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Sample records for submucosa reduces stimulated

  1. Deep brain stimulation to reduce sexual drive

    PubMed Central

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  2. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  3. Tactile stimulation reduces fear in fish

    PubMed Central

    Schirmer, Annett; Jesuthasan, Suresh; Mathuru, Ajay S.

    2013-01-01

    Being groomed or touched can counter stress and negative affect in mammals. In two experiments we explored whether a similar phenomenon exists in non-mammals like zebrafish. In Experiment 1, we exposed zebrafish to a natural stressor, a chemical alarm signal released by injured conspecifics. Before moving them into an observation tank, one group of fish was washed and then subjected to a water current that served as the tactile stimulus. The other group was simply washed. Fish with tactile treatment demonstrated fewer fear behaviors (e.g., bottom dwelling) and lower cortisol levels than fish without. In Experiment 2, we ascertained a role of somatosensation in these effects. Using a similar paradigm as in Experiment 1, we recorded fear behaviors of intact fish and fish with damaged lateral line hair cells. Relative to the former, the latter benefited less from the tactile stimulus during fear recovery. Together these findings show that tactile stimulation can calm fish and that tactile receptors, evolutionarily older than those present in mammals, contribute to this phenomenon. PMID:24319415

  4. Emphysematous Eosinophilic Lymphangitis in the Ruminal Submucosa of Cattle.

    PubMed

    Ohfuji, S

    2015-11-01

    Twenty cattle (14 Holstein-Friesian, 3 Japanese Black, 3 Aberdeen Angus) ranging in age from 3 months to 8 years exhibited, at slaughter, emphysematous thickening of the ruminal submucosa owing to the appearance of numerous, contiguous, small gas bubbles. Microscopic changes in the ruminal submucosa consisted of (1) multiple cystic (emphysematous) lymphangiectasis that was frequently lined or occluded by granulomatous inflammatory infiltrates including macrophages, multinucleate giant cells, and eosinophils; (2) intralymphatic phagocytosis by macrophages and giant cells of eosinophils that showed positive labeling with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay; and (3) an inflammatory infiltrate extending from the area of lymphangitis into surrounding tissue, as well as edema, hemorrhage, fibrin exudation, fibroplasia, or capillary proliferation throughout the lesional submucosa. In addition, 15 (75%) of the cattle had globular leukocyte infiltrates in the mucosal epithelia of the rumen.

  5. Reduced Environmental Stimulation Techniques and Control of Psychological Dependencies.

    ERIC Educational Resources Information Center

    Cooper, G. David

    Three areas of research have supported the conceptual relevance of Reduced Environmental Stimulation (RES) techniques in the management of psychological dependencies. First, preliminary studies through the late l960's indicated that relatively short periods of RES had a facilitative effect on the type of subject who might be most vulnerable to…

  6. Immune stimulation reduces sleep and memory ability in Drosophila melanogaster

    PubMed Central

    Alghamdi, Akram; Holdbrook, Robert T.K.; Rosato, Ezio

    2014-01-01

    Psychoneuroimmunology studies the increasing number of connections between neurobiology, immunology and behaviour. We demonstrate the effects of the immune response on two fundamental behaviours: sleep and memory ability in Drosophila melanogaster. We used the Geneswitch system to upregulate peptidoglycan receptor protein (PGRP) expression, thereby stimulating the immune system in the absence of infection. Geneswitch was activated by feeding the steroid RU486, to the flies. We used an aversive classical conditioning paradigm to quantify memory and measures of activity to infer sleep. Immune stimulated flies exhibited reduced levels of sleep, which could not be explained by a generalised increase in waking activity. Immune stimulated flies also showed a reduction in memory abilities. These results lend support to Drosophila as a model for immune–neural interactions and provide a possible role for sleep in the interplay between the immune response and memory. PMID:24949247

  7. Crosslinking Decreases the Hemocompatibility of Decellularized, Porcine Small Intestinal Submucosa

    PubMed Central

    Glynn, Jeremy J.; Polsin, Elizabeth G.; Hinds, Monica T.

    2014-01-01

    Decellularized tissues have been widely used as scaffolds for biomedical applications due to their presentation of adhesion peptide sequences and growth factors, which facilitate integration with surrounding tissue. One of the most commonly used decellularized tissue is derived from porcine small intestinal submucosa (SIS). In some applications, SIS is crosslinked to modulate the mechanical properties or degradation rate of the scaffold. Despite the widespread use of SIS, there has been no mechanistic characterization of blood reactions with SIS, nor how crosslinking affects these reactions. Therefore, we characterized the effect of SIS and carbodiimide-crosslinked SIS (cSIS) on plasma coagulation, including targeted assessments of the intrinsic and extrinsic coagulation pathways, and thrombus formation using flowing whole blood. SIS inhibited plasma coagulation initiated by recalcification, as well as low concentrations of thrombin or tissue factor. SIS prolonged the activated partial thromboplastin time by 14.3±1.54 sec, indicating inhibition of the intrinsic coagulation pathway. Carbodiimide crosslinking abrogated all anticoagulant effects of SIS, as did heparinase I and III treatment, suggesting heparin and heparan sulfate are predominantly responsible for SIS anticoagulant effects. Inhibiting contact activation of the intrinsic pathway prevented cSIS-mediated coagulation. When tubular SIS devices were connected to a nonhuman primate arteriovenous shunt loop, which enables whole blood to flow across devices without the use of anticoagulants, SIS demonstrated remarkably limited platelet accumulation and fibrinogen incorporation, while cSIS initiated significantly higher platelet and fibrinogen accumulation. These results demonstrate that SIS is a thromboresistant material and crosslinking markedly reduces the hemocompatibility of SIS. PMID:25463505

  8. Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.

    PubMed

    Glynn, Jeremy J; Polsin, Elizabeth G; Hinds, Monica T

    2015-03-01

    Decellularized tissues have been widely used as scaffolds for biomedical applications due to their presentation of adhesion peptide sequences and growth factors, which facilitate integration with surrounding tissue. One of the most commonly used decellularized tissues is derived from porcine small intestinal submucosa (SIS). In some applications, SIS is crosslinked to modulate the mechanical properties or degradation rate of the scaffold. Despite the widespread use of SIS, there has been no mechanistic characterization of blood reactions with SIS, or how crosslinking affects these reactions. Therefore, we characterized the effect of SIS and carbodiimide-crosslinked SIS (cSIS) on plasma coagulation, including targeted assessments of the intrinsic and extrinsic coagulation pathways, and thrombus formation using flowing whole blood. SIS inhibited plasma coagulation initiated by recalcification, as well as low concentrations of thrombin or tissue factor. SIS prolonged the activated partial thromboplastin time by 14.3 ± 1.54s, indicating inhibition of the intrinsic coagulation pathway. Carbodiimide crosslinking abrogated all anticoagulant effects of SIS, as did heparinase I and III treatment, suggesting that heparin and heparan sulfate are predominantly responsible for SIS anticoagulant effects. Inhibiting contact activation of the intrinsic pathway prevented cSIS-mediated coagulation. When tubular SIS devices were connected to a nonhuman primate arteriovenous shunt loop, which enables whole blood to flow across devices without the use of anticoagulants, SIS demonstrated remarkably limited platelet accumulation and fibrinogen incorporation, while cSIS initiated significantly higher platelet and fibrinogen accumulation. These results demonstrate that SIS is a thromboresistant material and crosslinking markedly reduces the hemocompatibility of SIS. PMID:25463505

  9. Reducing proactive aggression through non-invasive brain stimulation.

    PubMed

    Dambacher, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T

    2015-10-01

    Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.

  10. Vibratory or Visual Stimulation Reduces Self-Injury.

    ERIC Educational Resources Information Center

    Taylor, Caroline R.; Chamove, Arnold S.

    1986-01-01

    The effects of alternate forms of sensory stimulation on self-injurious behavior (SIB) in a profoundly retarded 24-year-old female were evaluated. Both vibratory stimulation (a massager) and visual stimulation (flashing red light) equally and significantly decreased the subject's SIB in both treatment and nontreatment environments. (Author/DB)

  11. Continuous theta burst stimulation of angular gyrus reduces subjective recollection.

    PubMed

    Yazar, Yasemin; Bergström, Zara M; Simons, Jon S

    2014-01-01

    The contribution of lateral parietal regions such as the angular gyrus to human episodic memory has been the subject of much debate following widespread observations of left parietal activity in healthy volunteers during functional neuroimaging studies of memory retrieval. Patients with lateral parietal lesions are not amnesic, but recent evidence indicates that their memory abilities may not be entirely preserved. Whereas recollection appears intact when objective measures such as source accuracy are used, patients often exhibit reduced subjective confidence in their accurate recollections. When asked to recall autobiographical memories, they may produce spontaneous narratives that lack richness and specificity, but can remember specific details when prompted. Two distinct theoretical accounts have been proposed to explain these results: that the patients have a deficit in the bottom-up capturing of attention by retrieval output, or that they have an impairment in the subjective experience of recollection. The present study aimed to differentiate between these accounts using continuous theta burst stimulation (cTBS) in healthy participants to disrupt function of specific left parietal subregions, including angular gyrus. Inconsistent with predictions of the attentional theory, angular gyrus cTBS did not result in greater impairment of free recall than cued recall. Supporting predictions of the subjective recollection account, temporary disruption of angular gyrus was associated with highly accurate source recollection accuracy but a selective reduction in participants' rated source confidence. The findings are consistent with a role for angular gyrus in the integration of memory features into a conscious representation that enables the subjective experience of remembering. PMID:25333985

  12. Transcranial magnetic stimulation reduces nociceptive threshold in rats.

    PubMed

    Ambriz-Tututi, Mónica; Sánchez-González, Violeta; Drucker-Colín, René

    2012-05-01

    Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate or inhibit nerve cells in the brain noninvasively. TMS induces an electromagnetic current in the underlying cortical neurons. Varying frequencies and intensities of TMS increase or decrease excitability in the cortical area directly targeted. It has been suggested that TMS has potential in the treatment of some neurological disorders such as Parkinson's disease, stroke, and depression. Initial case reports and open label trials reported by several groups support the use of TMS in pain treatment. In the present study, we evaluated the effect of TMS on the nociceptive threshold in the rat. The parameters used were a frequency of 60 Hz and an intensity of 2 and 6 mT for 2 hr twice per day. After 5 days of TMS treatment, rats were evaluated for mechanical, chemical, and cold stimulation. We observed a significant reduction in the nociceptive threshold in TMS-treated rats but not in sham-treated rats in all behavioral tests evaluated. When TMS treatment was stopped, a slow recovery to normal mechanic threshold was observed. Interestingly, i.c.v. MK-801 or CNQX administration reverted the TMS-induced pronociception. The results suggest that high-frequency TMS can alter the nociceptive threshold and produce allodynia in the rats; results suggest the involvement of NMDA and AMPA/KA receptors on TMS-induced allodynia in the rat. PMID:22315163

  13. Stimulants

    MedlinePlus

    Stimulants are drugs that increase your heart rate, breathing rate, and brain function. Some stimulants affect only a specific organ, such as the heart, lungs, brain, or nervous system. Epinephrine is a stimulant. It ...

  14. Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa.

    PubMed

    Nakatsu, Hiroki; Ueno, Tomio; Oga, Atsunori; Nakao, Mitsuhiro; Nishimura, Taku; Kobayashi, Sei; Oka, Masaaki

    2015-03-01

    Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.

  15. Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine

    PubMed Central

    Guleyupoglu, Berkan; Febles, Nicole; Minhas, Preet; Hahn, Christoph; Bikson, Marom

    2014-01-01

    Background: High-Definition transcranial Direct Current Stimulation (HD-tDCS) allows for non-invasive neuromodulation using an array of compact (approximately 1 cm2 contact area) “High-Definition” (HD) electrodes, as compared to conventional tDCS (which uses two large pads that are approximately 35 cm2). In a previous transcutaneous study, we developed and validated designs for HD electrodes that reduce discomfort over >20 min session with 2 mA electrode current. Objective: The purpose of this study was to investigate the use of a chemical pretreatment with 6% benzocaine (topical numbing agent) to further reduce subjective discomfort during transcutaneous stimulation and to allow for better sham controlled studies. Methods: Pre-treatment with 6% benzocaine was compared with control (no pretreatment) for 22 min 2 mA of stimulation, with either CCNY-4 or Lectron II electroconductive gel, for both cathodal and anodal transcutaneous (forearm) stimulation (eight different combinations). Results: Results show that for all conditions and polarities tested, stimulation with HD electrodes is safe and well tolerated and that pretreatment further reduced subjective discomfort. Conclusion: Pretreatment with a mild analgesic reduces discomfort during HD-tDCS. PMID:25071548

  16. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin.

    PubMed

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana

    2003-06-27

    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  17. Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.

