaki; Ruan, Changgeng; Wu, Yun; Xin, Xiaomin

    2004-02-01

    The effects of biological variations on platelet counts were investigated in 694 healthy subjects aged 18 to 60 years living in three cities including Chengdu (Sichuan Province), Suzhou (Jiangsu Province) and Harbin (Heilongjang Province) in China. Platelet counts in healthy subjects were significantly lower in Chengdu (52-202 x 10(9)/L) and Suzhou (60-259 x 10(9)/L) than in Harbin (154-348 x 10(9)/L) (p <0.0001), but the mean platelet volume (MPV) determined concurrently was negatively correlated with platelet count, the MPV values were significantly higher in Chengdu (11.8-15.6 fl) and Suzhou (10.9-15.8 fl) than in Harbin (9.5 approximately 12.9 fl) (p < 0.0001). Platelet counts were significantly higher in summer (73-289 x 10(9)/L) than in winter (52-202 x 10(9)/L) (p <0.0001), but the MPV values were lower in summer (11.2-14.7 fl) than in winter (11.8-15.6 fl) (p <0.05) in Chengdu. Platelet associated immunoglobulin (PA-IgG) in Chengdu was revealed to be significantly higher in the low platelet count group (<150 x 10(9)/L, 13.5 +/- 7.1 ng/10(7) PLT) than in the normal platelet count group (> or =150 x 10(9)/L, 8.3 +/- 2.7 ng/10(7) PLT) (p <0.0001). Similar results were observed in Suzhou for the reticulated platelet ratio, which was significantly higher in the low platelet count group (19.5 +/- 7.1%) than in the normal platelet count group (11.6 +/- 2.7%) (p <0.01). The bleeding time in Chengdu showed a significantly longer time in the low platelet count group (8.6 +/- 2.3 min) than in the normal platelet count group (6.0 +/- 1.2 min)(p <0.01). With regard to the effects of lipids on platelet counts, the HDL values were significantly higher in the normal platelet count group (1.60 +/- 0.76 mmol/L) than the low platelet count group (1.23 +/- 0.31 mmol/L) (p <0.01); but no significant differences in cholesterol and triglycerides values between the normal and low platelet count groups (p >0.05) were recorded. These findings suggest that the platelet counts could

  20. Quantitative Assessment of the Impact of Blood Pulsation on Intraocular Pressure Measurement Results in Healthy Subjects

    PubMed Central

    2017-01-01

    Background. Blood pulsation affects the results obtained using various medical devices in many different ways. Method. The paper proves the effect of blood pulsation on intraocular pressure measurements. Six measurements for each of the 10 healthy subjects were performed in various phases of blood pulsation. A total of 8400 corneal deformation images were recorded. The results of intraocular pressure measurements were related to the results of heartbeat phases measured with a pulse oximeter placed on the index finger of the subject's left hand. Results. The correlation between the heartbeat phase measured with a pulse oximeter and intraocular pressure is 0.69 ± 0.26 (p < 0.05). The phase shift calculated for the maximum correlation is equal to 60 ± 40° (p < 0.05). When the moment of measuring intraocular pressure with an air-puff tonometer is not synchronized, the changes in IOP for the analysed group of subjects can vary in the range of ±2.31 mmHg (p < 0.3). Conclusions. Blood pulsation has a statistically significant effect on the results of intraocular pressure measurement. For this reason, in modern ophthalmic devices, the measurement should be synchronized with the heartbeat phases. The paper proposes an additional method for synchronizing the time of pressure measurement with the blood pulsation phase. PMID:28250983

  1. Back muscle fatigue in healthy men and women studied by electromyography spectral parameters and subjective ratings.

    PubMed

    Elfving, B; Németh, G; Arvidsson, I

    2000-09-01

    To obtain reference data for future studies of patients with low back pain, back muscle fatigue was studied by surface electromyography at L1 and L5 lumbar levels in 55 healthy subjects exerting 80% of maximal voluntary contraction of the back extensors in a sitting position. Reference data were the initial value and rate of decrease (slope) of the median frequency during the contraction. The aim was also to study the effects of contraction time, gender differences, electrode locations and correlations with torque, age and subjective ratings. Initial median frequency was 52 Hz +/- 7.5, with no difference between electrode locations; steeper slopes were found at L5 level (-0.44%/s +/- 0.25) than at L1 (-0.36%/s +/- 0.26). No right-left differences and no gender differences were found for these parameters. A correlation was observed between slope and initial median frequency, higher for men (r approximately -0.7) than for women (r approximately -0.5). Intersubject coefficient of variation for the slope was smallest for the longest (45 seconds) recording time (60-70%), but still much higher than for the initial median frequency (14%). The torque and the subjective ratings of fatigue showed no correlation with the electromyography variables. We conclude that the same reference values can be used for men and women. Owing to the large intersubject range of the slope, the clinical use of this variable may, however, be impeded.

  2. Hypoglycemic effect of Lupinus mutabilis in healthy volunteers and subjects with dysglycemia.

    PubMed

    Fornasini, M; Castro, J; Villacrés, E; Narváez, L; Villamar, M P; Baldeón, M E

    2012-01-01

    Metabolic syndrome and type-2 diabetes are increasing health problems that negatively affect health care systems worldwide. There is a constant urge to develop new therapies with better effects, lower side effects at lower prices to treat these diseases. Lupinus species and their derivates are good candidates to be used as hypoglycaemic agents. A phase II clinical trial was conducted to assess the role of raw Lupinus mutabilis on blood glucose and insulin in normoglycemic and dysglycemic subjects. Results show that consumption of L. mutabilis by normal weight healthy young individuals did not change importantly blood glucose and insulin levels. On the other hand, consumption of similar doses of lupinus by dysglycemic individuals (fasting glucose > 100 mg/dL) decreased significantly blood glucose. Lupinus effects were greater in those subjects with higher basal glucose levels. Glucose lowering effects of lupinus were not observed after soy intake that was used as control. A statistically significant reduction in insulin levels was also observed in the lupinus group compared with the soy group after 60 minutes of treatment. Furthermore, only treatment with lupinus improved insulin resistance in dysglycemic subjects. These data demonstrate that lupinus consumption could be a feasible and low cost alternative to treat chronic hyperglycemic diseases.

  3. Clenching and grinding: effect on masseter and sternocleidomastoid electromyographic activity in healthy subjects.

    PubMed

    Venegas, Macarena; Valdivia, José; Fresno, María Javiera; Miralles, Rodolfo; Gutiérrez, Mario Felipe; Valenzuela, Saúl; Fuentes, Aler

    2009-07-01

    This study compares the effect of clenching and grinding on masseter and sternocleidomastoid electromyographic (EMG) activity during different jaw posture tasks in the sagittal plane. The study included 34 healthy subjects with natural dentition, Class I bilateral molar Angle relationship, and absence of posterior occlusal contacts during mandibular protrusion. An inclusion criterion was that subjects had to be free of signs and symptoms of any dysfunction of the masticatory system. Bipolar surface electrodes were located on the right masseter and sternocleidomastoid muscles. EMG activity was recorded while the subjects were in standing position, during the following jaw posture tasks: A. maximal clenching in the intercuspal position; B. grinding from intercuspal position to edge-to-edge protrusive contact position; C. maximal clenching in the edge-to-edge protrusive contact position; D. grinding from edge-to-edge protrusive contact position to intercuspal position; E. grinding from retrusive contact position to intercuspal position. EMG activities in tasks B, C, D, and E were significantly lower than in task A in both muscles (mixed model with unstructured covariance matrix). EMG activity among tasks B, C, D, and E did not show significant differences in both muscles, except between tasks D and E in the masseter muscle. A higher effect was observed on the masseter than on the sternocleidomastoid muscle to avoid excessive muscular activity during clenching and grinding. The EMG patterns observed could be of clinical importance in the presence of parafunctional habits, i.e., clenching and/or grinding.

  4. [Characterization of electrical brain activity related to hand motor imagery in healthy subjects].

    PubMed

    Cantillo-Negrete, Jessica; Gutiérrez-Martínez, Josefina; Flores-Rodríguez, Teodoro B; Cariño-Escobar, Rubén I; Elías-Viñas, David

    2014-07-01

    Brain computer interface systems (BCI) translate the intentions of patients affected with locked-in syndrome through the EEG signal characteristics, which are converted into commands used to control external devices. One of the strategies used, is to decode the motor imagery of the subject, which can modify the neuronal activity in the sensory-motor areas in a similar way to which it is observed in real movement. The present study shows the activation patterns that are registered in motor and motor imagery tasks of right and left hand movement in a sample of young healthy subjects of Mexican nationality. By means of frequency analysis it was possible to determine the difference conditions of motor imagery and movement. Using U Mann- Whitney tests, differences with statistical significance (p < 0.05) where obtained, in the EEG channels C3, Cz, C4, T3 and P3 in the mu and beta rhythms, for subjects with similar characteristics (age, gender, and education). With these results, it would be possible to define a classifier or decoder by gender that improves the performance rate and diminishes the training time, with the goal of designing a functional BCI system that can be transferred from the laboratory to the clinical application in patients with motor disabilities.

  5. Comparison of Resting Energy Expenditure Between Cancer Subjects and Healthy Controls: A Meta-Analysis.

    PubMed

    Nguyen, Thi Yen Vi; Batterham, Marijka J; Edwards, Cheree

    2016-01-01

    There is conflicting evidence surrounding the extent of changes in resting energy expenditure (REE) in cancer. This meta-analysis aimed to establish the mean difference in REE, as kilojoules per kilogram fat-free mass, among cancer patients when compared to healthy control subjects. The secondary aim was to determine differences among different cancer types. PubMed, Cochrane Library, Medline, Science Direct, Scopus, Web of Science, Wiley Online Library, and ProQuest Central were searched from the earliest records until March 2014. Studies were included if measured REE was reported as kilojoules or kilocalories per kilogram fat-free mass (FFM) in adult subjects with cancer. Twenty-seven studies were included in the meta-analysis. Fourteen studies included both cancer (n = 1453) and control (n = 1145) groups. The meta-analysis shows an average increase in REE of 9.66 (95% confidence interval: 3.34, 15.98) kJ/kgFFM/day in cancer patients when compared to control subjects. Heterogeneity was detected (P < 0.001) which suggest variations in REE among cancer types. Elevations are most noticeable in patients with cancers of metabolically demanding organs.

  6. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis

    PubMed Central

    Zhu, Zhong-Zheng; Hou, Lifang; Bollati, Valentina; Tarantini, Letizia; Marinelli, Barbara; Cantone, Laura; Yang, Allen S; Vokonas, Pantel; Lissowska, Jolanta; Fustinoni, Silvia; Pesatori, Angela C; Bonzini, Matteo; Apostoli, Pietro; Costa, Giovanni; Bertazzi, Pier Alberto; Chow, Wong-Ho; Schwartz, Joel; Baccarelli, Andrea

    2012-01-01

    Background Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results Age [β = −0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) −0.020 to −0.001%5mC/year] and alcohol drinking (β = −0.214, 95% CI −0.415 to −0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = −0.385, 95% CI −0.665 to −0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = −0.038, 95% CI −0.065 to −0.012) association with LINE-1 methylation, respectively. Conclusions Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. PMID:20846947

  7. Creatine metabolism: detection of creatine and guanidinoacetate in saliva of healthy subjects.

    PubMed

    Martínez, Lidia D; Bezard, Miriam; Brunotto, Mabel; Dodelson de Kremer, Raquel

    2016-04-01

    Creatine (Cr) plays an important role in storage and transmission of phosphate-bound energy. Cerebral creatine deficiency syndromes comprise three inherited defects in Cr biosynthesis and transport. The aim of this study was to investigate whether Cr and Guanidinoacetate (GAA) can be detected in saliva of healthy subjects and to establish the relationship between salivary and plasma levels of these molecules. An adapted gas chromatography (GC) method is described for the quantification of Cr and GAA biomarkers in saliva. Reference values were established for GAA and Cr in saliva. These values were age dependent (p= 0.001). No difference between genders was observed. We detected a difference between GAA and Cr concentrations in saliva and in plasma. The GC method for simultaneous determination of GAA and Cr in human saliva is fast, reliable, sensitive, non-invasive and precise to use as a biochemical approach in early detection of cerebral creatine deficiency syndromes.

  8. Absence of food effect on the pharmacokinetics of telbivudine following oral administration in healthy subjects.

    PubMed

    Zhou, Xiao-Jian; Lloyd, Deborah M; Chao, George C; Brown, Nathaniel A

    2006-03-01

    The influence of food on the pharmacokinetics of telbivudine, a candidate antiviral agent against hepatitis B virus (HBV), was investigated in healthy adult subjects following a 600-mg oral dose administered with and without a high-fat/high-calorie meal. Telbivudine was well tolerated under fasting and fed conditions. Oral absorption of telbivudine as measured by maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC(0-t) and AUC(0-infinity)) was not altered by food intake immediately before oral dosing. Values of Cmax, Tmax, and AUC were comparable when telbivudine was administered under fed and fasting conditions. Results from this study indicated that the absorption of telbivudine was not affected by a high-fat/high-calorie meal; telbivudine can therefore be administered orally with no regard to the timing of meals.

  9. Regional cerebral blood flow during comprehension and speech (in cerebrally healthy subjects)

    SciTech Connect

    Lechevalier, B.; Petit, M.C.; Eustache, F.; Lambert, J.; Chapon, F.; Viader, F. )

    1989-07-01

    Regional cerebral blood flow (rCBF) was measured by the xenon-133 inhalation method in 10 cerebrally healthy subjects at rest and during linguistic activation tests. These consisted of a comprehension test (binaural listening to a narrative text) and a speech test (making sentences from a list of words presented orally at 30-s intervals). The comprehension task induced a moderate increase in the mean right CBF and in both inferior parietal areas, whereas the speech test resulted in a diffuse increase in the mean CBF of both hemispheres, predominating regionally in both inferior parietal, left operculary, and right upper motor and premotor areas. It is proposed that the activation pattern induced by linguistic stimulation depends on not only specific factors, such as syntactic and semantic aspects of language, but also the contents of the material proposed and the attention required by the test situation.

  10. Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects

    PubMed Central

    Mathur, Sandeep Kumar; Jain, Priyanka; Mathur, Prashant; Punjabi, Poonam; Agarwal, Atima; Sharma, Abhay

    2013-01-01

    Understanding the role of visceral fat accumulation in the occurrence and progression of metabolic syndrome is of considerable interest. In order to understand the difference between visceral tissue biology of healthy and unhealthy obese individuals, we have used microarray profiling to compare genome-wide expression differences between visceral adipose tissue biopsies obtained from obese diabetics, and those from age and body mass index (BMI) matched normal glucose tolerance subjects. Whereas genes upregulated in diabetics showed enrichment of natural killer cell mediated cytotoxicity, the downregulated genes showed enrichment of biosynthesis of unsaturated fatty acids. Given the known inhibitory effect of unsaturated fatty acids on inflammation and natural killer cell number or activity, our results suggest that visceral inflammation resulting from decreased levels of unsaturated fatty acids may underlie progression of diabetes in obese individuals. PMID:23869300

  11. Effects of active hexose correlated compound on the seasonal variations of immune competence in healthy subjects.

    PubMed

    Takanari, Jun; Hirayama, Yosuke; Homma, Kohei; Miura, Takehito; Nishioka, Hiroshi; Maeda, Takahiro

    2015-01-01

    The aim of this study was to evaluate the effects of active hexose correlated compound intake on the immune competence in healthy volunteers. Thirty-four subjects were randomized to receive placebo or active hexose correlated compound at 1.0 g/d for 4 weeks in early winter. Natural killer cell activity was significantly increased in both groups during the study period, the natural killer cell number, however, was not altered in the active hexose correlated compound group while placebo group showed remarkable decline. In addition, the score of immunological vigor, an index of total immune competence, was maintained in the active hexose correlated compound group although that of placebo group lowered during the test period. These results suggested that the continuous active hexose correlated compound intake maintained the immune competence against the seasonal change.

  12. Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

    PubMed

    Yeri, Ashish; Courtright, Amanda; Reiman, Rebecca; Carlson, Elizabeth; Beecroft, Taylor; Janss, Alex; Siniard, Ashley; Richholt, Ryan; Balak, Chris; Rozowsky, Joel; Kitchen, Robert; Hutchins, Elizabeth; Winarta, Joseph; McCoy, Roger; Anastasi, Matthew; Kim, Seungchan; Huentelman, Matthew; Van Keuren-Jensen, Kendall

    2017-03-17

    Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18-25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual's exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals.

  13. [Continuous nocturnal automassage of an acupuncture point modifies sleep in healthy subjects].

    PubMed

    Buguet, A; Sartre, M; Le Kerneau, J

    1995-01-01

    To test the somnogenic properties of the automassage of point 7 heart of acupuncture, polygraphic night sleep was studied in six healthy volunteers (age: 27.8 +/- 1.6 years) from 23:00 h to 07:00 h. After one night of adaptation, two PEBA cones (Polyether Block Amides; Isocones) were fixed bilaterally at both points 7 heart (active application, AA) or on the back of hand (placebo application, AP). The alternate application was used 2 weeks later, using a randomized, double-blind, and cross-over protocol. Cyclic alternating patterns (CAP) were also analysed on the electroencephalogram during non-REM sleep. Sleep efficiency increased in AA, due to a decrease in wakefulness, and an increase in total sleep time due to an increase in non-REM sleep. The number of CAP decreased in AA, as did the number of CAP sequences and the ratio of CAP duration to total sleep time (CAP rate) and to the duration of slow-wave sleep. In conclusion, the application of Isocones at point 7 heart during the night induced a decrease in wakefulness and an increase in non-REM sleep during night sleep in healthy subjects.

  14. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects.

    PubMed

    Faris, Mo'ez Al-Islam E; Kacimi, Safia; Al-Kurd, Ref'at A; Fararjeh, Mohammad A; Bustanji, Yasser K; Mohammad, Mohammad K; Salem, Mohammad L

    2012-12-01

    Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects. Fifty (21 men and 29 women) healthy volunteers who practiced Ramadan fasting were recruited for the investigation of circulating proinflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor α), immune cells (total leukocytes, monocytes, granulocytes, and lymphocytes), and anthropometric and dietary assessments. The investigations were conducted 1 week before Ramadan fasting, at the end of the third week of Ramadan, and 1 month after the cessation of Ramadan month. The proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor α; systolic and diastolic blood pressures; body weight; and body fat percentage were significantly lower (P < .05) during Ramadan as compared with before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. These results indicate that RIF attenuates inflammatory status of the body by suppressing proinflammatory cytokine expression and decreasing body fat and circulating levels of leukocytes.

  15. Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

    PubMed Central

    Yeri, Ashish; Courtright, Amanda; Reiman, Rebecca; Carlson, Elizabeth; Beecroft, Taylor; Janss, Alex; Siniard, Ashley; Richholt, Ryan; Balak, Chris; Rozowsky, Joel; Kitchen, Robert; Hutchins, Elizabeth; Winarta, Joseph; McCoy, Roger; Anastasi, Matthew; Kim, Seungchan; Huentelman, Matthew; Van Keuren-Jensen, Kendall

    2017-01-01

    Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual’s exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals. PMID:28303895

  16. Safety, tolerability and pharmacokinetics of phenoprolamine hydrochloride floating sustained-release tablets in healthy Chinese subjects.

    PubMed

    Zhao, Libo; Yang, Xiaoyan; Xu, Rong; Wu, Jianhong; Gu, Shifen; Zhang, Li; Gong, Peili; Chen, Hui; Zeng, Fandian

    2009-07-30

    The present study was designed to assess the safety, tolerability and pharmacokinetics of phenoprolamine hydrochloride floating sustained tablets (PHFST) in healthy Chinese subjects. 116 volunteers were randomized into single- or multiple-dose groups for oral administration 30-240 mg of PHFST once or 60-120 mg twice daily. Safety and tolerability were appraised by monitoring adverse events and laboratory parameters. Pharmacokinetics was assessed by determining the plasma concentrations of phenoprolamine hydrochloride with a validated HPLC method. In single-dose studies, no severe adverse events were observed in volunteers, and all adverse events were mild; the percentages of treatment-emergent events judged to be possibly related to the drug were 3/6 in the 240 mg dose group, 1/6 in the 180-210 mg dose groups, and none in the 30-150 mg dose groups; system exposure (AUC, C(max)) increased with respect to dose at 30-120 mg, whereas AUC raised disproportionately with dose escalating from 120 to 240 mg; the absorption of phenoprolamine hydrochloride was unaffected by food. In multiple studies, no safety concerns were revealed up to 7 days; steady-state plasma concentration was achieved after approximately 4-5 days of repeated twice-daily dosing. PHFST is safe and well tolerated in healthy Chinese subjects. The mean C(max) of PHFST is proportional to dose, but not the AUC. Oral dosing regimen selected for subsequent Phase II/III clinical trials was 60 mg of PHFST, b.i.d., and dose up to 120 mg, b.i.d. - may be used to achieve better antihypertensive effect.

  17. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects.

    PubMed

    Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob; Høst, Ulla; Holm, Søren; Kelbaek, Henning

    2002-12-01

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.

  18. Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects.

    PubMed

    Minh, Timothy D C; Oliver, Stacy R; Ngo, Jerry; Flores, Rebecca; Midyett, Jason; Meinardi, Simone; Carlson, Matthew K; Rowland, F Sherwood; Blake, Donald R; Galassetti, Pietro R

    2011-06-01

    Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ~100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects.

  19. Plasma Potassium Levels in Healthy Prehypertension Subjects and the Role of A High Potassium Drink.

    PubMed

    Farapti, Farapti; Sayogo, Savitri; Siregar, Parlindungan

    2017-02-24

    Most populations around the world consume less than the recommended levels of potassium. Long term low potassium intake could lead to decreased plasma potassium levels and induce hypokalemia. The increasing of plasma potassium levels 0,2-0,4 mmol/L by improving potassium intake decreased significantly blood pressure (BP). Assessing plasma potassium levels in healthy people related to potassium intake have not been studied. In this study, we analysed plasma potassium levels in prehypertension (PHT) subjects and to evaluate the effect of tender coconut water (TCW) as a high potassium drink on plasma potassium levels in PHT adults. Thirthy-two female aged 25-44 years were randomly allocated to 14 days on TCW or water in a parallel randomized clinical trial . The treatment (T) group received TCW 300 ml twice daily and the control (C) group received water 300 ml twice daily too. At baseline, plasma potassium levels was 3.71±0.41 mmol/L, and 22.58% were categorized as hypokalemia. After 14 days treatment, potassium plasma level between T and C groups were not significantly different (p=0,247). The change of plasma potassium levels in both groups showed tendency to increase but not statistically significant (p=0.166). In healthy prehypertension women, the low levels of potassium plasma may be caused by low potassium intake for long time and intervension with TCW 300 ml twice daily for 14 consecutive days has not proven yet to increase plasma potassium levels. It is necessary to give higher dose and longer time to increase potassium plasma in low potassium plasma level subjects.

  20. Baroreflex physiology studied in healthy subjects with very infrequent muscle sympathetic bursts

    PubMed Central

    Diedrich, André; Crossman, Alexandra A.; Beightol, Larry A.; Tahvanainen, Kari U. O.; Kuusela, Tom A.; Ertl, Andrew C.

    2013-01-01

    Because it is likely that, in healthy human subjects, baroreflex mechanisms operate continuously, independent of experimental interventions, we asked the question, In what ways might study of unprovoked, very infrequent muscle sympathetic bursts inform baroreflex physiology? We closely examined arterial pressure and R-R interval responses of 11 supine healthy young subjects to arterial pressure ramps triggered by large isolated muscle sympathetic bursts. We triggered data collection sweeps on the beginnings of sympathetic bursts and plotted changes of arterial pressure (finger volume clamp or intra-arterial) and R-R intervals occurring before as well as after the sympathetic triggers. We estimated baroreflex gain from regression of R-R intervals on systolic pressures after sympathetic bursts and from the transfer function between cross-spectra of systolic pressure and R-R intervals at low frequencies. Isolated muscle sympathetic bursts were preceded by arterial pressure reductions. Baroreflex gain, calculated with linear regression of R-R intervals on systolic pressures after bursts, was virtually identical to baroreflex gain, calculated with the cross-spectral modulus [mean and (range): 24 (7–43) vs. 24 (8–45) ms/mmHg], and highly significant, according to linear regression (r2 = 0.91, P = 0.001). Our results indicate that 1) since infrequent human muscle sympathetic bursts are almost deterministically preceded by arterial pressure reductions, their occurrence likely reflects simple baroreflex physiology, and 2) the noninvasive low-frequency modulus reliably reproduces gains derived from R-R interval responses to arterial pressure ramps triggered by infrequent muscle sympathetic bursts. PMID:23195626

  1. Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action

    PubMed Central

    Walter, Martin; Lehmann, Mick; Metzger, Coraline; Grimm, Simone; Boeker, Heinz; Boesiger, Peter; Henning, Anke; Seifritz, Erich

    2012-01-01

    Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the „dorsal nexus “(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression. PMID:23049758

  2. Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Sather, T. M.

    2000-01-01

    Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

  3. The measurement repeatability using different partition methods of intraretinal tomographic thickness maps in healthy human subjects

    PubMed Central

    Tan, Jia; Yang, Ye; Jiang, Hong; Liu, Che; Deng, Zhihong; Lam, Byron L; Hu, Liang; Oakley, Jonathan; Wang, Jianhua

    2016-01-01

    Purpose To determine the repeatability and profiles with different partition methods in intraretinal thickness layers in healthy human subjects, using optical coherence tomography (OCT). Methods A custom-built ultrahigh-resolution OCT was used to acquire three-dimensional volume of the macula in 20 healthy subjects. The dataset was acquired twice using the macular cube 512×128 protocol in an area of 6×6 mm2 centered on the fovea. Commercially available segmentation software (Orion™) was used to segment the dataset into thickness maps of six intraretinal layers. The coefficient of repeatability and intraclass coefficient of correlation (ICC) were analyzed using hemispheric zoning and sectors defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). Results All datasets were successfully segmented to create six thickness maps of individual intraretinal layers. Coefficients of repeatabilities of these layers in hemispheric zones ranged from 0.9 to 6.6 µm, with an average of 3.6 µm (standard deviation [SD] 1.4), which was not significantly different compared to ETDRS sectors (P>0.05). ICCs of these layers in hemispheric zones ranged from 0.68 to 0.99, with an average of 0.91 (SD 0.07). There were no significant differences in ICCs between two zoning methods (P>0.05). Significant variations of tomographic intraretinal thicknesses were found between the inner and outer annuli and among the quadrantal sectors within the inner and outer annuli (P<0.05). Significant variations of the quadrantal sectors including both inner and outer annuli were evident in intraretinal layers (P<0.05) except for the outer plexiform layer. Conclusion The measurement repeatabilities of tomographic thicknesses of intraretinal layers are comparable using both hemispheric and ETDRS partitions in volumetric data combined with the commercially available segmentation software. In keeping with known, normal anatomical variation, significant differences in tomographic thickness in

  4. The effect of apixaban on the pharmacokinetics of digoxin and atenolol in healthy subjects

    PubMed Central

    Frost, Charles; Song, Yan; Yu, Zhigang; Wang, Jessie; Lee, Lois S; Schuster, Alan; Pollack, Allyson; LaCreta, Frank

    2017-01-01

    Purpose Apixaban is often coadministered with treatments for cardiovascular comorbidities, which may lead to unintended drug–drug interactions (DDIs). The effects of apixaban on pharmacokinetics (PK) of multidose Lanoxin® (digoxin) and single-dose Tenormin® (atenolol) and the effects of single-dose atenolol on apixaban PK in healthy subjects were investigated in two Phase 1 studies. Patients and methods The digoxin DDI study was an open-label, multidose, two-treatment, single-sequence study in which subjects received digoxin 0.25 mg q6h on day 1, then once daily on days 2–10, followed by apixaban 20 mg and digoxin 0.25 mg once daily on days 11–20. The atenolol DDI study was an open-label, single-dose, randomized, three-period, three-treatment, crossover study in which subjects received a single oral dose of apixaban 10 mg, atenolol 100 mg, or apixaban 10 mg plus atenolol 100 mg. The 90% confidence intervals (CIs) for the ratios of geometric means of peak plasma concentration (Cmax) and area under the concentration–time curve (AUCtau), with and without apixaban were calculated. Absence of effect was concluded if the point estimates and 90% CI were within the equivalence interval of 80%–125% (digoxin) or 70%–143% (atenolol). A similar analysis was performed to assess the effect of atenolol on apixaban. Results Apixaban had no clinically relevant effect on the PK of either atenolol or digoxin: point estimates and 90% CI for both digoxin and atenolol Cmax and AUC were entirely within their respective no-effect intervals. Apixaban Cmax and AUCinf were slightly decreased (ie, 18% and 15% lower, respectively) following atenolol coadministration. No serious or major bleeding-related adverse events were reported during either study. Conclusion Apixaban had no effect on the PK of digoxin and there was no clinically relevant interaction between apixaban and atenolol. Coadministration of digoxin or atenolol with apixaban in healthy subjects was generally well

  5. Subjective - Objective Sleep Comparisons and Discrepancies Among Clinically-Anxious and Healthy Children.

    PubMed

    Alfano, Candice A; Patriquin, Michelle A; De Los Reyes, Andres

    2015-10-01

    We compared subjective and objective sleep patterns and problems, and examined cross-method correspondence across parent reports, child reports, and actigraphy-derived sleep variables in clinically-anxious children and healthy controls. In a multi-site, cross-sectional study, 75 pre-adolescent children (6 to 11 years; M = 8.7 years; SD = 1.4; n = 39/52 % female) were examined including 39 with a diagnosis of primary generalized anxiety disorder (GAD) and 36 controls recruited from university-based clinics in Houston, TX and Washington, DC. Structured interviews, validated sleep questionnaires, and 1 week of actigraphy data were utilized. Despite subjective reports of significantly greater sleep problems among anxious children, actigraphy data revealed no significant differences between the groups. All parents estimated earlier bedtimes and greater total sleep duration relative to actigraphy, and all children endorsed more sleep problems than parents. With few exceptions, subjective reports exhibited low and non-significant correspondence with actigraphy-based sleep patterns and problems. Our findings suggest that high rates of sleep complaints found among children with GAD (and their parents) are not corroborated by objective sleep abnormalities, with the exception of marginally prolonged sleep onset latency compared to controls. Objective-subjective sleep discrepancies were observed in both groups but more apparent overall in the GAD group. Frequent complaints of sleep problems and daytime tiredness among anxious youth might more accurately reflect difficulties prior to the actual sleep period, cognitive-affective biases associated with sleep, and/or poor sleep quality. Findings highlight the importance of considering sleep from multiple perspectives.

  6. Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects.

    PubMed

    Dvorchik, Barry H; Brazier, David; DeBruin, Michael F; Arbeit, Robert D

    2003-04-01

    The purpose of this paper is to establish the pharmacokinetics and safety of escalating, once-daily doses of daptomycin, a novel lipopeptide antibiotic active against gram-positive pathogens, including those resistant to methicillin and vancomycin. This phase 1, multiple-dose, double-blind study involved 24 healthy subjects in three dose cohorts (4, 6, and 8 mg/kg of body weight) who were randomized to receive daptomycin or the control at a 3:1 ratio and administered the study medication by a 30-min intravenous infusion every 24 h for 7 to 14 days. Daptomycin pharmacokinetics was assessed by blood and urine sampling. Safety and tolerability were evaluated by monitoring adverse events (AEs) and laboratory parameters. Daptomycin pharmacokinetics was linear through 6 mg/kg, with a slight ( approximately 20%) nonlinearity in the area under the curve and trough concentration at the highest dose studied (8 mg/kg). The pharmacokinetic parameters measured on the median day of the study period, (day 7) were half-life ( approximately 9 h), volume of distribution ( approximately 0.1 liters/kg), systemic clearance ( approximately 8.2 ml/h/kg), and percentage of the drug excreted intact in urine from 0 to 24 h ( approximately 54%). Daptomycin protein binding (mean amount bound, 91.7%) was independent of the drug concentration. No gender effect was observed. All subjects who received daptomycin completed the study. The frequencies and distributions of treatment-emergent AEs were similar for the subjects who received daptomycin and the control subjects. There were no serious AEs and no pattern of dose-related events. The pharmacokinetics of once-daily administration of daptomycin was linear through 6 mg/kg. For all three doses, plasma daptomycin concentrations were consistent and predictable throughout the dosing interval. Daptomycin was well tolerated when it was administered once daily at a dose as high as 8 mg/kg for 14 days.

  7. Aerobic fitness influences cerebral oxygenation response to maximal exercise in healthy subjects.

    PubMed

    Oussaidene, Kahina; Prieur, Fabrice; Tagougui, Semah; Abaidia, Abdelbasset; Matran, Regis; Mucci, Patrick

    2015-01-01

    The study examined whether the aerobic fitness level modifies the cerebral oxygenation response to incremental ramp exercise, and more specifically the decline in cerebral oxygenation from heavy exercise up to maximal intensities. 11 untrained (VO2max 47.3±4.0 mL min(-1) kg(-1)) and 13 endurance-trained (VO2max 61.2±8.0 mL min(-1) kg(-1)) healthy men performed a maximal ramp cycle exercise. Left prefrontal cortex oxygenation (ΔHbO2) was monitored by near-infrared spectroscopy. A cerebral oxygenation threshold decline (ThCOx) during exercise was determined. ThCox occurred in all subjects but for higher VO2 (mL min(-1) kg(-1)) in endurance-trained than in untrained subjects (P<0.01). At submaximal exercise intensity corresponding to ThCOx, ΔHbO2 was higher in endurance-trained than in untrained subjects (P<0.05). VO2 at ThCox was related to VO2 at respiratory compensation point (n=24, r=0.93, P<0.001) and to VO2max (n=24, r=0.92, P<0.001). These findings indicate that above the respiratory compensation point the prefrontal O2 demand exceeds the supply in untrained and in endurance-trained subjects. In addition, the occurrence of ThCOx was delayed to higher absolute exercise intensities in endurance-trained in relation with their higher VO2max than untrained men. These results demonstrated that aerobic fitness influences cerebral oxygenation during exercise.

  8. Subjective, psychomotor, and physiological effects of cumulative doses of opioid mu agonists in healthy volunteers.

    PubMed

    Walker, D J; Zacny, J P

    1999-06-01

    The subjective, psychomotor, and physiological effects of three opioid mu-receptor agonists were studied in healthy volunteers using a cumulative-dosing procedure. Sixteen volunteers with no history of drug abuse received i.v. injections of saline (SAL), morphine (MOR), hydromorphone (HM), or meperidine (MEP) in a randomized double-blind crossover design. Subjects received 1 injection/h for the first 4 h, and a 3-h recovery period followed. SAL was injected first during each session, then SAL or increasing doses of each drug were administered every hour for the next 3 h. The absolute doses per injection were MOR: 2.5, 5, and 10 mg/70 kg; HM: 0.33, 0.65, and 1.3 mg/70 kg; and MEP: 17.5, 35, and 70 mg/70 kg. These injections resulted in cumulative doses of MOR: 2.5, 7.5, and 17.5; HM: 0.33, 0.98, and 2.28; and MEP: 17.5, 52.5, and 122.5 mg/70 kg. Subjects completed mood forms and psychomotor tests, and physiological measures were recorded at various times after each injection and during recovery. MEP tended to produce the most intense effects immediately after drug injection, which dissipated rapidly. MOR produced the mildest effects but was associated with unpleasant side effects during recovery and after the session. HM's effects were stronger than MOR's, and the recovery from HM was slower than with MEP. None of the opioids produced consistent effects that are typically associated with abuse liability. Orderly dose-response functions suggested that our cumulative-dosing procedure is an efficient way of determining dose-response functions for multiple opioids within the same subjects within the same study.

