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Healthy Human Subjects (healthy + human_subject)
Selected AbstractsCNS response to a thermal stressor in human volunteers and rats may predict the clinical utility of analgesicsDRUG DEVELOPMENT RESEARCH, Issue 1 2007David Borsook Abstract fMRI was used to test the hypothesis that global brain activation following a stressor (a thermal stimulus) that activates multiple brain circuits in healthy subjects can predict which drugs have higher potential for clinical utility for neuropathic pain. The rationale is that a drug will modulate multiple neural circuits that are activated by the system-specific stressor (e.g., pain). In neuropathic pain, some brain circuits have altered function, but most brain systems are "normal." Thus, the manner in which a drug effect on neural circuits is modulated by the stressor may provide insight into the clinical utility based on the readout of brain activation in response to the stimulus. Six drugs with known clinical efficacy (or lack thereof) in treating neuropathic pain were selected and the CNS response to each drug in the presence or absence of a pain stimulus was examined. The present results suggest that it is possible to identify potentially effective drugs based on patterns of brain activation in healthy human subjects and indicate that CNS activity is a more sensitive measure of drug action than standard psychophysical measures of pain intensity. This approach was repeated in rats and showed that a similar fMRI paradigm segregates these drugs in a similar manner suggesting a potential "translational tool" in evaluating drug efficacy for neuropathic pain. The sensitivity of this paradigm using fMRI allows clinical screening in small groups of healthy subjects, suggesting it could become a useful tool for drug development as well as for elucidating the mechanisms of neuropathic disease and therapy. Drug Dev. Res. 68:23,41, 2007. © 2007 Wiley-Liss, Inc. [source] Cerebral Metabolism is Influenced by Muscle Ischaemia During Exercise in HumansEXPERIMENTAL PHYSIOLOGY, Issue 2 2003Mads K. Dalsgaard Maximal exercise reduces the cerebral metabolic ratio (O2/(glucose + 1/2lactate)) to < 4 from a resting value close to 6, and only part of this decrease is explained by the ,intent' to exercise. This study evaluated whether sensory stimulation of brain by muscle ischaemia would reduce the cerebral metabolic ratio. In 10 healthy human subjects the cerebral arterial-venous differences (a-v differences) for O2, glucose and lactate were assessed before, during and after three bouts of 10 min cycling with equal workload: (1) control exercise at light intensity, (2) exercise that elicited a high rating of perceived exertion due to a 100 mmHg thigh cuff, and (3) exercise followed by 5 min of post-exercise muscle ischaemia that increased blood pressure by , 20%. Control exercise did not significantly affect the a-v differences. However, during the recovery from exercise with thigh cuffs the cerebral metabolic ratio decreased from a resting value of 5.4 ± 0.2 to 4.0 ± 0.4 (mean ±s.e.m.. P < 0.05) as a discrete lactate efflux from the brain at rest shifted to a slight uptake. Also, following post-exercise muscle ischaemia, the cerebral metabolic ratio decreased to 4.5 ± 0.3 (P < 0.05). The results support the hypothesis that during exercise, cerebral metabolism is influenced both by the mental effort to exercise and by sensory input from skeletal muscles. [source] Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjectsHISTOPATHOLOGY, Issue 5 2007E P Wilder-Smith Aims:, The transient receptor potential vanilloid 1 (TRPV1) plays an important role in mediating pain and heat. In painful neuropathies, intraepidermal TRPV1 nerve fibre expression is low or absent, suggesting that pain generated is not directly related to sensory nerve fibres. Recent evidence suggests that keratinocytes may act as thermal receptors via TRPV1. The aim was to investigate epidermal TRPV1 expression in patients with neuropathic conditions associated with pain. Methods and results:, In a prospective study of distal small nerve fibre neuropathy (DISN; n = 13) and diabetic neuropathy (DN; n = 12) intraepidermal nerve fibre density was assessed using the pan axonal marker PGP 9.5 and epidermal TPVR1 immunoreactivity compared with controls (n = 9). Intraepidermal nerve fibres failed to show TRPV1 immunoreactivity across all groups. There was moderate and strong TRPV1 reactivity of epidermal keratinocytes in 41.8% and 6% for DISN, 32.9% and 2.9% for DN and 25.4% and 5.1% for controls, respectively. Moderate keratinocyte TRPV1 expression was significantly increased in DISN compared with controls (P = 0.01). Conclusion:, Our study suggests that in human painful neuropathies, epidermal TRPV1 expression is mainly in keratinocytes. [source] Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensityHUMAN BRAIN MAPPING, Issue 9 2006Jian Kong Abstract Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Plasma serotonin response to carbohydrate-rich food in chronic schizophrenic patients: clozapine versus classic antipsychotic agentsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2001Yaffa Vered Abstract Researchers have reported a stimulatory effect of carbohydrate-rich intake on platelet-poor plasma (PPP) serotonin (5-HT) levels in healthy human subjects. Dietary manipulation may serve as a safer and less invasive means than pharmacologic challenge to provoke serotonergic responsivity in studies of schizophrenia. In the present study, we used the carbohydrate-rich meal test as an indicator of 5-HT activity in 12 patients with chronic schizophrenia maintained for at least 6 months on clozapine. PPP 5-HT levels were measured at baseline and at 1, 2 and 3,h after administration of the test. Findings were compared with those in schizophrenic patients treated with classic antipsychotic agents for the same duration. The maximal PPP 5-HT response was reached 120 min after meal administration in the clozapine-treated group and 60 min after in the classic antipsychotic-treated group (P<0.05 vs baseline for both). The 5-HT level (as percentage of baseline) at 60 min was significantly lower in the clozapine-treated group (P<0.02), as were individual PPP 5-HT peak values (P<0.05). The individual time to reach the peak response was similar in the two groups. Our results indicate that in patients with chronic schizophrenia 5-HT responsivity to the natural challenge of carbohydrate-rich meals is lower in those treated with clozapine than in those given classic antipsychotic agents. Values in both groups were lower than those in an appropriate historical comparative group of healthy subjects. We suggest that both clozapine and classic antipsychotic agents suppress serotonergic system sensitivity, but to a different degree. Copyright © 2001 John Wiley & Sons, Ltd. [source] Crushed Clopidogrel Administered via Nasogastric Tube Has Faster and Greater Absorption than Oral Whole TabletsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009M. UROOJ ZAFAR M.B.B.S. Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers. Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading. Methods: Nine healthy human subjects (34.7 ± 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following ,2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points. Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28,0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84,1.32, P = 0.646). Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated. [source] Measurement of deep gray matter perfusion using a segmented true,fast imaging with steady-state precession (True-FISP) arterial spin-labeling (ASL) method at 3TJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Elan J. Grossman MS Abstract Purpose To study the feasibility of using the MRI technique of segmented true,fast imaging with steady-state precession arterial spin-labeling (True-FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T. Materials and Methods A flow-sensitive alternating inversion-recovery (FAIR) ASL perfusion preparation was used in which the echo-planar imaging (EPI) readout was replaced with a segmented True-FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years ± 9.9). Results Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET). Conclusion Segmented True-FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI-based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425,1431. © 2009 Wiley-Liss, Inc. [source] Plasma Agouti-Related Protein Level: A Possible Correlation with Fasted and Fed States in Humans and RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2002C.-P. Shen Abstract We measured plasma concentrations of agouti-related protein (AGRP) in humans and rats and determined whether these were affected by ingestion of a meal after fasting. In 17 healthy human subjects, the mean plasma concentration of AGRP was lower in the fed state than in the fasted state. Two hours after a breakfast meal, AGRP levels dropped by 39%. By contrast, a continued fast for 2 h increased the average AGRP concentration by 73%. In rats with diet-induced obesity, refeeding resulted in a 50% decrease in plasma AGRP concentrations following a fasting-refeeding protocol. Our results support the notion that plasma AGRP may serve as a biomarker for the transition from a fasted to the satiated state. [source] The influence of altered occlusal guidance on condylar displacement during submaximal clenchingJOURNAL OF ORAL REHABILITATION, Issue 10 2005N. OKANO summary As cited in literatures, canine protected occlusion has a potential to reduce clenching induced temporomandibular joint loadings. However, these previous studies did not perform a control of the clenching level which differed with the depending occlusal conditions. This result may be due largely to an associated reduced jaw closing muscle activity. The present study has investigated clenching induced condylar displacements with controlled clenching level. Twenty healthy human subjects (15 males and five females with an average age of 26·5 years) volunteered to participate in this study. Metallic occlusal