Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans.
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ABSTRACT:
SUBMITTER: Coulie B
PROVIDER: S-EPMC1727256 | biostudies-other | 1998 Sep
REPOSITORIES: biostudies-other
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Project description:Pancreatic polypeptide (PP) is known to affect food intake. In this exploratory study, we set out to investigate its supraphysiological effect on food tolerance, gastric accommodation, and emptying. In 12 healthy volunteers, 0, 3, or 10 pmol*kg-1 *min-1 PP was administered intravenously (PP0, PP3 or PP10). Thirty minutes thereafter, nutrient drink infusion (60 ml*min-1 ) through a nasogastric feeding tube was started until maximum satiation. Gastric accommodation was assessed by measuring the intragastric pressure (IGP; nasogastric manometry). In a separate test, the effect of PP0 or PP10 on gastric emptying was tested in 10 healthy volunteers and assessed using the 13 C breath test. Results are presented as mean ± SEM, and p < 0.05 was considered significant. For the IGP test, PP increased ingested nutrient volume: 886 ± 93, 1059 ± 124, and 1025 ± 125 ml for PP0, PP3, and PP10, respectively (p = 0.048). In all groups, Nadir IGP values were reached upon food intake (transformed values: 1.5 ± 0.2, 1.7 ± 0.3, and 1.6 ± 0.3 mmHg for PP0, PP3, and PP10, respectively; NS) to return to baseline thereafter. For the gastric emptying study, volunteers ingested a similar nutrient volume: 802 ± 119 and 1089 ± 128 ml (p = 0.016), and gastric half-emptying time was 281 ± 52 and 249 ± 37 min for PP0 and PP10, respectively (NS). No significant correlation between tolerated nutrient volume and IGP drop (R² < 0.01; p = 0.88 for PP0 vs. PP3 and R² =0.07; p = 0.40 for PP0 vs. PP10, respectively) or gastric half-emptying time (R² = 0.12; p = 0.32) was found. A supraphysiological PP dose enhances food tolerance; however, this effect is not mediated through gastric motility. CLINICAL TRIAL REGISTRY NUMBER: NCT03854708 is obtained from clinicaltrials.gov.
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Project description:Non-invasive, weak direct current stimulation can induce changes in excitability of underlying neural tissue. Many studies have used transcranial direct current stimulation to induce changes in the brain, however more recently a number of studies have used transcutaneous spinal direct current stimulation to induce changes in the spinal cord. This study further characterises the effects following cervical transcutaneous spinal direct current stimulation on motor pathways supplying the upper limb. In Study 1, on two separate days, participants (n = 12, 5 F) received 20 minutes of either real or sham direct current stimulation at 3 mA through electrodes placed in an anterior-posterior configuration over the neck (anode anterior). Biceps brachii, flexor carpi radialis and first dorsal interosseous responses to transcranial magnetic stimulation (motor evoked potentials) and cervicomedullary stimulation (cervicomedullary motor evoked potentials) were measured before and after real or sham stimulation. In Study 2, on two separate days, participants (n = 12, 7 F) received either real or sham direct current stimulation in the same way as for Study 1. Before and after real or sham stimulation, median nerve stimulation elicited M waves and H reflexes in the flexor carpi radialis. H-reflex recruitment curves and homosynaptic depression of the H reflex were assessed. Results show that the effects of real and sham direct current stimulation did not differ for motor evoked potentials or cervicomedullary motor evoked potentials for any muscle, nor for H-reflex recruitment curve parameters or homosynaptic depression. Cervical transcutaneous spinal direct current stimulation with the parameters described here does not modify motor responses to corticospinal stimulation nor does it modify H reflexes of the upper limb. These results are important for the emerging field of transcutaneous spinal direct current stimulation.
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Project description:BackgroundRecent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels.ObjectiveWe statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one.MethodsWe fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.ResultsUsing values of Akaike's information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to K(m) values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 muM/ppm of benzene, a value close to an independent estimate of 194 muM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 muM/ppm) than under the one-pathway model (68.6 muM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway.ConclusionBecause regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure-about 3-fold higher among nonsmoking females in the general population.