  9. Selective Cumulative Inhibition of Platelet Thromboxane Production by Low-dose Aspirin in Healthy Subjects

    PubMed Central

    Patrignani, Paola; Filabozzi, Paola; Patrono, Carlo

    1982-01-01

    Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB2 and renal prostaglandin (PG) and prostacyclin (PGI2) production. We measured, by radioimmunoassay, serum TXB2 levels after whole blood clotting and urinary excretion of PGE2, PGF2α, and 6-keto-PGF1α, before and after single or repeated oral aspirin doses given to 46 healthy subjects. Single doses of 6-100 mg aspirin resulted in a linear (r = 0.92, P < 0.01) inhibition of platelet TXB2 production, ranging from 12 to 95% after 24 h. A daily dose of 0.45 mg/kg given for 7 d produced a cumulative and virtually complete inhibition of platelet TXB2 production, without significantly reducing the urinary excretion of PGE2, PGF2α, and 6-keto-PGF1α in both healthy men and women. The platelet inhibitory effect of this regimen was maintained unaltered throughout 1 mo of therapy, with no evidence of cumulative inhibition of renal PG-synthesis. Moreover, furosemide-induced renal PGI2 synthesis and renin release were unaffected by chronic low-dose aspirin. Following cessation of aspirin therapy, platelet TXB2 production returned toward control values at a similar rate as after a single higher dose. We conclude that in healthy subjects: (a) aspirin causes a dose-dependent inhibition of platelet TXA2 production, with no obvious sex-related difference; (b) the inhibitory effect of daily low-dose aspirin is cumulative on platelet TXA2 but not on renal PG-synthesis; (c) during chronic low-dose aspirin therapy, renal PGI2-producing cells are readily activable by furosemide at a time of virtually complete suppression of platelet cyclooxygenase activity. PMID:7045161

  10. Absorption, metabolism, and excretion of cider dihydrochalcones in healthy humans and subjects with an ileostomy.

    PubMed

    Marks, Serena C; Mullen, William; Borges, Gina; Crozier, Alan

    2009-03-11

    The phloretin-O-glycosides, phloretin-2'-O-glucoside and phloretin-2'-O-(2''-O-xylosyl)glucoside, are thought to be unique to apples and apple products. To investigate the metabolism and bioavailability of these compounds, nine healthy and five ileostomy human subjects consumed 500 mL of Thatchers Redstreak apple cider containing 46 micromol of phloretin-O-glycosides. Over the ensuing 24 h period, plasma, urine, and ileal fluid were collected prior to analysis by high-performance liquid chromatography-mass spectrometry (HPLC-MS). The sole metabolite present in quantifiable amounts in plasma was phloretin-2'-O-glucuronide, which reached a peak concentration (C(max)) of 73 nmol/L and 0.6 h after ingestion (T(max)) with the healthy subjects, and statistically similar values were obtained with the ileostomy volunteers. Phloretin-2'-O-glucuronide was also detected in urine along with two additional phloretin-O-glucuronides and a phloretin-O-glucuronide-O-sulfate. The quantity of phloretin metabolites excreted in urine represented 5.0 + or - 0.9% of intake in healthy volunteers and 5.5 + or - 0.6% in ileostomy volunteers. The similarity in the excretion levels of the two groups and the rapid plasma T(max) indicate absorption of the dihydrochalcones in the small intestine. Of the two major phloretin-O-glycosides in cider, only phloretin-2'-O-(2''-O-xylosyl)glucoside was recovered in ileal fluid in quantities corresponding to 22% of intake. The absence of phloretin-2'-O-glucoside in ileal fluid suggests that it is more readily absorbed than phloretin-2'-O-(2''-O-xylosyl)glucoside. Phloretin-2'-O-glucuronide, two other phloretin-O-glucuronides, one phloretin-O-glucuronide-O-sulfate, two phloretin-O-sulfates, and the aglycone phloretin were also detected in the ileal fluid. This implies that the wall of the small intestine contains beta-glycosidase, sulfuryltransferase, and UDP-glucuronosyltransferase activities and that, as well as being absorbed, sizable amounts of the

  11. The effect of omega-3 polyunsaturated fatty acids on fibrin and thrombin generation in healthy subjects and subjects with cardiovascular disease.

    PubMed

    McEwen, Bradley J; Morel-Kopp, Marie-Christine; Tofler, Geoffrey H; Ward, Christopher M

    2015-04-01

    Hypercoagulability plays a key role in the progression of cardiovascular disease (CVD). Although omega-3 polyunsaturated fatty acid (PUFA) intake has been inversely related to the risk of cardiovascular events, the mechanisms are not fully understood. The aim of this study was to investigate the effects of omega-3 on novel markers of global coagulation. The generation of fibrin and thrombin, measured via overall hemostasis potential (OHP) assay and calibrated automated thrombography, respectively, was determined in 40 healthy subjects and 16 patients with CVD at baseline and after 4 weeks of 640 mg/day omega-3 PUFA. In healthy subjects, fibrin generation was significantly reduced, as measured by overall coagulation potential (p = 0.013), OHP (p < 0.001), velocity of fibrin polymerization (p = 0.002), and significant increase in delay to fibrin generation (p = 0.002). The peak of generated thrombin was significantly reduced (p = 0.043). In subjects with CVD, omega-3 PUFA significantly reduced OHP and significantly increased the lag time to thrombin generation (both p < 0.001). Treatment with omega-3 PUFA had no effect on other fibrin and thrombin generation parameters in CVD patients. Four-week omega-3 PUFA supplementation reduced thrombotic potential in healthy subjects, as shown by reduced fibrin generation and peak thrombin. There was a greater effect on fibrin generation in healthy subjects compared with those with CVD.

  12. Acute effects of inspiratory muscle warm-up on pulmonary function in healthy subjects.

    PubMed

    Özdal, Mustafa

    2016-06-15

    The acute effects of inspiratory muscle warm-up on pulmonary functions were examined in 26 healthy male subjects using the pulmonary function test (PFT) in three different trials. The control trial (CON) did not involve inspiratory muscle warm-up, while the placebo (IMWp) and experimental (IMW) trials involved inspiratory muscle warm-up. There were no significant changes between the IMWp and CON trials (p>0.05). All the PFT measurements, including slow vital capacity, inspiratory vital capacity, forced vital capacity, forced expiratory volume in one second, maximal voluntary ventilation, and maximal inspiratory pressure were significantly increased by 3.55%, 12.52%, 5.00%, 2.75%, 2.66%, and 7.03% respectively, in the subjects in the IMW trial than those in the CON trial (p<0.05). These results show that inspiratory muscle warm-up improved the pulmonary functions. The mechanisms responsible for these improvements are probably associated with the concomitant increase in the inspiratory muscle strength, and the cooperation of the upper thorax, neck, and respiratory muscles, and increased level of reactive O2 species in muscle tissue, and potentially improvement of muscle O2 delivery-to-utilization. However, further investigation is required to determine the precise mechanisms responsible from among these candidates.

  13. Nonlinear pharmacokinetics of oral quinidine and verapamil in healthy subjects: a clinical microdosing study.

    PubMed

    Maeda, K; Takano, J; Ikeda, Y; Fujita, T; Oyama, Y; Nozawa, K; Kumagai, Y; Sugiyama, Y

    2011-08-01

    Microdosing studies are effective in enabling the early identification of the pharmacokinetic properties of compounds administered to humans. However, the nonlinearity of the pharmacokinetics between microdose and therapeutic dose, attributable to the saturation of metabolic enzymes and transporters, is a major concern. Verapamil and quinidine are good substrates of both the multidrug resistance 1 transporter (MDR1) and the cytochrome P450 (CYP) 3A4 enzyme (CYP3A4). We investigated their dose-dependent pharmacokinetics in healthy subjects. Four different doses of verapamil or quinidine were administered orally to each subject, and the plasma concentrations of the parent drugs and their major metabolites were measured. The dose-normalized area under the plasma concentration-time curve (AUC) values of quinidine and verapamil increased in a dose-dependent manner and were 2.6- and 2.3-fold higher, respectively, at the therapeutic dose than at microdose. These results suggest that the nonlinear pharmacokinetics of these drugs is caused mainly by the saturation of MDR1 and/or CYP3A4 in the small intestine.

  14. Prediction of walking speed using single stance force or pressure measurements in healthy subjects.

    PubMed

    Keijsers, N L W; Stolwijk, N M; Renzenbrink, G J; Duysens, J

    2016-01-01

    Walking speed is one of the best measures of overall walking capacity. In plantar pressure measurements, walking speed can be assessed using contact time, but it is only moderately correlated with walking speed. The center of pressure might be of more value to indicate walking speed since walking speed alters foot loading. Therefore, the purpose of this study is to assess walking speed using the velocity of the center of pressure (VCOP). Thirty-three subjects walked over a Footscan pressure plate at three speed conditions; slow, preferred, and fast. Walking speed was measured by a motion analysis system. (Multiple) linear regression analysis was used to indicate the relation between walking speed and independent variables derived from the pressure plate such as mean VCOP and stance time for all walking conditions separately and together. The mean VCOP had the highest correlation coefficient value with walking speed for all walking conditions combined (0.94) and for the preferred walking condition (0.80). The multiple regression analysis, based on a number of additional parameters, revealed a small to modest increase in the performance of predicting walking speed (r=0.98 for combined and r=0.93 for preferred). The mean VCOP was the best predictor for walking speed when using a plantar pressure plate. The mean VCOP predicts the walking speed with a 95% accuracy of 0.20m/s when healthy subjects walk at their preferred walking speed.

  15. The 6-min walk distance in healthy subjects: reference standards from seven countries.

    PubMed

    Casanova, C; Celli, B R; Barria, P; Casas, A; Cote, C; de Torres, J P; Jardim, J; Lopez, M V; Marin, J M; Montes de Oca, M; Pinto-Plata, V; Aguirre-Jaime, A

    2011-01-01

    The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

  16. Effect of Ondansetron on Metformin Pharmacokinetics and Response in Healthy Subjects.

    PubMed

    Li, Qing; Yang, Hong; Guo, Dong; Zhang, Taolan; Polli, James E; Zhou, Honghao; Shu, Yan

    2016-04-01

    The 5-hydroxytryptamine-3 (5-HT3) receptor antagonists such as ondansetron have been used to prevent and treat nausea and vomiting for over 2 decades. This study was to determine whether ondansetron could serve as a perpetrator drug causing transporter-mediated drug-drug interactions in humans. Twelve unrelated male healthy Chinese volunteers were enrolled into a prospective, randomized, double-blind, crossover study to investigate the effects of ondansetron or placebo on the pharmacokinetics of and the response to metformin, a well-characterized substrate of organic cation transporters and multidrug and toxin extrusions (MATEs). Ondansetron treatment caused a statistically significantly higher Cmax of metformin compared with placebo (18.3 ± 5.05 versus 15.2 ± 3.23; P = 0.006) and apparently decreased the renal clearance of metformin by 37% as compared with placebo (P = 0.001). Interestingly, ondansetron treatment also statistically significantly improved glucose tolerance in subjects, as indicated by the smaller glucose area under the curve in the oral glucose tolerance test (10.4 ± 1.43) as compared with placebo (11.5 ± 2.29 mmol∙mg/l) (P = 0.020). It remains possible that ondansetron itself may affect glucose homeostasis in human subjects, but our clinical study, coupled with our previous findings in cells and in animal models, indicates that ondansetron can cause a drug-drug interaction via its potent inhibition of MATE transporters in humans.

  17. Immune response to acetaldehyde-human serum albumin adduct among healthy subjects related to alcohol intake.

    PubMed

    Romanazzi, Valeria; Schilirò, Tiziana; Carraro, Elisabetta; Gilli, Giorgio

    2013-09-01

    Acetaldehyde (AA) is the main metabolic product in ethanol metabolism, although it can also derive from sources of airborne pollution. As a typical aldehyde, AA is able to react with a variety of molecular targets, including DNA and protein. This property justifies the hypothesis of a immune reaction against this kind of adduct, to be studied by a seroprevalence screening approach. In this study, the correlation between drinking habits and the amount of circulating AA-human serum albumin adduct (AA-HSA) was evaluated in a group of healthy subjects, non alcohol-addicted. Daily ethanol intake (grams) was inferred for each subject using the information collected through a questionnaire, and AA-HSA antibodies (AA-HSA ab) analyses were performed using the Displacement Assay on whole blood samples. The findings showed a correlation between ethanol intake and immune response to molecular adduct. These results underscore the evaluation of AA-HSA ab amount as a suitable molecular marker for alcohol intake that can be applied in future investigations on a large scale for prevention screening.

  18. Assessment of Internal Jugular Vein Size in Healthy Subjects with Magnetic Resonance and Semiautomatic Processing

    PubMed Central

    Pelizzari, L.; Scaccianoce, E.; Dipasquale, O.; Ricci, C.; Baglio, F.; Cecconi, P.; Baselli, G.

    2016-01-01

    Background and Objectives. The hypothesized link between extracranial venous abnormalities and some neurological disorders awoke interest in the investigation of the internal jugular veins (IJVs). However, different IJV cross-sectional area (CSA) values are currently reported in literature. In this study, we introduced a semiautomatic method to measure and normalize the CSA and the degree of circularity (Circ) of IJVs along their whole length. Methods. Thirty-six healthy subjects (31.22 ± 9.29 years) were recruited and the 2D time-of-flight magnetic resonance venography was acquired with a 1.5 T Siemens scanner. The IJV were segmented on an axial slice, the contours were propagated in 3D. Then, IJV CSA and Circ were computed between the first and the seventh cervical levels (C1–C7) and normalized among subjects. Inter- and intrarater repeatability were assessed. Results. IJV CSA and Circ were significantly different among cervical levels (p < 0.001). A trend for side difference was observed for CSA (larger right IJV, p = 0.06), but not for Circ (p = 0.5). Excellent inter- and intrarater repeatability was obtained for all the measures. Conclusion. This study proposed a reliable semiautomatic method able to measure the IJV area and shape along C1–C7, and suitable for defining the normality thresholds for future clinical studies. PMID:27034585

  19. Assessment of Internal Jugular Vein Size in Healthy Subjects with Magnetic Resonance and Semiautomatic Processing.

    PubMed

    Laganà, M M; Pelizzari, L; Scaccianoce, E; Dipasquale, O; Ricci, C; Baglio, F; Cecconi, P; Baselli, G

    2016-01-01

    Background and Objectives. The hypothesized link between extracranial venous abnormalities and some neurological disorders awoke interest in the investigation of the internal jugular veins (IJVs). However, different IJV cross-sectional area (CSA) values are currently reported in literature. In this study, we introduced a semiautomatic method to measure and normalize the CSA and the degree of circularity (Circ) of IJVs along their whole length. Methods. Thirty-six healthy subjects (31.22 ± 9.29 years) were recruited and the 2D time-of-flight magnetic resonance venography was acquired with a 1.5 T Siemens scanner. The IJV were segmented on an axial slice, the contours were propagated in 3D. Then, IJV CSA and Circ were computed between the first and the seventh cervical levels (C1-C7) and normalized among subjects. Inter- and intrarater repeatability were assessed. Results. IJV CSA and Circ were significantly different among cervical levels (p < 0.001). A trend for side difference was observed for CSA (larger right IJV, p = 0.06), but not for Circ (p = 0.5). Excellent inter- and intrarater repeatability was obtained for all the measures. Conclusion. This study proposed a reliable semiautomatic method able to measure the IJV area and shape along C1-C7, and suitable for defining the normality thresholds for future clinical studies.

  20. The effects of scraping therapy on local temperature and blood perfusion volume in healthy subjects.

    PubMed

    Xu, Qin-Yan; Yang, Jin-Sheng; Zhu, Bing; Yang, Li; Wang, Ying-Ying; Gao, Xin-Yan

    2012-01-01

    Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P < 0.001). Compared with non-scraping area, an increase of body temperature with an average of 1°C was observed after scraping stimulation (P < 0.01). Conclusion. Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism.

  1. Body position and the neuroendocrine response to insulin-induced hypoglycemia in healthy subjects.

    PubMed

    Radikova, Z; Penesova, A; Jezova, D; Kvetnansky, R; Vigas, M; Macho, L; Koska, J

    2003-10-01

    Changes in body fluid distribution are known to influence neuroendocrine function. The aim of the present study was to test the hypothesis that changes in plasma volume affect the counterregulatory neuroendocrine response to hypoglycemia. The tests were performed in 12 subjects in two situations: 'head-up' (+60 degrees head-up tilt standing for 30 min and hypoglycemia in sitting position afterwards) and 'leg-up' (leg-up position for 30 min and hypoglycemia in leg-up position afterwards) in a random order. Insulin-induced hypoglycemia was adjusted to 2.7 mmol/l for 15 min by glucose infusion. Plasma volume was greater by 2.2% (p < 0.001) in leg-up and lower by 9.6% (p < 0.001) in head-up position compared to the basal value in sitting position. Head-up position was associated with increases in ACTH, aldosterone, norepinephrine levels and plasma renin activity (p < 0.01). Leg-up position resulted in decreases in plasma growth hormone and epinephrine concentrations (p < 0.05). Except epinephrine, the neuroendocrine response to hypoglycemia, if any, was mild. Hypoglycemia failed to activate ACTH release after head-up position. Body fluid redistribution did not modify hormonal changes during insulin hypoglycemia. In conclusion, we suggest that body position and accompanying plasma volume changes do not appear to affect neuroendocrine and counterregulatory responses to moderate, short duration hypoglycemia in healthy subjects.

  2. The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

    PubMed Central

    Bruce, M; Scott, N; Lader, M; Marks, V

    1986-01-01

    The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h. The concentrations of the metabolite 1,7-dimethylxanthine increased during the 5 h. The major urine metabolite was 1-methyluric acid. The EEG showed a dose-related decrease in log 'theta' power and a decrease in log 'alpha' power. Other dose-related effects were an increase in skin conductance level (sweat-gland activity) and self rating of alertness. Ratings of headache and tiredness were decreased by the caffeine. The study illustrates the complexities of studying a drug which is widely taken and which is often associated with withdrawal effects. PMID:3741730

  3. Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

    PubMed Central

    Giacomin, Elisa; Palmerini, Elisabetta; Ballo, Piercarlo; Zacà, Valerio; Bova, Giovanni; Mondillo, Sergio

    2008-01-01

    Background Few data exist regarding the direct effects of caffeine and smoking on cardiac function. We sought to explore the acute effects of caffeine assumption, cigarette smoking, or both on left ventricular (LV) and right ventricular (RV) function in a population of young normal subjects. Methods Forty-five healthy subjects aged 25 ± 2 years underwent echocardiography. Fifteen of them were non-smokers and habitual coffee consumers (group 1), 15 were smokers and not habitual coffee consumers (group 2), and 15 were smokers and habitual coffee consumers (group 3). Peak systolic (Sa), early diastolic Ea, and late diastolic (Aa) velocity of mitral annulus were measured by pulsed Tissue Doppler, and left atrioventricular plane displacement was determined by M-mode. Tricuspid annular velocities and systolic excursion (TAPSE) were also determined. Measurements were performed at baseline and after oral assumption of caffeine 100 mg in group 1, one cigarette smoking in group 2, and both in group 3. Results No changes in ventricular function were observed in group 1 after caffeine administration. In group 2, cigarette smoking yielded an acute increase in mitral Aa (+12.1%, p = 0.0026), tricuspid Sa (+9.8%, p = 0.012) and TAPSE (+7.9%, p = 0.017), and a decrease in the mitral Ea/Aa ratio (-8.5%, p = 0.0084). Sequential caffeine assumption and cigarette smoking in group 3 was associated with an acute increase in mitral Aa (+13.0%, p = 0.015) and tricuspid Aa (+11.6%, p < 0.0001) and a reduction in mitral Ea/Aa ratio (-8.5%, p = 0.0084) tricuspid Ea (-6.6%, p = 0.048) and tricuspid Ea/Aa ratio (-9.6%, p = 0.0003). In a two-way ANOVA model controlling for hemodynamic confounding factors, changes in the overall population remained significant for mitral Aa and Ea/Aa ratio, and for tricuspid Aa and Ea/Aa ratio. Conclusion In young healthy subjects, one cigarette smoking is associated to an acute impairment in LV diastolic function and a hyperdynamic RV systolic response

  4. Effect of standing on neurohumoral responses and plasma volume in healthy subjects

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Ertl, A. C.; Shannon, J. R.; Furlan, R.; Robertson, R. M.; Robertson, D.

    1998-01-01

    Upright posture leads to rapid pooling of blood in the lower extremities and shifts plasma fluid into surrounding tissues. This results in a decrease in plasma volume (PV) and in hemoconcentration. There has been no integrative evaluation of concomitant neurohumoral and PV shifts with upright posture in normal subjects. We studied 10 healthy subjects after 3 days of stable Na+ and K+ intake. PV was assessed by the Evans blue dye method and by changes in hematocrit. Norepinephrine (NE), NE spillover, epinephrine (Epi), vasopressin, plasma renin activity, aldosterone, osmolarity, and kidney response expressed by urine osmolality and by Na+ and K+ excretion of the subjects in the supine and standing postures were all measured. We found that PV fell by 13% (375 +/- 35 ml plasma) over approximately 14 min, after which time it remained relatively stable. There was a concomitant decrease in systolic blood pressure and an increase in heart rate that peaked at the time of maximal decrease in PV. Plasma Epi and NE increased rapidly to this point. Epi approached baseline by 20 min of standing. NE spillover increased 80% and clearance decreased 30% with 30 min of standing. The increase in plasma renin activity correlated with an increase in aldosterone. Vasopressin increased progressively, but there was no change in plasma osmolarity. The kidney response showed a significant decrease in Na+ and an increase in K+ excretion with upright posture. We conclude that a cascade of neurohumoral events occurs with upright posture, some of which particularly coincide with the decrease in PV. Plasma Epi levels may contribute to the increment in heart rate with maintained upright posture.

  5. Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations

    PubMed Central

    Luo, Xingguang; Zuo, Lingjun; Kranzler, Henry; Zhang, Huiping; Wang, Shuang; Gelernter, Joel

    2011-01-01

    Background Personality traits are among the most complex quantitative traits. Certain personality traits are associated with substance dependence (SD); genetic factors may influence both. Associations between opioid receptor (OPR) genes and SD have been reported. This study investigated the relationship between OPR genes and personality traits in a case-control sample. Methods We assessed dimensions of the five-factor model of personality in 556 subjects: 250 with SD [181 European-Americans (EAs) and 69 African-Americans (AAs)] and 306 healthy subjects (266 EAs and 40 AAs). We genotyped 20 OPRM1 markers, 8 OPRD1 markers, and 7 OPRK1 markers, and 38 unlinked ancestry-informative markers in these subjects. The relationships between OPR genes and personality traits were examined using MANCOVA, controlling for gene-gene interaction effects and potential confounders. Associations were decomposed by Roy-Bargmann Stepdown ANCOVA. Results Personality traits were associated as main or interaction effects with the haplotypes, diplotypes, alleles and genotypes at the three OPR genes (0.002

  6. Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

    PubMed Central

    Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.

    2010-01-01

    Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854

  7. Gender, personality, and serotonin-2A receptor binding in healthy subjects

    PubMed Central

    Soloff, Paul H.; Price, Julie C.; Mason, Neale Scott; Becker, Carl; Meltzer, Carolyn C.

    2009-01-01

    The vulnerability to mood disorders, impulsive-aggression, eating disorders, and suicidal behavior varies greatly with gender, and may reflect gender differences in central serotonergic function. We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT2A receptor binding in 21 healthy subjects using [18F]altanserin and PET neuro-imaging. Binding potentials in pre-defined Regions of Interest (ROI) were calculated using the Logan graphical method, corrected for partial volume effects, and compared by gender with age co-varied. SPM analysis was used for voxel level comparisons. Altanserin binding (BPp) was greater in male than female subjects in 9 ROIs: hippocampus (HIP) and Lt. HIP, lateral orbital frontal cortex (LOF) and Lt.LOF, left medial frontal cortex (Lt.MFC), left medial temporal cortex (Lt. MTC), left occipital cortex (Lt. OCC), thalamus (THL) and Lt. THL. Differences in Lt. HIP and Lt. MTL remained significant after Bonferroni correction. Gender differences were noted in the co-variation of psychological traits with BPp values in specific ROIs. Among males alone, aggression was negatively correlated with BPp values in Lt. LOF and Lt. MFC, and Suspiciousness positively correlated in LOF, Lt. LOF and Lt. MFC. Among female subjects alone, Negativism was positively correlated with BPp values in HIP, and Verbal Hostility in Lt. HIP. Altanserin binding in Lt. MTC was positively correlated with Persistence, with no significant gender effect. Gender differences in 5HT2A receptor function in specific ROIs may mediate expression of psychological characteristics such as aggression, suspiciousness and negativism. Future studies of 5HT2A receptor function and its relationship to behavior should control for gender. PMID:19959344

  8. Breathing exercises: influence on breathing patterns and thoracoabdominal motion in healthy subjects

    PubMed Central

    Vieira, Danielle S. R.; Mendes, Liliane P. S.; Elmiro, Nathália S.; Velloso, Marcelo; Britto, Raquel R.; Parreira, Verônica F.

    2014-01-01

    BACKGROUND: The mechanisms underlying breathing exercises have not been fully elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises (diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and intercostal exercise) the on breathing pattern and thoracoabdominal motion in healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23±1.5 years old and with normal pulmonary function tests, participated in the study. The subjects were evaluated using the optoelectronic plethysmography system in a supine position with a trunk inclination of 45° during quiet breathing and the breathing exercises. The order of the breathing exercises was randomized. Statistical analysis was performed by the Friedman test and an ANOVA for repeated measures with one factor (breathing exercises), followed by preplanned contrasts and Bonferroni correction. A p<0.005 value was considered significant. RESULTS: All breathing exercises significantly increased the tidal volume of the chest wall (Vcw) and reduced the respiratory rate (RR) in comparison to quiet breathing. The diaphragmatic breathing exercise was responsible for the lowest Vcw, the lowest contribution of the rib cage, and the highest contribution of the abdomen. The sustained maximal inspiration exercise promoted greater reduction in RR compared to the diaphragmatic and intercostal exercises. Inspiratory sighs and intercostal exercises were responsible for the highest values of minute ventilation. Thoracoabdominal asynchrony variables increased significantly during diaphragmatic breathing. CONCLUSIONS: The results showed that the breathing exercises investigated in this study produced modifications in the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well as in thoracoabdominal motion (e.g., increase in abdominal contribution during diaphragmatic breathing), among others. PMID:25590447

  9. Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects' gender and age.

    PubMed

    Ishikawa, Masaki; Maekawa, Keiko; Saito, Kosuke; Senoo, Yuya; Urata, Masayo; Murayama, Mayumi; Tajima, Yoko; Kumagai, Yuji; Saito, Yoshiro

    2014-01-01

    Blood is a commonly used biofluid for biomarker discovery. Although blood lipid metabolites are considered to be potential biomarker candidates, their fundamental properties are not well characterized. We aimed to (1) investigate the matrix type (serum vs. plasma) that may be preferable for lipid biomarker exploration, (2) elucidate age- and gender-associated differences in lipid metabolite levels, and (3) examine the stability of lipid metabolites in matrix samples subjected to repeated freeze-thaw cycles. Using liquid chromatography-mass spectrometry, we performed lipidomic analyses for fasting plasma and serum samples for four groups (15 subjects/group) of young and elderly (25-34 and 55-64 years old, respectively) males and females and for an additional aliquot of samples from young males, which were subjected to repeated freeze-thaw cycles. Lysophosphatidylcholine and diacylglycerol levels were higher in serum than in plasma samples, suggesting that the clotting process influences serum lipid metabolite levels. Gender-associated differences highlighted that the levels of many sphingomyelin species were significantly higher in females than in males, irrespective of age and matrix (plasma and serum). Age-associated differences were more prominent in females than in males, and in both matrices, levels of many triacylglycerols were significantly higher in elderly females than in young females. Plasma and serum levels of most lipid metabolites were reduced by freeze-thawing. Our results indicate that plasma is an optimal matrix for exploring lipid biomarkers because it represents the original properties of an individual's blood sample. In addition, the levels of some blood lipid species of healthy adults showed gender- and age-associated differences; thus, this should be considered during biomarker exploration and its application in diagnostics. Our fundamental findings on sample selection and handling procedures for measuring blood lipid metabolites is important

  10. Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations.

    PubMed

    Luo, Xingguang; Zuo, Lingjun; Kranzler, Henry; Zhang, Huiping; Wang, Shuang; Gelernter, Joel

    2008-10-05

    Personality traits are among the most complex quantitative traits. Certain personality traits are associated with substance dependence (SD); genetic factors may influence both. Associations between opioid receptor (OPR) genes and SD have been reported. This study investigated the relationship between OPR genes and personality traits in a case-control sample. We assessed dimensions of the five-factor model of personality in 556 subjects: 250 with SD [181 European-Americans (EAs) and 69 African-Americans (AAs)] and 306 healthy subjects (266 EAs and 40 AAs). We genotyped 20 OPRM1 markers, 8 OPRD1 markers, and 7 OPRK1 markers, and 38 unlinked ancestry-informative markers in these subjects. The relationships between OPR genes and personality traits were examined using MANCOVA, controlling for gene-gene interaction effects and potential confounders. Associations were decomposed by Roy-Bargmann Stepdown ANCOVA. We found that personality traits were associated as main or interaction effects with the haplotypes, diplotypes, alleles and genotypes at the three OPR genes (0.002 < P < 0.046 from MANCOVA; 0.0004 < P < 0.049 from ANCOVA). Diplotype TTAGGA/TTCAGA at OPRM1 had main effects on Extraversion (P = 0.008), and diplotypes OPRM1(insertion mark)TTCAGA/TTCAGA and OPRD1(insertion mark)CAC/TAC had interaction effects on Openness (P = 0.010) after conservative correction for multiple testing. The present study demonstrates that the genes encoding the mu-, delta-, and kappa-opioid receptors may contribute to variation in personality traits. Further, the three OPR genes have significant interaction effects on personality traits. This work provides additional evidence that personality traits and SD have a partially overlapping genetic basis.

  11. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    PubMed Central

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  12. Standardized Method of Measuring Acanthamoeba Antibodies in Sera from Healthy Human Subjects

    PubMed Central

    Chappell, Cynthia L.; Wright, John A.; Coletta, Michael; Newsome, Anthony L.

    2001-01-01

    Acanthamoeba species can cause serious, debilitating, and sometimes life-threatening infections. Three groups have been identified using morphological and immunological comparisons. Previous serological studies have utilized a variety of antigen preparations and assay methods and reported disparate (3 to 100%) results. This study was designed to (i) optimize an enzyme-linked immunosorbent assay for detecting serum antibodies to each of the Acanthamoeba serogroups and (ii) test 55 healthy individuals for specific immunoglobulin G reactivity. The highest signal-to-background ratio was found when 3,000 fixed, intact trophozoites per well were used with a 1:10 serum dilution. Sera yielding optical densities of <0.25 against all three Acanthamoeba serogroups were used to define the cutoff for positive results. The highest background reactivity with these sera was seen with Acanthamoeba polyphaga (serogroup 2), followed by Acanthamoeba culbertsoni (serogroup 3) and Acanthamoeba astronyxis (serogroup 1). Of 55 subjects tested, the highest number of positive results was seen with A. polyphaga (81.8%), followed by A. astronyxis (52.8%) and A. culbertsoni (40%). Seven serum samples (12.7%) were negative for all three Acanthamoeba serogroups, 16 (29.1%) were positive for one serogroup only, 16 were positive for two serogroups, and 16 reacted to all three serogroups. Further analysis showed no significant associations between serogroup reactivity and age or gender. However, some ethnic differences were noted, especially with A. polyphaga antigens. In that case, serum samples from Hispanic subjects were 14.5 times less likely to be positive (P = 0.0025) and had lower mean absorbance values (P = 0.047) than those from Caucasian subjects. Overall, these data suggest that Acanthamoeba colonization or infection is more common than previously thought. Mild or asymptomatic infections may contribute to the observed serum reactivities. PMID:11427418

  13. Comparison of Serum and Salivary Antioxidants in Patients with Temporomandibular Joint Disorders and Healthy Subjects

    PubMed Central

    Lawaf, Shirin; Tabarestani, Tohid

    2015-01-01

    Objectives: Temporomandibular dysfunction (TMD) is a group of disorders in the facial region and temporomandibular joint (TMJ). Biomarkers are assumed to play a role in pain and early detection of destruction. The aim of this study was to compare the saliva and serum antioxidant levels in patients with TMD and healthy subjects. Materials and Methods: This case-control study was conducted on 28 TMD patients without pain, 28 TMD patients with pain and 28 healthy controls. The total antioxidant capacity of saliva and serum of patients was measured. Data were analyzed using ANOVA and Tamhane’s test. Results: The mean (±SD) total antioxidant capacity of serum (plasma TAC) was 0.8900 (±0.11627) mmol/L in TMD patients with pain, 1.2717 (±0.18711) mmol/L in TMD patients without pain and 1.7500(±0.18711) mmol/L in the control group. Based on ANOVA, the difference in this regard among the three groups was statistically significant (P=0.000). The mean salivary TAC was 1.34 (±0.06721) mmol/L in TMD patients with pain, 1.42 (±0.16677) mmol/L in TMD patients without pain and 1.35 (±0.11627) mmol/L in the control group. The difference in this respect among the three groups was not significant (P>0.05). Conclusion: The mean plasma TAC in TMD patients with/without pain was significantly lower than that in the control group but no significant difference was detected in salivary TAC among the three groups. PMID:26622281

  14. Angular and linear spinal parameters associated with relaxed and erect postures in healthy subjects.

    PubMed

    Prushansky, Tamara; Geller, Shira; Avraham, Amir; Furman, Chen; Sela, Lee

    2013-04-01

    Spinal posture assessment is an essential component in physical evaluation. Establishing reproducible value of spinal curves is necessary for detecting postural changes. Therefore, the main objectives of this study were to assess the reproducibility of spinal curves in relaxed standing of healthy subjects and to explore the extent and pattern of change upon transition from relaxed to a fully erect posture. Thirty young women and men were measured twice over a 1 week interval for recording the cervical, thoracic, and lumbar curves values using an ultrasound-based system. Thereafter, additional 28 men and women extracted from the same reference group were assigned for a single measurement session, in which the same angular values were obtained in relaxed and fully erect standing postures, as well as stature using stadiometer. Excellent, good, and poor reproducibility indices, standard error of measurement (SEM), and smallest real difference (SRD), were noted for the thoracic (interclass correlation coefficient, ICC(3,3) = 0.95, SEM = 1.2°, SRD = 3.3°), lumbar (ICC(3,3) = 0.85, SEM = 2.6°, SRD = 7.2°), and cervical (ICC(3,3) = 0.68, SEM = 3.8°, SRD = 10.5°) curves, respectively. Erecting from relaxed posture was associated with a significant (>SRD) thoracic angle difference of 7.2° in men and 4.8° in women which was expressed in a height increase of 1.3 cm in men and 0.8 cm in women. These changes were significantly larger in men in whom the angular and height differences were also significantly correlated (r = 0.7). Using this system, angular measurements are highly reproducible in the thoracic curvature in young healthy adults, leading to the use of the associated SRD as a criterion for thoracic postural flexibility.

  15. Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects.

    PubMed

    Lucas, A; Holtmann, G; Gerken, G; Pietsch, A; Braun-Lang, U; Gilani, K; Strassburger, K; Gesing, S; Janssen, O E; Kavelaars, A; Heijnen, C J; Schedlowski, M; Elsenbruch, S

    2006-01-01

    Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2+/-3.5 post-distension vs. 36.6+/-3.8 post-speech, p<.05), but anxiety was also elevated at baseline (41.6+/-3.9 vs. 32+/-3.2 recovery, p<.01). This anticipatory effect was reflected by elevated baseline cortisol (p<.05) and baseline ACTH (p<.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p<.05) and increased CD16+CD56+ cells (p=.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8+/-9.4 mmHg in response to distension vs. +36.4+/-6.2 mmHg in response to speech for systolic BP, p<.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p<.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia.