    PubMed

    Cazzoli, Dario; Müri, René M; Schumacher, Rahel; von Arx, Sebastian; Chaves, Silvia; Gutbrod, Klemens; Bohlhalter, Stephan; Bauer, Daniel; Vanbellingen, Tim; Bertschi, Manuel; Kipfer, Stefan; Rosenthal, Clive R; Kennard, Christopher; Bassetti, Claudio L; Nyffeler, Thomas

    2012-11-01

    Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham

  18. Motor Cortex Stimulation Reduces Hyperalgesia in an Animal Model of Central Pain

    PubMed Central

    Lucas, Jessica M; Ji, Yadong; Masri, Radi

    2011-01-01

    Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. Here, using a rodent model of central pain, we perform a systematic study of stimulation parameters used for MCS and investigate the mechanisms by which MCS reduces hyperalgesia. Specifically, we study the role of the inhibitory nucleus zona incerta (ZI) in mediating the analgesic effects of MCS. In animals with mechanical and thermal hyperalgesia, we find that stimulation at 50 µA, 50 Hz, and 300 µs square pulses, for 30 minutes is sufficient to reverse mechanical and thermal hyperalgesia. We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia maybe due to MCS effects on ZI. PMID:21396776

  19. Reducing aggressive responses to social exclusion using transcranial direct current stimulation.

    PubMed

    Riva, Paolo; Romero Lauro, Leonor J; DeWall, C Nathan; Chester, David S; Bushman, Brad J

    2015-03-01

    A vast body of research showed that social exclusion can trigger aggression. However, the neural mechanisms involved in regulating aggressive responses to social exclusion are still largely unknown. Transcranial direct current stimulation (tDCS) modulates the excitability of a target region. Building on studies suggesting that activity in the right ventrolateral pre-frontal cortex (rVLPFC) might aid the regulation or inhibition of social exclusion-related distress, we hypothesized that non-invasive brain polarization through tDCS over the rVLPFC would reduce behavioral aggression following social exclusion. Participants were socially excluded or included while they received tDCS or sham stimulation to the rVLPFC. Next, they received an opportunity to aggress. Excluded participants demonstrated cognitive awareness of their inclusionary status, yet tDCS (but not sham stimulation) reduced their behavioral aggression. Excluded participants who received tDCS stimulation were no more aggressive than included participants. tDCS stimulation did not influence socially included participants' aggression. Our findings provide the first causal test for the role of rVLPFC in modulating aggressive responses to social exclusion. Our findings suggest that modulating activity in a brain area (i.e. the rVLPFC) implicated in self-control and emotion regulation can break the link between social exclusion and aggression. PMID:24748546

  20. Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses

    NASA Astrophysics Data System (ADS)

    Weitz, Andrew C.; Behrend, Matthew R.; Ahuja, Ashish K.; Christopher, Punita; Wei, Jianing; Wuyyuru, Varalakshmi; Patel, Uday; Greenberg, Robert J.; Humayun, Mark S.; Chow, Robert H.; Weiland, James D.

    2014-02-01

    Objective. Epiretinal prostheses are designed to restore functional vision to the blind by electrically stimulating surviving retinal neurons. These devices have classically employed symmetric biphasic current pulses in order to maintain a balance of charge. Prior electrophysiological and psychophysical studies in peripheral nerve show that adding an interphase gap (IPG) between the two phases makes stimulation more efficient than pulses with no gap. This led us to investigate the effect of IPG duration on retinal stimulation thresholds. Approach. We measured retinal ganglion cell (RGC) electrical thresholds in salamander retina and phosphene perceptual thresholds in epiretinal prosthesis patients during stimulation with different IPG lengths. We also built Hodgkin-Huxley-type models of RGCs to further study how IPG affects thresholds. Main results. In general, there was a negative exponential correlation between threshold and IPG duration. Durations greater than or equal to ˜0.5 ms reduced salamander RGC thresholds by 20-25%. Psychophysical testing in five retinal prosthesis patients indicated that stimulating with IPGs can decrease perceptual thresholds by 10-15%. Results from computational models of RGCs corroborated the observed behavior. Significance. Incorporating interphase gaps can reduce the power consumption of epiretinal prostheses and increase the available dynamic range of phosphene size and brightness.

  1. Reducing aggressive responses to social exclusion using transcranial direct current stimulation

    PubMed Central

    Romero Lauro, Leonor J.; DeWall, C. Nathan; Chester, David S.; Bushman, Brad J.

    2015-01-01

    A vast body of research showed that social exclusion can trigger aggression. However, the neural mechanisms involved in regulating aggressive responses to social exclusion are still largely unknown. Transcranial direct current stimulation (tDCS) modulates the excitability of a target region. Building on studies suggesting that activity in the right ventrolateral pre-frontal cortex (rVLPFC) might aid the regulation or inhibition of social exclusion-related distress, we hypothesized that non-invasive brain polarization through tDCS over the rVLPFC would reduce behavioral aggression following social exclusion. Participants were socially excluded or included while they received tDCS or sham stimulation to the rVLPFC. Next, they received an opportunity to aggress. Excluded participants demonstrated cognitive awareness of their inclusionary status, yet tDCS (but not sham stimulation) reduced their behavioral aggression. Excluded participants who received tDCS stimulation were no more aggressive than included participants. tDCS stimulation did not influence socially included participants’ aggression. Our findings provide the first causal test for the role of rVLPFC in modulating aggressive responses to social exclusion. Our findings suggest that modulating activity in a brain area (i.e. the rVLPFC) implicated in self-control and emotion regulation can break the link between social exclusion and aggression. PMID:24748546

  2. Reducing Procedural Pain and Discomfort Associated with Transcranial Direct Current Stimulation

    PubMed Central

    McFadden, James L.; Borckardt, Jeff J.; George, Mark S.; Beam, William

    2010-01-01

    Background tDCS appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic Mixture of Local Anesthetics (EMLA) on tDCS-related discomfort. Methods Nine healthy adults received both anodal and cathodal 2.0 mA tDCS for 5 minutes over the prefrontal cortex with the skin pretreated for 20 minutes with either EMLA or placebo cream. Participants rated procedural discomfort 6 times across 8 dimensions of sensation. Results On average, the mean sensation ratings for EMLA-associated tDCS stimulation were significantly lower than placebo-associated stimulation for every cutaneous sensation evaluated. Cathodal stimulation was associated with higher ratings of “sharpness” and intolerability than anodal stimulation. Conclusions Topical EMLA may reduce tDCS-related discomfort. PMID:21255753

  3. Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

    PubMed Central

    Deng, Quan-Jun; Deng, Ding-Jing; Che, Jin; Zhao, Hai-Rong; Yu, Jun-Jie; Lu, Yong-Yu

    2016-01-01

    AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in

  4. Adipose tissue-derived stem cell-seeded small intestinal submucosa for tunica albuginea grafting and reconstruction

    PubMed Central

    Ma, Limin; Yang, Yijun; Sikka, Suresh C.; Kadowitz, Philip J.; Ignarro, Louis J.; Abdel-Mageed, Asim B.; Hellstrom, Wayne J. G.

    2012-01-01

    Porcine small intestinal submucosa (SIS) has been widely used in tunica albuginea (TA) reconstructive surgery. Adipose tissue-derived stem cells (ADSCs) can repair damaged tissue, augment cellular differentiation, and stimulate release of multiple growth factors. The aim of this rat study was to assess the feasibility of seeding ADSCs onto SIS grafts for TA reconstruction. Here, we demonstrate that seeding syngeneic ADSCs onto SIS grafts (SIS-ADSC) resulted in significant cavernosal tissue preservation and maintained erectile responses, similar to controls, in a rat model of bilateral incision of TA, compared with sham-operated animals and rats grafted with SIS graft (SIS) alone. In addition to increased TGF-β1 and FGF-2 expression levels, cross-sectional studies of the rat penis with SIS and SIS-ADSC revealed mild to moderate fibrosis and an increase of 30% and 40% in mean diameter in flaccid and erectile states, respectively. SIS grafting induced transcriptional up-regulation of iNOS and down-regulation of endothelial NOS, neuronal NOS, and VEGF, an effect that was restored by seeding ADCSs on the SIS graft. Taken together, these data show that rats undergoing TA incision with autologous SIS-ADSC grafts maintained better erectile function compared with animals grafted with SIS alone. This study suggests that SIS-ADSC grafting can be successfully used for TA reconstruction procedures and can restore erectile function. PMID:22308363

  5. Congenital taurine deficiency in mice is associated with reduced sensitivity to nociceptive chemical stimulation.

    PubMed

    Lötsch, J; Hummel, T; Warskulat, U; Coste, O; Häussinger, D; Geisslinger, G; Tegeder, I

    2014-02-14

    The amino acid taurine is required for development and functioning of the central and peripheral nervous system where it exerts osmoregulatory, neuromodulatory and anti-apoptotic actions. It is subject to cellular import by the taurine transporter slc6a6. Absence of the transporter and consequently, absence of taurine leads to several neurologic deficits and sensory losses. In a slc6a6 knock-out mouse model, consequences of congenital taurine deficiency were assessed in nociceptive sensory processes. The formalin assay, hot plate assay, and summated generator potentials in response to local nociceptive stimulation with gaseous CO2 were applied. Reduced responsiveness of slc6a6(-/-) mice to nociceptive stimulation was observed in particular to chemical nociceptive stimuli. Scl6a6 knock-out mice spent significantly less time licking the formalin injected paw and displayed smaller amplitudes of the nociceptive nasal mucosa potentials than wild-type mice (p=0.002 and 0.01 respectively). In contrast, withdrawal latencies on a hot plate did not significantly differ, suggesting that intracellular taurine deficits lead in particular to a hyposensitivity of nociceptive sensory neurons sensitive to noxious chemical stimulation. As hereditary absence of taurine affects biological processes of anatomical structure development, the altered nociceptive responses likely reflect consequences of compromised peripheral nervous system development.

  6. Aged Male Rats Regenerate Cortical Bone with Reduced Osteocyte Density and Reduced Secretion of Nitric Oxide After Mechanical Stimulation

    PubMed Central

    Tayim, Riyad J.; McElderry, John-David; Morris, Michael D.; Goldstein, Steven A.

    2016-01-01

    Mechanical loading is integral to the repair of bone damage. Osteocytes are mechanosensors in bone and participate in signaling through gap junction channels, which are primarily comprised of connexin 43 (Cx43). Nitric oxide (NO) and prostaglandin E2 (PGE2) have anabolic and catabolic effects on bone, and the secretion of these molecules occurs after mechanical stimulation. The effect of age on the repair of bone tissue after damage and on the ability of regenerated bone to transduce mechanical stimulation into a cellular response is unexplored. The goal of this study was to examine (1) osteocytes and their mineralized matrix within regenerated bone from aged and mature animals and (2) the ability of regenerated bone explants from aged and mature animals to transduce cyclic mechanical loading into a cellular response through NO and PGE2 secretion. Bilateral cortical defects were created in the diaphysis of aged (21-month-old) or mature (6-month-old) male rats, and new bone tissue was allowed to grow into a custom implant of controlled geometry. Mineralization and mineral-to-matrix ratio were significantly higher in regenerated bone from aged animals, while lacunar and osteocyte density and phosphorylated (pCx43) and total Cx43 protein were significantly lower, relative to mature animals. Regenerated bone from mature rats had increased pCx43 protein and PGE2 secretion with loading and greater NO secretion relative to aged animals. Reduced osteocyte density and Cx43 in regenerated bone in aged animals could limit the establishment of gap junctions as well as NO and PGE2 secretion after loading, thereby altering bone formation and resorption in vivo. PMID:24370615

  7. Reduced WIF-1 expression stimulates skin hyperpigmentation in patients with melasma.

    PubMed

    Kim, Ji-Young; Lee, Tae-Ryong; Lee, Ai-Young

    2013-01-01

    The expression of Wnt inhibitory factor-1 (WIF-1) gene, which was detected by a microarray analysis of hyperpigmented and normally pigmented skin sets of melasma patients, was significantly reduced in the hyperpigmented skin from melasma patients, but not in healthy controls, regardless of UV irradiation. Wnt signals regulate skin pigmentation; however, WIF-1 is expressed in cultured skin keratinocytes and fibroblasts, but not in melanocytes. Therefore, we examined whether WIF-1 knockdown in neighboring keratinocytes and fibroblasts plays a role in melasma. Additionally, the effect of WIF-1 overexpression on the amelioration of hyperpigmentation was examined. WIF-1 knockdown, either in fibroblasts or in keratinocytes, significantly stimulated tyrosinase expression and melanosome transfer, whereas melanocytes with WIF-1 overexpression significantly reduced those parameters. The WIF-1 knockdown decreased glycogen synthase kinase-3β (GSK-3β), β-catenin, and NFATc2 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2) phosphorylation and increased microphthalmia-associated transcription factor (MITF) expression as in melanocytes with Wnt-1 overexpression, whereas the WIF-1 overexpression reversed the results. Expression of Wnts, both canonical and noncanonical, was increased in the hyperpigmented skin of melasma patients. Collectively, WIF-1 downregulation, which may occur in epidermal keratinocytes and in dermal fibroblasts, is involved in melasma development because of the stimulation of melanogenesis and melanosome transfer through upregulation of the canonical and the noncanonical Wnt signaling pathway.

  8. High Frequency Electrical Stimulation of Lateral Habenula Reduces Voluntary Ethanol Consumption in Rats

    PubMed Central

    Li, Jing; Zuo, Wanhong; Fu, Rao; Xie, Guiqin; Kaur, Amandeep; Bekker, Alex

    2016-01-01

    Background: Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanol-drinking behavior in rats. Methods: We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb. Results: c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior. Conclusions: Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics. PMID:27234303

  9. Noninvasive stimulation of prefrontal cortex strengthens existing episodic memories and reduces forgetting in the elderly

    PubMed Central

    Sandrini, Marco; Brambilla, Michela; Manenti, Rosa; Rosini, Sandra; Cohen, Leonardo G.; Cotelli, Maria

    2014-01-01

    Memory consolidation is a dynamic process. Reactivation of consolidated memories by a reminder triggers reconsolidation, a time-limited period during which existing memories can be modified (i.e., weakened or strengthened). Episodic memory refers to our ability to recall specific past events about what happened, including where and when. Difficulties in this form of long-term memory commonly occur in healthy aging. Because episodic memory is critical for daily life functioning, the development of effective interventions to reduce memory loss in elderly individuals is of great importance. Previous studies in young adults showed that the dorsolateral prefrontal cortex (DLPFC) plays a causal role in strengthening of verbal episodic memories through reconsolidation. The aim of the present study was to explore the extent to which facilitatory transcranial direct current stimulation (anodal tDCS) over the left DLPFC would strengthen existing episodic memories through reconsolidation in elderly individuals. On Day 1, older adults learned a list of 20 words. On Day 2 (24 h later), they received a reminder or not, and after 10 min tDCS was applied over the left DLPFC. Memory recall was tested on Day 3 (48 h later) and Day 30 (1 month later). Surprisingly, anodal tDCS over the left DLPFC (i.e., with or without the reminder) strengthened existing verbal episodic memories and reduced forgetting compared to sham stimulation. These results provide a framework for testing the hypothesis that facilitatory tDCS of left DLPFC might strengthen existing episodic memories and reduce memory loss in older adults with amnestic mild cognitive impairment. PMID:25368577

  10. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors.