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Project description:The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n?=?11; >55 years) versus younger (n?=?29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean±95% CI; older AHI 19.6±9.9 events/hr versus younger AHI 30.1±6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7±0.5 ms versus 11.1±0.2 ms; P ?=? 0.05), with similar amplitudes (395.2±25.1 µV versus 394.6±13.7 µV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7±6.5 µV versus 51.3±3.0 µV; P<0.05), with areas 24% larger (160.6±18.6 µV.ms versus 130.0±7.4 µV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility.
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Project description:How do physical interactions with others change our own motor behavior? Utilizing a novel motor learning paradigm in which the hands of two - individuals are physically connected without their conscious awareness, we investigated how the interaction forces from a partner adapt the motor behavior in physically interacting humans. We observed the motor adaptations during physical interactions to be mutually beneficial such that both the worse and better of the interacting partners improve motor performance during and after interactive practice. We show that these benefits cannot be explained by multi-sensory integration by an individual, but require physical interaction with a reactive partner. Furthermore, the benefits are determined by both the interacting partner's performance and similarity of the partner's behavior to one's own. Our results demonstrate the fundamental neural processes underlying human physical interactions and suggest advantages of interactive paradigms for sport-training and physical rehabilitation.
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Project description:In addition to motor functions, it has become clear that in humans the cerebellum plays a significant role in cognition too, through connections with associative areas in the cerebral cortex. Classical anatomy indicates that neo-cerebellar regions are connected with the contralateral cerebral cortex through the dentate nucleus, superior cerebellar peduncle, red nucleus and ventrolateral anterior nucleus of the thalamus. The anatomical existence of these connections has been demonstrated using virus retrograde transport techniques in monkeys and rats ex vivo. In this study, using advanced diffusion MRI tractography we show that it is possible to calculate streamlines to reconstruct the pathway connecting the cerebellar cortex with contralateral cerebral cortex in humans in vivo. Corresponding areas of the cerebellar and cerebral cortex encompassed similar proportion (about 80%) of the tract, suggesting that the majority of streamlines passing through the superior cerebellar peduncle connect the cerebellar hemispheres through the ventrolateral thalamus with contralateral associative areas. This result demonstrates that this kind of tractography is a useful tool to map connections between the cerebellum and the cerebral cortex and moreover could be used to support specific theories about the abnormal communication along these pathways in cognitive dysfunctions in pathologies ranging from dyslexia to autism.
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Project description:Despite the advancements in the cancer therapeutics, gastric cancer ranks as the second most common cancers with high global mortality rate. Integrative functional genomic investigation is a powerful approach to understand the major dysregulations and to identify the potential targets toward the development of targeted therapeutics for various cancers. Intestinal and diffuse type gastric tumors remain the major subtypes and the molecular determinants and drivers of these distinct subtypes remain unidentified. In this investigation, by exploring the network of gene coexpression association in gastric tumors, mRNA expressions of 20,318 genes across 200 gastric tumors were categorized into 21 modules. The genes and the hub genes of the modules show gastric cancer subtype specific expression. The expression patterns of the modules were correlated with intestinal and diffuse subtypes as well as with the differentiation status of gastric tumors. Among these, G1 module has been identified as a major driving force of diffuse type gastric tumors with the features of (i) enriched mesenchymal, mesenchymal stem cell like, and mesenchymal derived multiple lineages, (ii) elevated OCT1 mediated transcription, (iii) involvement of Notch activation, and (iv) reduced polycomb mediated epigenetic repression. G13 module has been identified as key factor in intestinal type gastric tumors and found to have the characteristic features of (i) involvement of embryonic stem cell like properties, (ii) Wnt, MYC and E2F mediated transcription programs, and (iii) involvement of polycomb mediated repression. Thus the differential transcription programs, differential epigenetic regulation and varying stem cell features involved in two major subtypes of gastric cancer were delineated by exploring the gene coexpression network. The identified subtype specific dysregulations could be optimally employed in developing subtype specific therapeutic targeting strategies for gastric cancer.