  16. Effects of recreational soccer on physical fitness and health indices in sedentary healthy and unhealthy subjects

    PubMed Central

    Chamari, K; Slimani, M; Shephard, RJ; Yousfi, N; Tabka, Z; Bouhlel, E

    2016-01-01

    Recreational soccer (RS) is becoming a popular alternative to the classical continuous exercise mode used for the improvement of cardiovascular and metabolic fitness in untrained people. The objective of this paper was to conduct a detailed systematic review of the literature, identifying the physiological responses to RS and the training effects of RS on aerobic fitness and health in untrained healthy individuals and clinical patients. PubMed, Google Scholar and ScienceDirect databases were searched using terms related to recreational soccer. Inclusion criteria were randomized controlled trials (RCT) that assessed acute physiological responses to RS or the training effects of RS on physical fitness and health in sedentary, untrained subjects of any age or health status. All studies were assessed for methodological quality using the PEDro scale. Thirty-five articles met the inclusion criteria; seven examined the acute response to RS, and 28 assessed training effects. Clear evidence was found that RS had positive effects on many health-related indices and variables, including VO2max (gains of 7-16%), blood pressure (reductions of 6-13 mmHg), body composition (decreased fat mass and improved indices of bone health), and metabolic and cardiac function. These positive effects were observed in both healthy individuals and clinical patients, irrespective of age or sex. Although this review provides clear evidence of the positive effects of RS on health, most studies had limitations of methodology (an average PEDro score < 6). Furthermore, many of the training studies were from a small number of research groups. Future studies should be extended to other countries and institutions to ensure generality of the results. Regular RS training leads to significant cardiovascular and muscular adaptations and gains of health both in sedentary individuals and clinical patients at all ages, suggesting that RS is a potentially highly motivational method to enhance population health

  17. Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects

    PubMed Central

    Uno, Tsukasa; Ohkubo, Tadashi; Motomura, Shigeru; Sugawara, Kazunobu

    2006-01-01

    Aim To examine the effect of grapefruit juice, an inhibitor of CYP3A4 in the small intestine, on the disposition of manidipine enantiomers in healthy subjects. Methods A randomized cross-over study with at least a 2-week wash-out period was performed. Seven healthy male volunteers received an oral 40-mg dose of racemic manidipine after an overnight fast with either grapefruit juice (GFJ) or water, as a control study. Plasma concentrations of (S)- and (R)-manidipine were monitored up to 10 h after the dosing. Results The plasma concentrations of (S)-manidipine were significantly higher (P < 0.001) than those of (R)-manidipine in the control phase with an S/R ratio for the AUC0–∞ of 1.62 (95% confidence interval 1.52, 1.73). GFJ significantly increased Cmax and AUC0–∞ of (S)-manidipine by 2.4-fold (P < 0.01) and 2.3-fold (P < 0.01), respectively, and Cmax and AUC0–∞ of (R)-manidipine were increased by 3.4-fold (P < 0.01) and 3.0-fold (P < 0.01), respectively. There were significant differences (P < 0.01) in GFJ-mediated percentage increases in Cmax and AUC0–∞ of (S)-manidipine compared with those of (R)-manidipine. The S/R ratio for AUC0–∞ was significantly decreased from 1.6 to 1.2 during the GFJ phase (P < 0.01). Conclusion These results indicate that the stereoselective disposition of manidipine was altered by GFJ, as an inhibitor of CYP3A4. GFJ appears to affect this metabolic disposal of (R)-manidipine to a greater extent than that of (S)-manidipine. PMID:16669846

  18. High Test-retest-reliability of pain-related evoked potentials (PREP) in healthy subjects.

    PubMed

    Özgül, Özüm Simal; Maier, Christoph; Enax-Krumova, Elena K; Vollert, Jan; Fischer, Marc; Tegenthoff, Martin; Höffken, Oliver

    2017-03-22

    Pain-related-evoked potentials (PREP) is an established electrophysiological method to evaluate the signal transmission of electrically stimulated A-delta fibres. Although prerequisite for its clinical use, test-retest-reliability and side-to-side differences of bilateral stimulation in healthy subjects have not been examined yet. We performed PREP twice within 3 to 14days in 33 healthy subjects bilaterally by stimulating the dorsal hand. Detection (DT) and pain thresholds (PT) after electrical stimulation, the corresponding pain ratings, latencies of P0, N1, P1 and N2 components and the corresponding amplitudes were assessed. Impact of electrically induced pain intensity, age, sex, and arm length on PREP was analysed. MANOVA, t-Test, interclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland-Altmann-Analysis as well as ANCOVA were used for statistical analysis. Measurement from both sides on both days resulted in mean N1-latencies from 142.39 ±18.12ms to 144.03 ±16.62ms and in mean N1P1-amplitudes from 39.04 ±12.26μV to 40.53 ±12.9μV. Analysis of a side-to-side effect showed for the N1-latency a F-value of 0.038 and for the N1P1-amplitude of 0.004 (p >0.8). We found intraclass correlation coefficients (ICC) from 0.88 to 0.93 and a standard error of measurement (SEM) < 10% of mean values for all measurements concerning the N1-Latency and N1P1-amplitude. Intraclass correlation coefficients, standard error of measurement and Bland-Altman-Analyses revealed excellent test-retest-reliability for N1-latency and N1P1-amplitude without systematic error and there was no side-to-side effect on PREP. N1-latency (r=0.35, p <0.05) and N1P1-amplitude (r=-0.45, p <0.05) correlated with age and additionally N1-latency correlated with arm length (r=0.45, p<0.001). In contrast, pain intensity during the stimulation had no effect on both N1-latency and N1P1-amplitude. In summary, PREP showed high test

  19. Sural sensory nerve action potential: A study in healthy Indian subjects

    PubMed Central

    Sreenivasan, Aarthika; Mansukhani, Khushnuma A; Sharma, Alika; Balakrishnan, Lajita

    2016-01-01

    Background: The sural sensory nerve action potential (SNAP) is an important electrodiagnostic study for suspected peripheral neuropathies. Incorrect technique and unavailability of reference data can lead to erroneous conclusions. Objectives: To establish reference data for sural SNAP in age-stratified healthy subjects at three sites of stimulation. Materials and Methods: A prospective study was conducted in 146 nerves from healthy subjects aged between 18 years and 90 years, stratified into six age groups (a = 18-30 years, b = 31–40 years, c = 41–50 years, d = 51–60 years, e = 61–70 years, and f >71 years). Sural SNAP was recorded antidromically, stimulating at three sites at distances of 14 cm, 12 cm, and 10 cm from the recording electrode. Mean – 2 standard deviation (SD) of the transformed data was used to generate reference values for amplitudes. Analysis of variance (ANOVA) test was used for inter-group and between three sites comparisons of amplitudes. Results: The lower limits of amplitude at 14 cm were 12.4 μV, 10.4 μV, 6.5 μV, 5.3 μV, 2.9 μV, and 1.9 μV; at 12 cm were 13.5 μV, 13.6 μV, 8.5 μV, 7.8 μV, 3.5 μV, and 2.8 μV; and at 10 cm were 16.3 μV, 16.3 μV, 11.1 μV, 10.0 μV, 4.8 μV, and 3.7 μV for groups a, b, c, d, e, and f, respectively. A statistically significant difference in amplitudes was noted from the three different sites of stimulation (P < 0.001). The amplitude differed significantly above the age of 60 years (P < 0.01) but not between groups e and f (P > 0.05). Conclusion: This study provides reference data for sural SNAP in Indian population at three different sites of stimulation along the calf in six age groups. It also shows significant variation in amplitude from the three different sites of stimulation. PMID:27570380

  20. Mutagenic activity of overnight urine from healthy non-smoking subjects.

    PubMed

    Pavanello, Sofia; Lupi, Silvia; Pulliero, Alessandra; Gregorio, Pasquale; Saia, Bruno Onofrio; Clonfero, Erminio

    2007-03-01

    Urinary mutagenicity was evaluated in relation to environmental mutagen exposure (i.e., diet, indoor/outdoor activities, residential area etc.) on the day prior to sample collection, and also considering factors that contribute to the variability of Salmonella mutagenicity assay results. Overnight urine samples from 283 healthy non-smoking residents of northeast Italy (46% males, 20-62 years) were analyzed for mutagenicity on sensitive Salmonella typhimurium strain YG1024 with S9 mix employing the preincubation version of the plate incorporation assay (i.e., the Salmonella reverse mutation test). Urinary mutagenicity varied between 0.02 and 9.84 rev/ equiv. ml, and 7% of samples were positive (i.e., sample elicited a two-fold increase in revertants). There was an evident increase in mutagenicity in subjects with increased intake of mutagen-rich meals (n = 80) (P < 0.01 and positive urine 13% vs. 5%, P = 0.025). Indoor-exposed subjects (n = 65) also showed a higher percentage of positive urine (14% vs. 5%, P = 0.015). In particular, those subjects exposed to cooking fumes the previous evening (n = 28) revealed higher urinary mutagenicity (P = 0.035, positive urine 25% vs. 5%, P < 0.001) than non-indoor exposed. The sources of variability of the mutagenicity assay, mainly the histidine content of the urine concentrate (z = 4.06, P < 0.0001), and to a lesser extent bacterial inoculum size (z = 2.33, P = 0.019), also significantly influenced urinary mutagenicity values. In a linear multiple regression analysis, their effects were still significant (i.e., histidine content P = 0.026 and inoculum size P = 0.021), but the effects of diet, indoor exposure, and other environmental exposures (i.e., traffic and heating system exhausts, residential area) were not. It is concluded that the previous day's exposure to mutagen-rich meals and cooking fumes may influence the presence of mutagenic activity in the overnight urine of non-smoking subjects. This mutagenic activity, which

  1. Measurement duration impacts variability but not impedance measured by the forced oscillation technique in healthy, asthma and COPD subjects

    PubMed Central

    Watts, Joanna C.; Farah, Claude S.; Seccombe, Leigh M.; Handley, Blake M.; Schoeffel, Robin E.; Bertolin, Amy; Dame Carroll, Jessica; King, Gregory G.

    2016-01-01

    The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system (Rrs) and respiratory system reactance (Xrs) at 5 and 19 Hz. With increasing duration, there was a decrease in total and expiratory Rrs for healthy controls, total and inspiratory Rrs for asthmatic subjects and magnitude of total and inspiratory Xrs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total Rrs and Xrs also decreased with duration. Similar results were found for Rrs and Xrs at 19 Hz. FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects. PMID:27730194

  2. Effect of Demographic Status and Lifestyle Habits on Glycaemic Levels in Apparently Healthy Subjects: A Cross-Sectional Study

    PubMed Central

    Walatara, Kasuni Nisansala Wijesena

    2016-01-01

    Aim. To identify the effects of sociodemographic status, family history, and lifestyle habits on fasting blood glucose (FBG) and fasting serum insulin (FSI) levels in apparently healthy subjects. Methods. Information was gathered using an interviewer-administered questionnaire from 227 apparently healthy nondiabetic subjects residing in a suburban area in Sri Lanka. Venous blood samples were collected after an overnight fast for FBG and FSI analysis. Correlations and differences were analyzed using SPSS (ver. 17) software. Results. The majority of the subjects were females, having secondary or tertiary education, monthly income ≥Rs. 25,000 (USD 175), and a positive family history of diabetes. Among the subjects, 10.1% were identified as prediabetics and the majority had familial diabetes with monthly income ≥Rs. 25,000 (USD 175). Subjects with high income had significantly higher mean FBG. In addition FBG had a significant correlation with age. Males and subjects with less than 6 hours/day sleeping duration at night had significantly higher FBG. Subjects with less vigorous physical activity and longer sitting duration had significantly higher FSI levels. Conclusions. Increasing age, higher income, positive familial history of diabetes, sedentary lifestyle, and short sleep at night have positive impact on glycaemic status in apparently healthy subjects. PMID:27995147

  3. Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel 5-HT1A agonist, in healthy subjects.

    PubMed

    Iyer, Ganesh R; Reinhard, John F; Oshana, Scott; Kauffman, Michael; Donahue, Stephen

    2007-07-01

    PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX-00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a half-life of approximately 12 hours. PRX-00023 treatment transiently increased blood prolactin levels 2 to 3 hours after administration, consistent with its mechanism as a 5-HT1A agonist.

  4. The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects

    SciTech Connect

    Keefe, M.J.; Bennett, W.D.; DeWitt, P.; Seal, E.; Strong, A.A.; Gerrity, T.R. )

    1991-07-01

    Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings.

  5. Effects of duloxetine on norepinephrine and serotonin transporter activity in healthy subjects.

    PubMed

    Chappell, Jill C; Eisenhofer, Graeme; Owens, Michael J; Haber, Harry; Lachno, D Richard; Dean, Robert A; Knadler, Mary Pat; Nemeroff, Charles B; Mitchell, Malcolm I; Detke, Michael J; Iyengar, Smriti; Pangallo, Beth; Lobo, Evelyn D

    2014-02-01

    Duloxetine selectively inhibits the serotonin (5-HT) and norepinephrine (NE) transporters (5-HTT and NET, respectively), as demonstrated in vitro and in preclinical studies; however, transporter inhibition has not been fully assessed in vivo at the approved dose of 60 mg/d. Here, the in vivo effects of dosing with duloxetine 60 mg once daily for 11 days in healthy subjects were assessed in 2 studies: (1) centrally (n = 11), by measuring concentrations of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylglycol (DHPG), and NE in cerebrospinal fluid, and (2) versus escitalopram 20 mg/d (n = 32) in a 2-period crossover study by assessing the ΔDHPG/ΔNE ratio in plasma during orthostatic testing and by pharmacokinetic/pharmacodynamic modeling of reuptake inhibition using subjects' serum in cell lines expressing cloned human 5-HTT or NET. At steady state, duloxetine significantly reduced concentrations of DHPG and 5-hydroxyindoleacetic acid (P < 0.05), but not NE, in cerebrospinal fluid; DHPG was also decreased in plasma and urine. The ΔDHPG/ΔNE ratio in plasma decreased significantly more with duloxetine than escitalopram (65% and 21%, respectively; P < 0.0001). Ex vivo reuptake inhibition of 5-HTT was comparable (EC50 = 44.5 nM) for duloxetine and escitalopram, but duloxetine inhibited NET more potently (EC50 = 116 nM and 1044 nM, respectively). Maximal predicted reuptake inhibition for 5-HTT was 84% for duloxetine and 80% for escitalopram, and that for NET was 67% and 14%, respectively. In summary, duloxetine significantly affected 5-HT and NE turnover in the central nervous system and periphery; these effects presumably occurred via inhibition of reuptake by the 5-HTT and NET, as indicated by effects on functional reuptake inhibition ex vivo.

  6. Daily hypoxia increases basal monocyte HSP72 expression in healthy human subjects.

    PubMed

    Taylor, Lee; Midgley, Adrian W; Chrismas, Bryna; Hilman, Angela R; Madden, Leigh A; Vince, Rebecca V; McNaughton, Lars R

    2011-02-01

    Heat shock protein 72 (HSP72) performs vital roles within the body at rest and during periods of stress. In vitro, research demonstrates HSP72 induction in response to hypoxia. Recently, in vivo, an acute hypoxic exposure (75 min at 2,980 m) was sufficient to induce significant increases in monocyte expressed HSP72 (mHSP72) and a marker of oxidative stress in healthy human subjects. The purpose of the current study was to identify the impact of 10 consecutive days of hypoxic exposures (75 min at 2,980 m) on mHSP72 and erythropoietin (EPO) expression, markers of oxidative stress, and maximal oxygen consumption in graded incremental aerobic exercise. Eight male subjects were exposed to daily normobaric hypoxic exposures for 75 min at 2,980 m for 10 consecutive days, commencing and ceasing at 0930 and 1045, respectively. This stressor was sufficient to induce significant increases in mHSP72, which was significantly elevated from day 2 of the hypoxic exposures until 48 h post-final exposure. Notably, this increase had an initial rapid (30% day on day compared to baseline) and final slow phase (16% day on day compared to baseline) of expression. The authors postulate that 7-day hypoxic exposure in this manner would be sufficient to induce near maximum hypoxia-mediated basal mHSP72 expression. Elevated levels of mHSP72 are associated with acquired thermotolerance and provide cross tolerance to non-related stressors in vivo, the protocol used here may provide a useful tool for elevating mHSP72 in vivo. Aside from these major findings, significant transient daily elevations were seen in a marker of oxidative stress, alongside sustained increases in EPO expression. However, no physiologically significant changes were seen in maximal oxygen consumption or time to exhaustion.

  7. Daily quadratic trend in basal monocyte expressed HSP72 in healthy human subjects.

    PubMed

    Taylor, Lee; Midgley, Adrian W; Chrismas, Bryna; Madden, Leigh A; Vince, Rebecca V; McNaughton, Lars R

    2010-05-01

    The inducible human stress protein heat shock protein 72 (HSP72) performs vital roles within the body at rest and during periods of stress. Recently it was shown over a 24 h period that basal HSP72 followed a diurnal variation. However, these results and previous literature demonstrate noticeable inter-subject variation in basal HSP72 expression. The notion of intra/inter-day variation in basal HSP72 expression has not been explored in detail. Basal monocyte expressed HSP72 was determined every 3 h, over a 9 h period in 12 healthy male subjects (20.2 +/- 1.9 years, 178.7 +/- 5.6 cm, 75.1 +/- 6.0 kg) within a temperature controlled laboratory. A significant quadratic trend was observed for time (F = 26.0, P = 0.001, partial eta(2) = 0.74), where HSP72 decreased between 0800 and 1100 hours (P < 0.001) and then increased between 1100 and 1400 hours (P = 0.015). The main effect for day (F = 2.6, P = 0.14) and the day x time interaction effect (F = 3.9, P = 0.08) were not significant. There was no correlation between serum and monocyte expressed HSP72, with no significant effect for time (F = 2.0, P = 0.21) in serum HSP72 expression. The results support findings by others that basal monocyte expressed HSP72 follows a diurnal variation which incorporates a quadratic trend, which is not compromised by any significant daily variation and that serum HSP72 expression has no endogenous circadian rhythm. The significant quadratic trend in basal monocyte HSP72 expression shown here highlights the need to tightly control variables, such as timing of sample collection, as it is known basal values influence the magnitude of HSP72 expression post-stressor/intervention.

  8. The Effect of Patellar Taping on Some Landing Characteristics During Counter Movement Jumps in Healthy Subjects

    PubMed Central

    Cámara, Jesús; Díaz, Francisco; Anza, María Soledad; Mejuto, Gaizka; Puente, Asier; Iturriaga, Gorka; Fernández, Juan-Ramón

    2011-01-01

    The aim of the present study was to determine the effect of patellar taping (PT) on landing characteristics of the vertical ground reaction force (VGRF) and on flight time during a counter movement jump (CMJ). Eleven healthy male subjects (age: 31.1 ± 4.2 years) volunteered for the study. Each subject performed six CMJs under two different jumping conditions: with PT and without PT (WPT). The order of the two conditions was randomized. All of the measured variables had fair-to-good reliability (intra-class correlation coefficient > 0.75). When we compared the PT and WPT groups, we did not find a significant difference in the magnitude of the first (F1) and second (F2) peaks of the VGRF. We also did not find a significant difference in the time to production of these peaks (T1 and T2), and the time to stabilization (TTS) (p < 0. 05). Furthermore, the flight time was similar in the two groups (0.475 ± 0.046 and 0.474 ± 0.056 s, respectively, for PT and WPT). These results suggest that PT does not jeopardize performance during CMJ. Furthermore, it also does not soften the VGRF generated during the landing, indicating that PT may be of limited utility in preventing injuries associated with this type of movement. Key points We investigated whether patellar taping interferes with athletic performance, as has been suggested by previous studies. We also explored the effect of patellar taping on the forces generated during the landing phase of counter movement jumps. Patellar taping had no effect on the flight time during counter movement jumps. Patellar taping also had no effect on the vertical ground reaction force variables measured during the landing phase of counter movement jumps. This information may be relevant to athletes and trainers who are concerned about the effects of patellar taping on performance. PMID:24149562

  9. Relationship between ocular surface temperature and peripheral vasoconstriction in healthy subjects: a thermographic study.

    PubMed

    Vannetti, Federica; Matteoli, Sara; Finocchio, Lucia; Lacarbonara, Francesco; Sodi, Andrea; Menchini, Ugo; Corvi, Andrea

    2014-03-01

    An impairment of ocular blood flow regulation is commonly considered one of the main pathogenetic mechanisms involved in the development of several eye diseases, like glaucoma. The aim of this study was to investigate whether an alteration of ocular blood supply induced by peripheral vasoconstriction might be detected by measuring the ocular surface temperature. The ocular surface temperature was evaluated in a group of 38 healthy young subjects (28 males and 10 females; mean age: 25.4 ± 4.1 years) by infrared thermography. For each subject, the experimental procedure consisted of two thermographic acquisitions both lasting 10 s, recorded before and during the immersion of both hands in a mixture of ice and water (1.6 °C ± 0.4 °C). Specifically, the second acquisition began 20 s after the hand immersion. Analysis of variance was used to compare the ocular surface temperature of the two profiles. The analysis of infrared images was carried out every 2 s: at the eye opening (t(0)) until 10 s (t(5)), for both profiles. Data showed that ocular surface temperature increased significantly (p-value < 0.05), especially near the sources of ocular blood supply, that is, temporal and nasal areas (mean increasing temperature at t(0) for P(1) = 0.12 °C ± 0.13 °C). Therefore, these results suggest a response of the ocular hemodynamic to the peripheral vasoconstriction. The ocular surface temperature may represent a cheap, non-invasive and non-time-consuming test to evaluate ocular vaso-regulation.

  10. Zinc balance of twenty healthy elderly subjects consuming self-selected diets

    SciTech Connect

    Souza, M.C.; Prather, E.S.; Rhodes, D.G. )

    1991-03-15

    Dietary zinc (Zn) intake and balance were determined in ten male and ten female free-living, healthy, elderly subjects on self-selected diets over a period of seven consecutive days. Zn content in the diet, fecal and urine composites for each subject was determined by atomic absorption spectrophotometry. Mean age for the 20 participants was 73.9 years. Mean Zn intakes were 8.9 and 23.3 mg/day for females and males, respectively. Female dietary intakes ranged from 8.2 to 26.8 mg Zn/day. However, three of the males took Zn supplements which extended the total intake range to 64.9 mg/day. Mean Zn balances were +0.1 and +5.1 mg/day for females and males, respectively; ranges for females were {minus}0.1 to +4.3 mg/day and for males were {minus}7.3 to +15.1 mg/day. The 1989 RDAs are 15 mg for males and 12 mg for females. Only three females consumed more than 12 mg Zn/day. Only 2 males consumed more than 15 mg/day from their diet; two other males consumed more than 15 mg due to Zn supplements. Total dietary phytate (TDP) and total dietary fiber (TDF) were calculated from the 7-day weighed food records. Mean TDP intake for females was 1,159 mg/day; mean TDP for the males was 1,661 mg/day. Mean TDF intake for females was 19 g/day; mean TDF for males was 30 g/day.

  11. Short-Term Heart Rate Variability—Influence of Gender and Age in Healthy Subjects

    PubMed Central

    Voss, Andreas; Schroeder, Rico; Heitmann, Andreas; Peters, Annette; Perz, Siegfried

    2015-01-01

    In the recent years, short-term heart rate variability (HRV) describing complex variations of beat-to-beat interval series that are mainly controlled by the autonomic nervous system (ANS) has been increasingly analyzed to assess the ANS activity in different diseases and under various conditions. In contrast to long-term HRV analysis, short-term investigations (<30 min) provide a test result almost immediately. Thus, short-term HRV analysis is suitable for ambulatory care, patient monitoring and all those applications where the result is urgently needed. In a previous study, we could show significant variations of 5-min HRV indices according to age in almost all domains (linear and nonlinear) in 1906 healthy subjects from the KORA S4 cohort. Based on the same group of subjects, general gender-related influences on HRV indices are to be determined in this study. Short-term 5-min HRV indices from linear time and frequency domain and from nonlinear methods (compression entropy, detrended fluctuation analysis, traditional and segmented Poincaré plot analysis, irreversibility analysis, symbolic dynamics, correlation and mutual information analysis) were determined from 782 females and 1124 males. First, we examined the gender differences in two age clusters (25–49 years and 50–74 years). Secondly, we investigated the gender-specific development of HRV indices in five age decade categories, namely for ages 25–34, 35–44, 45–54, 55–64 and 65–74 years. In this study, significant modifications of the indices according to gender could be obtained, especially in the frequency domain and correlation analyses. Furthermore, there were significant modifications according to age in nearly all of the domains. The gender differences disappeared within the last two age decades and the age dependencies disappeared in the last decade. To summarize gender and age influences need to be considered when performing HRV studies even if these influences only partly differ. PMID

  12. Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials.

    PubMed

    Braune, S; Groß, M; Walter, M; Zhou, S; Dietze, S; Rutschow, S; Lendlein, A; Tschöpe, C; Jung, F

    2016-01-01

    On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet-indicating the spreading and activation of the platelets-was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials.

  13. Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

    PubMed

    Newman, S; Malik, S; Hirst, R; Pitcairn, G; Heide, A; Pabst, J; Dinkelaker, A; Fleischer, W

    2002-12-01

    The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

  14. Longitudinal distribution of ozone absorption in the lung: quiet respiration in healthy subjects.

    PubMed

    Hu, S C; Ben-Jebria, A; Ultman, J S

    1992-10-01

    The objective of this research was to develop a bolus-response method for the noninvasive determination of O3 distribution in the human lung. A previously developed O3 analyzer and bolus generator were incorporated in a computer-controlled inhalation system, and measurements of O3 absorption from inhaled 10-ml boluses with a peak O3 concentration of 4 ppm were carried out on nine previously unexposed healthy male subjects engaged in quiet oral breathing. The fraction of O3 absorbed during a single breath was measured over a range of airway penetrations from 20 to 200 ml, with inspiratory and expiratory flows fixed at a nominal value of 250 ml/s. The resulting data indicated that 50% of the inhaled O3 was absorbed at a penetration of 70 ml, which roughly corresponds to the upper airways, and essentially complete absorption occurred at a penetration of 180 ml, which roughly corresponds to the 16th airway generation, the beginning of the proximal alveolar region. This compares favorably with the results of direct-sampling methods, which indicated that 40.4% of continuously inhaled O3 is removed by the extrathoracic airways (Gerrity et al. J. Appl. Physiol. 65: 393-400, 1988). The computation of an absorption rate constant, Ka, revealed that the efficiency of O3 uptake increased with longitudinal position throughout most of the conducting airways but began to fall off at a penetration of 160 ml.

  15. Parameters of oxidative stress status in healthy subjects: their correlations and stability after sample collection.

    PubMed

    Firuzi, Omidreza; Mladenka, Premysl; Riccieri, Valeria; Spadaro, Antonio; Petrucci, Rita; Marrosu, Giancarlo; Saso, Luciano

    2006-01-01

    It has been proposed that sample storage may have some influence on the parameters of oxidative stress status (OSS) in biological fluids. We measured four important OSS parameters in plasma of 23 healthy subjects and repeated the measurements in the same samples kept at -70 degrees C after different time intervals. Hydroperoxides and total antioxidant capacity (TAC) were determined by ferrous ion oxidation in presence of xylenol orange (FOX) and ferric reducing antioxidant power (FRAP) assays, respectively. Sulfhydryls and carbonyls were measured spectrophotometrically. In fresh samples, OSS seemed to increase with age and relatively good correlations were found among different parameters. The mean values of hydroperoxides (6.08 microM), TAC (0.334 mM Trolox equivalent), and sulfhydryls (0.562 mM) in fresh samples did not show any significant change after 1, 7, and 30 days of storage. Mean carbonyl concentration determined after 1 day storage (2.0 nmol/mg protein) did not change after 30 days. However, extents of changes in hydroperoxide concentrations varied considerably from one individual to another, even after 1 day. A similar phenomenon was observed in TAC, but after 7 days. We suggest measuring hydroperoxides in fresh samples and TAC maximally after 1 week. Sulfhydryls and carbonyls showed more stability and can be measured at least 1 month after sample collection.

  16. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

    PubMed Central

    Mungee, Aditya; Burger, Max; Bajbouj, Malek

    2016-01-01

    Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal) for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05). Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal) did not influence fear memories. PMID:27827903

  17. Fyn polymorphisms are associated with distinct personality traits in healthy Chinese-Han subjects.

    PubMed

    Li, Jingying; Ma, Huan; Deng, Shumin; Wu, Lijuan; Huang, Yinglin; Zhu, Gang

    2011-05-01

    The Src family tyrosine kinase Fyn regulates a myriad of neurophysiological processes, including learning and memory. To date, the role of Fyn in the neurological mechanisms that determine personality traits has not been addressed. To this end, we determined the association between the rs706895C/T polymorphism of the Fyn gene (FYN) and personality traits measured by the Tridimensional Personality Questionnaire in 502 healthy Chinese-Han subjects. There were no significant differences in the total scores for novelty seeking (χ² = 5.12, P = 0.077), harm avoidance (HA; χ² = 2.63, P = 0.269), or reward dependence (RD; χ² = 3.94, P = 0.139) among the rs706895C/T genotypes. In sub-item analyses, however, both fear of uncertainty (HA2; χ² = 7.84, P = 0.020) and sentimentality (RD1; χ² = 8.27; P = 0.016) scores were significantly different among rs706895C/T genotypes. Our results suggest that FYN alleles can contribute to the variance in human personality traits.

  18. Effects of Cremophor EL on the absorption of orally administered saquinavir and fexofenadine in healthy subjects.

    PubMed

    Tomaru, Atsuko; Takeda-Morishita, Mariko; Maeda, Kazuya; Banba, Hirokazu; Takayama, Kozo; Kumagai, Yuji; Kusuhara, Hiroyuki; Sugiyama, Yuichi

    2015-06-01

    Modulation of CYP3A and/or P-gp function by several excipients has been reported. However, relatively few studies have investigated their effects in humans. Therefore, the aim of this clinical study was to clarify the effects of Cremophor EL on the inhibition of CYP3A and P-gp in the human small intestine. Eight healthy Japanese subjects received an oral dose of saquinavir (2 mg, substrate of P-gp/CYP3A) or fexofenadine (50 μg, substrate of P-gp) without or with Cremophor EL (720 mg and 1440 mg). Significant increases in Cmax (1.3-fold) and AUC0-24 (1.6-fold) were observed for fexofenadine when administered with 1440 mg of Cremophor EL. In contrast, a significant decrease was observed for saquinavir when administered with 720 mg of Cremophor EL. The equilibrium dialysis experiment was performed to investigate the micellar interaction between Cremophor EL and drugs. The equilibrium dialysis study showed that saquinavir was far extensively entrapped into the micelles. The reduced concentration of free saquinavir by entrapping in micelles was considered to cause the reduction of systemic exposure for saquinavir. In conclusion, this clinical study suggests that Cremophor EL at least inhibits P-gp in the human small intestine.

  19. Symmetric corticospinal excitability and representation of vastus lateralis muscle in right-handed healthy subjects.

    PubMed

    Al Sawah, Mohomad; Rimawi, Mohammad; Concerto, Carmen; Amer, Bahaa; Cao, Yisheng; D'Antoni, Anthony V; Chusid, Eileen; Battaglia, Fortunato

    2014-10-01

    The purpose of this study was to determine the size and location of the representations of the anterior thigh muscles on the human motor cortex in the dominant and non-dominant hemispheres. Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation were recorded from the right and left vastus lateralis (rVL, lVL) muscles. A total of ten right-handed healthy volunteers participated in the study. In a single session experiment, we investigated VL muscle corticospinal excitability (motor threshold, MEP size, short interval intracortical inhibition, intracortical facilitation) and cortical representation (map area, volume, and location) in the dominant and non-dominant hemispheres. The motor threshold, MEPs, and intracortical excitability did not differ significantly between the hemispheres (P > 0.05). Furthermore, no difference between sides was found in the location of VL motor representation (mediolateral and anteroposterior axis) or in map area and volume (P > 0.05). Vastus lateralis muscle corticospinal excitability and cortical map were symmetrical in right-handed subjects. Future studies on patients with unilateral lower extremity injuries could examine side-to-side plastic reorganization in corticomotor output and map location in both hemispheres.

  20. Estimation of arterial PCO2 from a lung model during ramp exercise in healthy young subjects.

    PubMed

    Thomas, Vincent; Costes, Frédéric; Busso, Thierry

    2007-06-15

    The aim of this study is to propose a new approach to estimate non-invasively arterial carbon dioxide partial pressure (P(a)CO2) approach was based on the reconstruction of alveolar gas composition over each breath from a tidally ventilated lung model (P(M)(CO2)). Eight healthy young subjects were studied during a ramp exercise test on a cycle ergometer. Arterial samples were drawn at rest and every minute during the exercise test for determination of P(a)CO2 . P(a)CO2 was compared with indirect estimates of P(CO2) : P(M)(CO2), end-tidal P(CO2) (P(ET)(CO2)) and an empirical equation involving P(ET)(CO2) and tidal volume (P(J)(CO2)). The difference between estimated and measured P(a)CO2 on the whole ramp exercise was -0.3+/-1.9mmHg for P(M)(CO2), 1.0+/-2.2mmHg for P(ET)(CO2) and -1.7+/-1.7mmHg for P(J)(CO2) . P(ET)(CO2) and P(J)(CO2) were significantly different from actual P(a)CO2 (P<0.001). It is concluded that, on the basis of the bias, the breathing lung model gave better estimates of P(a)CO2 than the two other indirect methods during ramp exercise.

  1. Modulation of electroencephalograph activity by manual acupuncture stimulation in healthy subjects: An autoregressive spectral analysis

    NASA Astrophysics Data System (ADS)

    Yi, Guo-Sheng; Wang, Jiang; Deng, Bin; Wei, Xi-Le; Han, Chun-Xiao

    2013-02-01

    To investigate whether and how manual acupuncture (MA) modulates brain activities, we design an experiment where acupuncture at acupoint ST36 of the right leg is used to obtain electroencephalograph (EEG) signals in healthy subjects. We adopt the autoregressive (AR) Burg method to estimate the power spectrum of EEG signals and analyze the relative powers in delta (0 Hz-4 Hz), theta (4 Hz-8 Hz), alpha (8 Hz-13 Hz), and beta (13 Hz-30 Hz) bands. Our results show that MA at ST36 can significantly increase the EEG slow wave relative power (delta band) and reduce the fast wave relative powers (alpha and beta bands), while there are no statistical differences in theta band relative power between different acupuncture states. In order to quantify the ratio of slow to fast wave EEG activity, we compute the power ratio index. It is found that the MA can significantly increase the power ratio index, especially in frontal and central lobes. All the results highlight the modulation of brain activities with MA and may provide potential help for the clinical use of acupuncture. The proposed quantitative method of acupuncture signals may be further used to make MA more standardized.

  2. The cybernetic rehabilitation aid: preliminary results for wrist and elbow motions in healthy subjects.

    PubMed

    Akdogan, Erhan; Shima, Keisuke; Kataoka, Hitoshi; Hasegawa, Masaki; Otsuka, Akira; Tsuji, Toshio

    2012-09-01

    This paper proposes the cybernetic rehabilitation aid (CRA) based on the concept of direct teaching using tactile feedback with electromyography (EMG)-based motor skill evaluation. Evaluation and teaching of motor skills are two important aspects of rehabilitation training, and the CRA provides novel and effective solutions to potentially solve the difficulties inherent in these two processes within a single system. In order to evaluate motor skills, EMG signals measured from a patient are analyzed using a log-linearized Gaussian mixture network that can classify motion patterns and compute the degree of similarity between the patient's measured EMG patterns and the desired pattern provided by the therapist. Tactile stimulators are used to convey motion instructions from the therapist or the system to the patient, and a rehabilitation robot can also be integrated into the developed prototype to increase its rehabilitation capacity. A series of experiments performed using the developed prototype demonstrated that the CRA can work as a human-human, human-computer and human-machine system. The experimental results indicated that the healthy (able-bodied) subjects were able to follow the desired muscular contraction levels instructed by the therapist or the system and perform proper joint motion without relying on visual feedback.