    PubMed

    Austin, Adelaide; Jiga-Boy, Gabriela M; Rea, Sara; Newstead, Simon A; Roderick, Sian; Davis, Nick J; Clement, R Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  11. Correlations in V1 are reduced by stimulation outside the receptive field.

    PubMed

    Snyder, Adam C; Morais, Michael J; Kohn, Adam; Smith, Matthew A

    2014-08-20

    The trial-to-trial response variability of nearby cortical neurons is correlated. These correlations may strongly influence population coding performance. Numerous studies have shown that correlations can be dynamically modified by attention, adaptation, learning, and potent stimulus drive. However, the mechanisms that influence correlation strength remain poorly understood. Here we test whether correlations are influenced by presenting stimuli outside the classical receptive field (RF) of visual neurons, where they recruit a normalization signal termed surround suppression. We recorded simultaneously the activity of dozens of cells using microelectrode arrays implanted in the superficial layers of V1 in anesthetized, paralyzed macaque monkeys. We presented annular stimuli that encircled--but did not impinge upon--the RFs of the recorded cells. We found that these "extra-classical" stimuli reduced correlations in the absence of stimulation of the RF, closely resembling the decorrelating effects of stimulating the RFs directly. Our results suggest that normalization signals may be an important mechanism for modulating correlations. PMID:25143603

  12. Reduced postactivation depression of soleus H reflex and root evoked potential after transcranial magnetic stimulation.

    PubMed

    Andrews, Jennifer C; Stein, Richard B; Roy, François D

    2015-07-01

    Postactivation depression of the Hoffmann (H) reflex is associated with a transient period of suppression following activation of the reflex pathway. In soleus, the depression lasts for 100-200 ms during voluntary contraction and up to 10 s at rest. A reflex root evoked potential (REP), elicited after a single pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to exhibit similar suppression. The present study systematically characterized the effect of transcranial magnetic stimulation (TMS) on postactivation depression using double-pulse H reflexes and REPs. A TMS pulse reduced the period of depression to 10-15 ms for both reflexes. TMS could even produce postactivation facilitation of the H reflex, as the second reflex response was increased to 243 ± 51% of control values at the 75-ms interval. The time course was qualitatively similar for the REP, yet the overall increase was less. While recovery of the H reflex was slower in the relaxed muscle, the profile exhibited a distinct bimodal shape characterized by an early peak at the 25-ms interval, reaching 72 ± 23% of control values, followed by a trough at 50 ms, and then a gradual recovery at intervals > 50 ms. The rapid recovery of two successively depressed H reflexes, ∼ 25 ms apart, was also possible with double-pulse TMS. The effect of the TMS-induced corticospinal excitation on postactivation depression may be explained by a combination of pre- and postsynaptic mechanisms, although further investigation is required to distinguish between them.

  13. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

    PubMed Central

    Austin, Adelaide; Jiga-Boy, Gabriela M.; Rea, Sara; Newstead, Simon A.; Roderick, Sian; Davis, Nick J.; Clement, R. Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  14. Interpersonal multisensory stimulation reduces the overwhelming distracting power of self-gaze: psychophysical evidence for 'engazement'.

    PubMed

    Porciello, Giuseppina; Holmes, Brittany Serra; Liuzza, Marco Tullio; Crostella, Filippo; Aglioti, Salvatore Maria; Bufalari, Ilaria

    2014-10-20

    One's own face and gaze are never seen directly but only in a mirror. Yet, these stimuli capture attention more powerfully than others' face and gaze, suggesting the self is special for brain and behavior. Synchronous touches felt on one's own and seen on the face of others induce the sensation of including others in one's own face (enfacement). We demonstrate that enfacement may also reduce the overwhelming distracting power of self-gaze. This effect, hereafter called 'engazement', depends on the perceived physical attractiveness and inner beauty of the pair partner. Thus, we highlight for the first time the close link between enfacement and engazement by showing that changes of the self-face representation induced by facial visuo-tactile stimulation extend to gaze following, a separate process likely underpinned by different neural substrates. Moreover, although gaze following is a largely automatic, engazement is penetrable to the influence of social variables, such as positive interpersonal perception.

  15. A new technique of "midline anchoring" in spinal cord stimulation dramatically reduces lead migration.

    PubMed

    Mironer, Y Eugene; Brown, Christopher; Satterthwaite, John R; Cohen, Mary; Tonder, Lisa M; Grumman, Steve

    2004-01-01

    Spinal cord stimulation (SCS) is a popular method of treatment of chronic pain. Unfortunately, migration of the lead continues to be a serious complication of this therapy. In an attempt to reduce lateral migration of the SCS lead, we performed a retrospective assessment of a new technique of percutaneous lead placement. This new method of "midline anchoring" of the lead using the plica mediana dorsalis was tested against conventional technique in a retrospective study involving 122 trials and 91 implants of SCS over a period of five years. The use of "midline anchoring" resulted in a decrease in lead migration from 23% to 6% after trial insertion and from 24% to 7% after implantation. We conclude that "midline anchoring" of the SCS lead is an effective method of preventing lead migration.

  16. Interpersonal multisensory stimulation reduces the overwhelming distracting power of self-gaze: psychophysical evidence for 'engazement'.

    PubMed

    Porciello, Giuseppina; Holmes, Brittany Serra; Liuzza, Marco Tullio; Crostella, Filippo; Aglioti, Salvatore Maria; Bufalari, Ilaria

    2014-01-01

    One's own face and gaze are never seen directly but only in a mirror. Yet, these stimuli capture attention more powerfully than others' face and gaze, suggesting the self is special for brain and behavior. Synchronous touches felt on one's own and seen on the face of others induce the sensation of including others in one's own face (enfacement). We demonstrate that enfacement may also reduce the overwhelming distracting power of self-gaze. This effect, hereafter called 'engazement', depends on the perceived physical attractiveness and inner beauty of the pair partner. Thus, we highlight for the first time the close link between enfacement and engazement by showing that changes of the self-face representation induced by facial visuo-tactile stimulation extend to gaze following, a separate process likely underpinned by different neural substrates. Moreover, although gaze following is a largely automatic, engazement is penetrable to the influence of social variables, such as positive interpersonal perception. PMID:25327255

  17. Defoliation reduces soil biota - and modifies stimulating effects of elevated CO2.

    PubMed

    Dam, Marie; Christensen, Søren

    2015-11-01

    To understand the responses to external disturbance such as defoliation and possible feedback mechanisms at global change in terrestrial ecosystems, it is necessary to examine the extent and nature of effects on aboveground-belowground interactions. We studied a temperate heathland system subjected to experimental climate and atmospheric factors based on prognoses for year 2075 and further exposed to defoliation. By defoliating plants, we were able to study how global change modifies the interactions of the plant-soil system. Shoot production, root biomass, microbial biomass, and nematode abundance were assessed in the rhizosphere of manually defoliated patches of Deschampsia flexuosa in June in a full-factorial FACE experiment with the treatments: increased atmospheric CO 2, increased nighttime temperatures, summer droughts, and all of their combinations. We found a negative effect of defoliation on microbial biomass that was not apparently affected by global change. The negative effect of defoliation cascades through to soil nematodes as dependent on CO 2 and drought. At ambient CO 2, drought and defoliation each reduced nematodes. In contrast, at elevated CO 2, a combination of drought and defoliation was needed to reduce nematodes. We found positive effects of CO 2 on root density and microbial biomass. Defoliation affected soil biota negatively, whereas elevated CO 2 stimulated the plant-soil system. This effect seen in June is contrasted by the effects seen in September at the same site. Late season defoliation increased activity and biomass of soil biota and more so at elevated CO 2. Based on soil biota responses, plants defoliated in active growth therefore conserve resources, whereas defoliation after termination of growth results in release of resources. This result challenges the idea that plants via exudation of organic carbon stimulate their rhizosphere biota when in apparent need of nutrients for growth. PMID:26640664

  18. Biocompatibility of porcine small intestinal submucosa and rat endothelial progenitor cells in vitro

    PubMed Central

    Rong, Jian-Jie; Sang, Hong-Fei; Qian, Ai-Min; Meng, Qing-You; Zhao, Tie-Jun; Li, Xiao-Qiang

    2015-01-01

    Objective: This study investigated the biocompatibility of the small intestinal submucosa (SIS) and endothelial progenitor cells (EPCs) by co-cultivating EPCs and SIS in vitro and observing EPC growth on the SIS. Methods: The porcine SIS was prepared and bone marrow mononuclear cells (BMMNCs) were isolated from 3 or 4-week old male SD rats. Cellular morphology was observed by light microscopy and scanning electron microscopy (SEM) and viabilities by the MTT assays. Endothelial progenitor cells (EPCs) were phenotyped by immunocytochemistry, immunofluorescence microscopy and flow cytometry. Vascular lumen formation was evaluated by the Matrigel tube formation assays. EPCs were seeded onto the SIS and production of angiogenin-1 and endothelial cell growth factor (VEGF) by EPCs was examined by ELISA and immunoblotting assays. Results: Light microscopy and SEM showed that the mechanically and chemically treated small intestinal submucosa was composed of cell-free extracellular matrix. Immunohistochemistry, and flow cytometry revealed that the EPCs expressed appropriate surface markers including CD34, CD133, and VEGFR-2. Furthermore, the EPCs formed lumen-like structures and the SIS significantly enhanced the growth of EPCs in vitro. Conclusion: SIS has good biocompatibility with EPCs. SIS pre-seeded with EPCs can be potentially applied as an alternative scaffold material in artificial blood vessel prosthesis. PMID:25973012

  19. Histomorphometric analysis of early epithelialization and dermal changes in mid-partial-thickness burn wounds in humans treated with porcine small intestinal submucosa and silver-containing hydrofiber.

    PubMed

    Salgado, Rosa M; Bravo, Leonardo; García, Mario; Melchor, Juan M; Krötzsch, Edgar

    2014-01-01

    The objective of this study was to determine the healing rates of mid-partial-thickness burns treated with a porcine intestinal submucosa (SIS) vs. silver-containing cellulose hydrofiber (AgH) dressings. This was done by comparing healing response of burn wounds treated with SIS vs that of burns treated with AgH dressings. Five patients with mid-partial-thickness burns ≤10% of body surface were treated simultaneously, but in different areas, with SIS and AgH dressings; full-thickness biopsies were taken at days 0 and 7. Tissues treated with SIS presented higher epithelial maturation index (6.2 ± 0.84 vs. 3.2 ± 3.28; [mean ± standard deviation], P = .029), better orientation and differentiation of epithelial cells, as well as an appropriate basal lamina structure, collagen deposition, and higher transforming growth factor-β3 expression (7.4 ± 8.1 vs. 2.1 ± 2.6; P = .055) than tissues treated with AgH dressings. Importantly, after the treatment SIS was not integrated in healed tissues. After 3 months of treatment, SIS produced a lower score according to Vancouver Scar Scale (3.6 ± 2.6 vs. 7.2 ± 2.5, P = .025).The submucosa dressing does not simply act as scaffolding for the wound, it provides stimulation in the healing area, probably via growth factors initially present in SIS or matrikines derived from its digestion in the wound site. In conclusion, the present study demonstrated that biological matrices favor the wound-healing process.

  20. Deep Brain Stimulation for Obsessive Compulsive Disorder Reduces Symptoms of Irritable Bowel Syndrome in a Single Patient

    PubMed Central

    Langguth, Berthold; Sturm, Kornelia; Wetter, Thomas C.; Lange, Max; Gabriels, Loes; Mayer, Emeran A.; Schlaier, Juergen

    2016-01-01

    Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder that is difficult to treat. We describe findings from evaluation of a woman (55 years old) with obsessive compulsive disorder, which was treated with bilateral deep brain stimulation in the anterior limb of the internal capsule, and IBS. After the brain stimulation treatment she reported substantial relief of her IBS symptoms. This reduction depended on specific stimulation parameters, was reproducible over time, and was not directly associated with improvements in obsessive compulsive disorder symptoms. These observations indicate a specific effect of deep brain stimulation on IBS. This observation confirms involvement of specific brain structures in the pathophysiology of IBS and shows that symptoms can be reduced through modulation of neuronal activity in the central nervous system. Further studies of the effects of brain stimulation on IBS are required. PMID:25638586

  1. The mismatch repair system reduces meiotic homeologous recombination and stimulates recombination-dependent chromosome loss.

    PubMed

    Chambers, S R; Hunter, N; Louis, E J; Borts, R H

    1996-11-01

    Efficient genetic recombination requires near-perfect homology between participating molecules. Sequence divergence reduces the frequency of recombination, a process that is dependent on the activity of the mismatch repair system. The effects of chromosomal divergence in diploids of Saccharomyces cerevisiae in which one copy of chromosome III is derived from a closely related species, Saccharomyces paradoxus, have been examined. Meiotic recombination between the diverged chromosomes is decreased by 25-fold. Spore viability is reduced with an observable increase in the number of tetrads with only two or three viable spores. Asci with only two viable spores are disomic for chromosome III, consistent with meiosis I nondisjunction of the homeologs. Asci with three viable spores are highly enriched for recombinants relative to tetrads with four viable spores. In 96% of the class with three viable spores, only one spore possesses a recombinant chromosome III, suggesting that the recombination process itself contributes to meiotic death. This phenomenon is dependent on the activities of the mismatch repair genes PMS1 and MSH2. A model of mismatch-stimulated chromosome loss is proposed to account for this observation. As expected, crossing over is increased in pms1 and msh2 mutants. Furthermore, genetic exchange in pms1 msh2 double mutants is affected to a greater extent than in either mutant alone, suggesting that the two proteins act independently to inhibit homeologous recombination. All mismatch repair-deficient strains exhibited reductions in the rate of chromosome III nondisjunction. PMID:8887641

  2. High salt reduces the activation of IL-4– and IL-13–stimulated macrophages

    PubMed Central

    Binger, Katrina J.; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A.; Lang, Florian; Voehringer, David; Wright, Mark D.; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N.