overlays were fabricated for the lower working side canine and overlaid to the second molar and the non-working side second molar in order to simulate a canine protected occlusion, group function occlusion and bilateral balanced occlusion. Electromyographic (EMG) activity from the bilateral masseter, anterior temporalis, and posterior temporalis was recorded. These signals were rectified, summarized, and presented to each subject using an oscilloscope screen. Using this visual feedback, subjects were asked to perform clenching tasks at a 50% level of maximal voluntary contraction exerted with simulated group function occlusion and three-dimensional condylar displacements were recorded. An experimental occlusal pattern that shows statistically significant affects on condylar displacements (anova: P < 0·001) was found. When compared with the simulated canine protected occlusion, the simulated group function occlusion caused smaller working side condylar displacement and the simulated bilateral balanced occlusion caused significantly smaller non-working side and working side condylar displacements. These results suggest that the increased working side tooth contacts have a potential to reduce working side joint loadings, and a balancing side contact has a potential to reduce non-working side joint loadings, under the laboratory condition where the clenching level is controlled. [source] Stiffness, viscosity, and upper-limb inertia about the glenohumeral abduction axisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2000Li-Qun Zhang To evaluate the dynamic properties of the shoulder and understand how they are controlled by the central nervous system, glenohumeral-joint stiffness and viscosity and upper-limb inertia were quantified under various levels of muscle contraction in seven healthy human subjects. Through a cast attachment, the upper limb was perturbed in a precise pattern by a computer-controlled servomotor to manifest the dynamic properties of the joint. The recorded joint position and torque were used to estimate joint stiffness and viscosity and upper-limb inertia. With moderate muscle contraction, the stiffness and viscosity increased several fold. A stiffer shoulder joint associated with stronger muscle contraction made the shoulder more stable and protected it from potential injuries during strenuous tasks. Joint viscosity, especially the stronger viscous damping associated with more strenuous contraction, smoothed shoulder movement and stabilized the joint. From the control viewpoint, the glenohumeral joint responded to the central nervous system more quickly with increasing muscle contraction, which was useful during strenuous tasks. On the other hand, the central nervous system controlled stiffness and viscosity synchronously so that it dealt with only a nearly constant damping ratio of the joint over various levels of contraction, which simplified its task substantially. This approach quantified the dynamic and static properties of the shoulder under various levels of contraction more accurately and completely than a manual test, and it can potentially be used to evaluate changes in these properties caused by musculoskeletal injuries and their surgical treatments. [source] Continuous distal oesophageal acidification decreases postprandial gastric acidity in healthy human subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009K. BLONDEAU Summary Background, Previously, we hypothesized that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity. Aim, To test the hypothesis that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity. Methods, Twenty-two healthy humans ingested a standard meal containing [14C]octanoic acid and [13C]glycine over 30 min on 2 separate occasions. Gastric pH was measured for 90 min before and 240 min after the meal. 10 mm HCl was infused continuously at 1 mL/min into either the distal oesophagus or stomach in a 2-way crossover fashion for 60 min before and 240 min after the meal. Gastric emptying of solid and liquid were determined with breath tests. Results, Compared to gastric infusion, oesophageal infusion significantly decreased gastric acidity after the meal, but not before the meal and the magnitude of the decrease varied directly with gastric acidity. Gastric emptying of solid or liquid with oesophageal infusion was not significantly different from that with gastric infusion. Conclusions, These findings support the hypothesis of the existence of a physiological oesophago-gastric feedback mechanism that might contribute to regulation of postprandial gastric acidity. Oesophageal acidification might decode gastric information and signal the stomach to decrease gastric acidity. Further studies are needed to assess the characteristics of such feedback mechanism in-patients with gastro-oesophageal reflux disease (GERD). [source] Use of tissue water as a concentration reference for proton spectroscopic imagingMAGNETIC RESONANCE IN MEDICINE, Issue 6 2006Charles Gasparovic Abstract A strategy for using tissue water as a concentration standard in 1H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 ± 1.19 mM; WM [NAc] = 14.26 ± 1.38 mM; GM [Ch] = 3.27 ± 0.47 mM; WM [Ch] = 2.65 ± 0.25 mM; GM [Cr] = 13.98 ± 1.20 mM; and WM [Cr] = 7.10 ± 0.67 mM. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Mechanisms of force failure during repetitive maximal efforts in a human upper airway muscleMUSCLE AND NERVE, Issue 1 2002Christiana DelloRusso BS Abstract The upper airway respiratory muscles play an important role in the regulation of airway resistance, but surprisingly little is known about their contractile properties and endurance performance. We developed a technique that allows measurement of force and the electromyogram (EMG) of human nasal dilator muscles (NDMs). Endurance performance was quantified by measuring NDM "flaring" force and EMG activity as healthy human subjects performed 10 s maximal voluntary contractions (MVCs), separated by 10 s rest, until the area under the force curve fell to 50% MVC (the time limit of the fatigue task, Tlim), which was reached in 34.2 ± 3.1 contractions (685.0 ± 62.3 s). EMG activity was unchanged except at Tlim, where it averaged 78.7 ± 3.6% of pretest activity (P < 0.01). M-wave amplitude did not change, suggesting that neuromuscular propagation was not impaired. MVC force increased to 80% of the pretest level within 10 min of recovery but twitch force failed to recover, suggesting low-frequency fatigue. The data suggest that a failure of the nervous system to excite muscle could explain at most only a small fraction of the NDM force loss during an intermittent fatigue task, and then only at Tlim. Thus, the majority of the force failure during this task is due to impairment of mechanisms that reside within the muscle fibers. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 94,100, 2002 [source] Determination of corneal volume from anterior topography and topographic pachymetry: application to healthy and keratoconic eyesOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2009Alejandro Cerviño Abstract Purpose:, To describe a method to measure corneal volume from topography and pachymetry, and test its clinical use on a sample of healthy human subjects and a case of circumscribed posterior keratoconus. Methods:, Corneal curvature (PCT 200® corneal topography system; Optopol Technology SA, Zawiercie, Poland) and ultrasonic topographic pachometry on 25 points (Ophthasonic® A-Scan/Pachometer III; Teknar Inc., St Louis, MO, USA) were measured on each of 12 young healthy corneas and one cornea suffering from circumscribed posterior keratoconus. Topography and pachymetry data were used to calculate the coordinates for the corresponding points on the posterior surface of the cornea. TableCurve 3D software (Systat Software Inc., Chicago, IL, USA) was used to fit a surface to those points measured. Integration of the surface fitted to the data points, corresponding to the anterior and posterior corneal surfaces, was used to calculate the volume underneath each of them. Subtraction of volumes underneath anterior and posterior surfaces, taking into account an axial offset equal to the central corneal thickness, rendered corneal volume for the central 6 mm of the cornea. Results:, Central corneal thickness ranged from 520 to 630 ,m for the healthy corneas. Corneal volumes for this sample analyzed averaged 18.66 ± 1.15 mm3 (range 17.25,20.53 mm3). For the posterior keratoconic cornea, the affected area was located at about 1.5,2 mm from the corneal center on the 135° hemimeridian of the right eye, observed through topographic pachymetry. Calculated corneal volume for the central 6 mm was 16.072 mm3, noticeably lower than those found in the sample without pathology, but within the range for corneas presenting with keratoconus. Conclusions:, Corneal volume is a useful parameter for characterising dystrophic corneas and can aid in the detection of rare anomalies which are hardly detected with corneal topography and/or central corneal thickness evaluation. A potentially useful measure of corneal volume can be calculated from anterior corneal topography and topographic pachymetry data. Values obtained are in good agreement with previous studies using corneal tomography techniques. The methodology has been shown to have potential for retrospective analysis of data, or where no access is available to tomographical techniques. [source] Normal ranges of angiogenesis regulatory proteins in human platelets,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Jon E. Peterson Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/106 platelets); PDGF (23 ± 6 pg/106); PF4 (12 ± 5 ng/106); TSP-1 (31 ± 12 ng/106); bFGF (0.44 ± 0.15 pg/106); and endostatin (5.6 ± 3.0 pg/106). There was an excellent correlation (R2 = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF-4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Adaptation of the Human Skin by Chronic Solar-simulating UV Irradiation Prevents Ultraviolet-B Irradiation-induced Rise in Serum C-Reactive Protein Levels,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2005Jarmo K. Laihia ABSTRACT Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P= 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P= 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 ± 0.21 mg/L) declined by 35% (P= 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations. [source] Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortexTHE JOURNAL OF PHYSIOLOGY, Issue 12 2009Timothy Hunter Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot-induced velocity-dependent force fields. Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity-dependent force field (adaptation; 25 N s m,1) and once again in a null force field (de-adaptation). Active or sham tDCS was directed to the motor cortex representation of biceps brachii muscle during the adaptation phase of the motor learning protocol. During the adaptation phase, the global error in arm reaching (summed error from an ideal trajectory) was similar in both tDCS conditions. However, active tDCS induced a significantly greater global reaching (overshoot) error during the early stage of de-adaptation compared to the sham tDCS condition. The overshoot error may be representative of the development of a greater predictive movement to overcome the expected imposed force. An estimate of the predictive, initial movement trajectory (signed error in the first 150 ms of movement) was significantly augmented during the adaptation phase with active tDCS compared to sham tDCS. Furthermore, this increase was linearly related to the change of the overshoot summed error in the de-adaptation process. Together the results suggest that anodal tDCS augments the development of an internal model of the novel adapted movement and suggests that the primary motor cortex is involved in adaptation of reaching movements of healthy human subjects. [source] After-effects of near-threshold stimulation in single human motor axonsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Hugh Bostock Subthreshold electrical stimuli can generate a long-lasting increase in axonal excitability, superficially resembling the phase of superexcitability that follows a conditioning nerve impulse. This phenomenon of ,subthreshold superexcitability' has been investigated in single motor axons in six healthy human subjects, by tracking the excitability changes produced by conditioning stimuli of different amplitudes and waveforms. Near-threshold 1 ms stimuli caused a mean decrease in threshold at 5 ms of 22.1 ± 6.0% (mean ±s.d.) if excitation occurred, or 6.9 ± 2.6% if excitation did not occur. The subthreshold superexcitability was maximal at an interval of about 5 ms, and fell to zero at 30 ms. It appeared to be made up of two components: a passive component linearly related to conditioning stimulus amplitude, and a non-linear active component. The active component appeared when conditioning stimuli exceeded 60% of threshold, and accounted for a maximal threshold decrease of 2.6 ± 1.3%. The passive component was directly proportional to stimulus charge, when conditioning stimulus duration was varied between 0.2 and 2 ms, and could be eliminated by using triphasic stimuli with zero net charge. This change in stimulus waveform had little effect on the active component of subthreshold superexcitability or on the ,suprathreshold superexcitability' that followed excitation. It is concluded that subthreshold superexcitability in human motor axons is mainly due to the passive electrotonic effects of the stimulating current, but this is supplemented by an active component (about 12% of suprathreshold superexcitability), due to a local response of voltage-dependent sodium channels. [source] Circulating adiponectin levels during human endotoxaemiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2003P. KELLER SUMMARY Adiponectin, an adipocytokine secreted by fat tissue, may prevent development of diabetes type II, as high adiponectin levels are linked with insulin sensitivity. In contrast, tumour necrosis factor (TNF)- ,, which is also produced by fat tissue, leads to insulin resistance and furthermore inhibits adiponectin mRNA production and secretion of the protein. However, adiponectin also negatively regulates TNF- , levels. Therefore, we set out to test whether an infusion of endotoxin would influence circulating adiponectin levels in healthy human subjects. Twenty-three healthy human subjects were injected with endotoxin (2 ng/kg body weight); eight of these subjects were also injected with saline and served as controls. Plasma levels of adiponectin, TNF- , and interleukin-6 were measured at 0, 1·5, 2, 4, 8 and 24 h. TNF- , and interleukin-6 levels peaked at 1·5 h and 2 h, respectively. Control subjects injected with saline showed a decrease in adiponectin plasma levels with time (P < 0·05) presumably owing to the effect of fasting or physical inactivity. However, there was no change in adiponectin plasma levels in endotoxin injected subjects, thus the effect of fasting was opposed. In conclusion, circulating adiponectin levels are reduced during a resting and fasting state, an effect reversed by endotoxin injection. [source] | |||||||||||||