  3. Estimation of Circadian Body Temperature Rhythm Based on Heart Rate in Healthy, Ambulatory Subjects.

    PubMed

    Sim, Soo Young; Joo, Kwang Min; Kim, Han Byul; Jang, Seungjin; Kim, Beomoh; Hong, Seungbum; Kim, Sungwan; Park, Kwang Suk

    2017-03-01

    Core body temperature is a reliable marker for circadian rhythm. As characteristics of the circadian body temperature rhythm change during diverse health problems, such as sleep disorder and depression, body temperature monitoring is often used in clinical diagnosis and treatment. However, the use of current thermometers in circadian rhythm monitoring is impractical in daily life. As heart rate is a physiological signal relevant to thermoregulation, we investigated the feasibility of heart rate monitoring in estimating circadian body temperature rhythm. Various heart rate parameters and core body temperature were simultaneously acquired in 21 healthy, ambulatory subjects during their routine life. The performance of regression analysis and the extended Kalman filter on daily body temperature and circadian indicator (mesor, amplitude, and acrophase) estimation were evaluated. For daily body temperature estimation, mean R-R interval (RRI), mean heart rate (MHR), or normalized MHR provided a mean root mean square error of approximately 0.40 °C in both techniques. The mesor estimation regression analysis showed better performance than the extended Kalman filter. However, the extended Kalman filter, combined with RRI or MHR, provided better accuracy in terms of amplitude and acrophase estimation. We suggest that this noninvasive and convenient method for estimating the circadian body temperature rhythm could reduce discomfort during body temperature monitoring in daily life. This, in turn, could facilitate more clinical studies based on circadian body temperature rhythm.

  4. Pharmacokinetics of Dolutegravir When Administered With Mineral Supplements in Healthy Adult Subjects

    PubMed Central

    Song, Ivy; Borland, Julie; Arya, Niki; Wynne, Brian; Piscitelli, Stephen

    2015-01-01

    All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations. The purpose of this study was to evaluate the effect of calcium and iron supplements on dolutegravir pharmacokinetics and strategies (dose separation and food) to attenuate the effects if significant reductions in dolutegravir exposure were observed. This was an open-label, crossover study that randomized 24 healthy subjects into 1 of 2 cohorts to receive 4 treatments: (1) dolutegravir alone, fasting; (2) dolutegravir with calcium carbonate or ferrous fumarate, fasting; (3) dolutegravir with calcium carbonate or ferrous fumarate with a moderate-fat meal; (4) dolutegravir administered 2 hours before calcium carbonate or ferrous fumarate, fasting. Plasma dolutegravir AUC(0–∞), Cmax, and C24 were reduced by 39%, 37%, and 39%, respectively, when co-administered with calcium carbonate while fasting and were reduced by 54%, 57%, and 56%, respectively, when co-administered with ferrous fumarate while fasting. Dolutegravir administration 2 hours before calcium or iron supplement administration (fasted), as well as administration with a meal, counteracted the effect. Dolutegravir and calcium or iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium or iron supplements. PMID:25449994

  5. The relationships between interoception and alexithymic trait. The Self-Awareness Questionnaire in healthy subjects

    PubMed Central

    Longarzo, Mariachiara; D'Olimpio, Francesca; Chiavazzo, Angela; Santangelo, Gabriella; Trojano, Luigi; Grossi, Dario

    2015-01-01

    Interoception is the basic process enabling evaluation of one's own bodily states. Several previous studies suggested that altered interoception might be related to disorders in the ability to perceive and express emotions, i.e., alexithymia, and to defects in perceiving and describing one's own health status, i.e., hypochondriasis. The main aim of the present study was to investigate the relationships between alexithymic trait and interoceptive abilities evaluated by the “Self-Awareness Questionnaire” (SAQ), a novel self-report tool for assessing interoceptive awareness. Two hundred and fifty healthy subjects completed the SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two-factor structure, with good internal consistency (Cronbach's alpha = 0.88). We observed significant direct correlations between SAQ, TAS-20 and two of its subscales, and the IAS. Regression analysis confirmed that the difficulty in identifying and expressing emotions is significantly related with awareness for one's own interoceptive feelings and with a tendency to misinterpret and amplify bodily sensations. From a clinical point of view, the assessment of interoceptive awareness by the SAQ could be pivotal in evaluating several psychopathological conditions, such as the somatoform disorders. PMID:26300829

  6. Patients with extratemporal lobe epilepsy do not differ from healthy subjects with respect to subcortical volumes

    PubMed Central

    Gartner, B; Seeck, M; Michel, C; Delavelle, J; Lazeyras, F

    2004-01-01

    Background: Evidence from previous volumetric magnetic resonance studies has revealed that patients with chronic temporal lobe epilepsy show atrophy of distinct subcortical nuclei, predominantly ipsilateral to the focus side. We were interested to find out if there is also selective subcortical atrophy in patients suffering from long standing extratemporal lobe epilepsy. Methods: Thirty one patients in whom pre-surgical evaluation unambiguously localised an extratemporal focus were included in this study. Using high resolution magnetic resonance imaging, the volumes of the caudate nuclei, putamen, pallidum, and thalamus were measured bilaterally in both hemispheres and compared with measurements obtained in 15 healthy volunteers. Results: No significant difference in volumes was found between the two subject groups, or in any subgroup of extratemporal lobe epilepsy patients, nor was there any relation to clinical variables such as age of onset, overall seizure frequency, or disease duration. However, patients who had no or only rare generalised tonic–clonic seizures seemed to differ from the other patients and controls in that they had smaller putamen volumes bilaterally (p<0.001). Conclusion: We concluded that extratemporal lobe epilepsy in general is not associated with diminished volumes in the studied subcortical structures, which contrasts with findings in temporal lobe epilepsy patients. Thus, both entities differ both cortically and subcortically. However, we found that small putamen volume was bilaterally associated with absent or rare generalised tonic–clonic seizures, implicating the putamen in the control of the most disabling seizure type, independent of the site of neocortical focus. PMID:15026503

  7. Faecal metabolomic fingerprint after moderate consumption of red wine by healthy subjects.

    PubMed

    Jiménez-Girón, Ana; Ibáñez, Clara; Cifuentes, Alejandro; Simó, Carolina; Muñoz-González, Irene; Martín-Álvarez, Pedro J; Bartolomé, Begoña; Moreno-Arribas, M Victoria

    2015-02-06

    Faecal metabolome contains information on the metabolites found in the intestine, from which knowledge about the metabolic function of the gut microbiota can be obtained. Changes in the metabolomic profile of faeces reflect, among others, changes in the composition and activity of the intestinal microorganisms. In an effort to improve our understanding of the biological effects that phenolic compounds (including red wine polyphenols) exert at the gut level, in this foodomic study we have undertaken a metabolome characterization of human faeces after moderate consumption of red wine by healthy subjects for 4 weeks. Namely, a nontargeted metabolomic approach based on the use of UHPLC-TOF MS was developed to achieve the maximum metabolite information on 82 human faecal samples. After data processing and statistical analysis, 37 metabolites were related to wine intake, from which 20 could be tentatively or completely identified, including the following: (A) wine compounds, (B) microbial-derived metabolites of wine polyphenols, and (C) endogenous metabolites and/or others derived from other nutrient pathways. After wine consumption, faecal metabolome was fortified in flavan-3-ols metabolites. Also, of relevance was the down regulation of xanthine and bilirubin-derived metabolites such as urobilinogen and stercobilin after moderate wine consumption. As far as we know, this is the first study of the faecal metabolome after wine intake.

  8. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    SciTech Connect

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. )

    1990-11-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

  9. Neurocognition in depression: patients on and off medication versus healthy comparison subjects.

    PubMed

    Gualtieri, C Thomas; Johnson, Lynda G; Benedict, Kenneth B

    2006-01-01

    Patients with depression have neuropsychological deficits in attention, memory, psychomotor speed, processing speed, and executive function. It is not clear, however, whether neurocognition in depression is impaired in a global or nonspecific way or if specific cognitive domains are selectively impaired. This naturalistic cross-sectional study employed a computerized neurocognitive screening battery to evaluate 38 depressed, drug-free patients, compared to 31 patients who responded to antidepressant monotherapy and to 69 healthy comparison subjects. There was evidence for global neuropsychological impairment in untreated depressed patients. In patients who had been successfully treated, performance was improved but not normalized. There was also evidence for specific depression-related deficits in executive function and processing speed but not in memory, psychomotor speed, or reaction time. Although depressed patients have global neurocognitive impairments, deficits in certain cognitive domains are more important than in others. In particular, impairments are noted in tests of executive control and in tests that demand effortful attention. Information processing speed is also impaired but not reaction time. Computerized testing in the clinic setting demonstrates a range of neurocognitive problems in patients with depression. These problems may have a bearing on treatment and outcome.

  10. Factors Associated with Visual Fatigue from Curved Monitor Use: A Prospective Study of Healthy Subjects

    PubMed Central

    Lee, Haeng Jin; Kim, Seong-Joon

    2016-01-01

    Purpose To investigate the factors associated with visual fatigue using monitors with various radii of curvature. Methods Twenty normal healthy adults (8 men, 12 women; mean age, 26.2 ± 2.5 years) prospectively watched five types of monitors including flat, 4000R, 3000R, 2000R, and 1000R curved monitors for 30 min. An experienced examiner measured the ophthalmological factors including near point of accommodation (NPA), near point of convergence (NPC), refraction, parameters during pupil response at light and saccadic movement just before and after the visual tasks. The questionnaires about subjective ocular symptoms were also investigated just before and after the visual tasks. Results The NPA increased after the visual tasks with a flat monitor compared with the curved monitors, with the 1000R curved monitor showing the smallest change (p = 0.020). The NPC increased for every monitor after the visual tasks; the largest increase occurred with the flat monitor (p = 0.001). There was no difference in refractive error, pupil response, or saccadic movement in the comparison of before and after the visual tasks. Among the nine factors in the questionnaire, the score of “eye pain” was significantly higher for the flat monitor versus the 1000R curved monitor after the visual tasks (p = 0.034). Conclusions We identified NPA, NPC, and eye pain as factors associated with visual fatigue. Also, the curvature of the monitor was related to the visual fatigue. PMID:27701441

  11. Effects of regional anesthesia with ropivacaine on arterial pressure and heart rate in healthy subjects.

    PubMed

    Oliveira, Nilton E; Lima Filho, Nelson S; Lima, Eliudem G; Vasquez, Elisardo C

    2006-02-01

    The anesthetic, ropivacaine, has been used extensively in clinical practice, but few studies have evaluated this long-acting local anesthetic in dentistry. In this study we evaluated the effects of ropivacaine alone and ropivacaine + vasoconstrictor on the cardiovascular system when used as a dental anesthetic in volunteers. Thirty-two healthy subjects received two consecutive infiltrations of 1.8 ml of either 0.75% ropivacaine or ropivacaine + epinephrine into the pterygomandibular region. Pain sensation, numbness of the lip, arterial pressure, heart rate, and electrocardiogram changes were monitored for 2 h. The onset of anesthesia was 10 min after the injection and lasted for more than 2 h, and numbness of the lip lasted for approximately 8 h. Ropivacaine alone did not cause significant changes in the cardiovascular parameters, but ropivacaine + epinephrine caused a transient increase in arterial pressure and heart rate 2 min postinjection. We conclude that ropivacaine alone injected into the pterygomandibular region does not affect the cardiovascular system and that the addition of epinephrine has no beneficial effect. This finding may be relevant to dentists endeavoring to find an anesthetic of minimal cardiovascular risk to produce regional anesthesia for long-lasting procedures without the need of a vasoconstrictor.

  12. Safety, pharmacokinetics and pharmacodynamics of the anti‐hepcidin Spiegelmer lexaptepid pegol in healthy subjects

    PubMed Central

    Boyce, M; Warrington, S; Cortezi, B; Zöllner, S; Vauléon, S; Swinkels, D W; Summo, L; Schwoebel, F

    2016-01-01

    Background and Purpose Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured l‐oligoribonucleotide, binds and inactivates hepcidin. Experimental Approach We conducted a placebo‐controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8 mg·kg−1. Key Results After treatment with lexaptepid, serum iron concentration and transferrin increased dose‐dependently. Iron increased from approximately 20 μmol·L−1 at baseline by 67% at 8 h after i.v. infusion of 1.2 mg·kg−1 lexaptepid. The pharmacokinetics showed dose‐proportional increases in peak plasma concentrations and moderately over‐proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti‐drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg−1 and with local injection site reactions after s.c. but not after i.v. administration. Conclusions and Implications Lexaptepid pegol inhibited hepcidin and dose‐dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease. PMID:26773325

  13. Bioequivalence studies of 2 oral cefaclor capsule formulations in chinese healthy subjects.

    PubMed

    Chen, J; Jiang, B; Lou, H; Yu, L; Ruan, Z

    2012-03-01

    An open-label, single-dose, randomized, crossover study was carried out in 20 Chinese healthy male subjects to compare the pharmacokinetics of 2 cefaclor (CAS 53994-73-3) formulations after administration of a single 250 mg dose of each drug with a 1-week wash-out period. Blood samples were collected before and with 6 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detector. 2 formulations were evaluated using the following pharmacokinetic parameters: AUC0-t, Cmax and tmax was analyzed nonparametrically. The 90% confidence interval (CI) of the ratios (teat/reference) of log-transformed AUC0-t and Cmax fell within the bioequivalence acceptance range of 80-125%. The results showed that the 90% CI of the ratios of AUC0-t and Cmax were 105.1% (101.0-109.4%) and 92.4% (82.5-103.4%), respectively, which therefore could conclude 2 oral cefaclor capsule formulations of cefaclor are bioequivalent. Both treatments showed similar tolerability and safety.

  14. Serum zinc concentrations in two cohorts of 153 healthy subjects and 100 cirrhotic patients from Mexico City.

    PubMed

    Poo, J L; Rosas-Romero, R; Rodríguez, F; Silencio, J L; Muñoz, R; Bourges, H; Uribe, M

    1995-01-01

    The aim of this study was to assess serum zinc levels in a cohort of healthy subjects and cirrhotic patients from Mexico City. A total of 153 healthy subjects and 100 cirrhotic patients, males and females aged 18-65, were studied. Inclusion criteria for healthy subjects were (1) Mexican-born with first and second generation relatives born in Mexico, and (2) somatometric (body mass index under 30) and clinical evaluation establishing that they had no underlying disease. Entry criteria for cirrhotic patients were (1) clinical and histological proven cirrhosis, (2) compensated liver disease (absence of coma, bleeding hemorrhage or refractory ascitis), and (3) cirrhosis of any cause. Zinc serum levels were measured with atomic absorption spectrophotometry. In healthy subjects, mean serum levels were 77.4 +/- 4.2 micrograms/dl (range 42.9-105.2 micrograms/dl). In cirrhotic patients zinc serum levels (58.9 +/- 16.1 micrograms/dl, range 22-88 micrograms/dl) were significantly lower than in healthy subjects (p < 0.05). A stepwise decline in serum zinc with worsening Child class (A, 73.4 +/- 13; B, 64.4 +/- 12; C, 55.8 +/- 15.6; p < 0.05 by ANOVA test) was found. In conclusion, this study confirms that zinc serum levels are significantly lower in cirrhotic patients and shows that zinc serum levels in a cohort of 153 healthy subjects from Mexico City were unexpectedly lower compared to those found in other countries. This last finding might be explained by different dietetic patterns and deserves further investigation.

  15. Effect of Pseudocereal-Based Breakfast Meals on the First and Second Meal Glucose Tolerance in Healthy and Diabetic Subjects

    PubMed Central

    Gabrial, Shreef G. N.; Shakib, Marie-Christine R.; Gabrial, Gamal N.

    2016-01-01

    BACKGROUND: Many studies have indicated that the incidence of serious diabetic complications may be reduced through strict glycemic control. A low glycemic index diet is one tool to improve insulin resistance and improve glycemic control in type 2 diabetes mellitus (T2DM). AIM: The objective was to study the effect of pseudocereals-based breakfasts (quinoa and buckwheat) on glucose variations at first meal (breakfast) and second meal (standardised lunch) in healthy and diabetic subjects. SUBJECTS AND METHODS: Twelve healthy subjects and 12 patients with Type 2 DM (not- insulin dependent) were recruited in the study. Subjects were provided with quinoa and buckwheat breakfast meals. A standardised lunch was provided 4 h after breakfast. Postprandial blood glucose response after breakfast and the second meal effect was measured in healthy and diabetic subjects. Incremental area under the curve (IAUC) values for glucose was measured in response to the breakfast and lunch. The glycemic index of the 2 pseudocereals-based test breakfasts was determined. A white wheat bread (WWB) was served as a reference breakfast meal. RESULTS: In post-breakfast analyses, healthy subjects showed that buckwheat meal had significantly lower IAUC values for blood glucose compared to WWB reference meal (P < 0.001) while quinoa meal showed no significance. In diabetic subjects, buckwheat and quinoa meals had significantly lower IAUC values for blood glucose compared to WWB reference meal (P < 0.001 and P < 0.05 respectively). Blood glucose concentrations started to decline gradually for the quinoa and buckwheat but not for WWB in all healthy and diabetic subjects and returned to near-fasting baseline levels by 210 min. Post-lunch analyses indicated higher IAUC for the two breakfast types in healthy and diabetic subjects. In addition, the quinoa and buckwheat breakfast meals were followed by a significantly flatter blood glucose response to the second meal for the period between 270 and 330

  16. The effect of hyperoxia on central blood pressure in healthy subjects

    PubMed Central

    Siński, Maciej; Dobosiewicz, Anna; Przybylski, Jacek; Abramczyk, Piotr; Gaciong, Zbigniew

    2016-01-01

    Introduction Hyperoxia increases total peripheral resistance by acting locally but also inhibits the activity of carotid body chemoreceptors. We studied the effect of hyperoxia on central pressure in normotensive subjects. Material and methods Medical air followed by 100% oxygen was provided to 19 subjects (12/7 female/male, age 28.2 ±1.1 years) for 15 min through a non-rebreather mask. Central blood pressure was then measured using applanation tonometry. Results After the first 2 min of hyperoxia, heart rate decreased significantly (65 ±2.6 beats/min vs. 61 ±2.1 beats/min, p = 0.0002). Peripheral and central blood pressure remained unchanged, while hemoglobin oxygen saturation and subendocardial viability ratio index increased (97 ±0.4% vs. 99 ±0.2%, p = 0.03; 168 ±8.4% vs. 180 ±8.2%, p = 0.009). After 15 min of 100% oxygen ventilation, heart rate and peripheral and central blood pressures remained unchanged from the first 2 min. The augmentation index, augmentation pressure and ejection duration increased as compared to baseline values and those obtained at 2 min (–5.1 ±2.9% vs. –1.2 ±2.6%, p = 0.005 and –4.6 ±2.7% vs. –1.2 ±2.6%, p = 0.0015; –1.3 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.003 and –1.1 ±0.7 mm Hg vs. –0.2 ±1.2 mm Hg, p = 0.012; 323 ±3.6 ms vs. 330 ±3.5 ms, p = 0.0002 and 326 ±3.5 ms vs. 330 ±3.5 ms, p = 0.021, respectively). Conclusions The present study shows that hyperoxia does not affect central blood pressure in young healthy subjects and may improve myocardial blood supply estimated indirectly from applanation tonometry. PMID:27695489

  17. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    PubMed

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  18. Assessment of salivary calcium, phosphate, magnesium, pH, and flow rate in healthy subjects, periodontitis, and dental caries

    PubMed Central

    Rajesh, K. S.; Zareena; Hegde, Shashikanth; Arun Kumar, M. S.

    2015-01-01

    Aim: This study was conducted to estimate and compare inorganic salivary calcium, phosphate, magnesium, salivary flow rate, and pH of unstimulated saliva and oral hygiene status of healthy subjects, subjects with periodontitis and dental caries, and to correlate salivary calcium level with number of intact teeth. Materials and Methods: The study population consisted of 48 systemically healthy subjects in the age group of 18-55 years, which was further divided into three groups: healthy, periodontitis, and dental caries. Oral hygiene index-simplified, probing pocket depth, clinical attachment level, the number of intact teeth, and active carious lesions were recorded. Estimation of inorganic salivary calcium, phosphate, and magnesium was performed spectrophotometrically using Vitros 5.1 FS. Statistical analysis was performed using the one-way analysis of variance test at 5% significance level. Results: There was a statistically significant increase in inorganic salivary calcium, phosphate, pH, flow rate, and poor oral hygiene status in periodontitis group compared to dental caries and healthy group. Conclusion: Subjects with increased inorganic salivary calcium, phosphate, pH, flow rate, and poor oral hygiene are at a higher risk of developing periodontitis. Since there is increased remineralization potential, these subjects have more number of intact teeth compared to the dental caries group. PMID:26681848

  19. Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

    PubMed Central

    Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

    2015-01-01

    Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the

  20. Ultrafine and fine particulate matter inhalation decreases exercise performance in healthy subjects.

    PubMed

    Rundell, Kenneth W; Caviston, Renee

    2008-01-01

    The purpose of this study was to investigate effects of PM1 (particulate matter with aerodynamic diameter 0.02-2 microm) inhalation on exercise performance in healthy subjects. Inhalation of internal combustion-derived PM is associated with adverse effects to the pulmonary and muscle microcirculation. No data are available concerning air pollution and exercise performance. Fifteen healthy college-aged males performed 4 maximal effort 6-min cycle ergometer trials while breathing low or high PM1 to achieve maximal work accumulation (kJ). Low PM1 inhalation trials 1 and 2 were separated by 3 days; then after a 7 day washout, trials 3 and 4 (separated by 3 days) were done while breathing high PM1 generated from a gasoline engine; CO was kept below 10 ppm. Lung function was done after trial 1 to verify nonasthmatic status. Lung function was normal before and after low PM1 exercise. PM1 number counts were not different between high PM1 trials (336,730 +/- 149,206 and 396,200 +/- 82,564 for trial 3 and 4, respectively) and were different from low PM1 trial number counts (2,260 +/- 500) (P < 0.0001). Mean heart rate was not different between trials (189 +/- 6.0, 188 +/- 7.6, 188 +/- 7.6, 187 +/- 7.4, for low and high PM1 trials; respectively). Work accumulated was not different between low PM1 trials (96.1 +/- 9.38 versus 96.6 +/- 10.83 kJ) and the first high PM1 trial (trial 3, 96.8 +/- 10.65 kJ). Work accumulated in the second high PM1 trial 4, 91.3 +/- 10.04 kJ) was less than in low PM1 trials 1 and 2, and high PM1 trial 3 (P = 0.004, P = 0.003, P = 0.0008; respectively). Acute inhalation of high (PM1) typical of many urban environments could impair exercise performance.

  1. Effect of Honey Vinegar Syrup on Blood Sugar and Lipid Profile in Healthy Subjects

    PubMed Central

    Derakhshandeh-Rishehri, Seyedeh-Masomeh; Heidari-Beni, Motahar; Feizi, Awat; Askari, Gholam-Reza; Entezari, Mohammad-Hassan

    2014-01-01

    Background: The impact of honey or vinegar on several metabolic abnormalities has been studied separately, a mixture of these two ingredients known as honey vinegar syrup (HVS) has not been investigated previously so far. The aim of this study was to assess the impact of HVS consumption (Iranian's traditional syrup) on glycemic parameters and lipid profiles in healthy individuals. Methods: We conducted a 4-week, randomized, controlled, parallel study consisting of two groups of nonobese healthy volunteers. All subjects were asked to stay on their normal diet. Intervention group (n = 36) received a cup of HVS daily in the evening snack for 4-week (250 cc syrup contains 21.66 g honey vinegar). Assessments of fasting blood sugar (FBS), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were conducted at the baseline and after 4-week of study. Results: We observed no significant effect of HVS on FBS, HOMA-IR, LDL-C and TG. A significant effect of HVS was found on increasing fasting insulin and HOMA-IR and reduction in TC level only in intervention group (Δ =3.39 P = 0.01, Δ =1.65 P = 0.03, Δ = −9.43 P = 0.005, respectively). Changes of FBS, TG and LDL-C were 1.83 mg/dl, −1.53 mg/dl and − 3.99 mg/dl respectively in the intervention group. These changes were not significant. An unfavorable and significant reduction in HDL-C level was also observed between two groups (Δ = −4.82 P < 0.001 in the intervention group). Conclusions: Honey vinegar syrup increased fasting insulin level and decreased TC level in the intervention group. HVS had an unfavorable effect on HDL-C level. Further prospective investigations are warranted to confirm these findings. PMID:25709798

  2. Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects

    PubMed Central

    Santiago, João C. P.; Hallschmid, Manfred

    2017-01-01

    Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m2) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m2) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery

  3. Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects.

    PubMed

    Santiago, João C P; Hallschmid, Manfred

    2017-01-01

    Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m(2)) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m(2)) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin

  4. Variability of FeNO in healthy subjects at 2240 meters above sea level.

    PubMed

    Gochicoa-Rangel, Laura; Rojas-Cisneros, Fermín; Miguel-Reyes, José Luis; Guerrero-Zúñiga, Selene; Mora-Romero, Uri; Maldonado-Mortera, Ana Karen; Torre-Bouscoulet, Luis

    2016-08-01

    Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. Altitude above sea level can affect measurements of this index, but there is only limited information regarding the diurnal variation (ante meridiem vs. post meridiem) and reproducibility of FeNO on consecutive days at moderate altitudes. To evaluate the diurnal variability of FeNO and assess its reproducibility over five consecutive days in healthy individuals living at 2240 m, and to compare the FeNO readings taken with two different analyzers. Healthy non-smoking adults were measured using NIOX MINO(®) or NOA 280i(®) devices. One group (n = 10) had readings taken morning and afternoon for five consecutive days with the NIOX MINO(®) equipment; while the second group (n = 17) was measured on only one morning but by both the electrochemical analyzer (NIOX MINO(®)) and the chemiluminescence method (NOA 280i(®)). The study group consisted of 27 subjects aged 28.7 ± 6 years. Morning and afternoon FeNO measurements were 15.2 ± 7.5 ppb and 15.2 ± 7.9 ppb (p = 0.9), respectively. The coefficient of variation (CV) of these measurements (a.m. vs. p.m.) was 10.7 %, and the coefficient of repeatability (CR), 4.2 ppb. The concordance correlation coefficient (CCC) between the two measures (morning vs. afternoon) was 0.91. The CV and CR of the five morning readings were 15.4 % and 4.3 ppb, respectively; while those of the five afternoon measures were 13.6 % and 3.5 ppb, respectively. The CCC between the NIOX MINO(®) equipment and the NOA-280i(®) device was 0.8, with 95 % limits of agreement of -8.35 to 0.29 ppb. In adults living at 2240 m above sea level, FeNO measurements show minimal diurnal variation, and readings are reproducible (<15 %) over a period of at least five consecutive days; however, the FeNO measurements obtained with the NIOX MINO(®) and NOA 280i(®) devices are not interchangeable due to the wide limits of agreement recorded.

  5. Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges

    PubMed Central

    2013-01-01

    significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge. Conclusions This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters. PMID:24160467

  6. Beta Oscillatory Changes and Retention of Motor Skills during Practice in Healthy Subjects and in Patients with Parkinson's Disease

    PubMed Central

    Nelson, Aaron B.; Moisello, Clara; Lin, Jing; Panday, Priya; Ricci, Serena; Canessa, Andrea; Di Rocco, Alessandro; Quartarone, Angelo; Frazzitta, Giuseppe; Isaias, Ioannis U.; Tononi, Giulio; Cirelli, Chiara; Ghilardi, M. Felice

    2017-01-01

    Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson's disease (PD). As such changes might reflect use-dependent modifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive days during a 40-min reaching task divided in fifteen blocks of 56 movements each. The results confirmed that, with practice, beta modulation depth over the contralateral sensory-motor area significantly increased across blocks in controls but not in PD, while performance improved in both groups without significant correlations between behavioral and EEG data. The same changes were seen the following day in both groups. Also, beta modulation increased within each block with similar values in both groups and such increases were partially transferred to the successive block in controls, but not in PD. Retention of performance improvement was present in the controls but not in the patients and correlated with the increase in day 1 modulation depth. Therefore, the lack of practice-related increase beta modulation in PD is likely due to deficient potentiation mechanisms that permit between-block saving of beta power enhancement and trigger mechanisms of memory formation. PMID:28326029

  7. SEMI-AUTOMATED VECTORIAL ANALYSIS OF ANORECTAL MOTION BY MAGNETIC RESONANCE DEFECOGRAPHY IN HEALTHY SUBJECTS AND FECAL INCONTINENCE

    PubMed Central

    Noelting, Jessica; Bharucha, Adil E.; Lake, David S.; Manduca, Armando; Fletcher, J.G.; Riederer, Stephen J.; Melton, L. Joseph; Zinsmeister, Alan R.

    2012-01-01

    Background Inter-observer variability limits the reproducibility of pelvic floor motion measured by magnetic resonance imaging (MRI). Our aim was to develop a semi-automated program measuring pelvic floor motion in a reproducible and refined manner. Methods Pelvic floor anatomy and motion during voluntary contraction (squeeze) and rectal evacuation were assessed by MRI in 64 women with fecal incontinence (FI) and 64 age-matched controls. A radiologist measured anorectal angles and anorectal junction motion. A semi-automated program did the same and also dissected anorectal motion into perpendicular vectors representing the puborectalis and other pelvic floor muscles, assessed the pubococcygeal angle, and evaluated pelvic rotation. Key Results Manual and semi-automated measurements of anorectal junction motion (r = 0.70; p < 0.0001) during squeeze and evacuation were correlated, as were anorectal angles at rest, squeeze, and evacuation; angle change during squeeze or evacuation were less so. Semi-automated measurements of anorectal and pelvic bony motion were also reproducible within subjects. During squeeze, puborectalis injury was associated (p ≤ 0.01) with smaller puborectalis but not pelvic floor motion vectors, reflecting impaired puborectalis function. The pubococcygeal angle, reflecting posterior pelvic floor motion, was smaller during squeeze and larger during evacuation. However, pubococcygeal angles and pelvic rotation during squeeze and evacuation did not differ significantly between FI and controls. Conclusion & Inferences This semi-automated program provides a reproducible, efficient and refined analysis of pelvic floor motion by MRI. Puborectalis injury is independently associated with impaired motion of puborectalis, not other pelvic floor muscles in controls and women with FI. PMID:22765510

  8. Effect of Wheat Flour Noodles with Bombyx mori Powder on Glycemic Response in Healthy Subjects

    PubMed Central

    Suk, Wanhee; Kim, JiEun; Kim, Do-Yeon; Lim, Hyunjung; Choue, Ryowon

    2016-01-01

    Recent trial results suggest that the consumption of a low glycemic index (GI) diet is beneficial in the prevention of high blood glucose levels. Identifying active hypoglycemic substances in ordinary foods could be a significant benefit to the management of blood glucose. It has been hypothesized that noodles with Bombyx mori powder are a low GI food. We evaluated GI and changes in postprandial glucose levels following consumption of those noodles and compared them with those following consumption of plain wheat flour noodles (control) and glucose (reference) in healthy subjects. Thirteen males (age: 34.2±4.5 years, body mass index: 23.2±1.1 kg/m2) consumed 75 g carbohydrate portions of glucose and the 2 kinds of noodle after an overnight fast. Capillary blood was measured at time 0 (fasting), 15, 30, 45, 60, 90, 120, and 180 min from the start of each food intake. The GI values were calculated by taking the ratio of the incremental area under the blood glucose response curve (IAUC) for the noodles and glucose. There was a significant difference in postprandial glucose concentrations at 30 and 45 min between the control noodles and the noodles with Bombyx mori powder: the IAUC and GI for the noodles with Bombyx mori powder were significantly lower than those for glucose and plain wheat flour noodles. The wheat flour noodles with Bombyx mori powder could help prevent an increase in postprandial glucose response and possibly provide an alternative to other carbohydrate staple foods for glycemic management. PMID:27752491

  9. Tafenoquine at therapeutic concentrations does not prolong fridericia-corrected QT interval in healthy subjects

    PubMed Central

    Green, Justin A; Patel, Apurva K; Patel, Bela R; Hussaini, Azra; Harrell, Emma J; McDonald, Mirna J; Carter, Nick; Mohamed, Khadeeja; Duparc, Stephan; Miller, Ann K

    2014-01-01

    Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18–65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine–QTcF concentration–effect relationship demonstrated a shallow slope (0.5 ms/μg mL–1) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization. PMID:24700490

  10. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    PubMed

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

  11. Penetration of Ceftaroline into the Epithelial Lining Fluid of Healthy Adult Subjects

    PubMed Central

    Pushkin, Richard; Jandourek, Alena; Knebel, William; Khariton, Tatiana

    2016-01-01

    Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to (i) evaluate ceftaroline concentrations in human plasma and epithelial lining fluid (ELF) and (ii) develop a population pharmacokinetic (PK) model for plasma and ELF to be used in PK/pharmacodynamic (PD) target attainment simulations. Ceftaroline concentrations in ELF and plasma at steady state (day 4) were measured in healthy adult subjects for two dosages: 600 mg every 12 h (q12h) and 600 mg every 8 h (q8h). Both were well tolerated with no serious adverse events. The penetration of free ceftaroline into ELF, assuming 20% protein binding in plasma and no protein binding in ELF, was ≈23%. The population PK model utilized a two-compartment model for both ceftaroline fosamil and ceftaroline. Goodness-of-fit criteria revealed the model was consistent with observed data and no systematic bias remained. At 600 mg q12h and a MIC of 1 mg/liter, 98.1% of simulated patients would be expected to achieve a target free drug concentration above the MIC (fT>MIC) in plasma of 42%, and in ELF 81.7% would be expected to achieve a target fT>MIC of 17%; at 600 mg q8h, 100% were predicted to achieve an fT>MIC in plasma of 42% and 94.7% to achieve an fT>MIC of 17% in ELF. The literature and data suggest the 600 mg q12h dose is adequate for MICs of ≤1 mg/liter. There is a need for clinical data in patients with MRSA pneumonia and data to correlate PK/PD relationships in ELF with clinical outcomes. PMID:27431215

  12. Penetration of Ceftaroline into the Epithelial Lining Fluid of Healthy Adult Subjects.

    PubMed

    Riccobene, Todd A; Pushkin, Richard; Jandourek, Alena; Knebel, William; Khariton, Tatiana

    2016-10-01

    Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to (i) evaluate ceftaroline concentrations in human plasma and epithelial lining fluid (ELF) and (ii) develop a population pharmacokinetic (PK) model for plasma and ELF to be used in PK/pharmacodynamic (PD) target attainment simulations. Ceftaroline concentrations in ELF and plasma at steady state (day 4) were measured in healthy adult subjects for two dosages: 600 mg every 12 h (q12h) and 600 mg every 8 h (q8h). Both were well tolerated with no serious adverse events. The penetration of free ceftaroline into ELF, assuming 20% protein binding in plasma and no protein binding in ELF, was ≈23%. The population PK model utilized a two-compartment model for both ceftaroline fosamil and ceftaroline. Goodness-of-fit criteria revealed the model was consistent with observed data and no systematic bias remained. At 600 mg q12h and a MIC of 1 mg/liter, 98.1% of simulated patients would be expected to achieve a target free drug concentration above the MIC (fT>MIC) in plasma of 42%, and in ELF 81.7% would be expected to achieve a target fT>MIC of 17%; at 600 mg q8h, 100% were predicted to achieve an fT>MIC in plasma of 42% and 94.7% to achieve an fT>MIC of 17% in ELF. The literature and data suggest the 600 mg q12h dose is adequate for MICs of ≤1 mg/liter. There is a need for clinical data in patients with MRSA pneumonia and data to correlate PK/PD relationships in ELF with clinical outcomes.