    2015-01-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt–induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis. PMID:26485286

  3. Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake.

    PubMed

    Liang, Nu-Chu; Bello, Nicholas T; Moran, Timothy H

    2015-05-01

    The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) μ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain.

  4. Feeding Aspergillus awamori reduces skeletal muscle protein breakdown and stimulates growth in broilers.

    PubMed

    Saleh, Ahmed A; Eid, Yahya Z; Ebeid, Tarek A; Ohtsuka, Akira; Yamamoto, Masahiro; Hayashi, Kunioki

    2012-08-01

    This study was conducted to show that dietary supplementation of a fungus, Aspergillus awamori called Koji in Japan, reduces skeletal muscle protein breakdown and stimulates growth in broiler chickens. A total of 30 chicks at 15 days of age was divided into control and two treatment groups (10 birds per treatment). Control group was fed basal diet and treatment groups were fed the basal diets supplemented with A. awamori at levels of 0.05% and 0.2%. The birds were raised for 12 days from 15 to 27 days of age and then the effect on growth, organ weights and plasma 3-methylhistidine concentration and digestibilities of protein and energy was evaluated. The messenger RNAs (mRNAs) of atrogin-1, ubiquitin, proteasome, m-calpain, µ-calpain, β-actin, myosin and pax-7 in the breast muscle were also measured. Body weight gain and breast muscle weight were increased, although feed intake was decreased by the fungus and thus feed efficiency was increased. Protein and energy digestibilities were increased. Furthermore, plasma 3-methylhistidine concentration was decreased by the fungus. The mRNAs of atrogin-1, ubiquitin, proteasome, m-calpain and µ-calpain were all decreased. The mRNA of β-actin but not myosin and pax-7 was slightly increased by the fungus. In conclusion, feeding A. awamori improves growth performance because skeletal muscle proteolytic activity is reduced and digestibilities of energy and protein are increased.

  5. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    PubMed

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

  6. Low luminance/eyes closed and monochromatic stimulations reduce variability of flash visual evoked potential latency

    PubMed Central

    Subramanian, Senthil Kumar; Gaur, Giriwar Singh; Narayan, Sunil K.

    2013-01-01

    Context: Visual evoked potentials are useful in investigating the physiology and pathophysiology of the human visual system. Flash visual evoked potential (FVEP), though technically easier, has less clinical utility because it shows great variations in both latency and amplitude for normal subjects. Aim: To study the effect of eye closure, low luminance, and monochromatic stimulation on the variability of FVEPs. Subjects and Methods: Subjects in self-reported good health in the age group of 18-30 years were divided into three groups. All participants underwent FVEP recording with eyes open and with white light at 0.6 J luminance (standard technique). Next recording was done in group 1 with closed eyes, group 2 with 1.2 and 20 J luminance, and group 3 with red and blue lights, while keeping all the other parameters constant. Two trials were given for each eye, for each technique. The same procedure was repeated at the same clock time on the following day. Statistical Analysis: Variation in FVEP latencies between the individuals (interindividual variability) and the variations within the same individual for four trials (intraindividual variability) were assessed using coefficient of variance (COV). The technique with lower COV was considered the better method. Results: Recording done with closed eyes, 0.6 J luminance, and monochromatic light (blue > red) showed lower interindividual and intraindividual variability in P2 and N2 as compared to standard techniques. Conclusions: Low luminance flash stimulations and monochromatic light will reduce FVEP latency variability and may be clinically useful modifications of FVEP recording technique. PMID:24339591

  7. Electrical stimulation over bilateral occipito-temporal regions reduces N170 in the right hemisphere and the composite face effect.

    PubMed

    Yang, Li-Zhuang; Zhang, Wei; Shi, Bin; Yang, Zhiyu; Wei, Zhengde; Gu, Feng; Zhang, Jing; Cui, Guanbao; Liu, Ying; Zhou, Yifeng; Zhang, Xiaochu; Rao, Hengyi

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. Experiment 1 investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. Experiment 2 further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.

  8. Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Lee, Jong Ho; Shin, Yong Cheol; Jin, Oh Seong; Kang, Seok Hee; Hwang, Yu-Shik; Park, Jong-Chul; Hong, Suck Won; Han, Dong-Wook

    2015-07-01

    Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite the potential biomedical applications of graphene and its derivatives, only limited information is available regarding their osteogenic activity. This study concentrates upon the effects of reduced graphene oxide (rGO)-coated hydroxyapatite (HAp) composites on osteogenic differentiation of hMSCs. The average particle sizes of HAp and rGO were 1270 +/- 476 nm and 438 +/- 180 nm, respectively. When coated on HAp particulates, rGO synergistically enhanced spontaneous osteogenic differentiation of hMSCs, without hampering their proliferation. This result was confirmed by determining alkaline phosphatase activity and mineralization of calcium and phosphate as early and late stage markers of osteogenic differentiation. It is suggested that rGO-coated HAp composites can be effectively utilized as dental and orthopedic bone fillers since these graphene-based particulate materials have potent effects on stimulating the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential.Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite

  9. [A review of research on the application of small intestinal submucosa in repairing osteoarticular injury].

    PubMed

    Guo, Qi; Li, Chun-bao; Shen, Xue-zhen; Qu, Feng; Lu, Xi; Liu, Yu-jie

    2016-05-01

    The ideal treatment and recovery of osteoarticular injury remain to be resolved. Small intestinal submucosa (SIS), a naturally-occurring decellularized extracellular matrix, has been recognized as an ideal scaffold for tissue engineering and widely used in repairing various tissues and organs. Nowadays its application has also been gradually increased in the field of orthopedics. We reviewed laboratorial studies and clinical trails about the application of SIS in bone and joint repair, aiming to evaluate its effects on the repair of bone, cartilage, meniscus, ligament and tendon. SIS has showed promising results in repairing bone, meniscus, ligament or tendon. However, additional studies will be required to further evaluate its effects on articular cartilage and tendon-bone healing. How to optimize SIS material,is also a focused problem concerned with making SIS a potential therapeutic option with high value for orthopedic tissue repair. PMID:27505971

  10. Small Intestinal Submucosa Plug for Closure of Dilated Nephrostomy Tracts: A Pilot Study in Swine

    SciTech Connect

    Kakizawa, Hideyaki; Conlin, M. J.; Pavcnik, Dusan Uchida, Barry T.; Loriaux, Marc; Kim, Young Hwan; Keller, Frederick S.; Roesch, Josef

    2010-06-15

    The aim of this study was to evaluate efficacy of a plug made of small intestinal submucosa (SIS) for closure of dilated nephrostomy tract in the kidney after nephroscopy. Ten kidneys in 5 swine had nephrostomy tracts dilated up to 8 mm. The SIS plug was placed into the dilated renal cortex under nephroscopic control. Follow-up arteriograms, retrograde pyelograms, and macroscopic and histologic studies at 24 h (n = 4), 6 weeks (n = 2), and 3 months (n = 4) were performed to evaluate the efficacy of the plug. The SIS plug effectively closed the dilated nephrostomy tract. Follow-up studies showed minimal changes of the kidneys, except for 1 small infarction, regarding inflammatory and foreign-body reactions and progressive scarring of the SIS. SIS plug is effective for occlusion of dilated nephrostomy tract after nephroscopy. Its efficacy should be compared with other therapeutic options.

  11. Cytokine refacing effect reduces granulocyte macrophage colony-stimulating factor susceptibility to antibody neutralization.

    PubMed

    Heinzelman, Pete; Carlson, Sharon J; Cox, George N

    2015-10-01

    Crohn's Disease (CD) afflicts over half a million Americans with an annual economic impact exceeding $10 billion. Granulocyte macrophage colony-stimulating factor (GM-CSF) can increase patient immune responses against intestinal microbes that promote CD and has been effective for some patients in clinical trials. We have made important progress toward developing GM-CSF variants that could be more effective CD therapeutics by virtue of being less prone to neutralization by the endogenous GM-CSF autoantibodies that are highly expressed in CD patients. Yeast display engineering revealed mutations that increase GM-CSF variant binding affinity by up to ∼3-fold toward both GM-CSF receptor alpha and beta subunits in surface plasmon resonance experiments. Increased binding affinity did not reduce GM-CSF half-maximum effective concentration (EC50) values in conventional in vitro human leukocyte proliferation assays. Affinity-enhancing mutations did, however, promote a 'refacing effect' that imparted all five evaluated GM-CSF variants with increased in vitro bioactivity in the presence of GM-CSF-neutralizing polyclonal antisera. The most improved variant, H15L/R23L, was 6-fold more active than wild-type GM-CSF. Incorporation of additional known affinity-increasing mutations could augment the refacing effect and concomitant bioactivity improvements described here. PMID:25855658

  12. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  13. Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency

    PubMed Central

    Zhou, Fei; Guo, Jingchun; Cheng, Jieshi; Wu, Gencheng

    2011-01-01

    Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA. PMID:21836043

  14. Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease.

    PubMed

    Shannon, Kathleen M; Keshavarzian, Ali; Mutlu, Ece; Dodiya, Hemraj B; Daian, Delia; Jaglin, Jean A; Kordower, Jeffrey H

    2012-05-01

    The diagnosis of Parkinson's disease rests on motor signs of advanced central dopamine deficiency. There is an urgent need for disease biomarkers. Clinicopathological evidence suggests that α-synuclein aggregation, the pathological signature of Parkinson's disease, can be detected in gastrointestinal tract neurons in Parkinson's disease. We studied whether we could demonstrate α-synuclein pathology in specimens from unprepped flexible sigmoidoscopy of the distal sigmoid colon in early subjects with Parkinson's disease. We also looked for 3-nitrotyrosine, a marker of oxidative stress. Ten subjects with early Parkinson's disease not treated with dopaminergic agents (7 men; median age, 58.5 years; median disease duration, 1.5 years) underwent unprepped flexible sigmoidoscopy with biopsy of the distal sigmoid colon. Immunohistochemistry studies for α-synuclein and 3-nitrotyrosine were performed on biopsy specimens and control specimens from a tissue repository (23 healthy subjects and 23 subjects with inflammatory bowel disease). Nine of 10 Parkinson's disease samples were adequate for study. All showed staining for α-synuclein in nerve fibers in colonic submucosa. No control sample showed this pattern. A few showed light α-synuclein staining in round cells. 3-Nitrotyrosine staining was seen in 87% of Parkinson's disease cases but was not specific for Parkinson's disease. This study suggests a pattern of α-synuclein staining in Parkinson's disease that was distinct from healthy subjects and those with inflammatory bowel disease. The absence of this pattern in subjects with inflammatory bowel disease suggests it is not a sequel of inflammation or oxidative stress. 3-Nitrotyrosine immunostaining was common in all groups studied, suggesting oxidative stress in the colonic submucosa. PMID:21766334

  15. Differential efficacy of gels derived from small intestinal submucosa as an injectable biomaterial for myocardial infarct repair.

    PubMed

    Okada, Masaho; Payne, Thomas R; Oshima, Hideki; Momoi, Nobuo; Tobita, Kimimasa; Huard, Johnny

    2010-10-01

    Injectable biomaterials have been recently investigated as a therapeutic approach for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is currently used in the clinic to promote accelerated wound healing for a variety of disorders. In this study, we hypothesized that gels derived from SIS extracellular matrix would be advantageous as an injectable material for cardiac repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their ability to provide a therapeutic effect when injected directly into ischemic myocardium using a murine model of an acute myocardial infarction. Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated preservation of end-systolic left ventricular geometry and improvement of cardiac contractility in the hearts injected with SIS-B when compared with control hearts injected with saline. However, the SIS-C gel provided no functional efficacy in comparison with control. Histological analysis revealed that SIS-B reduced infarct size and induced angiogenesis relative to control, whereas injection of SIS-C had minimal effect on these histological parameters. Characterization of both gels revealed differential growth factor content with SIS-B exhibiting higher levels of basic fibroblast growth factor than SIS-C, which may explain, at least in part, the differential histological and functional results. This study suggests that SIS gel offers therapeutic potential as an injectable material for the repair of ischemic myocardium. Further understanding of SIS gel characteristics, such as biological and physical properties, that are critical determinants of efficacy would be important for optimization of this biomaterial for cardiac repair. PMID:20674011

  16. Evaluation of decellularization protocols for production of tubular small intestine submucosa scaffolds for use in oesophageal tissue engineering.

    PubMed

    Syed, Omaer; Walters, Nick J; Day, Richard M; Kim, Hae-Won; Knowles, Jonathan C

    2014-12-01

    Small intestine submucosa (SIS) has emerged as one of a number of naturally derived extracellular matrix (ECM) biomaterials currently in clinical use. In addition to clinical applications, ECM materials form the basis for a variety of approaches within tissue engineering research. In our preliminary work it was found that SIS can be consistently and reliably made into tubular scaffolds which confer certain potential advantages. Given that decellularization protocols for SIS are applied to sheet-form SIS, it was hypothesized that a tubular-form SIS would behave differently to pre-existing protocols. In this work, tubular SIS was produced and decellularized by the conventional peracetic acid-agitation method, peracetic acid under perfusion along with two commonly used detergent-perfusion protocols. The aim of this was to produce a tubular SIS that was both adequately decellularized and possessing the mechanical properties which would make it a suitable scaffold for oesophageal tissue engineering, which was one of the goals of this work. Analysis was carried out via mechanical tensile testing, DNA quantification, scanning electron and light microscopy, and a metabolic assay, which was used to give an indication of the biocompatibility of each decellularization method. Both peracetic acid protocols were shown to be unsuitable methods with the agitation-protocol-produced SIS, which was poorly decellularized, and the perfusion protocol resulted in poor mechanical properties. Both detergent-based protocols produced well-decellularized SIS, with no adverse mechanical effects; however, one protocol emerged, SDS/Triton X-100, which proved superior in both respects. However, this SIS showed reduced metabolic activity, and this cytotoxic effect was attributed to residual reagents. Consequently, the use of SIS produced using the detergent SD as the decellularization agent was deemed to be the most suitable, although the elimination of the DNase enzyme would give further

  17. In vivo evaluation of an episcleral multielectrode array for stimulation of the retina with reduced retinal ganglion cell mass.