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Project description:The embodied cognition hypothesis suggests that motor and premotor areas are automatically and necessarily involved in understanding action language, as word conceptual representations are embodied. This transcranial magnetic stimulation (TMS) study explores the role of the left primary motor cortex in action-verb processing. TMS-induced motor-evoked potentials from right-hand muscles were recorded as a measure of M1 activity, while participants were asked either to judge explicitly whether a verb was action-related (semantic task) or to decide on the number of syllables in a verb (syllabic task). TMS was applied in three different experiments at 170, 350 and 500 ms post-stimulus during both tasks to identify when the enhancement of M1 activity occurred during word processing. The delays between stimulus onset and magnetic stimulation were consistent with electrophysiological studies, suggesting that word recognition can be differentiated into early (within 200 ms) and late (within 400 ms) lexical-semantic stages, and post-conceptual stages. Reaction times and accuracy were recorded to measure the extent to which the participants' linguistic performance was affected by the interference of TMS with M1 activity. No enhancement of M1 activity specific for action verbs was found at 170 and 350 ms post-stimulus, when lexical-semantic processes are presumed to occur (Experiments 1-2). When TMS was applied at 500 ms post-stimulus (Experiment 3), processing action verbs, compared with non-action verbs, increased the M1-activity in the semantic task and decreased it in the syllabic task. This effect was specific for hand-action verbs and was not observed for action-verbs related to other body parts. Neither accuracy nor RTs were affected by TMS. These findings suggest that the lexical-semantic processing of action verbs does not automatically activate the M1. This area seems to be rather involved in post-conceptual processing that follows the retrieval of motor representations, its activity being modulated (facilitated or inhibited), in a top-down manner, by the specific demand of the task.
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Project description:BackgroundEndocrine disrupting chemicals are widely distributed in the environment and derive from many different human activities or can also be natural products synthesized by plants or microorganisms. The phytoestrogen, genistein (4', 5, 7-trihydroxy-isoflavone), is a naturally occurring compound found in soy products. Genistein has been the subject of numerous studies because of its known estrogenic activity.Methodology/principal findingsWe report that genistein exposure of zebrafish embryos induces apoptosis, mainly in the hindbrain and the anterior spinal cord. Timing experiments demonstrate that apoptosis is induced during a precise developmental window. Since adding ICI 182,780, an ER antagonist, does not rescue the genistein-induced apoptosis and since there is no synergistic effect between genistein and estradiol, we conclude that this apoptotic effect elicited by genistein is estrogen-receptors independent. However, we show in vitro, that genistein binds and activates the three zebrafish estrogen receptors ERalpha, ERbeta-A and ERbeta-B. Furthermore using transgenic ERE-Luciferase fish we show that genistein is able to activate the estrogen pathway in vivo during larval stages. Finally we show that genistein is able to induce ectopic expression of the aromatase-B gene in an ER-dependent manner in the anterior brain in pattern highly similar to the one resulting from estrogen treatment at low concentration.Conclusion/significanceTAKEN TOGETHER THESE RESULTS INDICATE THAT GENISTEIN ACTS THROUGH AT LEAST TWO DIFFERENT PATHWAYS IN ZEBRAFISH EMBRYOS: (i) it induces apoptosis in an ER-independent manner and (ii) it regulates aromatase-B expression in the brain in an ER-dependent manner. Our results thus highlight the multiplicity of possible actions of phytoestrogens, such as genistein. This suggests that the use of standardized endpoints to study the effect of a given compound, even when this compound has well known targets, may carry the risk of overlooking interesting effects of this compound.
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Project description:BACKGROUND:This study examined the motor unit (MU) control strategies for non-fatiguing isometric elbow flexion tasks at 40% and 70% maximal voluntary isometric contraction. METHODS:Nineteen healthy individuals performed two submaximal tasks with similar torque levels: contracting against an immovable object (force task), and maintaining the elbow joint angle against an external load (position task). Surface electromyographic (EMG) signals were collected from the agonist and antagonist muscles. The signals from the agonist were decomposed into individual action potential trains. The linear regression analysis was used to examine the MU recruitment threshold (RT) versus mean firing rates (MFR), and RT versus derecruitment threshold (DT) relationships. RESULTS:Both agonist and antagonist muscles' EMG amplitudes did not differ between two tasks. The linear slopes of the MU RT versus MFR and RT versus DT relationships during the position task were more negative (p = 0.010) and more positive (p = 0.023), respectively, when compared to the force task. CONCLUSIONS:To produce a similar force output, the position task may rely less on the recruitment of relatively high-threshold MUs. Additionally, as the force output decreases, MUs tend to derecruit at a higher force level during the position task.
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