  13. Effects of grapefruit juice on cortisol metabolism in healthy male Chinese subjects.

    PubMed

    Xiao, Ya-Jie; Hu, Miao; Tomlinson, Brian

    2014-12-01

    Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β-OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200, 400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and following GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from 0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P <0.05) and the ratio of cortisol to cortisone (P <0.005) and reducing 6β-OHC excretion (P <0.05) and the ratio of 6β-OHC to cortisol (P <0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ significantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism although a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.

  14. Acute Effects of Modafinil on Brain Resting State Networks in Young Healthy Subjects

    PubMed Central

    Pieramico, Valentina; Ferretti, Antonio; Macchia, Antonella; Tommasi, Marco; Saggino, Aristide; Ciavardelli, Domenico; Manna, Antonietta; Navarra, Riccardo; Cieri, Filippo; Stuppia, Liborio; Tartaro, Armando; Sensi, Stefano L.

    2013-01-01

    Background There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. Methodology A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Principal Findings Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed. Conclusions and Significance Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. Trial Registration ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306. PMID:23935959

  15. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects.

    PubMed

    Pöyhiä, R; Seppälä, T; Olkkola, K T; Kalso, E

    1992-06-01

    1. The pharmacokinetics and metabolism of oxycodone were studied in nine healthy young volunteers in a cross-over study. Each subject received oxycodone chloride once intramuscularly (0.14 mg kg-1) and twice orally (0.28 mg kg-1) at intervals of 2 weeks. A double-blind randomized pretreatment with amitriptyline (10-50 mg a day) or placebo was given prior to oral oxycodone. 2. The concentrations of oxycodone, noroxycodone and oxymorphone in plasma and the 24 h urine recoveries of their conjugated and unconjugated forms were measured by gas chromatography. 3. No differences were found between treatments in mean Cmax and AUC values of oxycodone which varied from 34 to 38 ng ml-1 and from 208 to 245 ng ml-1 h, respectively. The median tmax of oxycodone was 1 h in all groups. The bioavailability of oral relative to i.m. oxycodone was 60%. The mean renal clearance of oxycodone was 0.07-0.08 l min-1. The kinetics of oxycodone were unaffected by amitriptyline. 4. The mean ratio of the AUC(0.24 h) values of unconjugated noroxycodone to oxycodone was 0.45 after i.m. oxycodone and 0.6-0.8 after oral oxycodone. Plasma oxymorphone concentrations were below the limit of the assay. Eight to 14% of the dose of oxycodone was excreted in the urine as unconjugated and conjugated oxycodone over 24 h. Oxymorphone was excreted mainly as a conjugate whereas noroxycodone was recovered mostly in an unconjugated form.

  16. The botanical integrity of wheat products influences the gastric distention and satiety in healthy subjects

    PubMed Central

    Hlebowicz, Joanna; Lindstedt, Sandra; Björgell, Ola; Höglund, Peter; Almér, Lars-Olof; Darwiche, Gassan

    2008-01-01

    Background Maintenance of the botanical integrity of cereal kernels and the addition of acetic acid (as vinegar) in the product or meal has been shown to lower the postprandial blood glucose and insulin response and to increase satiety. However, the mechanism behind the benefits of acetic acid on blood glucose and satiety is not clear. We hypothesized that the gastric emptying rate could be involved. Thus, the aim of this study was to evaluate the possible influence of maintained botanical integrity of cereals and the presence of acetic acid (vinegar) on gastric emptying rate (GER), postprandial blood glucose and satiety. Methods Fifteen healthy subjects were included in a blinded crossover trial, and thirteen of the subjects completed the study. Equicarbohydrate amounts of the following wheat-based meals were studied: white wheat bread, whole-kernel wheat bread or wholemeal wheat bread served with white wine vinegar. The results were compared with a reference meal consisting of white wheat bread without vinegar. The GER was measured with standardized real-time ultrasonography using normal fasting blood glucose <6.1 mmol/l or plasma glucose <7.0 mmol/l as an inclusion criterion. The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of the various meals. Satiety scores were estimated and blood glucose was measured before and 15, 30, 45, 60, 90 and 120 min after the start of the meal. Results The whole-kernel wheat bread with vinegar resulted in significantly higher (<0.05) satiety than the wholemeal wheat bread and white wheat bread with vinegar and the reference bread. Wheat fiber present in the wholemeal wheat bread, or the presence of wheat kernels per se, did not affect the postprandial blood glucose or GER significantly compared with white wheat bread, neither did the addition of vinegar to white bread affect these variables. There was no correlation found between the satiety with antral areas or

  17. Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects: A Crossover Study

    PubMed Central

    Lim, K. Sheng; Nau, Cherie B.; O’Byrne, Megan M.; Hodge, David O.; Toris, Carol B.; McLaren, Jay W.; Johnson, Douglas H.

    2009-01-01

    Purpose To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. Design Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). Participants Thirty healthy adult subjects. Methods Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. Main Outcome Measures Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. Results All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P≤0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. Conclusions Bimatoprost, latanoprost, and travoprost

  18. Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects

    PubMed Central

    Klumpers, Linda E; Fridberg, Marianne; de Kam, Marieke L; Little, Paul B; Jensen, Niels Ole; Kleinloog, Hendrik D; Elling, Christian E; van Gerven, Joop M A

    2013-01-01

    Aim Cannabinoid receptor type 1 (CB1) antagonists show central side effects, whereas beneficial effects are most likely peripherally mediated. In this study, the peripherally selective CB1 antagonist TM38837 was studied in humans. Methods This was a double-blind, randomized, placebo-controlled, crossover study. On occasions 1–4, 24 healthy subjects received 5 × 4 mg THC with TM38837 100 mg, 500 mg or placebo, or placebos only. During occasion 5, subjects received placebo TM38837 + THC with rimonabant 60 mg or placebo in parallel groups. Blood collections and pharmacodynamic (PD) effects were assessed frequently. Pharmacokinetics (PK) and PD were quantified using population PK−PD modelling. Results The TM38837 plasma concentration profile was relatively flat compared with rimonabant. TM38837 showed an estimated terminal half-life of 771 h. THC induced effects on VAS feeling high, body sway and heart rate were partly antagonized by rimonabant 60 mg [−26.70% [90% confidence interval (CI) −40.9, −12.6%]; −7.10%, (90%CI −18.1, 5.3%); −7.30%, (90% CI −11.5%, −3.0%) respectively] and TM38837 500 mg [−22.10% (90% CI −34.9, −9.4%); −12.20% (90% CI −21.6%, −1.7%); −8.90% (90% CI −12.8%, −5.1%) respectively]. TM38837 100 mg had no measurable feeling high or body sway effects and limited heart rate effects. Conclusions Rimonabant showed larger effects than TM38837, but the heart rate effects were similar. TM38837 100 mg had no impact on CNS effects, suggesting that this dose does not penetrate the brain. This TM38837 dose is predicted to be at least equipotent to rimonabant with regard to metabolic disorders in rodent models. These results provide support for further development of TM38837 as a peripherally selective CB1 antagonist for indications such as metabolic disorders, with a reduced propensity for psychiatric side effects. PMID:23601084

  19. Analysis of hand synergies in healthy subjects during bimanual manipulation of various objects

    PubMed Central

    2014-01-01

    Background Hand synergies have been extensively studied over the last few decades. Objectives of such research are numerous. In neuroscience, the aim is to improve the understanding of motor control and its ability to reduce the control dimensionality. In applied research fields like robotics the aim is to build biomimetic hand structures, or in prosthetics to design more performant underactuated replacement hands. Nevertheless, most of the synergy schemes identified to this day have been obtained from grasping experiments performed with one single (generally dominant) hand to objects placed in a given position and orientation in space. Aiming at identifying more generic synergies, we conducted similar experiments on postural synergy identification during bimanual manipulation of various objects in order to avoid the factors due to the extrinsic spatial position of the objects. Methods Ten healthy naive subjects were asked to perform a selected “grasp-give-receive” task with both hands using 9 objects. Subjects were wearing Cyberglove Ⓒ on both hands, allowing a measurement of the joint posture (15 degrees of freedom) of each hand. Postural synergies were then evaluated through Principal Component Analysis (PCA). Matches between the identified Principal Components and the human hand joints were analyzed thanks to the correlation matrix. Finally, statistical analysis was performed on the data in order to evaluate the effect of some specific variables on the hand synergies: object shape, hand side (i.e., laterality) and role (giving or receiving hand). Results Results on PCs are consistent with previous literature showing that a few principal components might be sufficient to describe a large variety of different grasps. Nevertheless some simple and strong correlations between PCs and clearly identified sets of hand joints were obtained in this study. In addition, these groupings of DoF corresponds to well-defined anatomo-functional finger joints according to

  20. Prevalence of temporomandibular disorder pain in Chinese adolescents compared to an age-matched Swedish population.

    PubMed

    Hongxing, L; Astrøm, A N; List, T; Nilsson, I-M; Johansson, A

    2016-04-01

    This study aimed to (i) assess the prevalence and perceived need for treatment of TMD pain, and its association with socio-economic factors and gender, in adolescents in Xi᾽an, Shaanxi Province, China, and (ii) compare the prevalence and association with gender of TMD pain in Xi᾽an to an age-matched Swedish population. We surveyed Chinese adolescents aged 15 to 19 years in Xi'an, China (n = 5524), using a questionnaire with two-stage stratified sampling and the school as the sampling unit. The study included second-year students at selected high schools. It also included an age-matched Swedish population (n = 17,015) surveyed using the same diagnostic criteria for TMD pain as that used in the Chinese sample. The survey found TMD pain in 14·8% (n = 817) of the Chinese sample and 5·1% (n = 871) of the Swedish sample (P < 0·0001). Girls had significantly more TMD pain than boys in both the Chinese (P < 0·05) and Swedish (P < 0·001) samples. TMD pain increased with age in the Chinese population. Of the Chinese adolescents with TMD pain, 47% reported that they felt a need for treatment. Rural schools, low paternal education levels, poverty, living outside the home, poor general and oral health, and dissatisfaction with teeth all showed significant positive correlations with TMD pain. Prevalence of TMD pain in Chinese adolescents was significantly higher than in the Swedish sample.

  1. A proteomic study of protein variation between osteopenic and age-matched control bone tissue.

    PubMed

    Chaput, Christopher D; Dangott, Lawrence J; Rahm, Mark D; Hitt, Kirby D; Stewart, Donald S; Wayne Sampson, H

    2012-05-01

    The focus of this study was to identify changes in protein expression within the bone tissue environment between osteopenic and control bone tissue of human femoral neck patients with osteoarthritis. Femoral necks were compared from osteopenic patients and age-matched controls. A new method of bone protein extraction was developed to provide a swift, clear view of the bone proteome. Relative changes in protein expression between control and osteopenic samples were quantified using difference gel electrophoresis (DIGE) technology after affinity chromatographic depletion of albumin and IgG. The proteins that were determined to be differentially expressed were identified using standard liquid chromatography mass spectrometry (LC/MS/MS) and database searching techniques. In order to rule out blood contamination, blood from age-matched osteoporotic, osteopenic and controls were analyzed in a similar manner. Image analysis of the DIGE gels indicated that 145 spots in the osteopenic bone samples changed at least ± 1.5-fold from the control samples (P < 0.05). Three of the proteins were identified by LC/MS/MS. Of the proteins that increased in the osteopenic femurs, two were especially significant: carbonic anhydrase I and phosphoglycerate kinase 1. Apolipoprotein A-I was the most prominent protein that significantly decreased in the osteopenic femurs. The blood samples revealed no significant differences between groups for any of these proteins. In conclusion, carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis.

  2. Comparison of intraduodenal and intravenous administration of amino acids on gastric secretion in healthy subjects and patients with duodenal ulcer.

    PubMed Central

    Konturek, S J; Kwiecień, N; Obtułowicz, W; Mikoś, E; Sito, E; Oleksy, J

    1978-01-01

    The ability of an amino acid mixture given intraduodenally or intravenously to stimulate gastric secretion is compared in healthy subjects and in duodenal ulcer patients. Graded amounts of amino acids by both routes produced a similar increase in acid output in healthy subjects, reaching about 30% of the maximal response to pentagastrin. Serum gastrin concentrations remained virtually unchanged but serum alpha amino acid nitrogen levels were about twice as high with intravenous as with intraduodenal administration. Intravenously administered amino acids produced a significantly higher acid output in patients with duodenal ulcer than in healthy subjects, but did not produce a significant increase in gastric acid or pepsin secretion when combined with a pentagastrin infusion as compared with pentagastrin alone. Cimetidine (2 mg/kg/h) added to intravenous amino acid infusions caused almost complete suppression of acid secretion. This study indicates that amino acids are capable of stimulating gastric secretion after intraduodenal and after intravenous administration. The response to the latter is significantly higher in patients with duodenal ulcer than in healthy subjects, does not appear to involve gastrin release, is not affected by pentagastrin, and is strongly suppressed by histamine H2-blocker. PMID:361509

  3. Differences in performance on the functional movement screen between chronic low back pain patients and healthy control subjects

    PubMed Central

    Ko, Min-Joo; Noh, Kyung-Hee; Kang, Min-Hyeok; Oh, Jae-Seop

    2016-01-01

    [Purpose] Differences in scores on the Functional Movement Screen between patients with chronic lower back pain and healthy control subjects were investigated. [Subjects and Methods] In all, 20 chronic lower back pain patients and 20 healthy control subjects were recruited. Chronic lower back pain patients and healthy controls performed the Functional Movement Screen (deep squat, hurdle step, inline lunge, shoulder mobility, active straight leg raise, trunk stability pushup, and rotary stability). The Mann-Whitney test was used to analyze differences in Functional Movement Screen scores between the two groups. [Results] Chronic lower back pain patients scored lower on the Functional Movement Screen total composite compared with healthy control subjects. Chronic lower back pain patients scored lower on Functional Movement Screen subtests including the deep squat, hurdle step, active straight leg raise, and rotary stability tests. [Conclusion] The deep squat, hurdle step, active straight leg raise, and rotary stability tasks of the Functional Movement Screen can be recommended as a functional assessment tools to identify functional deficits in chronic lower back pain patients. PMID:27512272

  4. Health effects of acute exposure to air polllution. Part II: Healthy subjects exposed to cencentrated ambient particles

    EPA Science Inventory

    The purpose of this study was to assess the impact of short-term exposure to concentrated ambient particles (CAPs*) on lung function and on inflammatory parameters in blood and airways of healthy human subjects. Particles were concentrated from the ambient air in Chapel Hill, Nor...

  5. Differences in performance on the functional movement screen between chronic low back pain patients and healthy control subjects.

    PubMed

    Ko, Min-Joo; Noh, Kyung-Hee; Kang, Min-Hyeok; Oh, Jae-Seop

    2016-07-01

    [Purpose] Differences in scores on the Functional Movement Screen between patients with chronic lower back pain and healthy control subjects were investigated. [Subjects and Methods] In all, 20 chronic lower back pain patients and 20 healthy control subjects were recruited. Chronic lower back pain patients and healthy controls performed the Functional Movement Screen (deep squat, hurdle step, inline lunge, shoulder mobility, active straight leg raise, trunk stability pushup, and rotary stability). The Mann-Whitney test was used to analyze differences in Functional Movement Screen scores between the two groups. [Results] Chronic lower back pain patients scored lower on the Functional Movement Screen total composite compared with healthy control subjects. Chronic lower back pain patients scored lower on Functional Movement Screen subtests including the deep squat, hurdle step, active straight leg raise, and rotary stability tests. [Conclusion] The deep squat, hurdle step, active straight leg raise, and rotary stability tasks of the Functional Movement Screen can be recommended as a functional assessment tools to identify functional deficits in chronic lower back pain patients.

  6. Alertness in Young Healthy Subjects: An fMRI Study of Brain Region Interactivity Enhanced by a Warning Signal

    ERIC Educational Resources Information Center

    Perin, B.; Godefroy, O.; Fall, S.; de Marco, G.

    2010-01-01

    An effective connectivity study was carried out on 16 young, healthy subjects performing an alertness task. The objective of this study was to develop and to evaluate a putative network model of alertness by adapting structural equation modeling to fMRI data. This study was designed to evaluate the directed interactivity of an attentional network…

  7. Effect of traditional Arabic coffee consumption on the glycemic index of Khalas dates tested in healthy and diabetic subjects.

    PubMed

    Alkaabi, Juma; Al-Dabbagh, Bayan; Saadi, Hussein; Gariballa, Salah; Yasin, Javed

    2013-01-01

    The consumption of dates with coffee is common among Arabs and may affect postprandial hyperglycemia ex-cursion. The study aimed to determine the effect of coffee on the glycemic index of a common variety of dates (Khalas) tested in healthy and type 2 diabetes mellitus individuals. Study subjects were thirteen healthy volunteers (mean age: 40.2±6.7 years) and ten diabetic participants with a mean HbA1c of 6.6±(0.7%) and a mean age of 40.8±5.7 years. Each subject participated in five days of tests with 50 g of glucose and 50 g equivalent of available carbohydrates from the dates (with/without coffee). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min, and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. Glycemic indices were determined as ratios of the incremental areas under the response curves for the interventions. Statistical analyses were performed using the independent samples and paired t-tests. Mean±SE glycemic indices of the Khalas dates for the healthy individuals were 55.1±7.7 and 52.7±6.2 without and with coffee consumption, respectively. Similar values were observed for those with diabetes (53.0±6.0 and 41.5±5.4). Differences between glycemic indices of Khalas with or without coffee were not significant (p=0.124). There were no significant differences in glycemic index between the diabetic and healthy subjects (p=0.834 and p=0.202 without and with coffee respectively). In conclusion, at least in the short term, coffee does not adversely affect capillary glucose levels following Khalas dates consumption in healthy and diabetic volunteers.

  8. A genome-wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects.

    PubMed

    Raum, Heidelore; Dietsche, Bruno; Nagels, Arne; Witt, Stephanie H; Rietschel, Marcella; Kircher, Tilo; Krug, Axel

    2015-01-01

    The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the NCAN gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. NCAN encodes neurocan, a brain-specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of NCAN on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the NCAN SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that NCAN risk status, defined as AA or AG genotype, was associated with a lack of task-related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal pole. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in NCAN influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function.

  9. Inter- and Intra-individual Variability in the Pharmacokinetics of Agomelatine Tablets in Chinese Healthy Male Subjects.

    PubMed

    Wang, X-l; Du, A-h; Zhang, D; Meng, L-j; Liu, M; Zhang, L-n; Zhao, H-n; Liu, H-c

    2015-10-01

    Agomelatine is an antidepressant with a unique action mechanism differing from conventional antidepressants. The high inter- and intra-individual variability of agomelatine was previously reported, but no exact data values about the inter- and intra-individual variability in AUC and Cmax were mentioned. The current study aimed to determine and evaluate the inter- and intra-individual variability in AUC and Cmax of agomelatine tablets in Chinese healthy male subjects, providing useful information for designing bioequivalence studies of agomelatine. Each of 12 Chinese healthy male subjects received a 25-mg agomelatine tablet on 2 separate periods, and plasma samples were collected up to 24 h after dose and analyzed for agomelatine. Inter- and intra-individual variability in the pharmacokinetic parameters (Cmax, AUC0-t and AUC0-∞) of agomelatine was assessed. High variations in the plasma concentrations of agomelatine could be observed at each sampling time between the different subjects and in one subject on different periods. The inter-individual CVs of Cmax, AUC0-t and AUC0-∞ were 102.20%, 131.74% and 130.59%, respectively. The intra-individual CVs of Cmax, AUC0-t and AUC0-∞ were 84.34%, 49.61% and 50.83%, respectively. The results showed high inter- and intra-individual variability in the pharmacokinetics of agomelatine in Chinese healthy male subjects, and the intra-individual variability at CV>80% should be considered in the design of bioequivalence studies.

  10. Activity of neutrophil β-glucuronidase in diabetic and nondiabetic patients with chronic generalized periodontitis and healthy subjects.

    PubMed

    Surna, Algimantas; Sakalauskienė, Jurgina; Gleiznys, Alvydas; Ivanauskienė, Eglė; Saferis, Viktoras

    2011-01-01

    OBJECTIVE. The aim of the study was to establish the dynamics of β-glucuronidase activity in subjects suffering from type 1 diabetes and chronic untreated generalized periodontitis, subjects suffering from chronic untreated generalized periodontitis only, and control subjects not suffering from generic diseases with healthy periodontal tissue. MATERIAL AND METHODS. The study involved 165 19-50-year-old subjects who were divided into three groups: healthy subjects (n=55), subjects with chronic untreated generalized periodontitis (n=55), and subjects with type 1 diabetes and chronic untreated generalized periodontitis (n=55). Neutrophilic leukocytes of peripheral venous blood were exposed to bacterial stimuli: opsonized zymosan, nonopsonized Staphylococcus aureus, and prodigiosan. The activity of β-glucuronidase was determined by the spectrofluorimetry method. RESULTS. The diagnostic value of changes in β-glucuronidase activity of neutrophilic leukocytes markedly increased in all study groups after stimulation of neutrophilic leukocytes by opsonized zymosan, nonopsonized Staphylococcus aureus, and prodigiosan as compared to control media not exposed to any stimulus (P<0.001). The strongest relationship (canonical correlation coefficient eta, 0.993) between the intensity of periodontal pathology markers and the activity of β-glucuronidase of neutrophilic leukocytes in incubated media in patients with type 1 diabetes mellitus and periodontitis was found under the effect of nonopsonized Staphylococcus aureus. CONCLUSIONS. If periodontal impairment is severe, diabetes mellitus possibly causes a faster destruction of the periodontal tissue and presents a higher risk of periodontitis for patients with diabetes.

  11. Comparison of Brachial Artery Vasoreactivity in Elite Power Athletes and Age-Matched Controls

    PubMed Central

    Welsch, Michael A.; Blalock, Paul; Credeur, Daniel P.; Parish, Tracie R.

    2013-01-01

    Elite endurance athletes typically have larger arteries contributing to greater skeletal muscle blood flow, oxygen and nutrient delivery and improved physical performance. Few studies have examined structural and functional properties of arteries in power athletes. Purpose To compare the size and vasoreactivity of the brachial artery of elite power athletes to age-matched controls. It was hypothesized brachial artery diameters of athletes would be larger, have less vasodilation in response to cuff occlusion, but more constriction after a cold pressor test than age-matched controls. Methods Eight elite power athletes (age = 23±2 years) and ten controls (age = 22±1 yrs) were studied. High-resolution ultrasonography was used to assess brachial artery diameters at rest and following 5 minutes of forearm occlusion (Brachial Artery Flow Mediated Dilation = BAFMD) and a cold pressor test (CPT). Basic fitness measures included a handgrip test and 3-minute step test. Results Brachial arteries of athletes were larger (Athletes 5.39±1.51 vs. Controls: 3.73±0.71 mm, p<0.05), had greater vasodilatory (BAFMD%: Athletes: 8.21±1.78 vs. Controls: 5.69±1.56%) and constrictor (CPT %: Athletes: -2.95±1.07 vs. Controls: −1.20±0.48%) responses, compared to controls. Vascular operating range (VOR = Peak dilation+Peak Constriction) was also greater in athletes (VOR: Athletes: 0.55±0.15 vs. Controls: 0.25±0.18 mm, p<0.05). Athletes had superior handgrip strength (Athletes: 55.92±17.06 vs. Controls: 36.77±17.06 kg, p<0.05) but similar heart rate responses at peak (Athletes: 123±16 vs. Controls: 130±25 bpm, p>0.05) and 1 minute recovery (Athletes: 88±21 vs. Controls: 98±26 bpm, p>0.05) following the step test. Conclusion Elite power athletes have larger brachial arteries, and greater vasoreactivity (greater vasodilatory and constrictor responses) than age-matched controls, contributing to a significantly greater VOR. These data extend the existence of an

  12. Effects of Administration of Fostamatinib on Blood Concentrations of an Oral Contraceptive in Healthy Female Subjects

    ClinicalTrials.gov

    2012-02-17

    Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction; Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction

  13. Corneal endothelial cell analysis using two non-contact specular microscopes in healthy subjects.

    PubMed

    Garza-Leon, Manuel

    2016-08-01

    To compare specular microscopy values obtained using the Perseus (CSO, Italy) and the Nidek CEM-530 (NIDEK Co., Ltd. Japan) specular microscopes. This prospective study used specular microscopy to examine sixty eyes from thirty healthy subjects (29.83 ± 9.41 years; range 18-79 years). This was done with both the Nidek CEM-530 and the Perseus on three occasions and results were evaluated by one independent observer. Measurement differences between instruments and agreement between devices were determined. The endothelial cell sample was larger with the Perseus than with the CEM-530 (235.92 ± 38.26 vs. 184.38 ± 43.88, respectively) with a statistically significant difference (P = 0.001). Mean endothelial cell density (ECD) with the Perseus and CEM-530 was 2692.75 ± 306.66 and 2556.47 ± 257.38 cells/mm(2) (P = 0.001), respectively; mean coefficient of variation (CV) was 33.43 ± 4.29 and 28.70 ± 3.82 (P = 0.001), respectively, and hexagonality 56.66 ± 6.19 % and 68.50 ± 3.64 (P = 0.001), respectively. The mean of the differences (Perseus minus CEM-530) for ECD was 136.27 ± 106.16 cells/mm(2) (95 % CI 108.85-163.70 cells/mm(2)); 4.73 ± 2.70 % (95 % CI 4.03-5.41) in CV; and -11.83 ± 5.05 for percentage of hexagonal cells. Both instruments showed significant differences in the measurement of all cell forms, predominantly higher values were found with the Perseus vs the CEM-530, except 4-sided cells. Endothelial cell density, coefficient of variation, and percentage of hexagonal cells between the Perseus and CEM-530 differ statistically. This shows that these instruments should not be used interchangeably.

  14. Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects

    PubMed Central

    Mohamed, Khadeeja; Goyal, Navin; Bouhired, Samia; Hussaini, Azra; Jones, Siôn W.; Koh, Gavin C. K. W.; Kostov, Ivan; Taylor, Maxine; Wolstenholm, Allen; Duparc, Stephan

    2016-01-01

    Tafenoquine is in development as a single-dose treatment for relapse prevention in individuals with Plasmodium vivax malaria. Tafenoquine must be coadministered with a blood schizonticide, either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine and artemether-lumefantrine. Healthy volunteers of either sex aged 18 to 65 years without glucose-6-phosphate dehydrogenase deficiency were randomized into five cohorts (n = 24 per cohort) to receive tafenoquine on day 1 (300 mg) plus once-daily dihydroartemisinin-piperaquine on days 1, 2, and 3 (120 mg/960 mg for 36 to <75 kg of body weight and 160 mg/1,280 mg for ≥75 to 100 kg of body weight), or plus artemether-lumefantrine (80 mg/480 mg) in two doses 8 h apart on day 1 and then twice daily on days 2 and 3, or each drug alone. The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined by using noncompartmental methods. Point estimates and 90% confidence intervals were calculated for area under the concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) comparisons of tafenoquine plus ACT versus tafenoquine or ACT. All subjects receiving dihydroartemisinin-piperaquine experienced QTc prolongation (a known risk with this drug), but tafenoquine coadministration had no clinically relevant additional effect. Tafenoquine coadministration had no clinically relevant effects on dihydroartemisinin, piperaquine, artemether, or lumefantrine pharmacokinetics. Dihydroartemisinin-piperaquine coadministration increased the tafenoquine Cmax by 38% (90% confidence interval, 25 to 52%), the AUC from time zero to infinity (AUC0–∞) by 12% (1 to 26%), and the half-life (t1/2) by 29% (19 to 40%), with no effect on the AUC from time zero to the time of the last nonzero concentration (AUC0

  15. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects

    PubMed Central

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K.; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T.; Sameshima, Yoshihiro

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m2) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration

  16. Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects

    SciTech Connect

    Takahashi, Kei; Yokota, Shin-ichi; Tatsumi, Naoyuki; Fukami, Tatsuki; Yokoi, Tsuyoshi; Nakajima, Miki

    2013-10-01

    Circulating microRNAs (miRNAs) are receiving attention as potential biomarkers of various diseases, including cancers, chronic obstructive pulmonary disease, and cardiovascular disease. However, it is unknown whether the levels of circulating miRNAs in a healthy subject might vary with external factors in daily life. In this study, we investigated whether cigarette smoking, a habit that has spread throughout the world and is a risk factor for various diseases, affects plasma miRNA profiles. We determined the profiles of 11 smokers and 7 non-smokers by TaqMan MicroRNA array analysis. A larger number of miRNAs were detected in smokers than in non-smokers, and the plasma levels of two-thirds of the detected miRNAs (43 miRNAs) were significantly higher in smokers than in non-smokers. A principal component analysis of the plasma miRNA profiles clearly separated smokers and non-smokers. Twenty-four of the miRNAs were previously reported to be potential biomarkers of disease, suggesting the possibility that smoking status might interfere with the diagnosis of disease. Interestingly, we found that quitting smoking altered the plasma miRNA profiles to resemble those of non-smokers. These results suggested that the differences in the plasma miRNA profiles between smokers and non-smokers could be attributed to cigarette smoking. In addition, we found that an acute exposure of ex-smokers to cigarette smoke (smoking one cigarette) did not cause a dramatic change in the plasma miRNA profile. In conclusion, we found that repeated cigarette smoking substantially alters the plasma miRNA profile, interfering with the diagnosis of disease or signaling potential smoking-related diseases. - Highlights: • Plasma miRNA profiles were unambiguously different between smokers and non-smokers. • Smoking status might interfere with the diagnosis of disease using plasma miRNAs. • Changes of plasma miRNA profiles may be a signal of smoking-related diseases.

  17. Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects.

    PubMed

    Green, Justin A; Mohamed, Khadeeja; Goyal, Navin; Bouhired, Samia; Hussaini, Azra; Jones, Siôn W; Koh, Gavin C K W; Kostov, Ivan; Taylor, Maxine; Wolstenholm, Allen; Duparc, Stephan

    2016-12-01

    Tafenoquine is in development as a single-dose treatment for relapse prevention in individuals with Plasmodium vivax malaria. Tafenoquine must be coadministered with a blood schizonticide, either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine and artemether-lumefantrine. Healthy volunteers of either sex aged 18 to 65 years without glucose-6-phosphate dehydrogenase deficiency were randomized into five cohorts (n = 24 per cohort) to receive tafenoquine on day 1 (300 mg) plus once-daily dihydroartemisinin-piperaquine on days 1, 2, and 3 (120 mg/960 mg for 36 to <75 kg of body weight and 160 mg/1,280 mg for ≥75 to 100 kg of body weight), or plus artemether-lumefantrine (80 mg/480 mg) in two doses 8 h apart on day 1 and then twice daily on days 2 and 3, or each drug alone. The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined by using noncompartmental methods. Point estimates and 90% confidence intervals were calculated for area under the concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) comparisons of tafenoquine plus ACT versus tafenoquine or ACT. All subjects receiving dihydroartemisinin-piperaquine experienced QTc prolongation (a known risk with this drug), but tafenoquine coadministration had no clinically relevant additional effect. Tafenoquine coadministration had no clinically relevant effects on dihydroartemisinin, piperaquine, artemether, or lumefantrine pharmacokinetics. Dihydroartemisinin-piperaquine coadministration increased the tafenoquine Cmax by 38% (90% confidence interval, 25 to 52%), the AUC from time zero to infinity (AUC0-∞) by 12% (1 to 26%), and the half-life (t1/2) by 29% (19 to 40%), with no effect on the AUC from time zero to the time of the last nonzero concentration (AUC0

  18. Gait in male trans-tibial amputees: a comparative study with healthy subjects in relation to walking speed.

    PubMed

    Hermodsson, Y; Ekdahl, C; Persson, B M; Roxendal, G

    1994-08-01

    Walking speed, stance duration and ground reaction forces were studied with the use of a stable force platform (Kistler) in 24 male transtibial amputees and 12 healthy subjects matched for sex and age. The aim of the study was to compare the gait performance of two groups with unilateral trans-tibial amputations for either vascular disease or trauma and also to compare the results of the two groups with the results of a group of healthy subjects. Multiple linear regression analysis was used to compare the stance duration and the ground reaction forces in relation to walking speed. The vascular and traumatic amputees had significantly reduced walking speeds compared with the healthy subjects, 0.85 +/- 0.2 m/s and 0.99 +/- 0.2 m/s. respectively, as compared to 1.42 +/- 0.2 m/s. By comparing the vascular and traumatic amputees with the healthy subjects in relation to walking speed, it was shown that the gait performance of the vascular amputee differed from that of the traumatic amputee, a difference that was not caused by the reduced walking speed. The active forces during push off on both the healthy (p = 0.02) and the prosthetic leg (p = 0.003) in the trauma group were not found in the vascular group. This disparity could be an effect of the systemic disease. It may be argued that the results of this study contribute to the understanding of the reduced walking ability of the vascular amputee and should be borne in mind when planning rehabilitation.

  19. Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients

    PubMed Central

    Arita, Reiko; Morishige, Naoyuki; Sakamoto, Ichiro; Imai, Natsuko; Shimada, Yuko; Igaki, Michihito; Suzuki, Atsushi; Itoh, Kouzo; Tsubota, Kazuo

    2017-01-01

    Menthol is thought to stimulate lacrimation via activation of cold-sensitive primary afferent neurons in the cornea. We evaluated a warm compress containing menthol as a potential treatment for dry eye by examining its effects on the tear film in healthy subjects (n = 20) and dry eye patients (n = 35). Disposable eyelid-warming steamers that either did (MH) or did not (HO) contain menthol were applied to one eye of each subject either once only for 10 min or repeatedly over 2 weeks. Single application of MH significantly increased tear meniscus volume (P = 8.6 × 10−5, P = 1.3 × 10−5) and tear film breakup time (P = 0.006, P = 0.002) as well as improved meibum condition in healthy subjects and dry eye patients, respectively. Repeated application of MH significantly increased tear meniscus volume (P = 0.004, P = 1.7 × 10−4) and tear film breakup time (P = 0.037, P = 0.010) in healthy subjects and dry eye patients, respectively. Repeated application of MH thus induced persistent increases in tear fluid volume and tear film stability in dry eye patients, suggesting that repeated use of a warm compress containing menthol is a potential novel treatment for dry eye disease. PMID:28378793

  20. Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients.

    PubMed

    Arita, Reiko; Morishige, Naoyuki; Sakamoto, Ichiro; Imai, Natsuko; Shimada, Yuko; Igaki, Michihito; Suzuki, Atsushi; Itoh, Kouzo; Tsubota, Kazuo

    2017-04-05

    Menthol is thought to stimulate lacrimation via activation of cold-sensitive primary afferent neurons in the cornea. We evaluated a warm compress containing menthol as a potential treatment for dry eye by examining its effects on the tear film in healthy subjects (n = 20) and dry eye patients (n = 35). Disposable eyelid-warming steamers that either did (MH) or did not (HO) contain menthol were applied to one eye of each subject either once only for 10 min or repeatedly over 2 weeks. Single application of MH significantly increased tear meniscus volume (P = 8.6 × 10(-5), P = 1.3 × 10(-5)) and tear film breakup time (P = 0.006, P = 0.002) as well as improved meibum condition in healthy subjects and dry eye patients, respectively. Repeated application of MH significantly increased tear meniscus volume (P = 0.004, P = 1.7 × 10(-4)) and tear film breakup time (P = 0.037, P = 0.010) in healthy subjects and dry eye patients, respectively. Repeated application of MH thus induced persistent increases in tear fluid volume and tear film stability in dry eye patients, suggesting that repeated use of a warm compress containing menthol is a potential novel treatment for dry eye disease.

  1. Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy young and elderly subjects: comparison with elderly rheumatic patients.