    PubMed

    Siu, Timothy L; Morley, John W

    2008-05-01

    A visual prosthesis is an experimental device designed to activate residual functional neurons in the visual pathway to generate artificial vision for blind patients. Specifically, for photoreceptor disease, a microelectrode array applied to the surface of the sclera could potentially serve to stimulate the remaining interneurons in the retina to produce topographically mapped visual percepts. However, of those neurons spared in the disease process, the retinal ganglion cells (RGC), which represent the final output neurons of the retina, can be markedly reduced in number. Using an albino rabbit model with RGC deficits, acute recording of cortical electrical evoked potential was performed to ascertain whether such a stimulation strategy is feasible. By analyzing the strength-duration curve (current threshold vs. pulse duration) and cortical activation profiles, our results prove that bioelectrically safe and spatially differentiated stimulation of the retina is feasible notwithstanding the condition of markedly reduced RGC counts.

  18. Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD

    PubMed Central

    Jalal, Diana I.; Greco, Barbara A.; Umeukeje, Ebele M.; Reisin, Efrain; Manley, John; Zeig, Steven; Negoi, Dana G.; Hiremath, Anand N.; Blumenthal, Samuel S.; Sika, Mohammed; Niecestro, Robert; Koury, Mark J.; Ma, Khe-Ni; Greene, Tom; Lewis, Julia B.; Dwyer, Jamie P.

    2015-01-01

    Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0–28.9] versus 26.8 [13.4–47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023–9695] versus 6954 [2664–12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders. PMID:25736045

  19. Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD.

    PubMed

    Umanath, Kausik; Jalal, Diana I; Greco, Barbara A; Umeukeje, Ebele M; Reisin, Efrain; Manley, John; Zeig, Steven; Negoi, Dana G; Hiremath, Anand N; Blumenthal, Samuel S; Sika, Mohammed; Niecestro, Robert; Koury, Mark J; Ma, Khe-Ni; Greene, Tom; Lewis, Julia B; Dwyer, Jamie P

    2015-10-01

    Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders. PMID:25736045

  20. Reduced sputum expression of interferon-stimulated genes in severe COPD

    PubMed Central

    Hilzendeger, Clarissa; da Silva, Jane; Henket, Monique; Schleich, Florence; Corhay, Jean Louis; Kebadze, Tatiana; Edwards, Michael R; Mallia, Patrick; Johnston, Sebastian L; Louis, Renaud

    2016-01-01

    Background Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients. Methods Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology. Results Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%). ISGs were easily detectable in both groups. In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects. No difference was found with respect to MxA. COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients. Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts. IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs. Conclusion ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. PMID:27418822

  1. Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans.

    PubMed Central

    Hussain, M A; Schmitz, O; Mengel, A; Keller, A; Christiansen, J S; Zapf, J; Froesch, E R

    1993-01-01

    To elucidate the effects of insulin-like growth factor I (IGF-I) on fuel oxidation and insulin sensitivity, eight healthy subjects were treated with saline and recombinant human (IGF-I (10 micrograms/kg.h) during 5 d in a crossover, randomized fashion, while receiving an isocaloric diet (30 kcal/kg.d) throughout the study period. On the third and fourth treatment days, respectively, an L-arginine stimulation test and an intravenous glucose tolerance test were performed. A euglycemic, hyperinsulinemic clamp combined with indirect calorimetry and a glucose tracer infusion were performed on the fifth treatment day. IGF-I treatment led to reduced fasting and stimulated (glucose and/or L-arginine) insulin and growth hormone secretion. Basal and stimulated glucagon secretion remained unchanged. Intravenous glucose tolerance was unaltered despite reduced insulin secretion. Resting energy expenditure and lipid oxidation were both elevated, while protein oxidation was reduced, and glucose turnover rates were unaltered on the fifth treatment day with IGF-I as compared to the control period. Enhanced lipolysis was reflected by elevated circulating free fatty acids. Moreover, insulin-stimulated oxidative and nonoxidative glucose disposal (i.e., insulin sensitivity) were enhanced during IGF-I treatment. Thus, IGF-I treatment leads to marked changes in lipid and protein oxidation, whereas, at the dose used, carbohydrate metabolism remains unaltered in the face of reduced insulin levels and enhanced insulin sensitivity. Images PMID:8227340

  2. Lateral Hypothalamic Stimulation Reduces Hyperalgesia Through Spinally Descending Orexin-A Neurons in Neuropathic Pain.

    PubMed

    Wardach, Jacob; Wagner, Monica; Jeong, Younhee; Holden, Janean E

    2016-03-01

    No evidence to date shows that lateral hypothalamic (LH) stimulation produces orexin-A-mediated antinociception in the spinal cord dorsal horn (SCDH) in a model of neuropathic pain. We conducted experiments to examine the effect of orexin-A-mediated LH stimulation in female rats with chronic constriction injury (CCI) on thermal hyperalgesia. Rats receiving carbachol into the LH demonstrated antinociception on both the left CCI and right nonligated paws (p < .05). Rats were given carbachol in the LH followed by intrathecal injection of the orexin-1 (OX1) receptor antagonist SB-334867, which blocked LH-induced antinociception compared with control groups (p < .05) in the left paw, but not in the right paw. These findings support the hypothesis that LH stimulation produces antinociception in rats with thermal hyperalgesia from neuropathic pain via an orexin-A connection between the LH and the SCDH. Identification of this pathway may lead to studies using orexins to manage clinical pain.

  3. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

    PubMed

    Spitoni, Grazia Fernanda; Pireddu, Giorgio; Galati, Gaspare; Sulpizio, Valentina; Paolucci, Stefano; Pizzamiglio, Luigi

    2016-01-01

    Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions. PMID:27028404

  4. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study

    PubMed Central

    2016-01-01

    Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient’s left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions. PMID:27028404

  5. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    PubMed

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  6. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    SciTech Connect

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-03-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects.

  7. Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage prostaglandin E(2) production via a mechanism involving phospholipases.

    PubMed

    Lakritz, Jeffrey; Tyler, Jeff W; Marsh, Antoinette E; Romesburg-Cockrell, Mary; Smith, Kathy; Holle, Julie M

    2002-01-01

    Tilmicosin is a potent antimicrobial with broad-spectrum activity against the bacterial agents involved in the bovine respiratory disease complex. Recent studies indicate that in addition to being bactericidal, tilmicosin is capable of modulating inflammation in the lung. A series of experiments were designed to determine whether tilmicosin alters alveolar macrophage-prostaglandin E(2) (PGE(2)) production induced by Escherichia coli (O55:B5) lipopolysaccharide (LPS). Twenty-two healthy Holstein bull calves were used to study the effects of LPS-induced PGE(2) production of alveolar macrophages after in vivo or in vitro treatment with tilmicosin. In Experiment 1, tilmicosin was given by subcutaneous injection (15 mg/kg) twice, 48 hours apart, to four calves; four control calves received no treatment. Twenty-four hours after the second treatment, alveolar macrophages were stimulated with LPS in vitro. In Experiment 2, alveolar macrophages from five untreated calves were harvested and treated in vitro with tilmicosin, followed by LPS stimulation. In Experiment 3, the ability of in vitro tilmicosin treatment to alter the expression of LPS-induced cyclooxygenase-2 (COX-2) mRNA was evaluated. In Experiments 4 and 5, secretory phospholipase A(2) activity was examined in untreated calves. Treatment of calves with tilmicosin resulted in reduced LPS-induced alveolar macrophage PGE(2) production. Similar reductions in PGE(2) by LPS-stimulated alveolar macrophages after in vitro tilmicosin treatment were noted. This in vitro tilmicosin treatment was not associated with reduction of the expression of LPS-induced COX-2. Alveolar macrophage phospholipase A(2) activity induced by LPS was significantly reduced by prior tilmicosin treatment in vitro. Tilmicosin (in vivo and in vitro) appears to reduce the PGE(2) eicosanoid response of LPS-stimulated alveolar macrophages by reducing the in vitro substrate availability without altering in vitro COX-2 mRNA expression.

  8. Chronic osmotic stimulation reduces vasopressin but not synaptophysin content in rat neurohypophysis.

    PubMed

    Ehrhart-Bornstein, M; Thorn, N A; Treiman, M

    1990-10-30

    The content of synaptophysin, a vesicular integral membrane protein of neurons and endocrine cells, and that of vasopressin was measured in neurohypophyses of rats during chronic osmotic stimulation. The animals received 2% NaCl in their drinking water for up to 4 days. Synaptophysin content of neurohypophyses was determined using quantitative immunoblotting, vasopressin content was measured by radioimmunoassay. Salt loading caused a decrease in the content of vasopressin to about 15% of that of control animals, whether expressed per neurohypophysis or relative to the total tissue protein. In contrast, no change was found in the synaptophysin content. Taken together with published evidence of changes in the relative numbers of the hormone-containing neurosecretory granules (NSGs) and the microvesicles (MVs) under the conditions of chronic osmotic stimulation, these results strongly indicate the surface density of synaptophysin on NSGs to be significantly lower than its surface density on MVs. PMID:2129060

  9. Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

    PubMed

    Macedo, I C; de Oliveira, C; Vercelino, R; Souza, A; Laste, G; Medeiros, L F; Scarabelot, V L; Nunes, E A; Kuo, J; Fregni, F; Caumo, W; Torres, I L S

    2016-08-01

    It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 μA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 μA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation. PMID:26972354

  10. Reducing Current Spread by Use of a Novel Pulse Shape for Electrical Stimulation of the Auditory Nerve

    PubMed Central

    Ballestero, Jimena; Recugnat, Matthieu; Laudanski, Jonathan; Smith, Katie E.; Jagger, Daniel J.; Gnansia, Daniel

    2015-01-01

    Improving the electrode-neuron interface to reduce current spread between individual electrodes has been identified as one of the main objectives in the search for future improvements in cochlear-implant performance. Here, we address this problem by presenting a novel stimulation strategy that takes account of the biophysical properties of the auditory neurons (spiral ganglion neurons, SGNs) stimulated in electrical hearing. This new strategy employs a ramped pulse shape, where the maximum amplitude is achieved through a linear slope in the injected current. We present the theoretical framework that supports this new strategy and that suggests it will improve the modulation of SGNs’ activity by exploiting their sensitivity to the rising slope of current pulses. The theoretical consequence of this sensitivity to the slope is a reduction in the spread of excitation within the cochlea and, consequently, an increase in the neural dynamic range. To explore the impact of the novel stimulation method on neural activity, we performed in vitro recordings of SGNs in culture. We show that the stimulus efficacy required to evoke action potentials in SGNs falls as the stimulus slope decreases. This work lays the foundation for a novel, and more biomimetic, stimulation strategy with considerable potential for implementation in cochlear-implant technology. PMID:26721928

  11. Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

    PubMed

    Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

    2006-01-01

    Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement. PMID:16049525

  12. Small intestinal submucosa seeded with intestinal smooth muscle cells in a rodent jejunal interposition model

    PubMed Central

    Qin, Harry H.; Dunn, James C.Y.

    2011-01-01

    Background Small intestinal submucosa (SIS) is a porcine-derived, acellular, collagen-based matrix that has been tested without seeded smooth muscle cells (SMCs) for intestinal tissue engineering. We examined the expression patterns of contractile proteins of SIS with SMCs implanted in an in vivo rodent model. Materials and methods Intestinal SMCs were isolated from Lewis rat pups. Four-ply tubular SMCs-seeded SIS or blank SIS scaffolds were implanted in an adult rat jejunal interposition model. Recipients were sacrificed at 2, 4, and 8 weeks following the implantation. The retrieved specimens were examined using antibodies against contractile proteins of SMCs. Results Cultured intestinal SMCs expressed α-smooth muscle actin (α-SMA), calponin, and less smooth muscle myosin heavy chain (SM-MHC) in vitro. Cell-seeded SIS scaffolds contracted significantly over 8 weeks of implantation but were comparable to SIS scaffolds without cell seeding. Implanted cell-seeded SIS scaffolds at 2 weeks expressed extensive α-SMA, some calponin, and minimal SM-MHC. At 4 weeks, α-SMA-expressing cells decreased significantly, whereas calponin or SM-MHC expressing cells were rarely detected. A small number of α-SMA-expressing cells were present at 8 weeks, whereas more calponin or SM-MHC expressing cells emerged in proximity with the anastomotic interface. Conclusions Cell-seeded SIS contracted significantly after implantation, but the expressions of contractile proteins were present at the site of SIS interposition. No organized smooth muscle was formed at the site of implantation. A better scaffold design is needed to produce structured smooth muscle. PMID:21937060

  13. Extracellular Matrix from Porcine Small Intestinal Submucosa (SIS) as Immune Adjuvants

    PubMed Central

    Aachoui, Youssef; Ghosh, Swapan K.