    PubMed Central

    Taylor, I W; Chasseaud, L F; Taylor, T; James, I; Dorf, G; Darragh, A

    1991-01-01

    The pharmacokinetics of ximoprofen were studied in young and elderly subjects after single and repeated doses up to 30 mg. In healthy elderly subjects (30 mg dose), a mean peak plasma drug concentration of 1.78 micrograms ml-1 +/- 0.83 s.d. occurred at a mean time of 1.95 h +/- 1.40 s.d. and, thereafter, concentrations declined monoexponentially with a mean half-life of 3.8 h +/- 1.4 s.d. Comparison of these data with those from younger healthy subjects showed that peak drug concentrations, areas under the curve and half-lives were about two-fold greater in the elderly, these differences probably reflecting a lower systemic drug clearance. Similar results were obtained on comparing data from young healthy subjects and elderly rheumatic patients receiving single and repeated doses of ximoprofen (15 mg twice daily). In patients, the half-life of ximoprofen was 2.5 h +/- 0.7 s.d. Within either group, pharmacokinetic parameters after single or repeated doses were similar: ximoprofen did not accumulate in the plasma of the young or elderly. PMID:1931475

  2. Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

    PubMed Central

    Piccirillo, Gianfranco; Ottaviani, Cristina; Fiorucci, Claudia; Petrocchi, Nicola; Moscucci, Federica; Di Iorio, Claudia; Mastropietri, Fabiola; Parrotta, Ilaria; Pascucci, Matteo; Magrì, Damiano

    2016-01-01

    Background Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05). Conclusion In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity. PMID:27895475

  3. Sleep deprivation disturbed regional brain activity in healthy subjects: evidence from a functional magnetic resonance-imaging study

    PubMed Central

    Wang, Li; Chen, Yin; Yao, Ying; Pan, Yu; Sun, Yi

    2016-01-01

    Objective The aim of this study was to use amplitude of low-frequency fluctuation (ALFF) to explore regional brain activities in healthy subjects after sleep deprivation (SD). Materials and methods A total of 16 healthy subjects (eight females, eight males) underwent the session twice: once was after normal sleep (NS), and the other was after SD. ALFF was used to assess local brain features. The mean ALFF-signal values of the different brain areas were evaluated to investigate relationships with clinical features and were analyzed with a receiver-operating characteristic curve. Results Compared with NS subjects, SD subjects showed a lower response-accuracy rate, longer response time, and higher lapse rate. Compared with NS subjects, SD subjects showed higher ALFF area in the right cuneus and lower ALFF area in the right lentiform nucleus, right claustrum, left dorsolateral prefrontal cortex, and left inferior parietal cortex. ALFF differences in regional brain areas showed high sensitivity and specificity. In the SD group, mean ALFF of the right claustrum showed a significant positive correlation with accuracy rate (r=0.687, P=0.013) and a negative correlation with lapse rate (r=−0.706, P=0.01). Mean ALFF of the dorsolateral prefrontal cortex showed a significant positive correlation with response time (r=0.675, P=0.016). Conclusion SD disturbed the regional brain activity of the default-mode network, its anticorrelated “task-positive” network, and the advanced cognitive function brain areas. PMID:27110113

  4. Cognitive Reserve in Young and Old Healthy Subjects: Differences and Similarities in a Testing-the-Limits Paradigm with DSST

    PubMed Central

    Zihl, Josef; Fink, Thomas; Pargent, Florian; Ziegler, Matthias; Bühner, Markus

    2014-01-01

    Cognitive reserve (CR) is understood as capacity to cope with challenging conditions, e.g. after brain injury or in states of brain dysfunction, or age-related cognitive decline. CR in elderly subjects has attracted much research interest, but differences between healthy older and younger subjects have not been addressed in detail hitherto. Usually, one-time standard individual assessments are used to characterise CR. Here we observe CR as individual improvement in cognitive performance (gain) in a complex testing-the-limits paradigm, the digit symbol substitution test (DSST), with 10 repeated measurements, in 140 younger (20–30 yrs) and 140 older (57–74 yrs) healthy subjects. In addition, we assessed attention, memory and executive function, and mood and personality traits as potential influence factors for CR. We found that both, younger and older subjects showed significant gains, which were significantly correlated with speed of information processing, verbal short-term memory and visual problem solving in the older group only. Gender, personality traits and mood did not significantly influence gains in either group. Surprisingly about half of the older subjects performed at the level of the younger group, suggesting that interindividual differences in CR are possibly age-independent. We propose that these findings may also be understood as indication that one-time standard individual measurements do not allow assessment of CR, and that the use of DSST in a testing-the-limits paradigm is a valuable assessment method for CR in young and elderly subjects. PMID:24404176

  5. [Application of transcranial magnetic stimulation for monitoring of the motor cortex condition in dynamics in healthy subjects].

    PubMed

    Gimranov, R F

    2002-01-01

    Transcranial magnetic stimulation (TMS) is used already for sixteen years for studying human central nervous system. The main objective of this work was to study motor thresholds and their hemispheric asymmetry in healthy subjects during TMS. We examined 31 righthanded healthy students. Their motor thresholds were measured in May (before vacations), September (immediately after vacations), and November (two months after vacations). Magnetic stimulator Neurosoft-MS (Ivanovo, Russia) was used for TNS of the motor cortex. It was shown that in the absence of regular active functional loads on the right hand, the motor thresholds in healthy righthanders significantly increased under the TMS of the left hemisphere, and hemispheric asymmetry disappeared under conditions both of muscle relaxation and voluntary contraction. Motor thresholds under the left-side TMS decreased and hemispheric asymmetry recovered with the restart of the regular active functional loads on the right hand.

  6. A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging

    PubMed Central

    Park, Ju-Yeon; Yun, Won-Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Heejin; Kwak, Ki-Chang; Lee, Jong-Min; Han, Seol-Heui

    2016-01-01

    Objective Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. Materials and Methods This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. Results A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). Conclusion The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases. PMID:27587951

  7. Comparison between elemental composition of human fingernails of healthy and opium-addicted subjects by laser-induced breakdown spectroscopy.

    PubMed

    Shadman, S; Bahreini, M; Tavassoli, S H

    2012-04-20

    The objective of the present work is to identify differences in elemental fingernail composition between opium-addicted and healthy adult human subjects using laser-induced breakdown spectroscopy. Thirty nails from normal, healthy male subjects and 30 nails from opium-addicted male individuals were analyzed. Measurements on 60 nail samples were carried out, identifying 13 key species including 11 neutral elements and 2 ions. Discriminant Function Analysis (DFA) was used to classify the samples between the two groups. Spectral line intensities of elements including Fe, C, Ti, Mg, Si, Al, Ca, H, K, O, and Na were considered variables in DFA. This analysis demonstrates the efficient discrimination between the two groups. However, the number of samples in this work is not sufficient for a decisive conclusion and further research is needed to generalize this idea.

  8. Vitamin D status of type 2 diabetic patients compared with healthy subjects in the Islamic Republic of Iran.

    PubMed

    Djalali, M; Taheri, E; Saedisomeolia, A; Djazayeri, A; Rahemi, A; Hashemi, M; Larijani, B

    2014-01-09

    An inverse relationship has been shown between vitamin D deficiency and type 2 diabetes mellitus (DM). In this cross-sectional study in Tehran, Islamic Republic of Iran, a country with a high prevalence of vitamin D deficiency, we determined the prevalence of vitamin D deficiency among 90 type 2 DM patients and 90 healthy subjects. Based on serum levels of 25-hydroxyvitamin D, the rates of deficiency (< 50 nmol/L) and insufficiency (50-75 nmol/L) were 59.0% and 27.0% respectively in patients with type 2 DM, and 47.0% and 24.0% respectively in healthy subjects. Using the national cut-offs for vitamin D deficiency, 64.0% women with DM and 47.4% of healthy women were suffering from different degrees of vitamin D deficiency. The prevalence of vitamin D deficiency in men with type 2 DM and healthy men were 42.7% and 22.2% respectively. None of the differences between the 2 groups was statistically significant.

  9. The Matching of Sinus Arrhythmia to Respiration: Are Trauma Patients without Serious Injury Comparable to Healthy Laboratory Subjects?

    DTIC Science & Technology

    2014-08-01

    the correlation between sinus arrhythmia (SA) rate, heart rate (HR), and respiratory rate (RR). Most segments with 2.4 ≤ HR/RR < 4.8 exhibited SA...variation (sinus arrhythmia [SA]; rhythmic fluctuations in heart rate [HR]) is wholly driven by the respiratory rate (RR), such that their rates will be...The Matching of Sinus Arrhythmia to Respiration: Are Trauma Patients without Serious Injury Comparable to Healthy Laboratory Subjects? Xiaoxiao

  10. Smart phone as a tool for measuring anticipatory postural adjustments in healthy subjects, a step toward more personalized healthcare.

    PubMed

    Rigoberto, Martinez M; Toshiyo, Tamura; Masaki, Sekine

    2010-01-01

    We present a study on using a smart phone as a tool to evaluate anticipatory postural adjustments (APA) before the beginning of normal gait in healthy subjects. The results show a significantly lower amplitude of anticipatory postural adjustments in the mediolateral axis (ML) when subjects used the non-dominant leg for the first step compared with the amplitude when using the dominant leg. The use of smart phones as a tool for measuring APA enables more personalized and active healthcare for the population without the necessity of their buying or carrying other devices.

  11. Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects.

    PubMed

    Nakagawa, Noriaki; Sakai, Shingo; Matsumoto, Masayuki; Yamada, Kenichi; Nagano, Masahiro; Yuki, Takuo; Sumida, Yasushi; Uchiwa, Hideyo

    2004-03-01

    Natural moisturizing factor (NMF) of the stratum corneum (SC) has been established to play important roles in the physical properties of the SC. Few studies, however, have investigated the specific influences of NMF components other than the amino acids. In this study, therefore, we focus on the relationship between the ion content and physical properties of the SC in 40 healthy subjects. Changes in the physical properties of the SC induced by the extraction of NMF were equivalent to the changes that took place from summer to winter, demonstrating the important role of NMF in the physical properties of the SC in healthy subjects. The seasonal changes in the physical properties of the SC from summer to winter were accompanied by significant decreases in the levels of lactate, potassium, sodium, and chloride in the SC. Lactate and potassium were the only components found to correlate significantly with the state of hydration, stiffness, and pH in the SC. Interestingly, the levels of lactate and potassium in the SC were also significantly correlated. Moreover, potassium lactate restored the SC hydration state decreased by extraction of NMF. These results suggest that lactate and potassium may play roles in maintaining the physical properties of the SC in healthy subjects.

  12. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects.

    PubMed

    Bardak, Handan; Gunay, Murat; Mumcu, Ugur; Bardak, Yavuz

    2016-01-01

    No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p > 0.05). A significant increase was observed in TF and HOA measurements following coffee intake (p = 0.029 and p = 0.009, resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

  13. Brain activation during oral exercises used for dysphagia rehabilitation in healthy human subjects: a functional magnetic resonance imaging study.

    PubMed

    Ogura, Emiko; Matsuyama, Miwa; Goto, Tazuko K; Nakamura, Yuko; Koyano, Kiyoshi

    2012-09-01

    Oral exercises, including tongue, lip, and jaw movements, are commonly used in clinical practice as training to improve oral and pharyngeal swallowing in dysphagia patients. These rehabilitation exercises are believed to affect the peripheral and central nervous system at various levels. However, few studies have examined healthy subjects' brain activity while performing oral exercises used in dysphagia rehabilitation. The current study sought to measure brain activation during oral exercises in healthy subjects using functional magnetic resonance imaging (fMRI). Lip-pursing and lip-stretching, tongue protrusion, lateral tongue movement, and oral ball-rolling were selected as tongue and lip exercise tasks. The tasks were performed by eight healthy subjects, and the fMRI data were submitted to conjunction analyses. The results confirmed that head movements during all tasks exhibited translation of <1.0 mm and rotation of <1.0° in x, y, and z coordinates. We found several clear regions of increased brain activity during all four oral exercises. Commonly activated regions during tongue and lip exercises included the precentral gyrus and cerebellum. Brain activation during ball-rolling was more extensive and stronger compared to the other three oral exercises.

  14. Comparison of fMRI coregistration results between human experts and software solutions in patients and healthy subjects.

    PubMed

    Gartus, Andreas; Geissler, Alexander; Foki, Thomas; Tahamtan, Amir Reza; Pahs, Gerald; Barth, Markus; Pinker, Katja; Trattnig, Siegfried; Beisteiner, Roland

    2007-06-01

    Functional magnetic resonance imaging (fMRI) performed by echo-planar imaging (EPI) is often highly distorted, and it is therefore necessary to coregister the functional to undistorted anatomical images, especially for clinical applications. This pilot study provides an evaluation of human and automatic coregistration results in the human motor cortex of normal and pathological brains. Ten healthy right-handed subjects and ten right-handed patients performed simple right hand movements during fMRI. A reference point chosen at a characteristic anatomical location within the fMRI sensorimotor activations was transferred to the high resolution anatomical MRI images by three human fMRI experts and by three automatic coregistration programs. The 3D distance between the median localizations of experts and programs was calculated and compared between patients and healthy subjects. Results show that fMRI localization on anatomical images was better with the experts than software in 70% of the cases and that software performance was worse for patients than healthy subjects (unpaired t-test: P = 0.040). With 45.6 mm the maximum disagreement between experts and software was quite large. The inter-rater consistency was better for the fMRI experts compared to the coregistration programs (ANOVA: P = 0.003). We conclude that results of automatic coregistration should be evaluated carefully, especially in case of clinical application.

  15. Quantification of the outer retinal layers: correlation to visual acuity in healthy subjects and patients with central serous chorioretinopathy

    NASA Astrophysics Data System (ADS)

    Sander, Birgit; Christensen, Ulrik; Larsen, Michael; Jørgensen, Thomas M.

    2007-07-01

    Purpose: Quantification of outer retinal layers in humans. Method: 11 eyes in healthy subjects and 3 eyes in patients after resolution of central serous chorioretinopathy (CSCR). Multiple line scans were obtained using OCT Stratus and scans were registered and averaged to enhance contrast. The distance from the inner-outer segment junction to the posterior part of the retinal pigment epithelium (RPE-OS complex) was calculated. In addition, the reflectance of the outer photoreceptor layer in the foveal center was compared to that peripheral to the fovea. Results: Mean thickness of the RPE-OS complex in healthy subjects was 77.3 μm, in CSCR 52.9 μm. The thickness of the RPE-OS complex was significantly correlated to visual acuity (r=0.95, p<0.01). The ratio of reflectance (fovea/parafovea) was 1.06 in healthy subjects, 1.18 in CSCR eyes. Conclusion: The RPE-OS complex thickness was markedly reduced in eyes after resolution of CSCR and highly correlated to the visual acuity, the correlation to total foveal thickness was less. An increased backscatter was seen in CSCR, probably due to photoreceptor disorganization and atrophy.

  16. Postural strategies assessed with inertial sensors in healthy and parkinsonian subjects

    PubMed Central

    Baston, Chiara; Mancini, Martina; Schoneburg, Bernadette; Horak, Fay; Rocchi, Laura

    2015-01-01

    The present study introduces a novel instrumented method to characterize postural movement strategies to maintain balance during stance (ankle and hip strategy), by means of inertial sensors, positioned on the legs and on the trunk. We evaluated postural strategies in subjects with2 types of parkinsonism: idiopathic Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP),and inage-matched control subjects standing under perturbed conditions implementedby the Sensory Organization Test (SOT).Coordination between the upper and lower segments of the body during postural sway was measured using a covariance index over time, by a sliding-window algorithm. Afterwards, a postural strategy index was computed. We also measuredthe amount of postural sway, as adjunctive information to characterize balance, by the root mean square of the horizontal trunk acceleration signal (RMS). Results showed that control subjects were able to change their postural strategy, whilst PSP and PD subjects persisted in use of an ankle strategy in all conditions.PD subjects had RMS values similar to control subjects even without changing postural strategy appropriately, whereas PSP subjects showed much larger RMS values than controls, resulting in several falls during the most challenging SOT conditions (5 and 6). Results are in accordance with the corresponding clinical literature describing postural behavior in the same kind of subjects. The proposed strategy index, based on the use ofinertial sensors on the upper and lower body segments, isa promising and unobtrusive toolto characterize postural strategies performed to attain balance. PMID:24656713

  17. Incidence of ectopic gray matter in patients with schizophrenia and healthy control subjects studied with MRI.

    PubMed

    Nopoulos, P; Swayze, V; Flaum, M; Andreasen, N C

    1998-01-01

    Magnetic resonance imaging scans were visually inspected to investigate the incidence of gray matter heterotopia (GMH) in a group of 55 schizophrenic patients and a group of 75 control subjects. No GMHs were found in the control subjects. In the patient group, 1 GMH was found, an incidence of 1.8%.

  18. The effects of practice on the concurrent performance of a speech and postural task in persons with Parkinson disease and healthy controls.

    PubMed

    Foreman, K Bo; Sondrup, Stuart; Dromey, Christopher; Jarvis, Eon; Nissen, Shawn; Dibble, Leland E

    2013-01-01

    Purpose. Persons with Parkinson disease (PD) demonstrate deficits in motor learning as well as bidirectional interference (the performance of one task concurrently interferes with the performance of another task) during dual-task performance. Few studies have examined the practice dosages necessary for behavioral change in rehabilitation relevant tasks. Therefore, to compare the effects of age and PD on motor learning during dual-task performance, this pilot study examined persons with PD as well as neurologically healthy participants during concurrent performance of postural and speaking tasks. Methods. Seven persons with PD and 7 healthy age-matched and 10 healthy young control subjects were tested in a motion capture facility. Task performances were performed concurrently and recorded during 3 time periods (acquisition (beginning and ending), 48-hour retention, and 1-week retention). Postural control and speech articulatory acoustic variables were measured. Results. Healthy young participants consistently performed better than other groups on all measured postural and speech variables. Healthy young participants showed decreased variability at retention, while persons with PD and healthy age-matched controls were unable to consistently improve their performance as a result of practice. No changes were noted in the speech variables. Conclusion. The lack of consistent changes in motor performance in any of the tasks, except in the healthy young group, suggests a decreased efficiency of motor learning in the age-matched and PD groups and argues for increased practice dosages during balance training.

  19. The Effects of Practice on the Concurrent Performance of a Speech and Postural Task in Persons with Parkinson Disease and Healthy Controls

    PubMed Central

    Foreman, K. Bo; Sondrup, Stuart; Dromey, Christopher; Jarvis, Eon; Nissen, Shawn; Dibble, Leland E.

    2013-01-01

    Purpose. Persons with Parkinson disease (PD) demonstrate deficits in motor learning as well as bidirectional interference (the performance of one task concurrently interferes with the performance of another task) during dual-task performance. Few studies have examined the practice dosages necessary for behavioral change in rehabilitation relevant tasks. Therefore, to compare the effects of age and PD on motor learning during dual-task performance, this pilot study examined persons with PD as well as neurologically healthy participants during concurrent performance of postural and speaking tasks. Methods. Seven persons with PD and 7 healthy age-matched and 10 healthy young control subjects were tested in a motion capture facility. Task performances were performed concurrently and recorded during 3 time periods (acquisition (beginning and ending), 48-hour retention, and 1-week retention). Postural control and speech articulatory acoustic variables were measured. Results. Healthy young participants consistently performed better than other groups on all measured postural and speech variables. Healthy young participants showed decreased variability at retention, while persons with PD and healthy age-matched controls were unable to consistently improve their performance as a result of practice. No changes were noted in the speech variables. Conclusion. The lack of consistent changes in motor performance in any of the tasks, except in the healthy young group, suggests a decreased efficiency of motor learning in the age-matched and PD groups and argues for increased practice dosages during balance training. PMID:23841022

  20. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers

    PubMed Central

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Gertsik, Lev; Dutta, Sandeep

    2014-01-01

    Aims 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. Methods 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. Results 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. Conclusions 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. PMID:24215171

  1. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review.

    PubMed

    Battleday, R M; Brem, A-K

    2015-11-01

    Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine levels, and indirectly decreases cerebral gamma-amino-butrytic acid levels. In addition to its approved use treating excessive somnolence, modafinil is thought to be used widely off-prescription for cognitive enhancement. However, despite this popularity, there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy, non-sleep-deprived humans. This problem is compounded by methodological discrepancies within the literature, and reliance on psychometric tests designed to detect cognitive effects in ill rather than healthy populations. In order to provide an up-to-date systematic evaluation that addresses these concerns, we searched MEDLINE with the terms "modafinil" and "cognitive", and reviewed all resultant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans. We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning. Importantly, we did not observe any preponderances for side effects or mood changes. Finally, in light of the methodological discrepancies encountered within this literature, we conclude with a series of recommendations on how to optimally detect valid, robust, and consistent effects in healthy populations that should aid future assessment of neuroenhancement.

  2. Inverse relationship of cardioankle vascular index with BMI in healthy Japanese subjects: a cross-sectional study

    PubMed Central

    Nagayama, Daiji; Imamura, Haruki; Sato, Yuta; Yamaguchi, Takashi; Ban, Noriko; Kawana, Hidetoshi; Ohira, Masahiro; Saiki, Atsuhito; Shirai, Kohji; Tatsuno, Ichiro

    2017-01-01

    Objective The objective of this study is to investigate the association of body mass index (BMI) with arterial stiffness assessed by cardioankle vascular index (CAVI). Subjects and methods A retrospective cross-sectional study was conducted in 23,257 healthy Japanese subjects (12,729 men and 10,528 women, aged 47.1 ± 12.5 years, BMI 22.9 ± 3.4 kg/m2) who underwent health screening between 2004 and 2006 in Japan. Exclusion criteria were current medication use and a past history of cardiovascular disease, hypertension, stroke, diabetes, and nephritis. Results Male subjects showed significantly higher BMI, CAVI, and triglycerides and lower high-density lipoprotein (HDL)-cholesterol compared with female subjects. Next, the subjects were divided into tertiles of BMI: lower, middle, and upper, in a gender-specific manner. After adjusting for confounders including age, systolic blood pressure, and HDL-cholesterol identified by multiple regression analysis, the mean CAVI decreased progressively as BMI tertile increased in both genders. Furthermore, a negative inverse relationship between BMI and adjusted CAVI was observed throughout the BMI distribution. Multivariate logistic regression model for contributors of high CAVI (≥90th percentile) identified obesity (odds ratios (95% confidence interval): 0.804 (0.720–0.899)], older age [15.6 (14.0–17.4)], male gender [2.26 (2.03–2.51)], hypertension [2.28 (2.06–2.54)], impaired fasting glucose [1.17 (1.01–1.37)], and low HDL-cholesterol [0.843 (0.669–1.06)] as independent factors. Conclusion We demonstrated an inverse relationship between CAVI and BMI in healthy Japanese subjects, suggesting that systemic accumulation of adipose tissue per se may lead to a linear decrease of arterial stiffness in nonobese and obese subjects without metabolic disorders. PMID:28053538

  3. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

    PubMed

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian P J; Dougherty, Sonia L; Chand, Vibhasha; Lyons, Jasmine G; Bertovic, David; Coughlan, Melinda T; Schlaich, Markus P; Soldatos, Georgia; Cooper, Mark E; Straznicky, Nora E; Kingwell, Bronwyn A; de Courten, Barbora

    2014-02-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

  4. Performance on a probabilistic inference task in healthy subjects receiving ketamine compared with patients with schizophrenia

    PubMed Central

    Almahdi, Basil; Sultan, Pervez; Sohanpal, Imrat; Brandner, Brigitta; Collier, Tracey; Shergill, Sukhi S; Cregg, Roman; Averbeck, Bruno B

    2012-01-01

    Evidence suggests that some aspects of schizophrenia can be induced in healthy volunteers through acute administration of the non-competitive NMDA-receptor antagonist, ketamine. In probabilistic inference tasks, patients with schizophrenia have been shown to ‘jump to conclusions’ (JTC) when asked to make a decision. We aimed to test whether healthy participants receiving ketamine would adopt a JTC response pattern resembling that of patients. The paradigmatic task used to investigate JTC has been the ‘urn’ task, where participants are shown a sequence of beads drawn from one of two ‘urns’, each containing coloured beads in different proportions. Participants make a decision when they think they know the urn from which beads are being drawn. We compared performance on the urn task between controls receiving acute ketamine or placebo with that of patients with schizophrenia and another group of controls matched to the patient group. Patients were shown to exhibit a JTC response pattern relative to their matched controls, whereas JTC was not evident in controls receiving ketamine relative to placebo. Ketamine does not appear to promote JTC in healthy controls, suggesting that ketamine does not affect probabilistic inferences. PMID:22389244

  5. Diet-microbiota-health interactions in older subjects: implications for healthy aging.

    PubMed

    Lynch, D B; Jeffery, I B; Cusack, S; O'Connor, E M; O'Toole, P W

    2015-01-01

    With modern medicine and an awareness of healthy lifestyle practices, people are living longer and generally healthier lives than their ancestors. These successes of modern medicine have resulted in an increasing proportion of elderly in society. Research groups around the world have investigated the contribution of gut microbial communities to human health and well-being. It was established that the microbiota composition of the human gut is modulated by lifestyle factors, especially diet. The microbiota composition and function, acting in concert with direct and indirect effects of habitual diet, is of great importance in remaining healthy and active. This is not a new concept, but until now the scale of the potential microbiota contribution was not appreciated. There are an estimated ten times more bacteria in an individual than human cells. The bacterial population is relatively stable in adults, but the age-related changes that occur later in life can have a negative impact on host health. This loss of the adult-associated microbiota correlates with measures of markers of inflammation, frailty, co-morbidity and nutritional status. This effect may be greater than that of diet or in some cases genetics alone. Collectively, the recent studies show the importance of the microbiota and associated metabolites in healthy aging and the importance of diet in its modulation.

  6. Comparison of bacterial communities in the throat swabs from healthy subjects and pharyngitis patients by terminal restriction fragment length polymorphism.

    PubMed

    Balaji, Kannan; Thenmozhi, Ramalingam; Sundaravadivel, Marimuthu; Pandian, Shunmugiah Karutha

    2012-07-01

    Terminal restriction fragment length polymorphism (T-RFLP) analysis was applied to characterize bacterial flora present in the throats of healthy subjects and pharyngitis patients. The 16S rRNA genes of bacteria present in throat metagenome were amplified by PCR with 6-carboxy-fluorescein (6-FAM)-labeled universal forward primer (27 F) and a universal reverse primer (1513R). The 16S rDNAs were digested with restriction enzymes with 4-bp recognition sites (MspI or RsaI) and analyzed by using an automated DNA sequencer. T-RFLP patterns were numerically analyzed using computer programs. From analysis of the throat bacterial community, patterns derived from MspI and RsaI digested samples of healthy subjects and pharyngitis patients were grouped into different clusters, though RsaI digested samples showed some uncertainty. Pharyngitis throats generated an average species richness of 9 [±2.1 (SD)] and 10 (±2.9) for MspI and RsaI digests, respectively, whereas healthy throats generated 6.3 (±1.2) and 6.1 (±1.5) in MspI and RsaI digests, respectively. These results suggest that samples from pharyngitis patients contain an unexpected diversity of causative bacteria. The pharyngitis throats were colonized with a rich diversity of bacterial species than that of healthy throats. Using T-RFLP, we are able to detect a model bacterium, Streptococcus pyogenes SF370, and T-RF patterns were consistent with the Streptococcal T-RFLP patterns. Our study indicates that T-RFLP analysis is useful for the assessment of diversity of throat bacterial flora and rapid comparison of the community structure between subjects with and without pharyngitis.

  7. The Rematee Bumper Belt(®) positional therapy device for snoring and obstructive sleep apnea: Positional effectiveness in healthy subjects.

    PubMed

    Matthews, Les; Fortier, Normand

    2013-01-01

    The present study was designed to investigate body position changes resulting from wearing a Rematee Bumper Belt (Rematee, Canada) during sleep. The majority of obstructive sleep apnea (OSA) patients will experience up to two times as many apneas and hypopneas while supine relative to lateral or prone body positions during sleep. It has been suggested that a positional therapy device could reduce the number of apneas and hypopneas in such patients. The present study was conducted to determine whether the Rematee Bumper Belt positional therapy device could prevent healthy subjects from sleeping in the supine position. Test subjects wore the belt for one to two nights. Each belt was equipped with an accelerometer that was used to measure the orientation of the belt relative to the horizontal plane. The results suggest that the belt creates an exclusion zone approximately 80° wide centred near the supine orientation, where subjects are effectively prevented to enter. Results of the present preliminary study suggests that the Rematee Bumper Belt positional therapy device is effective at limiting healthy subjects from sleeping in a supine position. The device appears to be most effective between 150° and 230°. A device with this capability may provide an inexpensive and potentially effective alternative treatment option for patients with OSA. This device has the capacity for reducing snoring and the apnea-hypopnea index in individuals with positional OSA.

  8. Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex

    PubMed Central

    Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Cipolotti, Lisa; Oliveri, Massimiliano

    2015-01-01

    Objective The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. Method 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. Results Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. Conclusion Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects. PMID:26679936

  9. Preserved Learning during the Symbol–Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly

    PubMed Central

    Cornelis, Claudia; De Picker, Livia J.; Hulstijn, Wouter; Dumont, Glenn; Timmers, Maarten; Janssens, Luc; Sabbe, Bernard G. C.; Morrens, Manuel

    2015-01-01

    Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit–symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol–digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. Methods: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol–Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol–digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. Results: The repetition of the same symbol–digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. Conclusion: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the

  10. Group analysis and the subject factor in functional magnetic resonance imaging: analysis of fifty right-handed healthy subjects in a semantic language task.

    PubMed

    Seghier, Mohamed L; Lazeyras, François; Pegna, Alan J; Annoni, Jean-Marie; Khateb, Asaid

    2008-04-01

    Before considering a given fMRI paradigm as a valid clinical tool, one should first assess the reliability of functional responses across subjects by establishing a normative database and defining a reference activation map that identifies major brain regions involved in the task at hand. However, the definition of such a reference map can be hindered by inter-individual functional variability. In this study, we analysed functional data obtained from 50 healthy subjects during a semantic language task to assess the influence of the number of subjects on the reference map and to characterise inter-individual functional variability. We first compared different group analysis approaches and showed that the extent of the activated network depends not only on the choice of the analysis approach but also on the statistical threshold used and the number of subjects included. This analysis suggested that, while the RFX analysis is suitable to detect confidently true positive activations, the other group approaches are useful for exploratory investigations in small samples. The application of quantitative measures at the voxel and regional levels suggested that while approximately 15-20 subjects were sufficient to reveal reliable and robust left hemisphere activations, >30 subjects were necessary for revealing more variable and weak right hemisphere ones. Finally, to visualise inter-individual variability, we combined two similarity indices that assess the percentages of true positive and false negative voxels in individual activation patterns relative to the group map. We suggest that these measures can be used for the estimation of the degree of 'normality' of functional responses in brain-damaged patients, where this question is often raised, and recommend the use of different quantifications to appreciate accurately the inter-individual functional variability that can be incorporated in group maps.

  11. Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis

    PubMed Central

    Widegren, Henrik; Erjefält, Jonas; Korsgren, Magnus; Andersson, Morgan; Greiff, Lennart

    2008-01-01

    Background TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge. Methods Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α2-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored. Results Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α2-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils. Conclusion TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation. PMID:18234086

  12. A functional polymorphism in the promoter region of MAOA gene is associated with daytime sleepiness in healthy subjects.

    PubMed

    Ojeda, Diego A; Niño, Carmen L; López-León, Sandra; Camargo, Andrés; Adan, Ana; Forero, Diego A

    2014-02-15

    Excessive daytime sleepiness (EDS) is one of the main causes of car and industrial accidents and it is associated with increased morbidity and alterations in quality of life. Prevalence of EDS in the general population around the world ranges from 6.2 to 32.4%, with a heritability of 38-40%. However, few studies have explored the role of candidate genes in EDS. Monoamine oxidase A (MAOA) gene has an important role in the regulation of neurotransmitter levels and a large number of human behaviors. We hypothesized that a functional VNTR in the promoter region of the MAOA gene might be associated with daytime sleepiness in healthy individuals. The Epworth sleepiness scale (ESS) was applied to 210 Colombian healthy subjects (university students), which were genotyped for MAOA-uVNTR. MAOA-uVNTR showed a significant association with ESS scores (p = 0.01): 3/3 genotype carriers had the lowest scores. These results were supported by differences in MAOA-uVNTR frequencies between diurnal somnolence categories (p = 0.03). Our finding provides evidence for the first time that MAOA-uVNTR has a significant association with EDS in healthy subjects. Finally, these data suggest that functional variations in MAOA gene could have a role in other phenotypes of neuropsychiatric relevance.

  13. Effects of ethanol and acetaldehyde load on erythrocyte deformability in healthy subjects and patients with liver cirrhosis.

    PubMed

    Shiraishi, Koichi; Tsuruya, Kota; Anzai, Kazuya; Arase, Yoshitaka; Hirose, Shunji; Kagawa, Tatehiro; Mine, Tetsuya; Matsuzaki, Shohei

    2015-02-01

    Alcohol intake leads to the distribution of alcohol and its metabolite, acetaldehyde throughout the blood and organs. Hepatic cirrhosis is associated with abnormal red blood cell morphology and function, particularly impaired red blood cell deformability. To investigate the effect of drinking on red blood cells in patients with hepatic cirrhosis, erythrocyte deformability was evaluated in response to alcohol and acetaldehyde tolerance. Erythrocyte deformability in 10 healthy and 15 cirrhotic subjects was examined by filterability of the red blood cells. Erythrocyte deformability decreased markedly in the cirrhosis group compared with the healthy group (p < 0.05). No significant change in erythrocyte deformability was observed in healthy or cirrhotic subjects due to ethanol 100 mM tolerance. Acetaldehyde tolerance elicited a significant decrease in erythrocyte deformability at 2 mM in the cirrhosis group (p < 0.05). Alcohol consumption in cirrhotic patients was suggested to worsen erythrocyte deformability and red blood cell function. Decreased erythrocyte deformability worsens microcirculation in the liver, resulting in more severe hepatic dysfunction.

  14. Comparative assessment of essential and toxic metals in the blood of rheumatoid arthritis patients and healthy subjects.

    PubMed

    Hashmi, G M Mujtba; Shah, Munir H

    2012-04-01

    The present study deals with the comparative evaluation of essential and toxic metals in rheumatoid arthritis and healthy donors. Blood samples collected from rheumatoid arthritis patients and healthy subjects were analysed for selected essential and toxic metals (Ca, Mg, Fe, Zn, Cu, Co, Mn, Cr, Cd and Pb). The samples were digested in nitric acid and perchloric acid mixture, followed by quantification of the metals using atomic absorption spectrometry. Mean levels of Ca, Mg, Fe and Zn were significantly higher in the blood of healthy donors; however, elevated levels of Cd, Co, Cr, Cu and Pb were observed in blood of the patients. The correlation coefficients among the selected metals in the blood of arthritis patients were significantly different compared with the healthy counterparts. Multivariate cluster analysis revealed mutual apportionment of the essential and toxic metals in blood of the patients, whereas, in controls, the essential and toxic metals revealed diverse apportionment. Variations in the metal levels with gender, residence and smoking habits were also evaluated in both donor groups. Relative distribution, correlation and apportionment of the essential and toxic metals in the blood of the patients were significantly different than of controls.

  15. Effects of exercise on glomerular passage of macromolecules in patients with diabetic nephropathy and in healthy subjects.

    PubMed

    Ala-Houhala, I

    1990-02-01

    The effects of exercise on glomerular permeability were investigated in 12 proteinuric insulin-dependent diabetic patients and in 12 healthy controls by measuring the fractional protein and dextran clearances at rest and after exercise. Exercise significantly reduced the glomerular filtration rate (GFR) and the renal plasma flow (RPF) and markedly increased the filtration fraction (FF) in both diabetics and controls. The fractional clearances of albumin and IgG increased significantly during exercise in diabetics. Exercise also significantly increased the fractional clearance of albumin in healthy controls. The changes in the fractional protein clearances correlated significantly with the changes in the FF. In diabetics the fractional dextran clearances of molecules with a radius greater than or equal to 4.8 nm were significantly elevated after exercise. This was not found in healthy controls. It is concluded that exercise increases glomerular permeability by influencing the renal haemodynamics. Probably partial depletion of negative charges on the glomerular capillary wall plays a role in exercise-induced proteinuria in both healthy and diabetic subjects. In addition, the altered glomerular permeability during exercise is associated with increased size of the filtering pores in diabetic nephropathy.

  16. Effect of transcutaneous electrical nerve stimulation on muscle metaboreflex in healthy young and older subjects.

    PubMed

    Vieira, Paulo J C; Ribeiro, Jorge P; Cipriano, Gerson; Umpierre, Daniel; Cahalin, Lawrence P; Moraes, Ruy S; Chiappa, Gaspar R

    2012-04-01

    Transcutaneous electrical nerve stimulation (TENS) increases local blood flow. It is not known whether increase in blood flow may be caused by inhibition of sympathetic activity, mediated by muscle metaboreflex activity. The purpose of this study was to evaluate the effect of TENS on metaboreflex activation and heart rate variability (HRV) in young and older individuals. Eleven healthy young (age 25 ± 1.3 years) and 11 healthy older (age 63 ± 4.2 years) were randomized to TENS (30 min, 80 Hz, 150 μs) or placebo (same protocol without electrical output) applied on the ganglion region. Frequency domain indices of HRV and hemodynamic variables were evaluated during the pressor response to static handgrip exercise at 30% of maximal voluntary contraction, followed by recovery with (PECO+) or without (PECO-) circulatory occlusion, in a randomized order. At the peak exercise, the increase in mean blood pressure was attenuated by TENS (P < 0.05), which was sustained during PECO+ and PECO-. TENS promoted a higher calf blood flow and lower calf vascular resistance during exercise and recovery. Likewise, TENS induced a reduction in the estimated muscle metaboreflex control both in young (placebo: 28 ± 4 units vs. TENS: 6 ± 3, P < 0.01) and in older individuals (placebo: 13 ± 3 units vs. TENS: 5 ± 3, P < 0.01). HRV analysis showed similar improvement in sympatho-vagal balance with TENS in young and older individuals. We conclude that application of TENS attenuates blood pressure and vasoconstrictor responses during exercise and metaboreflex activation, associated with improved sympatho-vagal balance in healthy young and older individuals.

  17. The Bitter Taste Receptor Agonist Quinine Reduces Calorie Intake and Increases the Postprandial Release of Cholecystokinin in Healthy Subjects

    PubMed Central

    Andreozzi, Paolo; Sarnelli, Giovanni; Pesce, Marcella; Zito, Francesco P; D’Alessandro, Alessandra; Verlezza, Viviana; Palumbo, Ilaria; Turco, Fabio; Esposito, Katherine; Cuomo, Rosario

    2015-01-01

    Background/Aims Bitter taste receptors are expressed throughout the digestive tract. Data on animals have suggested these receptors are involved in the gut hormone release, but no data are available in humans. Our aim is to assess whether bitter agonists influence food intake and gut hormone release in healthy subjects. Methods Twenty healthy volunteers were enrolled in a double-blind cross-over study. On 2 different days, each subject randomly received an acid-resistant capsule containing either placebo or 18 mg of hydrochloride (HCl) quinine. After 60 minutes, all subjects were allowed to eat an ad libitum meal until satiated. Plasma samples were obtained during the experiment in order to evaluate cholecystokinin (CCK) and ghrelin levels. Each subject was screened to determine phenylthiocarbamide (PTC) tasting status. Results Calorie intake was significantly lower when subjects received HCl quinine than placebo (514 ± 248 vs 596 ± 286 kcal; P = 0.007). Significantly higher CCK ΔT90 vs T0 and ΔT90 vs T60 were found when subjects received HCl quinine than placebo (0.70 ± 0.69 vs 0.10 ± 0.86 ng/mL, P = 0.026; 0.92 ± 0.75 vs 0.50 ± 0.55 ng/mL, P = 0.033, respectively). PTC tasters ingested a significantly lower amount of calories when they received HCl quinine compared to placebo (526 ± 275 vs 659 ± 320 kcal; P = 0.005), whereas no significant differences were found for PTC non-tasters (499 ± 227 vs 519 ± 231 kcal; P = 0.525). Conclusions This study showed that intra-duodenal release of a bitter compound is able to significantly affect calorie intake and CCK release after a standardized meal. Our results suggest that bitter taste receptor signaling may have a crucial role in the control of food intake. PMID:26351252

  18. Activation during the Trail Making Test measured with functional near-infrared spectroscopy in healthy elderly subjects.

    PubMed

    Hagen, Katja; Ehlis, Ann-Christine; Haeussinger, Florian B; Heinzel, Sebastian; Dresler, Thomas; Mueller, Laura D; Herrmann, Martin J; Fallgatter, Andreas J; Metzger, Florian G

    2014-01-15

    Cognitive decline is very common in age and particularly in subjects with neurodegenerative conditions. Besides memory and language, executive functions are very often affected in elderly and patients with Alzheimer's disease or Parkinson's disease. However, the neural alterations associated with these executive deficits are still not fully understood. Therefore, we measured cortical activation using functional near-infrared spectroscopy (fNIRS) in 16 healthy elderly subjects (50-75 years) performing the Trail Making Test (TMT), a widely used neuropsychological instrument measuring executive function. In line with previous studies focusing on younger subjects, the results showed frontal activation during the TMT A and the TMT B in the dorsolateral prefrontal cortex, the frontopolar area and also Broca's area. Furthermore, significant activation in the left motor, somatosensory cortices and somatosensory association cortices was demonstrated. Additionally, after a median split the differences between younger (<58 years) and older (>58 years) subjects were analyzed with the older subjects showing a less focused prefrontal activation. Altogether, fNIRS was found to be suitable to detect cortical activation in elderly subjects during performance of the TMT as well as aging-related differences in prefrontal activation topography. These neural correlates of executive functions should be further investigated as a potential prodromal neural marker of executive deficits and neurodegenerative processes.

  19. Cortico-subcortical metabolic correlates of olfactory processing in healthy resting subjects

    PubMed Central

    Alessandrini, Marco; Micarelli, Alessandro; Chiaravalloti, Agostino; Candidi, Matteo; Bruno, Ernesto; Di Pietro, Barbara; Schillaci, Orazio; Pagani, Marco

    2014-01-01

    A wide network of interconnected areas was previously found in neuroimaging studies involving normal as well as pathological subjects; however literature seems to suffer from a lack of investigation in glucose metabolism behaviour under olfactory condition. Thus, the present work describe for the first time a pure olfactory related brain response of metabolism by using 18F-fluorodeoxyglucose-Positron Emission Tomography/Computer Tomography in eleven resting subjects undergoing a neutral and a pure olfactory condition. By contrasting these experimental phases, it was possible to depict a re-organization pattern of default mode network structures in a relatively ecological environment. Moreover, by correlating such pattern with a battery of validated olfactory and neuropsychological tests, our work allowed in showing peculiar correlation data that could cluster the subjects sample in a certain range of normality. We believe the present study could integrate the current knowledge in olfactory research and could be a start-up for future contributions. PMID:24888510

  20. Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.

    PubMed

    Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

    2011-03-01

    Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects.

  1. Assessment of pharmacokinetic interaction between piracetam and l-carnitine in healthy subjects.

    PubMed

    Mendes, Gustavo D; Zaffalon, Gabriela Traldi; Silveira, Antonio Sérgio; Ramacciato, Juliana Cama; Motta, Rogério Heládio Lopes; Gagliano-Jucá, Thiago; Lopes, Anibal Gil; de Almeida Magalhães, José Cássio; De Nucci, Gilberto

    2016-04-01

    A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption.

  2. Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects

    PubMed Central

    Deplanque, Xavier; Muscente-Paque, Delphine; Chappuis, Eric

    2016-01-01

    Background Low-density lipoprotein (LDL) oxidation is a risk factor for atherosclerosis. Lycopene and tomato-based products have been described as potent inhibitors of LDL oxidation. Objectives To evaluate the effect of a 2-week supplementation with a carotenoid-rich tomato extract (CRTE) standardized for a 1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a high-fat meal. Design In a randomized, double-blind, parallel-groups, placebo-controlled study, 146 healthy normal weight individuals were randomly assigned to a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2 weeks. Oxidized LDL (OxLDL), glucose, insulin, and triglyceride (TG) responses were measured for 8 h after ingestion of a high-fat meal before and at the end of intervention. Results Plasma lycopene, phytofluene, and phytoene were increased throughout the study period in the CRTE group compared to placebo. CRTE ingestion significantly improved changes in OxLDL response to high-fat meal compared to placebo after 2 weeks (p<0.0001). Changes observed in glucose, insulin, and TG responses were not statistically significant after 2 weeks of supplementation, although together they may suggest a trend of favorable effect on metabolic outcomes after a high-fat meal. Conclusions Two-week supplementation with CRTE increased carotenoids levels in plasma and improved oxidized LDL response to a high-fat meal in healthy normal weight individuals. PMID:27707453

  3. Effect of oral theaflavin administration on body weight, fat, and muscle in healthy subjects: a randomized pilot study.

    PubMed

    Aizawa, Teruki; Yamamoto, Ayaka; Ueno, Tomoya

    2017-02-01

    Theaflavins are reddish-colored polyphenols in black tea. To test the efficacy of theaflavin administration on body fat and muscle, we performed a randomized, double-blind, placebo-controlled study and investigated the effect of theaflavins administration on the body composition using of healthy subjects. In this study, 30 male and female Japanese were enrolled and participants were randomly allocated to receive placebo, theaflavin (50 or 100 mg/day), or catechin (400 mg/ml) for 10 weeks. The effects were evaluated using body weight, body fat percentage, subcutaneous fat percentage, and skeletal muscle percentage. Theaflavin administration significantly improved body fat percentage, subcutaneous fat percentage, and skeletal muscle percentage when compared to with the placebo. In contrast, there was no significant difference in all measured outcomes between the catechin and the placebo groups. The results indicate that oral administration of theaflavin had a beneficial effect on body fat and muscle in healthy individuals.

  4. Characterizing coordination of grasp and twist in hand function of healthy and post-stroke subjects.

    PubMed

    Kazemi, Hamed; Kearney, Robert; Milner, Theodore

    2013-06-01

    The goal of this study was to characterize the coordination of grasp and twist in hand function of normal and post-stroke subjects using a two degree of freedom hand robot. Results of the analysis of data from eight control subjects indicated that normal grip coordination involves the linear modulation of grip force with load torque. Thus, there was a high correlation between grip force and load torque. Also, the force generated by the thumb was highly correlated with the force generated by the index, middle and ring fingers. Finally, the safety margin used to stabilize grasp and avoid slip was consistent across normal subjects. In contrast, results from chronic post-stroke subjects indicated that they generally: (1) exerted excessive grip force to stabilize grasp using their ipsilesional hand; (2) lost the close amplitude coupling between grip force and load torque; and (3) lost the close modulation of the thumb force with finger force. These results suggest that our methods may provide objective, quantitative means of characterizing coordination problems following stroke.

  5. Noradrenergic function in generalized anxiety disorder, major depressive disorder, and healthy subjects.

    PubMed

    Sevy, S; Papadimitriou, G N; Surmont, D W; Goldman, S; Mendlewicz, J

    1989-01-15

    Plasma norepinephrine (NE), free 3-methoxy-4-hydroxyphenethylene glycol (MHPG), and binding of tritiated yohimbine to platelet membranes were measured in 14 patients with generalized anxiety disorder (GAD), who were matched for age and sex with 14 patients with unipolar major depressive disorder (MDD) and 14 normal subjects. Plasma NE and MHPG levels were increased and the number of alpha2-adrenoreceptors (Bmax) was decreased in GAD patients compared with MDD and normal subjects. No differences were found between MDD patients and normal subjects for plasma NE, MHPG, and alpha2-adrenoreceptor binding. Plasma NE and MHPG were significantly correlated in MDD patients and tended toward a significant positive correlation in GAD patients. Plasma MHPG and affinity of binding platelet alpha2-adrenoreceptors (Kd) were significantly correlated in normal subjects. Thus, noradrenergic activity seems to be increased in patients with GAD, but not in patients with MDD. In GAD patients, higher levels of catecholamines may lead to a down-regulation of presynaptic alpha2-adrenoreceptors.

  6. Low-level laser therapy reduces the fatigue index in the ankle plantar flexors of healthy subjects.

    PubMed

    de Souza, Clécio Gabriel; Borges, Daniel Tezoni; de Brito Macedo, Liane; Brasileiro, Jamilson Simões

    2016-12-01

    Low-level laser therapy (LLLT) has been suggested as a resource capable of increasing resistance to fatigue and enhancing muscle performance through its metabolic and photochemical effects. This study evaluated the immediate effects of the application of LLLT on neuromuscular performance of the plantar ankle flexors in healthy subjects through a fatigue-induced protocol. This is a randomized controlled clinical trial, attended by 60 young and physically active volunteers of both genders. The subjects were randomly assigned into three groups, control, placebo, and laser, and underwent a preliminary evaluation of the isokinetic performance of plantar flexors and electromyographic activity of the soleus muscle to ensure homogeneity between groups. After the application of the respective intervention protocols, participants were induced to fatigue by performing 100 isokinetic concentric contractions of ankle plantar flexors at a speed of 90°/s. The dynamometric fatigue index (DFI) and median frequency were recorded during the fatigue protocol for comparison between groups. The group receiving the laser application showed significantly lower dynamometric fatigue index (p = 0.036) when compared to control and placebo groups. In relation to the median frequency during the fatigue test, there was a decrease in all groups, however with no differences between them. We suggest that LLLT being applied prior to exercise can reduce the fatigue index in the ankle plantar flexors of healthy subjects.

  7. Quantitative performance of E-Scribe warehouse in detecting quality issues with digital annotated ECG data from healthy subjects.

    PubMed

    Sarapa, Nenad; Mortara, Justin L; Brown, Barry D; Isola, Lamberto; Badilini, Fabio

    2008-05-01

    The US Food and Drug Administration recommends submission of digital electrocardiograms in the standard HL7 XML format into the electrocardiogram warehouse to support preapproval review of new drug applications. The Food and Drug Administration scrutinizes electrocardiogram quality by viewing the annotated waveforms and scoring electrocardiogram quality by the warehouse algorithms. Part of the Food and Drug Administration warehouse is commercially available to sponsors as the E-Scribe Warehouse. The authors tested the performance of E-Scribe Warehouse algorithms by quantifying electrocardiogram acquisition quality, adherence to QT annotation protocol, and T-wave signal strength in 2 data sets: "reference" (104 digital electrocardiograms from a phase I study with sotalol in 26 healthy subjects with QT annotations by computer-assisted manual adjustment) and "test" (the same electrocardiograms with an intentionally introduced predefined number of quality issues). The E-Scribe Warehouse correctly detected differences between the 2 sets expected from the number and pattern of errors in the "test" set (except for 1 subject with QT misannotated in different leads of serial electrocardiograms) and confirmed the absence of differences where none was expected. E-Scribe Warehouse scores below the threshold value identified individual electrocardiograms with questionable T-wave signal strength. The E-Scribe Warehouse showed satisfactory performance in detecting electrocardiogram quality issues that may impair reliability of QTc assessment in clinical trials in healthy subjects.

  8. Four-week exercise program does not change rotator cuff muscle activation and scapular kinematics in healthy subjects

    PubMed Central

    Lin, Yin-Liang; Karduna, Andrew

    2016-01-01

    Rotator cuff and scapular muscle strengthening exercises are an essential part of shoulder rehabilitation and sports training. Although the effect of exercise training on pain and function have been widely investigated, few studies have focused on the changes in shoulder kinematics and muscle activity after exercise training. Therefore, the purpose of the present study was to investigate the effect of rotator cuff and scapular strengthening exercises on shoulder kinematics and the activation of rotator cuff and scapular muscles in healthy subjects. Thirty-six healthy subjects were recruited and randomly assigned into either a training or control group. Subjects in the training group were trained with rotator cuff and scapular strengthening exercises for four weeks. Scapular kinematics and shoulder muscle activity during arm elevation were measured before and after exercise training. After the four-week training protocol, there was an increase in strength and a decrease in upper trapezius activation in the training group, which is consistent with previous studies. However, no difference was found in scapular kinematics and activation of rotator cuff muscles between the control and training groups after the training protocol. Although the exercise protocol resulted in strength gains for the rotator cuff, these gains did not transfer to an increase in muscle activation during motion. These results demonstrate the difficulty in changing activation patterns of the rotator cuff muscles. PMID:26996811

  9. Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

    PubMed Central

    Tosri, Nisanuch; Rojanasthien, Noppamas; Srichairatanakool, Somdet; Sangdee, Chaichan

    2013-01-01

    The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The Cmax and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster Tmax. The t1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally. PMID:23533801

  10. A diet based on multiple functional concepts improves cardiometabolic risk parameters in healthy subjects

    PubMed Central

    2012-01-01

    Background Different foods can modulate cardiometabolic risk factors in persons already affected by metabolic alterations. The objective of this study was to assess, in healthy overweight individuals, the impact of a diet combining multiple functional concepts on risk markers associated with cardiometabolic diseases (CMD). Methods Fourty-four healthy women and men (50-73 y.o, BMI 25-33, fasting glycemia ≤ 6.1 mmol/L) participated in a randomized crossover intervention comparing a multifunctional (active) diet (AD) with a control diet (CD) devoid of the "active" components. Each diet was consumed during 4 wk with a 4 wk washout period. AD included the following functional concepts: low glycemic impact meals, antioxidant-rich foods, oily fish as source of long-chain omega-3 fatty acids, viscous dietary fibers, soybean and whole barley kernel products, almonds, stanols and a probiotic strain (Lactobacillus plantarum Heal19/DSM15313). Results Although the aim was to improve metabolic markers without promoting body weight loss, minor weight reductions were observed with both diets (0.9-1.8 ± 0.2%; P < 0.05). CD did not modify the metabolic variables measured. AD promoted significant changes in total serum cholesterol (-26 ± 1% vs baseline; P < 0.0001), LDL-cholesterol (-34 ± 1%; P < 0.0001), triglycerides (-19 ± 3%; P = 0.0056), LDL/HDL (-27 ± 2%; P < 0.0001), apoB/apoA1 (-10 ± 2%; P < 0.0001), HbA1c (-2 ± 0.4%; P = 0.0013), hs-CRP (-29 ± 9%; P = 0.0497) and systolic blood pressure (-8 ± 1%¸ P = 0.0123). The differences remained significant after adjustment for weight change. After AD, the Framingham cardiovascular risk estimate was 30 ± 4% (P < 0.0001) lower and the Reynolds cardiovascular risk score, which considers CRP values, decreased by 35 ± 3% (P < 0.0001). Conclusion The improved biomarker levels recorded in healthy individuals following the multifunctional regime suggest preventive potential of this dietary approach against CMD. PMID:22472183

  11. Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients

    PubMed Central

    Kunz, V.C.; Borges, E.N.; Coelho, R.C.; Gubolino, L.A.; Martins, L.E.B.; Silva, E.

    2012-01-01

    The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation. PMID:22370707

  12. Immunohistological findings in lip biopsy specimens from patients with Crohn's disease and healthy subjects.

    PubMed

    Crama-Bohbouth, G; Bosman, F T; Vermeer, B J; van der Wal, A M; Biemond, I; Weterman, I T; Peńa, A S

    1983-03-01

    Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM.

  13. [Evaluation of portal circulation in healthy subjects with duplex scanning before and after meal].

    PubMed

    Kuntsevich, G I; Belolapotko, E A; Kokova, N I

    1994-01-01

    Duplex scanning was used to functionally assess the arterial and venous vascular bed in the portal circulatory system in 11 healthy persons aged 17 to 22 years before and after taking the food containing normal levels of calories. A circulatory response was studied in the celiac trunk, superior mesenteric artery, splenic and portal veins. The normal values of the diameter, linear and volumetric blood flow velocities of the vessels under study were defined. There was their increased velocity of arterial and venous flows. A nevous response to a meal was ahead of an arterial one and the increase in blood flow in the celiac trunk occurred more rapidly than in the superior mesenteric artery. It is concluded that duplex scanning is an informative and reliable tool in the study of blood flow in the portal circulatory system.

  14. Pharmacokinetics of Lidocaine and Its Metabolites Following Vaginal Administration of Lidocaine Gel to Healthy Female Subjects

    PubMed Central

    Kushner, Harvey; Richardson, Elaine; Mize, Amy; Mayer, Philip

    2016-01-01

    Abstract Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single‐dose and multiple‐dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose‐proportional manner, and there was little systemic accumulation. Plasma concentrations were 10‐ to 20‐fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product. PMID:27297519

  15. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

    PubMed Central

    Shenker, Y; Sider, R S; Ostafin, E A; Grekin, R J

    1985-01-01

    Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID:2932471

  16. Yersinia enterocolitica: its isolation by cold enrichment from patients and healthy subjects.

    PubMed Central

    Van Noyen, R; Vandepitte, J; Wauters, G; Selderslaghs, R

    1981-01-01

    Routine culture and cold enrichment were compared in a prospective study on the isolation of Yersinia enterocolitica from patients with intestinal disease. Healthy controls were examined with the cold enrichment method only. Y enterocolitica was isolated from 5.9% of 1635 patient stools, 3.4% of 206 appendices, and 4.0% of 555 control stools. Serotypes 0:3 and 0:9 were eight times more prevalent in patients than in controls. Other serotypes were twice as prevalent in controls than in patients. Cold enrichment did not significantly increase the recovery of serotypes 0:3 and 0:9 in acute enteritis, but it was responsible for all isolates of the other serotypes. Evidence is presented that the other serotypes are not pathogenic. In patient stools, Y enterocolitica was demonstrated less frequently than Salmonella (9.1%), and more often than Campylobacter jejuni (1.8%) and Shigella (0.1%). PMID:7024325

  17. Redox stress unbalances the inflammatory cytokine network: role in autoinflammatory patients and healthy subjects.

    PubMed

    Lavieri, Rosa; Rubartelli, Anna; Carta, Sonia

    2016-01-01

    The cell stress and redox responses are increasingly acknowledged as factors contributing to the generation and development of the inflammatory response. Several inflammation-inducing stressors have been identified, inside and outside of the cell. Furthermore, many hereditary diseases associate with inflammation and oxidative stress, suggesting a role for mutated proteins as stressors. The nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is an important node at the crossroad between redox response and inflammation. Remarkably, monocytes from patients with mutations in the NLRP3 gene undergo oxidative stress after stimulation with minute amounts of TLR agonists, resulting in unbalanced production of IL-1β and regulatory cytokines. Similar alterations in cytokine production are found in healthy monocytes upon TLR overstimulation. This mini-review summarizes recent progress in this field, discusses the molecular mechanisms underlying the loss of control of the cytokine network following oxidative stress, and proposes new therapeutic opportunities.

  18. Immunohistological findings in lip biopsy specimens from patients with Crohn's disease and healthy subjects.

    PubMed Central

    Crama-Bohbouth, G; Bosman, F T; Vermeer, B J; van der Wal, A M; Biemond, I; Weterman, I T; Peńa, A S

    1983-01-01

    Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM. PMID:6826103

  19. Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.

    PubMed

    Yi, Buqing; Nichiporuk, Igor; Nicolas, Michel; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

    2016-06-03

    Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.

  20. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer.

    PubMed

    Chi, Kim N; Spratlin, Jennifer; Kollmannsberger, Christian; North, Scott; Pankras, Catherine; Gonzalez, Martha; Bernard, Apexa; Stieltjes, Hans; Peng, Lixian; Jiao, James; Acharya, Milin; Kheoh, Thian; Griffin, Thomas W; Yu, Margaret K; Chien, Caly; Tran, Nam Phuong

    2015-12-01

    Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients. Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0.5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety.

  1. Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects.

    PubMed

    Smith, Matthew J; Cobia, Derin J; Wang, Lei; Alpert, Kathryn I; Cronenwett, Will J; Goldman, Morris B; Mamah, Daniel; Barch, Deanna M; Breiter, Hans C; Csernansky, John G

    2014-03-01

    Cannabis use is associated with working memory (WM) impairments; however, the relationship between cannabis use and WM neural circuitry is unclear. We examined whether a cannabis use disorder (CUD) was associated with differences in brain morphology between control subjects with and without a CUD and between schizophrenia subjects with and without a CUD, and whether these differences related to WM and CUD history. Subjects group-matched on demographics included 44 healthy controls, 10 subjects with a CUD history, 28 schizophrenia subjects with no history of substance use disorders, and 15 schizophrenia subjects with a CUD history. Large-deformation high-dimensional brain mapping with magnetic resonance imaging was used to obtain surface-based representations of the striatum, globus pallidus, and thalamus, compared across groups, and correlated with WM and CUD history. Surface maps were generated to visualize morphological differences. There were significant cannabis-related parametric decreases in WM across groups. Similar cannabis-related shape differences were observed in the striatum, globus pallidus, and thalamus in controls and schizophrenia subjects. Cannabis-related striatal and thalamic shape differences correlated with poorer WM and younger age of CUD onset in both groups. Schizophrenia subjects demonstrated cannabis-related neuroanatomical differences that were consistent and exaggerated compared with cannabis-related differences found in controls. The cross-sectional results suggest that both CUD groups were characterized by WM deficits and subcortical neuroanatomical differences. Future longitudinal studies could help determine whether cannabis use contributes to these observed shape differences or whether they are biomarkers of a vulnerability to the effects of cannabis that predate its misuse.

  2. Erotic Stimulus Processing under Amisulpride and Reboxetine: A Placebo-Controlled fMRI Study in Healthy Subjects

    PubMed Central

    Wiegers, Maike; Metzger, Coraline D.; Walter, Martin; Grön, Georg; Abler, Birgit

    2015-01-01

    Background: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Methods: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Results: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. Conclusions: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. PMID:25612894

  3. Noninvasive Ambulatory Assessment of Cardiac Function and Myocardial Ischemia in Healthy Subjects Exposed to Carbon Monoxide

    DTIC Science & Technology

    1994-06-30

    change at 19% COWb. Other studies at rest found increases in cardiac output at 5%, 33%, and 48% COHb (Ayres et al., 1969; Asmussen and Chiodi , 1941... Chiodi et al. 1941), and were shown to be linearly related to COHb saturation (Stewart et al., 1973). In exercising subjects, Vogel and Gleser (1972...Exposure on Onset & Duration of Angina Pectoris." Ann Intern Med 1973;79:46-50. Asmussen, E., and H. Chiodi . "The Effect of Hypoxemia on Ventilation and

  4. [Characteristics of slow electrical potentials in healthy subjects and in patients with various forms of neuroses].

    PubMed

    Slezin, V B; Kamenskaia, V G; Tomanov, L V; Shchukina, N V

    1988-01-01

    The shapes of the slow brain potentials--conditioned negative wave (CNW) and postimperative negative wave (PNW)--were compared in normal and neurotic subjects. Instruction-directed performance was used to investigate the physiological mechanisms of neuroses and to develop the diagnostic psychophysiologic tests with simultaneous recording of the slow potentials. These were evaluated by calculation of asymmetry and power amplification coefficients for CNW and PNW while more and more complicated instructions were given.

  5. Developmental Level and Psychopathology: Comparing Children with Developmental Delays to Chronological and Mental Age Matched Controls

    PubMed Central

    Caplan, Barbara; Neece, Cameron L.; Baker, Bruce L.

    2015-01-01

    Children with developmental delays (DD) are at heightened risk for developing clinically significant behavioral and emotional difficulties as compared to children with typical development (TD). However, nearly all studies comparing psychopathology in youth with DD employ TD control groups of the same chronological age (CA). It is unclear, then, whether the heightened symptomology found in age-matched children with DD is beyond what would be expected given their developmental level. The present study assessed rates of behavior problems and mental disorder in 35 children with DD at age 9 years. These were compared with rates from 35 children with TD matched for CA at age 9 and also earlier rates for these same children at age 6, when matched for mental age (MA). Children with DD had significantly more behavior problems in 7 of the 17 scales of the CBCL when compared to TD children matched for CA, and 6 of 17 scales when compared to the MA-matched group. Rates of meeting DSM-IV criteria for a psychiatric disorder were significantly higher in the DD group than both the CA- and MA-matched TD groups for three and four, respectively, of the seven diagnoses examined. Descriptively, the mean ratings for all variables assessed were higher for the DD group than both TD comparison groups, with the exception of the Anxious/Depressed scale of the CBCL. These findings validate the heightened risk for clinically significant behavior problems and mental disorders in youth with DD above and beyond their developmental functioning. PMID:25498740

  6. Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

    ERIC Educational Resources Information Center

    Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

    2011-01-01

    Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

  7. Evaluation of visual stress symptoms in age-matched dyslexic, Meares-Irlen syndrome and normal adults

    PubMed Central

    Alanazi, Mana A.; Alanazi, Saud A.; Osuagwu, Uchechukwu L.

    2016-01-01

    AIM To examine the prevalence of dyslexia and Meares-Irlen syndrome (MIS) among female students and determine their level of visual stress in comparison with normal subjects. METHODS A random sample of 450 female medical students of King Saud University Riyadh (age range, 18-30y) responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions (CQ and NCQ) and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal (control), dyslexic with or without MIS (Group 1) and subjects with MIS only (Group 2). Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score (TVSS=NCQ+CQ), critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test. RESULTS The completion rate was 97.6% and majority of the respondents (92%) were normal readers, 2% dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommended eye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects (3/9, 33%) were significantly more likely to be diagnosed of lazy eye than Group 2 (2/27, 7%) and control (27/414, 7%) subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9 for CQ and 19±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive (82%) in Group 2 and less positive (46%) in Group 1 than control. With NCQ, the responses were

  8. The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

    PubMed

    Maruthy, K N; Vaz, M

    1999-04-01

    A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

  9. Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety rating in healthy human subjects

    SciTech Connect

    Woods, S.W.; Krystal, J.H.; Heninger, G.R.; Charney, D.S.

    1989-01-01

    In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO/sub 2/-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO/sub 2/-induced increases in ratings of anxiety. Neither drug altered CO/sub 2/-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO/sub 2/ induces anxiety-like effects involve neural systems regulated by benzodiazepine receptors and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.

  10. Effect of potassium and calcium loading on healthy subjects under hypokinesia and physical exercise with fluid and salt supplements

    NASA Astrophysics Data System (ADS)

    Zorbas, Yan G.; Naexu, Konstantin A.; Federenko, Youri F.

    1995-08-01

    The objective of this investigation was to determine the acute responses to the electrolyte challenges under hypokinesia and physical exercise (PE) of different intensities with fluid and salt supplementation (FSS). The studies were performed on 12 physically healthy male volunteers aged 19-24 years under 364 days of hypokinesia (decreased number of steps per day) with a set of PE with FSS. The volunteers were divided into two equal groups. The first group was subjected to a set of intensive PE and the second group was submitted to a set of moderate PE. Both groups of subjects consumed daily water and salt supplements that aimed to increase the body hydration level. For simulation of the hypokinetic effect all subjects were kept under an average of 3000 steps per day. Functional tests with a potassium chloride (KCl) and calcium lactate (Cal) load were performed during the hypokinetic period of 364 days and the 60-day prehypokinetic period that served as control, while both groups of subjects consumed daily calcium and potassium supplements. The concentration of electrolyte and hormone levels in the blood and their excretion rate in urine were determined. Renal excretion of calcium and potassium and the blood concentration thereof increased markedly in both groups of subjects. With the potassium chloride load tests the increased potassium excretion was accompanied by higher aldosterone and insulin blood levels, and with the calcium lactate load tests the increased calcium excretion was accompanied by a decreased parathyroid content in the blood. FSS and PE, regardless of intensity, failed to attenuate calcium and potassium losses. Additional intake of KCl and Cal also failed to normalize potassium and calcium abnormalities. It was concluded that during the KCl and Cal loading tests, the increased losses of potassium and calcium in the hypokinetic subjects were due to the inability of their bodies to retain these electrolytes, and that electrolyte abnormalities could

  11. Cognitive Behavior Evaluation Based on Physiological Parameters among Young Healthy Subjects with Yoga as Intervention

    PubMed Central

    Nagendra, H.; Kumar, Vinod; Mukherjee, S.

    2015-01-01

    Objective. To investigate the effect of yoga practice on cognitive skills, autonomic nervous system, and heart rate variability by analyzing physiological parameters. Methods. The study was conducted on 30 normal young healthy engineering students. They were randomly selected into two groups: yoga group and control group. The yoga group practiced yoga one and half hour per day for six days in a week, for a period of five months. Results. The yoga practising group showed increased α, β, and δ EEG band powers and significant reduction in θ and γ band powers. The increased α and β power can represent enhanced cognitive functions such as memory and concentration, and that of δ signifies synchronization of brain activity. The heart rate index θ/α decreased, neural activity β/θ increased, attention resource index β/(α + θ) increased, executive load index (δ + θ)/α decreased, and the ratio (δ + θ)/(α + β) decreased. The yoga practice group showed improvement in heart rate variability, increased SDNN/RMSSD, and reduction in LF/HF ratio. Conclusion. Yoga practising group showed significant improvement in various cognitive functions, such as performance enhancement, neural activity, attention, and executive function. It also resulted in increase in the heart rate variability, parasympathetic nervous system activity, and balanced autonomic nervous system reactivity. PMID:25759746

  12. Cardioprotective Efficacy of Red Wine Extract of Onion in Healthy Hypercholesterolemic Subjects.

    PubMed

    Chiu, Hui-Fang; Shen, You-Cheng; Huang, Ting-Yun; Venkatakrishnan, Kamesh; Wang, Chin-Kun

    2016-03-01

    The objective of this study was to evaluate the efficacy of the red wine extract of onion (RO) and red wine (RW) on alleviating the risk factors of cardiovascular disease. During in vitro studies, various antioxidant activities [trolox equivalent antioxidant capacity (TEAC), DPPH, and H2 O2 scavenging ability] of RO and RW group were evaluated. Both RO and RW showed the maximum antioxidant capacity. During in vivo studies, 23 healthy hypercholesterolemic volunteers were randomly selected and assigned into two groups, who drunk 250 mL of RO (n = 11) or RW (n = 10) for 10 weeks. No significant changes were observed in anthropometric parameters (body weight, height, body mass, and BMI) in each group. Both RW and RO extracts elevated (p < 0.05) antioxidant activity and thereby prolonging the lag time of low-density lipoprotein oxidation. However, RO extract intake substantially suppressed (p < 0.05) the total cholesterol and low-density lipoprotein cholesterol levels when equivalence with RW thus, indicating its additional hypocholesterolemic effect. The inflammatory markers such as factor VII were also positively modulated by RO extract. Results indicated that RO extract consumption rendered better cardio protective effect than RW by altering cholesterol, improving antioxidation and suppressing inflammatory marker levels and thereby, attenuating the cardiovascular disease incidence.