    2011-01-01

    Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and hapten-protein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomes-related genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of chemotactic factors LIX and KC (neutrophil chemotactic factors), MCP-1 (monocytes chemotactic factors), MIP 1-α (macrophage chemotactic factor) and lymphotactin, as well as, growth factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specific antibody response, primarily of IgG1 type. PMID:22087247

  14. Nano-hydroxyapatite–thermally denatured small intestine sub-mucosa composites for entheses applications

    PubMed Central

    Perla, Venu; Webster, Thomas J

    2006-01-01

    The objective of the present in vitro study was to estimate the adhesion strength of nanometer crystalline hydroxyapatite (HA)–small intestine sub-mucosa (SIS) composites on model implant surfaces. Techniques of thermal denaturation (60°C, 20 min) of SIS were used to enhance the adhesion strength of entheses materials to underlying implants. Specifically, results indicated that the adhesion strength of thermally denatured SIS was 2–3 times higher than that for normal unheated SIS. In addition, aqua-sonicated, hydrothermally treated nano-HA dispersions enhanced the adhesion strength of SIS on implant surfaces. Importantly, results of the present study demonstrated that human skeletal muscle cell (hSkMC) numbers were not affected by thermally denaturing SIS in nano-HA composite coatings; however, they increased on aqua-sonicated nano-HA/SIS composites compared with SIS alone. Interestingly, thermally denatured SIS that contained aqua-sonicated, hydrothermally treated nano-HA decreased human osteoblasts (hOBs) numbers compared with respective unheated composites; all other composites when thermally denatured did not influence hOB numbers. Results also showed that the number of hOBs increased on nano-HA/SIS composites compared with SIS composites alone. Human mesenchymal stem cell (hMSC) numbers were not affected by the presence of nano-HA in SIS composites. For these reasons, the collective results of this in vitro study demonstrated a technique to increase the coating strength of entheses coatings on implant surfaces (using thermally denatured SIS and aqua-sonicated, hydrothermally prepared nano-HA) while, at the same time, supporting cell functions important for entheses regeneration. PMID:17717975

  15. Percutaneous Vein Occlusion with Small Intestinal Submucosa: An Experimental Pilot Study in Swine and Sheep

    SciTech Connect

    Kim, Man Deuk; Hoppe, Hanno; Pavcnik, Dusan Kaufman, John A.; Uchida, Barry T.; Correa, Luiz O.; Timmermans, Hans A.; Park, Won Kyu; Corless, Christopher L.; Keller, Frederick S.; Roesch, Josef

    2007-07-15

    Purpose. The objective of this study was to investigate the feasibility, outcomes, and amount of small intestinal submucosa (SIS) material needed for embolization of jugular vein (JV) in a swine and sheep model. Our hypothesis was that SIS would cause vein occlusion. Materials and Methods. The external JVs (EJV) in swine (n = 6) and JVs in sheep (n = 6) were occluded with SIS fan-folded compressed strips. After percutaneous puncture of the peripheral portion of the EJV or JV, a TIPS set was used to exit their lumen centrally through the skin. The SIS strips were delivered into the isolated venous segment with a pull-through technique via a 10-Fr sheath. Follow-up venograms were done immediately after placement and at the time of sacrifice at 1 or 3 months. Gross examinations focused on the EJV or JV and their surrounding structures. Specimens were evaluated by histology. Results. SIS strip(s) placement was successful in all cases, with immediate vein occlusion seen in 23 of 24 veins (95.8%). All EJVs treated with two strips and all JVs treated with three or four strips remained closed on 1- and 3-month follow-up venograms. Two EJVs treated with one strip and one JV treated with two strips were partially patent on venograms at 1 and 3 months. There has been one skin inflammatory reaction. Necropsies revealed excluded EJV or JV segments with SIS incorporation into the vein wall. Histology demonstrated various stages of SIS remodeling with fibrocytes, fibroblasts, endothelial cells, capillaries, and inflammatory cells. Conclusion. We conclude that EJV and JV ablation with SIS strips using percutaneous exit catheterization is feasible and effective in animal models. Further exploration of SIS as vein ablation material is recommended.

  16. Chronic methamphetamine administration reduces histamine-stimulated phosphoinositide hydrolysis in mouse frontal cortex.

    PubMed

    Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko

    2003-01-24

    In the present study, it was hypothesized that in vivo pretreatment with repeated methamphetamine would alter the agonist-stimulated phosphoinositide hydrolysis in mouse frontal cortical slices. Male ICR mice that received the methamphetamine injection (1.0mg/kg, intraperitoneally) once a day for five consecutive days showed behavioral sensitization to the same dose of methamphetamine 5 days after the last injection of the initial chronic treatment regimen (test day 10). On test day 10, the reduction of histamine (0.1-1.0mM)-stimulated phosphoinositide hydrolysis in the mouse frontal cortex was observed. The reduction was specific to histamine, but not to norepinephrine (10 microM-0.1mM) or L-glutamate (0.1-0.5mM). The reduction occurred without any change in the expression level of histamine H(1) receptor mRNA. The reduction recovered 25 days after the last injection of the initial chronic treatment regimen (test day 30). The direct application to the slices of a pharmacologically effective concentration of methamphetamine in vitro (10 microM) did not alter the histamine signal transduction. The present results suggest that the reduction is probably one of neuroadaptations in the frontal cortex contributing to behavioral sensitization.

  17. Galvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin.

    PubMed

    Kaur, Simarna; Lyte, Peter; Garay, Michelle; Liebel, Frank; Sun, Ying; Liu, Jue-Chen; Southall, Michael D

    2011-10-01

    The human body has its own innate electrical system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level electrical stimulation on wound repair has been reported, few studies have examined the effect of electric potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to determine the effects of low-level electrical stimulation on intact skin physiology using a Dermacorder device. Zn-Cu induced the electrical potential recorded on intact skin, enhanced H(2)O(2) production and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus observed via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by production of low level of hydrogen peroxide since this activity is reversed by the addition of Catalase enzyme. Collectively, these results show that a galvanic couple containing Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of electric stimulation in non-wounded skin. PMID:21465312

  18. Galvanic zinc-copper microparticles produce electrical stimulation that reduces the inflammatory and immune responses in skin.

    PubMed

    Kaur, Simarna; Lyte, Peter; Garay, Michelle; Liebel, Frank; Sun, Ying; Liu, Jue-Chen; Southall, Michael D

    2011-10-01

    The human body has its own innate electrical system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level electrical stimulation on wound repair has been reported, few studies have examined the effect of electric potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to determine the effects of low-level electrical stimulation on intact skin physiology using a Dermacorder device. Zn-Cu induced the electrical potential recorded on intact skin, enhanced H(2)O(2) production and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus observed via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by production of low level of hydrogen peroxide since this activity is reversed by the addition of Catalase enzyme. Collectively, these results show that a galvanic couple containing Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of electric stimulation in non-wounded skin.

  19. Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model

    PubMed Central

    Melega, William P.; Lacan, Goran; Gorgulho, Alessandra A.; Behnke, Eric J.; De Salles, Antonio A. F.

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID:22295102

  20. Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.

    PubMed

    Melega, William P; Lacan, Goran; Gorgulho, Alessandra A; Behnke, Eric J; De Salles, Antonio A F

    2012-01-01

    Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.

  1. Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

    PubMed

    Chiao, H; Foster, S; Thomas, R; Lipton, J; Star, R A

    1996-05-01

    Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade. PMID:8621792

  2. Reduced salmonella fecal shedding in swine administered porcine granulocyte-colony stimulating factor (G-CSF)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella colonization of food animals is a concern for animal health, food safety and public health. Key objectives of pre-harvest food safety programs are to detect asymptomatic Salmonella carriage in food animals, reduce colonization, and prevent transmission of Salmonella to other animals and ...

  3. Acetylation stimulates the epithelial sodium channel by reducing its ubiquitination and degradation.

    PubMed

    Butler, Phillip L; Staruschenko, Alexander; Snyder, Peter M

    2015-05-15

    The epithelial Na(+) channel (ENaC) functions as a pathway for Na(+) absorption in the kidney and lung, where it is crucial for Na(+) homeostasis and blood pressure regulation. ENaC is regulated in part through signaling pathways that control the ubiquitination state of ENaC lysines. A defect in ubiquitination causes Liddle syndrome, an inherited form of hypertension. Here we determined that α-, β-, and γENaC are also substrates for lysine acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, enhanced ENaC acetylation and increased ENaC abundance in the total cell lysate and at the cell surface. Moreover, TSA increased ENaC current in Fischer rat thyroid and kidney collecting duct epithelia. We found that HDAC7 is expressed in the kidney collecting duct, supporting a potential role for this histone deacetylase in ENaC regulation. HDAC7 overexpression reduced ENaC abundance and ENaC current, whereas ENaC abundance and current were increased by silencing of HDAC7. ENaC and HDAC7 form a complex, as detected by coimmunoprecipitation. We observed a reciprocal relationship between acetylation and ubiquitination; TSA reduced ENaC ubiquitination, whereas HDAC7 increased ubiquitination. By reducing ENaC ubiquitination, TSA decreased the rate of ENaC degradation. Thus, acetylation increases epithelial Na(+) absorption by antagonizing ENaC ubiquitination. This stabilizes ENaC, and hence, increases its abundance at the cell surface. PMID:25787079

  4. Stimulated emission reduced fluorescence microscopy: a concept for extending the fundamental depth limit of two-photon fluorescence imaging.

    PubMed

    Wei, Lu; Chen, Zhixing; Min, Wei

    2012-06-01

    Two-photon fluorescence microscopy has become an indispensable tool for imaging scattering biological samples by detecting scattered fluorescence photons generated from a spatially confined excitation volume. However, this optical sectioning capability breaks down eventually when imaging much deeper, as the out-of-focus fluorescence gradually overwhelms the in-focal signal in the scattering samples. The resulting loss of image contrast defines a fundamental imaging-depth limit, which cannot be overcome by increasing excitation efficiency. Herein we propose to extend this depth limit by performing stimulated emission reduced fluorescence (SERF) microscopy in which the two-photon excited fluorescence at the focus is preferentially switched on and off by a modulated and focused laser beam that is capable of inducing stimulated emission of the fluorophores from the excited states. The resulting image, constructed from the reduced fluorescence signal, is found to exhibit a significantly improved signal-to-background contrast owing to its overall higher-order nonlinear dependence on the incident laser intensity. We demonstrate this new concept by both analytical theory and numerical simulations. For brain tissues, SERF is expected to extend the imaging depth limit of two-photon fluorescence microscopy by a factor of more than 1.8.

  5. Stimulated emission reduced fluorescence microscopy: a concept for extending the fundamental depth limit of two-photon fluorescence imaging

    PubMed Central

    Wei, Lu; Chen, Zhixing; Min, Wei

    2012-01-01

    Two-photon fluorescence microscopy has become an indispensable tool for imaging scattering biological samples by detecting scattered fluorescence photons generated from a spatially confined excitation volume. However, this optical sectioning capability breaks down eventually when imaging much deeper, as the out-of-focus fluorescence gradually overwhelms the in-focal signal in the scattering samples. The resulting loss of image contrast defines a fundamental imaging-depth limit, which cannot be overcome by increasing excitation efficiency. Herein we propose to extend this depth limit by performing stimulated emission reduced fluorescence (SERF) microscopy in which the two-photon excited fluorescence at the focus is preferentially switched on and off by a modulated and focused laser beam that is capable of inducing stimulated emission of the fluorophores from the excited states. The resulting image, constructed from the reduced fluorescence signal, is found to exhibit a significantly improved signal-to-background contrast owing to its overall higher-order nonlinear dependence on the incident laser intensity. We demonstrate this new concept by both analytical theory and numerical simulations. For brain tissues, SERF is expected to extend the imaging depth limit of two-photon fluorescence microscopy by a factor of more than 1.8. PMID:22741091

  6. Angiographic Evaluation of Carotid Artery Grafting with Prefabricated Small-Diameter, Small-Intestinal Submucosa Grafts in Sheep

    SciTech Connect

    Pavcnik, Dusan; Obermiller, Josef; Uchida, Barry T.; Van Alstine, William; Edwards, James M.; Landry, Gregory J.; Kaufman, John A.; Keller, Frederick S.; Roesch, Josef

    2009-01-15

    The purpose of this study was to report the longitudinal angiographic evaluation of prefabricated lyophilized small-intestinal submucosa (SIS) grafts placed in ovine carotid arteries and to demonstrate a variety of complications that developed. A total of 24 grafts, 10 cm long and 6 mm in diameter, were placed surgically as interposition grafts. Graft patency at 1 week was evaluated by Doppler ultrasound, and angiography was used for follow-up at 1 month and at 3 to 4 months. A 90% patency rate was found at 1 week, 65% at 1 month, and 30% at 3 to 4 months. On the patent grafts, angiography demonstrated a variety of changes, such as anastomotic stenoses, graft diffuse dilations and dissections, and aneurysm formation. These findings have not been previously demonstrated angiographically by other investigators reporting results with small-diameter vessel grafts made from fresh small-intestinal submucosa (SIS). The complications found were partially related to the graft construction from four SIS layers. Detailed longitudinal angiographic study should become an essential part of any future evaluation of small-vessel SIS grafting.

  7. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    PubMed Central

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

  8. Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation

    PubMed Central

    Kanemi, O; Zhang, X; Sakamoto, Y; Ebina, M; Nagatomi, R

    2005-01-01

    There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors. PMID:15606610

  9. Pulsed electromagnetic field stimulates osteoprotegerin and reduces RANKL expression in ovariectomized rats.

    PubMed

    Zhou, Jun; Chen, Shiju; Guo, Hua; Xia, Lu; Liu, Huifang; Qin, Yuxi; He, Chengqi

    2013-05-01

    Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17β-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG.

  10. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.

    PubMed

    Wilkins, Heather M; Harris, Janna L; Carl, Steven M; E, Lezi; Lu, Jianghua; Eva Selfridge, J; Roy, Nairita; Hutfles, Lewis; Koppel, Scott; Morris, Jill; Burns, Jeffrey M; Michaelis, Mary L; Michaelis, Elias K; Brooks, William M; Swerdlow, Russell H

    2014-12-15

    Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1α, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor κB nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis.

  11. Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

    PubMed

    Bravo, Gabriela L; Poje, Albert B; Perissinotti, Iago; Marcondes, Bianca F; Villamar, Mauricio F; Manzardo, Ann M; Luque, Laura; LePage, Jean F; Stafford, Diane; Fregni, Felipe; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS. PMID:26590516

  12. Elevated CO2 and phosphate limitation favor Micromonas pusilla through stimulated growth and reduced viral impact.

    PubMed

    Maat, Douwe S; Crawfurd, Katherine J; Timmermans, Klaas R; Brussaard, Corina P D

    2014-05-01

    Growth and viral infection of the marine picoeukaryote Micromonas pusilla was studied under a future-ocean scenario of elevated partial CO2 (pCO2; 750 μatm versus the present-day 370 μatm) and simultaneous limitation of phosphorus (P). Independent of the pCO2 level, the ratios of M. pusilla cellular carbon (C) to nitrogen (N), C:P and N:P, increased with increasing P stress. Furthermore, in the P-limited chemostats at growth rates of 0.32 and 0.97 of the maximum growth rate (μmax), the supply of elevated pCO2 led to an additional rise in cellular C:N and C:P ratios, as well as a 1.4-fold increase in M. pusilla abundance. Viral lysis was not affected by pCO2, but P limitation led to a 150% prolongation of the latent period (6 to 12 h) and an 80% reduction in viral burst sizes (63 viruses per cell) compared to P-replete conditions (4 to 8 h latent period and burst size of 320). Growth at 0.32 μmax further prolonged the latent period by another 150% (12 to 18 h). Thus, enhanced P stress due to climate change-induced strengthened vertical stratification can be expected to lead to reduced and delayed virus production in picoeukaryotes. This effect is tempered, but likely not counteracted, by the increase in cell abundance under elevated pCO2. Although the influence of potential P-limitation-relieving factors, such as the uptake of organic P and P utilization during infection, is unclear, our current results suggest that when P limitation prevails in future oceans, picoeukaryotes and grazing will be favored over larger-sized phytoplankton and viral lysis, with increased matter and nutrient flow to higher trophic levels. PMID:24610859

  13. The perceived position of moving objects: transcranial magnetic stimulation of area MT+ reduces the flash-lag effect.

    PubMed

    Maus, Gerrit W; Ward, Jamie; Nijhawan, Romi; Whitney, David

    2013-01-01

    How does the visual system assign the perceived position of a moving object? This question is surprisingly complex, since sluggish responses of photoreceptors and transmission delays along the visual pathway mean that visual cortex does not have immediate information about a moving object's position. In the flash-lag effect (FLE), a moving object is perceived ahead of an aligned flash. Psychophysical work on this illusion has inspired models for visual localization of moving objects. However, little is known about the underlying neural mechanisms. Here, we investigated the role of neural activity in areas MT+ and V1/V2 in localizing moving objects. Using short trains of repetitive Transcranial Magnetic Stimulation (TMS) or single pulses at different time points, we measured the influence of TMS on the perceived location of a moving object. We found that TMS delivered to MT+ significantly reduced the FLE; single pulse timings revealed a broad temporal tuning with maximum effect for TMS pulses, 200 ms after the flash. Stimulation of V1/V2 did not significantly influence perceived position. Our results demonstrate that area MT+ contributes to the perceptual localization of moving objects and is involved in the integration of position information over a long time window.

  14. EPINEPHRINE OR GV-26 ELECTRICAL STIMULATION REDUCES INHALANT ANESTHESTIC RECOVERY TIME IN COMMON SNAPPING TURTLES (CHELYDRA SERPENTINA).

    PubMed

    Goe, Alexandra; Shmalberg, Justin; Gatson, Bonnie; Bartolini, Pia; Curtiss, Jeff; Wellehan, James F X

    2016-06-01

    Prolonged anesthetic recovery times are a common clinical problem in reptiles following inhalant anesthesia. Diving reptiles have numerous adaptations that allow them to submerge and remain apneic for extended periods. An ability to shunt blood away from pulmonary circulation, possibly due to changes in adrenergic tone, may contribute to their unpredictable inhalant anesthetic recovery times. Therefore, the use of epinephrine could antagonize this response and reduce recovery time. GV-26, an acupuncture point with reported β-adrenergic and respiratory effects, has reduced anesthetic recovery times in other species. In this prospective randomized crossover study, six common snapping turtles (Chelydra serpentina) were anesthetized with inhalant isoflurane for 90 min. Turtles were assigned one of three treatments, given immediately following discontinuation of isoflurane: a control treatment (0.9% saline, at 0.1 ml/kg i.m.), epinephrine (0.1 mg/kg i.m.), or acupuncture with electrical stimulation at GV-26. Each turtle received all treatments, and treatments were separated by 48 hr. Return of spontaneous ventilation was 55% faster in turtles given epinephrine and 58% faster in the GV-26 group versus saline (P < 0.001). The times to movement and to complete recovery were also significantly faster for both treatments than for saline (P < 0.02). Treated turtles displayed increases in temperature not documented in the control (P < 0.001). Turtles administered epinephrine showed significantly increased heart rates and end-tidal CO(2) (P < 0.001). No adverse effects were noted in the study animals. The mechanisms of action were not elucidated in the present investigation. Nevertheless, the use of parenteral epinephrine or GV-26 stimulation in the immediate postanesthetic period produces clinically relevant reductions in anesthetic recovery time in common snapping turtle. Further research is necessary to evaluate the effects of concurrent GV-26 and epinephrine administration

  15. EPINEPHRINE OR GV-26 ELECTRICAL STIMULATION REDUCES INHALANT ANESTHESTIC RECOVERY TIME IN COMMON SNAPPING TURTLES (CHELYDRA SERPENTINA).

    PubMed

    Goe, Alexandra; Shmalberg, Justin; Gatson, Bonnie; Bartolini, Pia; Curtiss, Jeff; Wellehan, James F X

    2016-06-01

    Prolonged anesthetic recovery times are a common clinical problem in reptiles following inhalant anesthesia. Diving reptiles have numerous adaptations that allow them to submerge and remain apneic for extended periods. An ability to shunt blood away from pulmonary circulation, possibly due to changes in adrenergic tone, may contribute to their unpredictable inhalant anesthetic recovery times. Therefore, the use of epinephrine could antagonize this response and reduce recovery time. GV-26, an acupuncture point with reported β-adrenergic and respiratory effects, has reduced anesthetic recovery times in other species. In this prospective randomized crossover study, six common snapping turtles (Chelydra serpentina) were anesthetized with inhalant isoflurane for 90 min. Turtles were assigned one of three treatments, given immediately following discontinuation of isoflurane: a control treatment (0.9% saline, at 0.1 ml/kg i.m.), epinephrine (0.1 mg/kg i.m.), or acupuncture with electrical stimulation at GV-26. Each turtle received all treatments, and treatments were separated by 48 hr. Return of spontaneous ventilation was 55% faster in turtles given epinephrine and 58% faster in the GV-26 group versus saline (P < 0.001). The times to movement and to complete recovery were also significantly faster for both treatments than for saline (P < 0.02). Treated turtles displayed increases in temperature not documented in the control (P < 0.001). Turtles administered epinephrine showed significantly increased heart rates and end-tidal CO(2) (P < 0.001). No adverse effects were noted in the study animals. The mechanisms of action were not elucidated in the present investigation. Nevertheless, the use of parenteral epinephrine or GV-26 stimulation in the immediate postanesthetic period produces clinically relevant reductions in anesthetic recovery time in common snapping turtle. Further research is necessary to evaluate the effects of concurrent GV-26 and epinephrine administration

  16. Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome.

    PubMed

    Iodice, P; Lessiani, G; Franzone, G; Pezzulo, G

    2016-01-01

    Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42±13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low-intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS.

  17. Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome.

    PubMed

    Iodice, P; Lessiani, G; Franzone, G; Pezzulo, G

    2016-01-01

    Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42±13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low-intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS. PMID:27358158

  18. Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients

    PubMed Central

    Gupta, Ajay; Lin, Vivian; Guss, Carrie; Pratt, Raymond; Ikizler, T Alp; Besarab, Anatole

    2015-01-01

    Ferric pyrophosphate citrate (FPC) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin. The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent (ESA) use and maintain hemoglobin in hemodialysis patients. This 9-month, randomized, placebo-controlled, double-blind, multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly. The FPC group received dialysate containing 2 μmol/l of iron. The placebo group received standard dialysate. A blinded central anemia management group facilitated ESA dose adjustments. Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l. The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment. Secondary end points included intravenous iron use and safety. At the end of treatment, there was a significant 35% reduction in prescribed ESA dose in FPC-treated patients compared with placebo. The FPC patients used 51% less intravenous iron than placebo. Adverse and serious adverse events were similar in both groups. Thus, FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients. PMID:26154926

  19. Adenosine A(2A) receptor stimulation reduces inflammation and neointimal growth in a murine carotid ligation model.

    PubMed

    McPherson, J A; Barringhaus, K G; Bishop, G G; Sanders, J M; Rieger, J M; Hesselbacher, S E; Gimple, L W; Powers, E R; Macdonald, T; Sullivan, G; Linden, J; Sarembock, I J

    2001-05-01

    Endothelial activation and leukocyte recruitment are early events in atherosclerosis and the vascular response to injury. Adenosine has anti-inflammatory effects on leukocytes and endothelial cells mediated through its A(2A) receptor. We tested the hypothesis that A(2A) activation would reduce inflammation and neointimal formation in a murine carotid ligation model. Before injury, mice were randomized to a 7-day subcutaneous infusion of a specific A(2A) receptor agonist (ATL-146e, 0.004 microg/kg per minute), vehicle control, ATL-146e plus ZM241385 (a selective A(2A) antagonist), or ZM241385 alone. Leukocyte recruitment and adhesion molecule expression were assessed at early time points, and the neointimal area was measured at 14 and 28 days after injury. Compared with control mice, ATL-146e-treated mice had significantly less neutrophil and macrophage recruitment and vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and P-selectin expression in the first 7 days after injury. Neointimal area was markedly and persistently reduced by 80% at 14 and 28 days, despite termination of ATL infusion at 7 days. ATL-146e+ZM241385-treated and ZM241385-treated animals had neointimal areas similar to those of control animals, confirming that the observed effects of ATL-146e were mediated specifically by the A(2A) receptor. These data demonstrate that novel stimulation of adenosine A(2A) receptors can inhibit early inflammatory processes that are important in neointimal formation after vascular injury.

  20. Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain

    PubMed Central

    Chen, Wanqiu; Guo, Yi; Walker, Espen J.; Shen, Fanxia; Jun, Kristine; Oh, S. Paul; Degos, Vincent; Lawton, Michael T.; Tihan, Tarik; Davalos, Dimitrios; Akassoglou, Katerina; Nelson, Jeffrey; Pile-Spellman, John; Su, Hua; Young, William L.

    2013-01-01

    Objective Vessels in brain arteriovenous malformations (bAVM) are prone to rupture. The underlying pathogenesis is not clear. Hereditary hemorrhagic telangiectasia type 2 (HHT2) patients with activin receptor-like kinase 1 (Alk1) mutation have a higher incidence of bAVM than the general population. We tested the hypothesis that vascular endothelial growth factor (VEGF) impairs vascular integrity in the Alk1-deficient brain through reduction of mural cell-coverage. Methods and Results Adult Alk11f/2f mice (loxP sites flanking exons 4-6) and wild-type (WT) mice were injected with 2×107 PFU Ad-Cre and 2×109 genome copies of AAV-VEGF to induce focal homozygous Alk1 deletion (in Alk11f/2f mice) and angiogenesis. Brain vessels were analyzed eight weeks later. Compared to WT mice, the Alk1-deficient brain had more fibrin (99±30×103 pixels/mm2 vs. 40±13×103, P=0.001), iron deposition (508±506 pixels/mm2 vs. 6 ±49, P=0.04), and Iba1+ microglia/macrophage infiltration (888±420 Iba1+ cells/mm2 vs. 240±104 Iba1+, P=0.001) after VEGF stimulation. In the angiogenic foci, the Alk1-deficient brain had more α-SMA- vessels (52±9% vs. 12±7%, P<0.001), fewer vascular associated pericytes (503±179/mm2 vs. 931±115, P<0.001), and reduced PDGFR-β expression (26±9%, P<0.001). Conclusion Reduction of mural cell coverage in response to VEGF stimulation is a potential mechanism for the impairment of vessel wall integrity in HHT2-associated bAVM. PMID:23241407

  1. Grafts of porcine small intestinal submucosa seeded with cultured homologous smooth muscle cells for bladder repair in dogs

    PubMed Central

    2013-01-01

    Background Due to numerous complications associated to gastrointestinal augmented cystoplasty, this study aimed to analyze the anatomic repair of the bladder of 10 female dogs using grafts of porcine small intestinal submucosa (SIS) seeded with cultured homologous smooth muscle cells, and compare them with the acellular SIS grafts. Results We assessed the possible side effects and complications of each type of graft by clinical examination, abdominal ultrasound and laboratory findings. Anatomic repair of neoformed bladder was assessed by histological staining for H/E and Masson's Trichrome, analyzed with a Nikon Photomicroscope connected to the system of image analysis Image J. Conclusions We propose that SIS associated to homologous smooth cells can improve the quality of tissue repair, and consequently decrease the potential complications inherent to acellular SIS. PMID:23651843

  2. Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

    PubMed Central

    Coffey, M J; Phare, S M; George, S; Peters-Golden, M; Kazanjian, P H

    1998-01-01

    Neutrophil (PMN) dysfunction occurs in HIV infection. Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway that play a role in host defense and are synthesized by PMN. We investigated the synthesis of LT by PMN from HIV-infected subjects. There was a reduction (4.0+/-1.3% of control) in LT synthesis in PMN from HIV-infected compared with normal subjects. This was associated with reduced expression of 5-LO-activating protein (31.2+/-9.6% of normal), but not of 5-LO itself. Since HIV does not directly infect PMN, we considered that these effects were due to reduced release of cytokines, such as granulocyte colony-stimulating factor (G-CSF). We examined the effect of G-CSF treatment (300 microgram daily for 5 d) on eight HIV-infected subjects. PMN were studied in vitro before therapy (day 1) and on days 4 and 7. LTB4 synthesis was increased on day 4 of G-CSF treatment, and returned toward day 1 levels on day 7. 5-LO and 5-LO-activating protein expression were increased in parallel. As a functional correlate to this increase in PMN LT synthesis by G-CSF, we examined the effects on killing of Cryptococcus neoformans. Anticryptococcal activity of PMN from HIV-infected subjects was less than that of PMN from normal subjects. G-CSF treatment improved fungistatic activity of PMN. This increase in antifungal activity was attenuated by in vitro treatment with the LT synthesis inhibitor, MK-886. In conclusion, PMN from HIV-infected subjects demonstrate reduced 5-LO metabolism and antifungal activity in vitro, which was reversed by in vivo G-CSF therapy. PMID:9710433

  3. Isolation, characterization, and in vitro evaluation of bovine rumen submucosa films of collagen or chitosan-treated collagen.