  13. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

    PubMed

    Misaka, S; Yatabe, J; Müller, F; Takano, K; Kawabe, K; Glaeser, H; Yatabe, M S; Onoue, S; Werba, J P; Watanabe, H; Yamada, S; Fromm, M F; Kimura, J

    2014-04-01

    This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

  14. Safety, tolerability, and pharmacokinetics of KNS-760704 (dexpramipexole) in healthy adult subjects.

    PubMed

    Bozik, Michael E; Mather, James L; Kramer, William G; Gribkoff, Valentin K; Ingersoll, Evan W

    2011-08-01

    Dexpramipexole (KNS-760704; [6R]-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine) is a novel synthetic amino-benzothiazole in development for the treatment of amyotrophic lateral sclerosis (ALS). Preclinical studies have shown that dexpramipexole is neuroprotective in vitro and in vivo, is highly orally bioavailable and water soluble, and rapidly achieves and maintains high central nervous system concentrations relative to plasma. Two phase 1 clinical studies were conducted to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of dexpramipexole in 54 healthy male and female adults. The effect of food on the single-dose PK of dexpramipexole was also evaluated. Single doses (50 mg, 150 mg, or 300 mg) and multiple doses (50 mg twice daily, 100 mg twice daily, or 150 mg twice daily) of dexpramipexole over 4.5 days were safe and well tolerated. Dexpramipexole was rapidly absorbed, with time to maximum plasma concentration ranging from 1.8 to 2.6 hours and half-life ranging from 6.4 to 8.1 hours under fasted conditions, and was mostly eliminated in urine as unchanged parent drug (84%-90% of dose). Food had no effect on the single-dose PK of dexpramipexole. These findings support the ongoing development of dexpramipexole for the treatment of ALS and further evaluation of the compound's therapeutic potential in other neurodegenerative diseases.

  15. Assessing autonomic function by analysis of heart rate recovery from exercise in healthy subjects.

    PubMed

    Pierpont, Gordon L; Voth, Eric J

    2004-07-01

    Although delayed recovery of heart rate (HR) after exercise indicates poor prognosis, the relative role of parasympathetic reactivation versus sympathetic withdrawal in controlling exercise HR recovery remains controversial. Quantifying HR recovery is difficult because the rate of recovery varies with exercise level. This study develops a model of HR recovery applicable to multiple exercise levels simultaneously. Using the Levenberg-Marquardt method for nonlinear models, HR curves for 11 healthy volunteers recovering from 4 different levels of exercise were fit to equations incorporating 1 first-order time constant for parasympathetic reactivation and 1 for sympathetic withdrawal. Results provided time constants for parasympathetic reactivation of 44 +/- 37 seconds and for sympathetic withdrawal of 65 +/- 56 seconds. The model fit the HR recovery curves very closely, explaining 99.7 +/- 0.1% of the variance in the data. In conclusion, this study presents a unique method for quantitatively testing theories on the relative roles of sympathetic withdrawal and parasympathetic reactivation during recovery from exercise. It provides indexes of dynamic sympathetic and parasympathetic functions, with the parasympathetic system having a faster response time. It supports theories of coordinated interaction of parasympathetic reactivation and sympathetic withdrawal during exercise recovery and does not support using simple measures of exercise HR recovery as indexes of vagal function alone.

  16. Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration

    PubMed Central

    Jochemsen, Roeline; Wesselman, J. G. J.; Hermans, J.; van Boxtel, C. J.; Breimer, D. D.

    1983-01-01

    1 Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. 2 Kinetic parameters after i.v. administration were: volume of distribution 0.66 ± 0.19 1/kg, total plasma clearance 113 ± 28 ml/min, distribution half-life 11 ± 6 min, and elimination half-life 4.8 ± 1.4 h (mean values ± s.d.). 3 Kinetic parameters after oral administration were: absorption lag-time 8 ± 12 min, absorption half-life 10 ± 11 min, and elimination half-life 5.1 ± 1.2 h (mean values ± s.d.). 4 Bioavailability of brotizolam was 70 ± 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 ± 24% (range: 47-117%). PMID:6661374

  17. The proteomic profile of whole and glandular saliva in healthy pain-free subjects

    PubMed Central

    Jasim, Hajer; Olausson, Patrik; Hedenberg-Magnusson, Britt; Ernberg, Malin; Ghafouri, Bijar

    2016-01-01

    Determination of the variability in the salivary proteome is a prerequisite for the development of saliva as a diagnostic and prognostic tool in particular physiological states. In this context, it is important that technical variability induced by sample collection and processing is kept at minimum to be able to reproducibly assess variability in states of health and disease. In the current study, the proteome profile in unstimulated and stimulated whole, parotid and sublingual saliva was investigated using two-dimensional gel electrophoresis. Saliva samples were structurally collected from ten examined and characterized healthy individuals during the exactly same conditions. The results demonstrated that different collection methods provide clear differences in the snapshot of the salivary proteome and also in the relative amount of specific proteins. The variable nature of the salivary proteome suggests that different approaches may have to be adopted when studying its composition or its possible role as an indicator for particular physiological states. The results emphasize the importance of consistency when collecting saliva samples for proteomic analysis. PMID:27976689

  18. What Limits Cardiac Performance during Exercise in Normal Subjects and in Healthy Fontan Patients?

    PubMed Central

    La Gerche, André; Gewillig, Marc

    2010-01-01

    Exercise is an important determinant of health but is significantly reduced in the patient with a univentricular circulation. Normal exercise physiology mandates an increase in pulmonary artery pressures which places an increased work demand on the right ventricle (RV). In a biventricular circulation with pathological increases in pulmonary vascular resistance and/or reductions in RV function, exercise-induced augmentation of cardiac output is limited. Left ventricular preload reserve is dependent upon flow through the pulmonary circulation and this requires adequate RV performance. In the Fontan patient, the reasons for exercise intolerance are complex. In those patients with myocardial dysfunction or other pathologies of the circulatory components, it is likely that these abnormalities serve as a limitation to cardiac performance during exercise. However, in the healthy Fontan patient, it may be the absence of a sub-pulmonary pump which limits normal increases in pulmonary pressures, trans-pulmonary flow requirements and cardiac output. If so, performance will be exquisitely dependent on pulmonary vascular resistance. This provides a potential explanation as to why pulmonary vasodilators may improve exercise tolerance. As has recently been demonstrated, these agents may offer an important new treatment strategy which directly addresses the physiological limitations in the Fontan patient. PMID:20871839

  19. Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects

    PubMed Central

    Holmberg, Mikko T; Tornio, Aleksi; Joutsi-Korhonen, Lotta; Neuvonen, Mikko; Neuvonen, Pertti J; Lassila, Riitta; Niemi, Mikko; Backman, Janne T

    2013-01-01

    Aim This study examined the effects of grapefruit juice on the new P2Y12 inhibitor ticagrelor, which is a substrate of CYP3A4 and P-glycoprotein. Methods In a randomized crossover study, 10 healthy volunteers ingested 200 ml of grapefruit juice or water thrice daily for 4 days. On day 3, they ingested a single 90 mg dose of ticagrelor. Results Grapefruit juice increased ticagrelor geometric mean peak plasma concentration (Cmax) to 165% (95% confidence interval 147, 184%) and area under the concentration–time curve (AUC(0,∞)) to 221% of control (95% confidence interval 200, 245%). The Cmax and AUC(0,34 h) (P < 0.05) but not the AUC(0,∞) of the active metabolite C12490XX were decreased significantly. Grapefruit juice had a minor effect on ticagrelor elimination half-life prolonging it from 6.7 to 7.2 h (P = 0.036). In good correlation with the elevated plasma ticagrelor concentrations, grapefruit juice enhanced the antiplatelet effect of ticagrelor, assessed with VerifyNow® and Multiplate® methods, and postponed the recovery of platelet reactivity. Conclusions Grapefruit juice increased ticagrelor exposure by more than two-fold, leading to an enhanced and prolonged ticagrelor antiplatelet effect. The grapefruit juice–ticagrelor interaction seems clinically important and indicates the significance of intestinal metabolism to ticagrelor pharmacokinetics. PMID:23126367

  20. Directional effects of biofeedback on trunk sway during gait tasks in healthy young subjects.

    PubMed

    Janssen, Lindy J F; Verhoeff, Lonneke L; Horlings, Corinne G C; Allum, John H J

    2009-06-01

    Biofeedback of trunk sway is a possible remedy for patients with balance disorders. Because these patients have a tendency to fall more in one direction, we investigated whether biofeedback has a directional effect on trunk sway during gait. Forty healthy young participants (mean age 23.1 years) performed 10 gait tasks with and without biofeedback. Combined vibrotactile, auditory and visual feedback on trunk sway in either the lateral or anterior-posterior (AP) direction was provided by a head-mounted actuator system. Trunk roll and pitch angles, calculated from trunk angular velocities measured with gyroscopes, were used to drive the feedback. A reduction in sway velocities occurred across all tasks regardless of feedback direction. Reductions in sway angles depended on the task. Generally, reductions were greater in pitch. For walking up and down stairs, or over barriers, pitch angle reductions were greater with AP than lateral feedback. For tandem and normal walking, reductions were similar in pitch and roll angles for both feedback directions. For walking while rotating or pitching the head or with eyes closed, only pitch angle was reduced for both feedback directions. These results indicate that the central nervous system is able to incorporate biofeedback of trunk sway from either the AP or lateral direction to achieve a reduction in both pitch and roll sway. Greater reductions in pitch suggest a greater ability to use this direction of trunk sway biofeedback during gait.

  1. The absolute systemic availability of a new oral formulation of co-dergocrine in healthy subjects.

    PubMed

    Dominiak, P; Grevel, J; Abisch, E; Grobecker, H; Dennler, H J; Welzel, D

    1988-01-01

    We have studied the absolute systemic availability (f) of an oral formulation (Hydergin spezial = Hydergine FASR 4 mg per tablet) of co-dergocrine by three different methods. Twelve healthy volunteers received single doses of 0.9 mg co-dergocrine intravenously and 8.0 mg orally in a randomized crossover design. The pharmacological effect of co-dergocrine was monitored as a reduction in plasma prolactin. Maximal plasma concentrations of co-dergocrine after oral dosing ranged between 0.181 and 1.307 ng.ml-1. Maximal urinary excretion ranged between 4.7 and 9.9 micrograms.h-1 and between 0.3 and 2.3 micrograms.h-1 after intravenous and oral doses respectively. Clearance was measured as 90 +/- 22 l.h-1 and the absolute systemic availability (f) as 2.25 +/- 0.65% by using the areas under the plasma concentration-time curves extrapolated to infinity. Calculation of f by comparing areas up to 32 h or the fractions of the dose excreted in urine led to identical results. The intravenous and oral doses produced similar pharmacological effects (reduction of plasma prolactin concentrations) despite the small value of f.

  2. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects.

    PubMed

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; Todd King, M; Musa-Veloso, Kathy; Ho, Manki; Roberts, Ashley; Robertson, Jeremy; Vanitallie, Theodore B; Veech, Richard L

    2012-08-01

    Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of β-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1h for β-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.

  3. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects

    PubMed Central

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; King, M. Todd; Musa-Veloso, Kathy; Ho, Manki; Roberts, Ashley; Robertson, Jeremy; VanItallie, Theodore B.; Veech, Richard L.

    2013-01-01

    Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of β-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1–2 h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8–3.1 h for β-hydroxybutyrate and 8–14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet. PMID:22561291

  4. 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects.

    PubMed

    Cerasa, Antonio; Quattrone, Aldo; Piras, Fabrizio; Mangone, Graziella; Magariello, Angela; Fagioli, Sabrina; Girardi, Paolo; Muglia, Maria; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-10-01

    Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into 'no anxiety' and 'subclinical anxiety' groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours.

  5. 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects

    PubMed Central

    Cerasa, Antonio; Quattrone, Aldo; Piras, Fabrizio; Mangone, Graziella; Magariello, Angela; Fagioli, Sabrina; Girardi, Paolo; Muglia, Maria; Caltagirone, Carlo

    2014-01-01

    Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into ‘no anxiety’ and ‘subclinical anxiety’ groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours. PMID:23986266

  6. The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy.

    PubMed

    Bell, Caroline; Vanderlinden, Hilde; Hiersemenzel, Reinhard; Otoul, Christian; Nutt, David; Wilson, Sue

    2002-09-01

    Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges.

  7. Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects

    PubMed Central

    Jain, Renu T.; Panda, J.; Srivastava, A.

    2011-01-01

    Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole. PMID:22923863

  8. Randomized, Controlled, Thorough QT/QTc Study Shows Absence of QT Prolongation with Luseogliflozin in Healthy Japanese Subjects

    PubMed Central

    Kumagai, Yuji; Hasunuma, Tomoko; Sakai, Soichi; Ochiai, Hidekazu; Samukawa, Yoshishige

    2015-01-01

    Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor. To evaluate the cardiac safety of luseogliflozin, a thorough QT/QTc study was conducted in healthy Japanese subjects. The effects of moxifloxacin on QT prolongation in Japanese subjects were also evaluated. In this double-blind, placebo- and open-label positive-controlled, 4-way crossover study, 28 male and 28 female subjects received a single dose of luseogliflozin 5 mg (therapeutic dose), luseogliflozin 20 mg (supratherapeutic dose), placebo, and moxifloxacin 400 mg. Serial triplicate digital 12-lead electrocardiograms (ECGs) were recorded before and after dosing, and results were analyzed using the Fridericia correction (QTcF) method. Serial blood sampling was performed for pharmacokinetic analyses of luseogliflozin and moxifloxacin to analyze the relationship between QTcF interval and plasma concentration. The upper limits of the two-sided 90% confidence intervals (CIs) for baseline and placebo-adjusted QTcF intervals (ΔΔQTcF) in the 5 mg and 20 mg luseogliflozin groups were less than 10 ms at all time points. No correlation between plasma luseogliflozin concentrations and ΔΔQTcF was observed. In the moxifloxacin group, the lower limits of the two-sided 90% CIs for ΔΔQTcF were greater than 5 ms at all time points. A positive relationship was observed between plasma moxifloxacin concentration and change in ΔΔQTcF. Luseogliflozin was well tolerated at both dose levels. The majority of adverse events were mild in severity, and no serious or life-threatening adverse events occurred. Neither therapeutic (5 mg) nor supratherapeutic (20 mg) doses of luseogliflozin affected QT prolongation in healthy Japanese subjects. PMID:26444986

  9. Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects

    PubMed Central

    Anic-Milic, T.; Oreskovic, K.; Padovan, J.; Brouwer, K. L. R.; Zuo, P.; Schmith, V. D.

    2013-01-01

    Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.) PMID:23629714

  10. Voclosporin food effect and single oral ascending dose pharmacokinetic and pharmacodynamic studies in healthy human subjects.

    PubMed

    Mayo, Patrick R; Huizinga, Robert B; Ling, Spencer Y; Freitag, Derrick G; Aspeslet, Launa J; Foster, Robert T

    2013-08-01

    Voclosporin (VCS) is a novel calcineurin (CN) inhibitor intended for prevention of organ graft rejection and treatment of lupus nephritis. These studies evaluated the single ascending dose pharmacokinetics (PK) and pharmacodynamics (PD, CN activity) of VCS and the effect of food. VCS was administered orally in single doses of 0.25 through 4.5 mg/kg in 62 subjects in the single ascending dose study and as a single oral 1.5 mg/kg dose to 18 subjects after fasting, consumption of a low-fat and high-fat meal. Non-compartmental PK, PD, and PKPD correlation were evaluated. Following single oral doses, systemic exposure increased in a linear manner and demonstrated 1:1 dose-proportional, first-order linear PK above 1.5 mg/kg. VCS inhibited CN activity in a dose-related fashion with maximal inhibition peaking at 3.0 mg/kg. PKPD correlation indicated an EC50 of 78.3 ± 6.8 ng/mL. Administration of VCS with a low-fat and high-fat meal decreased C(max) by 29% and 53%, respectively, and AUC(inf) by 15% and 25%, respectively. Following ascending single doses of VCS, exposure increased in a linear fashion. A food effect on exposure was demonstrated, with a more pronounced effect following a high-fat meal. VCS concentrations were also found to correlate with CN activity.

  11. Adrenocortical responses to repeated parachute jumping and subsequent h-CRH challenge in inexperienced healthy subjects.

    PubMed

    Deinzer, R; Kirschbaum, C; Gresele, C; Hellhammer, D H

    1997-04-01

    The present study examined the adrenocortical response to 3 consecutive parachute jumps and a poststress h-CRH challenge. Fifteen participants in a parachute-jumping course took saliva samples for later cortisol analysis every 20 min throughout the day, when they accomplished their very first 3 parachute jumps and throughout a control day. The effects of an h-CRH challenge on salivary cortisol were assessed in the evening of the jumping day and on a control day. Parachute jumping induced 3 distinct highly significant adrenocortical responses. The respective cortisol increases for the first, second, and third jump were 39.4 +/- 26.5 nmol/1, 31.4 +/- 21.4 nmol/l, and 16.5 +/- 11.9 nmol/l. Cortisol responses to the first and second jump did not differ but the response to the third jump was significantly reduced [t(13) = 3.11; p = 0.008]. Two groups of subjects were identified, "decreasers," whose response decreased from one to the other jump, and "increasers," whose response remained unchanged or increased. The magnitude of the preceding cortisol response of decreasers exceeded that of increasers significantly by about 30 nmol. The mean adrenocortical effects of the poststress h-CRH challenge and the time-matched challenge on a control day did not differ although, in 4 subjects, the poststress adrenocortical response to h-CRH was completely suppressed.

  12. Inhalation of a Short-Acting β2-Adrenoreceptor Agonist Induces a Hypercoagulable State in Healthy Subjects

    PubMed Central

    Ali-Saleh, Mais; Sarig, Galit; Ablin, Jacob N.; Brenner, Benjamin; Jacob, Giris

    2016-01-01

    Background Catecholamine infusion elicits an increase in clotting factors and this increase has been attributed to stimulation of β2-adrenorecptors (β2AR). Accordingly, we tested the hypothesis that inhalation of a short-acting selective β2AR agonist can induce a procoagulant state in healthy individuals. Methods We recruited 23 healthy volunteers (nine females; mean age: 26±0.8 years; body mass index: 24.7±0.5 kg/m2) and randomly allocated them into two groups, the β2AR arm (seventeen subjects) and the saline arm (six subjects). Hemodynamics, plasma norepinephrine concentration, and procoagulant, anticoagulant, and fibrinolytic profiles of each participant were determined using specific assays before and after inhalation of either 2 mL nebulized normal saline or a mixture of 1 mL saline and 1 mL of salbutamol (5 mg salbutamol sulfate), a selective β2AR agonist, which were delivered by a nebulizer over ten minutes. Results Saline inhalation had no effect on the procoagulant, anticoagulant and fibrinolytic profiles of the six healthy volunteer in the study's saline arm. Salbutamol inhalation caused (a) a significant increase in the activity or levels of the procoagulant factors; FVIII increased by 11±3% (p = 0.04), von Willebrand factor increased by 7±1% (p = 0.03), and (b) a significant decrease in the activated partial prothrombin time from 27.4±0.4 seconds to 25.5 ±0.5 seconds (p<0.001) in the 17 volunteers in the study's β2AR arm. D-dimer and prothrombin fragments F1+2 were elevated by 200 ±90% and 505.0 ±300.0%, respectively. In addition, the activity of the anticoagulant protein C pathway (demonstrated by the protein C Global assay) decreased from 1.0±0.08 to 0.82±0.06 (p<0.001). Although plasma levels of tissue plasminogen activator decreased, all other indices of the fibrinolytic system did not change following salbutamol inhalation. Conclusion We found that a single inhalation of salbutamol, a short-acting β2AR agonist, activates the

  13. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects

    PubMed Central

    Almeida, Germana P. L.; Trombetta, Ivani C.; Cepeda, Felipe X.; Hatanaka, Elaine; Curi, Rui; Mostarda, Cristiano; Irigoyen, Maria C.; Barreto-Filho, José A. S.; Krieger, Eduardo M.; Consolim-Colombo, Fernanda M.

    2017-01-01

    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX–reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2

  14. Investigation of decision-making under uncertainty in healthy subjects: a multi-centric fMRI study.

    PubMed

    Krug, A; Cabanis, M; Pyka, M; Pauly, K; Walter, H; Landsberg, M; Shah, N Jon; Winterer, G; Wölwer, W; Musso, F; Müller, B W; Wiedemann, G; Herrlich, J; Schnell, K; Vogeley, K; Schilbach, L; Langohr, K; Rapp, A; Klingberg, S; Kircher, T

    2014-03-15

    Decision-making is an everyday routine that entails several subprocesses. Decisions under uncertainty occur when either prior information is incomplete or the outcomes of the decision are unclear. The aim of the present study was to disentangle the neural correlates of information gathering as well as reaching a decision and to explore effects of uncertainty acceptance or avoidance in a large sample of healthy subjects. Sixty-four healthy volunteers performed a decision-making under uncertainty task in a multi-center approach while BOLD signal was measured with fMRI. Subjects either had to indicate via button press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or they had to indicate whether 8 red balls had been presented (baseline condition). During the information gathering phase (contrasted against the counting phase) a widespread network was found encompassing (pre-)frontal, inferior temporal and inferior parietal cortices. Reaching a decision was correlated with activations in the medial frontal cortex as well as the posterior cingulate and the precuneus. Effects of uncertainty acceptance were found within a network comprising of the superior frontal cortex as well as the insula and precuneus while uncertainty avoidance was correlated with activations in the right middle frontal cortex. The results depict two distinct networks for information gathering and the indication of having made a decision. While information-gathering networks are modulated by uncertainty avoidance and - acceptance, underlying networks of the decision itself are independent of these factors.

  15. Tissue Damage Markers after a Spinal Manipulation in Healthy Subjects: A Preliminary Report of a Randomized Controlled Trial

    PubMed Central

    Achalandabaso, A.; Plaza-Manzano, G.; Lomas-Vega, R.; Martínez-Amat, A.; Camacho, M. V.; Gassó, M.; Hita-Contreras, F.; Molina, F.

    2014-01-01

    Spinal manipulation (SM) is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM). In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; n = 10), a single lower cervical manipulation (cervical group; n = 10), and a thoracic manipulation (n = 10). Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK), lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, myoglobin, neuron-specific enolase (NSE), and aldolase were determined in samples. Statistical analysis was performed through a 3 × 3 mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects. PMID:25609853

  16. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects.

    PubMed

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-02-17

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin.

  17. Influence of forward leaning and incentive spirometry on inspired volumes and inspiratory electromyographic activity during breathing exercises in healthy subjects.

    PubMed

    Santos, Thalita Vilaboim; Ruas, Gualberto; Sande de Souza, Luciane Aparecida Pascucci; Volpe, Marcia Souza

    2012-12-01

    Breathing exercises (BE), incentive spirometry and positioning are considered treatment modalities to achieve lung re-expansion. This study evaluated the influence of incentive spirometry and forward leaning on inspired tidal volumes (V(T)) and electromyographic activity of inspiratory muscles during BE. Four modalities of exercises were investigated: deep breathing, spirometry using both flow and volume-oriented devices, and volume-oriented spirometry after modified verbal instruction. Twelve healthy subjects aged 22.7 ± 2.1 years were studied. Surface electromyography activity of diaphragm, external intercostals, sternocleidomastoid and scalenes was recorded. Comparisons among the three types of exercises, without considering spirometry after modified instruction, showed that electromyographic activity and V(T) were lower during volume-oriented spirometry (p = 0.000, p = 0.054, respectively). Forward leaning resulted in a lower V(T) when compared to upright sitting (p = 0.000), but electromyographic activity was not different (p = 0.606). Inspired V(T) and electromyographic activity were higher during volume-oriented spirometry performed after modified instruction when compared with the flow-oriented device (p = 0.027, p = 0.052, respectively). In conclusion BE using volume-oriented spirometry before modified instruction resulted in a lower work of breathing as a result of a lower V(T) and was not a consequence of the device type used. Forward leaning might not be assumed by healthy subjects during situations of augmented respiratory demand.

  18. Neglect-like behavior in healthy subjects: dissociation of space exploration and goal-directed pointing after vestibular stimulation.

    PubMed

    Karnath, Hans-Otto; Himmelbach, Marc; Perenin, Marie-Thérèse

    2003-11-01

    Evidence has been reported favoring the view of a dual mode of space representation for action and spatial cognition. While the dorsal system seems to be mainly involved in direct coding of space for action by means of several effector-specific representations, the ventral system appears to be responsible for more enduring and conscious representations underlying spatial cognition and awareness. In accordance with this view are recent studies documenting dissociations between exploratory and goal-directed movements in patients with brain damage. Patients with neglect exhibit a spatial bias of exploratory movements to the ipsilesional side, while goal-directed movements land precisely on target. The exploratory bias was found susceptible to asymmetric sensory stimulation such as caloric vestibular stimulation, inducing transient reduction of contralateral neglect. The present study compared exploratory and goal-directed hand movements in healthy subjects following cold caloric stimulation of the right vestibular organ. We observed a rightward shift of tactile exploration, while goal-directed pointing remained unaffected. Asymmetric vestibular stimulation in healthy subjects thus produced a neglect-like behavior with a similar dissociation between impaired exploratory and nonimpaired goal-directed hand movements. The stimulation provoked a further, very characteristic symptom of neglect patients: a deviation of spontaneous head orientation toward the right. The present observations strengthen substantially the assumption of different modes of space representation for action and spatial cognition in humans.

  19. Interaction effect between the BDNF Val66Met polymorphism and parental rearing for interpersonal sensitivity in healthy subjects.

    PubMed

    Suzuki, Akihito; Matsumoto, Yoshihiko; Shibuya, Naoshi; Ryoichi, Sadahiro; Kamata, Mitsuhiro; Enokido, Masanori; Goto, Kaoru; Otani, Koichi

    2012-12-30

    Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behaviour and feelings of others and is one of the vulnerable factors to depression. In a twin study, it was suggested that this personality trait was characterised by both genetic and environmental factors. In the present study, we examined the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on interpersonal sensitivity in 725 healthy Japanese subjects. Assessment of interpersonal sensitivity was performed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. The BDNF polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. There was no main effect of the BDNF genotype on the IPSM score, while the PBI factors except maternal care had significant main effect on the IPSM score. There was significant interaction effect between the BDNF genotype and maternal care of the PBI on the IPSM score. Post-hoc analysis of simple slopes showed that the negative relationship between the IPSM score and maternal care was strongest and significant in the Met/Met genotype group, intermediate in the Val/Met genotype group and weakest in the Val/Val genotype group. The present study suggests that the interaction between the BDNF Val66Met polymorphism and parental rearing, especially maternal care, influences interpersonal sensitivity in healthy subjects.

  20. Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.

    PubMed

    Neuhaus, Andres H; Goldberg, Terry E; Hassoun, Youssef; Bates, John A; Nassauer, Katharine W; Sevy, Serge; Opgen-Rhein, Carolin; Malhotra, Anil K

    2009-06-01

    Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

  1. Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects

    PubMed Central

    Neuhaus, Andres H.; Goldberg, Terry E.; Hassoun, Youssef; Bates, John A.; Nassauer, Katharine W.; Sevy, Serge; Opgen-Rhein, Carolin; Malhotra, Anil K.

    2013-01-01

    Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research. PMID:19356906

  2. Tissue damage markers after a spinal manipulation in healthy subjects: a preliminary report of a randomized controlled trial.

    PubMed

    Achalandabaso, A; Plaza-Manzano, G; Lomas-Vega, R; Martínez-Amat, A; Camacho, M V; Gassó, M; Hita-Contreras, F; Molina, F

    2014-01-01

    Spinal manipulation (SM) is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM). In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; n = 10), a single lower cervical manipulation (cervical group; n = 10), and a thoracic manipulation (n = 10). Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK), lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, myoglobin, neuron-specific enolase (NSE), and aldolase were determined in samples. Statistical analysis was performed through a 3 × 3 mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects.

  3. Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects

    PubMed Central

    Michlig, Stéphanie; Merlini, Jenny Meylan; Beaumont, Maurice; Ledda, Mirko; Tavenard, Aude; Mukherjee, Rajat; Camacho, Susana; le Coutre, Johannes

    2016-01-01

    Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially ‘too intense’ by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin. PMID:26883089

  4. Integrated population pharmacokinetics of etanercept in healthy subjects and in patients with rheumatoid arthritis and ankylosing spondylitis.

    PubMed

    Zhou, Simon Y; Shu, Cathye; Korth-Bradley, Joan; Raible, Donald; Palmisano, Maria; Wadjula, Joseph; Fatenejad, Saeed; Bjornsson, Thorir

    2011-06-01

    Etanercept pharmacokinetics in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis were assessed separately with distinct models using population pharmacokinetics methods of limited precision. The different model structures and associated significant covariates identified by these earlier methods made it difficult to compare etanercept pharmacokinetics among disease groups. This integrated analysis aimed to establish a framework to evaluate previously established population pharmacokinetic models of etanercept, and to identify consistent and important demographic and disease factors that affected etanercept pharmacokinetics in a diverse population of healthy subjects and patients with RA and AS. In this integrated analysis, cumulative rich and sparse etanercept concentration data from 53 healthy volunteers, 212 patients with RA, and 346 patients with AS were examined and compared using nonlinear mixed effect methodology implemented the in NONMEM VI software package. A more precise estimation method (FOCEi) was employed and compared with the first-order method in population pharmacokinetics model building and evaluation. The integrated analysis found that an optimal population pharmacokinetics model with a 2-compartment structure adequately characterized etanercept pharmacokinetics in all subject groups. Health status or disease type did not significantly affect etanercept pharmacokinetics. In adult patients with RA and AS, age and body weight do not significantly affect etanercept pharmacokinetics.

  5. Effects of general fatigue induced by incremental maximal exercise test on gait stability and variability of healthy young subjects.

    PubMed

    Vieira, Marcus Fraga; de Sá E Souza, Gustavo Souto; Lehnen, Georgia Cristina; Rodrigues, Fábio Barbosa; Andrade, Adriano O

    2016-10-01

    The purpose of this study was to determine whether general fatigue induced by incremental maximal exercise test (IMET) affects gait stability and variability in healthy subjects. Twenty-two young healthy male subjects walked in a treadmill at preferred walking speed for 4min prior (PreT) the test, which was followed by three series of 4min of walking with 4min of rest among them. Gait variability was assessed using walk ratio (WR), calculated as step length normalized by step frequency, root mean square (RMSratio) of trunk acceleration, standard deviation of medial-lateral trunk acceleration between strides (VARML), coefficient of variation of step frequency (SFCV), length (SLCV) and width (SWCV). Gait stability was assessed using margin of stability (MoS) and local dynamic stability (λs). VARML, SFCV, SLCV and SWCV increased after the test indicating an increase in gait variability. MoS decreased and λs increased after the test, indicating a decrease in gait stability. All variables showed a trend to return to PreT values, but the 20-min post-test interval appears not to be enough for a complete recovery. The results showed that general fatigue induced by IMET alters negatively the gait, and an interval of at least 20min should be considered for injury prevention in tasks with similar demands.

  6. Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects.

    PubMed

    Eichler, Martin; Spinedi, Luca; Unfer-Grauwiler, Sandra; Bodmer, Michael; Surber, Christian; Luedi, Markus; Drewe, Juergen

    2012-05-01

    The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. SATIVA, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. SATIVA extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability.

  7. The effect of acute effort on EEG in healthy young and elderly subjects.

    PubMed

    Moraes, Helena; Deslandes, Andrea; Silveira, Heitor; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Pompeu, Fernando; Laks, Jerson

    2011-01-01

    The effects of physical exercise on mental health have been extensively investigated, mainly in older people. Recent studies have looked into the acute effect of exercise on the brain using standardized low-resolution brain electromagnetic tomography (sLORETA). We assessed EEG power and mood changes after 20 min of aerobic exercise in elderly (N = 10) and young (N = 19) healthy individuals. Both groups showed improvement in total mood disturbance (TMD) post exercise (young: P = 0.03; elderly: P = 0.02). Only the young group showed significant improvement in anger (P = 0.05) and vigor (P = 0.006). Comparison pre versus post-exercise for each group separately revealed significant changes in the young group (an increase in alpha, beta-1 and beta-2 activity in Brodmann areas 24, 33 and 23, respectively). However, the elderly group did not show significant changes. An inverse correlation was found between alpha asymmetry and STAI (rs = -0.50; P = 0.029) in the young group. On the other hand, a significant correlation between beta-1 activity and TMD was observed in the elderly group (rs = 0.67; P = 0.045). We conclude that acute exercise can have distinct effects on brain activity and mood variables in young individuals when compared with elderly adults. However, additional studies are necessary to further investigate the role of exercise intensity in these results.

  8. Enantioselective disposition of hydroxychloroquine after a single oral dose of the racemate to healthy subjects.

    PubMed

    Ducharme, J; Fieger, H; Ducharme, M P; Khalil, S K; Wainer, I W

    1995-08-01

    1. Stereoselectivity in the disposition of hydroxychloroquine was investigated in 23 healthy males following a single oral dose of 200 mg racemic HCQ (rac-HCQ) sulphate. Total concentrations (R+S) and R/S ratios of HCQ and its metabolites were measured by stereoselective h.p.l.c. 2. HCQ was detected in whole blood and urine, up to 91 and 85 days after dosing, respectively. Metabolites could not be detected in whole blood while in urine detectable concentrations were still present after 85 days. The blood concentrations of HCQ enantiomers were measurable until 168 h post-dose. 3. R(-)-HCQ accounted for 62 +/- 3% (mean +/- s.d.) of the AUC of rac-HCQ AUC. The elimination half-life of S(+)-HCQ (457 +/- 122 h) was significantly shorter than that of R(-)-HCQ (526 +/- 140 h), partly due to its faster urinary excretion and hepatic metabolism. Its renal clearance was twice that of R(-)-HCQ (4.61 +/- 4.01 vs 1.79 +/- 1.30 1 h-1), and metabolites derived from the S-isomer represented 80-90% of the urinary recovery of the dose. 4. Over 85 days, 4.4 +/- 2.9 and 3.3 +/- 1.8% of the dose was recovered in urine as unchanged S(+)-HCQ and R(-)-HCQ, respectively. For the first 2 weeks, S(+)-HCQ excretion rate clearly surpassed that of R(-)-HCQ whereas afterwards the inverse was observed. However, since the first 2 weeks account for 95% of rac-HCQ renal excretion, the total urinary excretion of S(+)-HCQ clearly surpassed that of R(-)-HCQ.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Reactivity of retinal blood flow to 100% oxygen breathing after lipopolysaccharide administration in healthy subjects.

    PubMed

    Kolodjaschna, Julia; Berisha, Fatmire; Lasta, Michael; Polska, Elzbieta; Fuchsjäger-Mayrl, Gabriele; Schmetterer, Leopold

    2008-08-01

    Administration of low doses of Escherichia coli endotoxin (LPS) to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate the retinal vascular reactivity after LPS infusion. In a randomized placebo-controlled cross-over study, 18 healthy male volunteers received 20 IU/kg LPS or placebo as an intravenous bolus infusion. Outcome parameters were measured at baseline and 4h after LPS/placebo administration. At baseline and at 4h after administration a short period of 100% oxygen inhalation was used to assess retinal vasoreactivity to this stimulus. Perimacular white blood cell velocity, density and flux were assessed with the blue-field entoptic technique, retinal branch arterial and venous diameters were measured with a retinal vessel analyzer and red blood cell velocity in retinal branch veins was measured with laser Doppler velocimetry. LPS is associated with peripheral blood leukocytosis and increased white blood cell density in ocular microvessels (p<0.001). In addition, retinal arterial (p=0.02) and venous (p<0.01) diameters were increased. All retinal hemodynamic parameters showed a decrease during 100% oxygen breathing. This decrease was significantly blunted by LPS for all retinal outcome parameters except venous diameter (p=0.04 for white blood cell velocity, p=0.0002 for white blood cell density, p<0.0001 for white blood cell flux, p=0.01 for arterial diameter, p=0.02 for red blood cell velocity and p=0.006 for red blood cell flux). These data indicate that LPS-induced inflammation induces vascular dysregulation in the retina. This may provide a link between inflammation and vascular dysregulation. Further studies are warranted to investigate whether this model may be suitable to study inflammation induced vascular dysregulation in the eye.

  10. Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects.

    PubMed

    Sweetser, Seth; Busciglio, Irene A; Camilleri, Michael; Bharucha, Adil E; Szarka, Lawrence A; Papathanasopoulos, Athanasios; Burton, Duane D; Eckert, Deborah J; Zinsmeister, Alan R

    2009-02-01

    Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 microg lubiprostone per day in a parallel-group, placebo-controlled trial