    PubMed

    Gopal Shankar, K; Udhaya Kumar, S; Sowndarya, S; Suresh Babu, P; Rose, C

    2016-01-01

    Bovine rumen is hitherto considered as an inedible waste of meat industry. The rumen tissues can be used as an alternative source of collagen to produce biocompatible materials for clinical application. In an effort to develop a functional biomaterial from the inedible mammalian tissues, this study aims to isolate and characterize bovine rumen submucosa. Initially, the rumen tissue was sequentially processed using chemical and enzymatic treatment to decellularize, neutralize, stabilize, and to produce a native collagen matrix which is referred as collagen film (COL-F). Thus, prepared matrix was treated with 1% (w/v) chitosan solution to produce a hybrid film which is referred as collagen-chitosan film (COL/CS-F). The comparative study includes the evaluation of physical, chemical, and biological properties of the biofilms prepared. The surface topology of COL-F exhibited a continuous collagenous network with fibrous nature, while the chitosan treatment provided smooth plain surface to the parent film. Incorporation of chitosan in COL-F increased the tensile properties, as well as the thermal stability and durability of the films. The Fourier Transform Infrared spectroscopy results revealed the presence of respective amide peaks, which corresponds to protein (collagen), and the evidence of collagen-chitosan interlinking. The submucosa layer was electrophoretically found to have type I collagen. The X-ray diffraction data showed the presence of amorphous and crystalline peak which attributes to the triple helical structure of collagen in the films. Cytotoxicity studies on the films were performed in vitro using human keratinocytes. The results of cell viability and proliferation demonstrated that COL-F and COL/CS-F exhibit good biocompatibility and therefore can augment cell infiltration and proliferation. However, enhanced cellular activity was observed on the chitosan treated COL-F. These observations demonstrate that the biofilms prepared in this study can be

  4. Naloxone reduces the amplitude of IPSPs evoked in lumbar motoneurons by reticular stimulation during carbachol-induced motor inhibition.

    PubMed

    Xi, M C; Liu, R H; Yamuy, J; Morales, F R; Chase, M H

    1999-02-20

    During active sleep or carbachol-induced motor inhibition, electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) evoked large amplitude, glycinergic inhibitory postsynaptic potentials (IPSPs) in cat motoneurons. The present study was directed to determine whether these IPSPs, that are specific to the state of active sleep, are modulated by opioid peptides. Accordingly, intracellular recordings were obtained from lumbar motoneurons of acute decerebrate cats during carbachol-induced motor inhibition while an opiate receptor antagonist, naloxone, was microiontophoretically released next to the recorded cells. Naloxone reversibly reduced by 26% the mean amplitude of NRGc-evoked IPSPs (1.9+/-0.2 mV (S.E.M.) vs. 1.4+/-0.2 mV; n=11, control and naloxone, respectively, p<0.05), but had no effect on the other waveform parameters of these IPSPs (e.g., latency-to-onset, latency-to-peak, duration, etc.). The mean resting membrane potential, input resistance and membrane time constant of motoneurons following naloxone ejection were not statistically different from those of the control. These data indicate that opioid peptides have a modulatory effect on NRGc-evoked IPSPs during carbachol-induced motor inhibition. We therefore suggest that endogenous opioid peptides may act as neuromodulators to regulate inhibitory glycinergic synaptic transmission at motoneurons during active sleep. PMID:10082872

  5. Angiogenesis Is Induced and Wound Size Is Reduced by Electrical Stimulation in an Acute Wound Healing Model in Human Skin

    PubMed Central

    Ud-Din, Sara; Sebastian, Anil; Giddings, Pamela; Colthurst, James; Whiteside, Sigrid; Morris, Julie; Nuccitelli, Richard; Pullar, Christine; Baguneid, Mo; Bayat, Ardeshir

    2015-01-01

    Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up

  6. Subcortical volumes are reduced in short-term and long-term abstinent alcoholics but not those with a comorbid stimulant disorder☆

    PubMed Central

    Fein, George; Fein, David

    2013-01-01

    Chronic alcohol abuse affects brain structure and function. We examined subcortical structure volumes in 77 short (6–15 week) and 90 long (multi-year) term abstinent alcoholics, along with 74 controls. We used a 3T Siemens MPRAGE sequence for image acquisition and FSL FIRST software for measuring subcortical volumes. When examining alcoholics without a comorbid stimulant disorder we found reduced hippocampal, pallidum and thalamus volumes in short term abstinence compared to a non-substance abusing control sample with numerically smaller yet still significant reductions compared to controls in long term abstinence. When examining alcoholics with a comorbid stimulant disorder, no difference from controls was found for any subcortical volume. Alcoholics with a stimulant disorder had significantly larger subcortical volumes than alcoholics without a stimulant disorder. This study replicates past research showing that chronic alcohol abuse is associated with lower subcortical volumes in short-term abstinent chronic alcoholics and extends this finding, although with smaller effects to long-term abstinent samples. The absence of this effect in the presence of a comorbid stimulant disorder suggests either a protective effect of stimulant abuse/dependence or that the measurements reflect the aggregate of alcohol dependence associated atrophy and stimulant abuse associated inflammation. Associations with function suggest the second of these two alternatives. PMID:24179848

  7. High- and low-frequency transcutaneous electrical nerve stimulation does not reduce experimental pain in elderly individuals

    PubMed Central

    Bergeron-Vézina, Kayla; Corriveau, Hélène; Martel, Marylie; Harvey, Marie-Philippe; Léonard, Guillaume

    2015-01-01

    Abstract Despite its widespread clinical use, the efficacy of transcutaneous electrical nerve stimulation (TENS) remains poorly documented in elderly individuals. In this randomized, double-blind crossover study, we compared the efficacy of high-frequency (HF), low-frequency (LF), and placebo (P) TENS in a group of 15 elderly adults (mean age: 67 ± 5 years). The effect of HF-, LF-, and P-TENS was also evaluated in a group of 15 young individuals (26 ± 5 years; same study design) to validate the effectiveness of the TENS protocols that were used in the elderly group. Each participant came to the laboratory on 3 separate occasions to receive, in random order, HF-, LF-, and P-TENS. Pain intensity and pain perception thresholds were assessed before, during, and after TENS, using an experimental heat pain paradigm. For the young group, there was a significant decrease in pain intensity during and after HF- and LF-TENS when compared with baseline, with both HF- and LF-TENS being superior to P-TENS. In the older group, HF- and LF-TENS did not reduce pain when compared with baseline and no difference was observed between the 2 active TENS sessions and P-TENS. High-frequency, LF-, and P-TENS all increased pain thresholds in young individuals, whereas in older individuals, only LF-TENS increased pain thresholds. Taken together, these results suggest that TENS is effective in young, but not in older, individuals. Future studies should be conducted to confirm these results in pain populations and to identify strategies that could enhance the effect of TENS in the elderly. PMID:26101836

  8. Inhibition of the pontine Kölliker-Fuse nucleus reduces genioglossal activity elicited by stimulation of the retrotrapezoid chemoreceptor neurons.

    PubMed

    Silva, Josiane N; Lucena, Elvis V; Silva, Talita M; Damasceno, Rosélia S; Takakura, Ana C; Moreira, Thiago S

    2016-07-22

    The Kölliker-Fuse (KF) region, located in the dorsolateral pons, projects to several brainstem areas involved in respiratory regulation, including the chemoreceptor neurons within the retrotrapezoid nucleus (RTN). Several lines of evidence indicate that the pontine KF region plays an important role in the control of the upper airways for the maintenance of appropriate airflow to and from the lungs. Specifically, we hypothesized that the KF region is involved in mediating the response of the hypoglossal motor activity to central respiratory chemoreflex activation and to stimulation of the chemoreceptor neurons within the RTN region. To test this hypothesis, we combined immunohistochemistry and physiological experiments. We found that in the KF, the majority of biotinylated dextran amine (BDA)-labeled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2), but few contained glutamic acid decarboxylase-67 (GAD67). The majority of the RTN neurons that were FluorGold (FG)-immunoreactive (i.e., projected to the KF) contained hypercapnia-induced Fos, but did not express tyrosine hydroxylase. In urethane-anesthetized sino-aortic denervated and vagotomized male Wistar rats, hypercapnia (10% CO2) or N-methyl-d-aspartate (NMDA) injection (0.1mM) in the RTN increased diaphragm (DiaEMG) and genioglossus muscle (GGEMG) activities and elicited abdominal (AbdEMG) activity. Bilateral injection of muscimol (GABA-A agonist; 2mM) into the KF region reduced the increase in DiaEMG and GGEMG produced by hypercapnia or NMDA into the RTN. Our data suggest that activation of chemoreceptor neurons in the RTN produces a significant increase in the genioglossus muscle activity and the excitatory pathway is dependent on the neurons located in the dorsolateral pontine KF region. PMID:27126558

  9. High- and low-frequency transcutaneous electrical nerve stimulation does not reduce experimental pain in elderly individuals.

    PubMed

    Bergeron-Vézina, Kayla; Corriveau, Hélène; Martel, Marylie; Harvey, Marie-Philippe; Léonard, Guillaume

    2015-10-01

    Despite its widespread clinical use, the efficacy of transcutaneous electrical nerve stimulation (TENS) remains poorly documented in elderly individuals. In this randomized, double-blind crossover study, we compared the efficacy of high-frequency (HF), low-frequency (LF), and placebo (P) TENS in a group of 15 elderly adults (mean age: 67 ± 5 years). The effect of HF-, LF-, and P-TENS was also evaluated in a group of 15 young individuals (26 ± 5 years; same study design) to validate the effectiveness of the TENS protocols that were used in the elderly group. Each participant came to the laboratory on 3 separate occasions to receive, in random order, HF-, LF-, and P-TENS. Pain intensity and pain perception thresholds were assessed before, during, and after TENS, using an experimental heat pain paradigm. For the young group, there was a significant decrease in pain intensity during and after HF- and LF-TENS when compared with baseline, with both HF- and LF-TENS being superior to P-TENS. In the older group, HF- and LF-TENS did not reduce pain when compared with baseline and no difference was observed between the 2 active TENS sessions and P-TENS. High-frequency, LF-, and P-TENS all increased pain thresholds in young individuals, whereas in older individuals, only LF-TENS increased pain thresholds. Taken together, these results suggest that TENS is effective in young, but not in older, individuals. Future studies should be conducted to confirm these results in pain populations and to identify strategies that could enhance the effect of TENS in the elderly.

  10. Inhibition of the pontine Kölliker-Fuse nucleus reduces genioglossal activity elicited by stimulation of the retrotrapezoid chemoreceptor neurons.

    PubMed

    Silva, Josiane N; Lucena, Elvis V; Silva, Talita M; Damasceno, Rosélia S; Takakura, Ana C; Moreira, Thiago S

    2016-07-22

    The Kölliker-Fuse (KF) region, located in the dorsolateral pons, projects to several brainstem areas involved in respiratory regulation, including the chemoreceptor neurons within the retrotrapezoid nucleus (RTN). Several lines of evidence indicate that the pontine KF region plays an important role in the control of the upper airways for the maintenance of appropriate airflow to and from the lungs. Specifically, we hypothesized that the KF region is involved in mediating the response of the hypoglossal motor activity to central respiratory chemoreflex activation and to stimulation of the chemoreceptor neurons within the RTN region. To test this hypothesis, we combined immunohistochemistry and physiological experiments. We found that in the KF, the majority of biotinylated dextran amine (BDA)-labeled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2), but few contained glutamic acid decarboxylase-67 (GAD67). The majority of the RTN neurons that were FluorGold (FG)-immunoreactive (i.e., projected to the KF) contained hypercapnia-induced Fos, but did not express tyrosine hydroxylase. In urethane-anesthetized sino-aortic denervated and vagotomized male Wistar rats, hypercapnia (10% CO2) or N-methyl-d-aspartate (NMDA) injection (0.1mM) in the RTN increased diaphragm (DiaEMG) and genioglossus muscle (GGEMG) activities and elicited abdominal (AbdEMG) activity. Bilateral injection of muscimol (GABA-A agonist; 2mM) into the KF region reduced the increase in DiaEMG and GGEMG produced by hypercapnia or NMDA into the RTN. Our data suggest that activation of chemoreceptor neurons in the RTN produces a significant increase in the genioglossus muscle activity and the excitatory pathway is dependent on the neurons located in the dorsolateral pontine KF region.

  11. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    SciTech Connect

    Miao, Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  12. Noninvasive low-frequency electromagnetic stimulation of the left stellate ganglion reduces myocardial infarction-induced ventricular arrhythmia

    PubMed Central

    Wang, Songyun; Zhou, Xiaoya; Huang, Bing; Wang, Zhuo; Zhou, Liping; Wang, Menglong; Yu, Lilei; Jiang, Hong

    2016-01-01

    Noninvasive magnetic stimulation has been widely used in autonomic disorders in the past few decades, but few studies has been done in cardiac diseases. Recently, studies showed that low-frequency electromagnetic field (LF-EMF) might suppress atrial fibrillation by mediating the cardiac autonomic nervous system. In the present study, the effect of LF-EMF stimulation of left stellate ganglion (LSG) on LSG neural activity and ventricular arrhythmia has been studied in an acute myocardium infarction canine model. It is shown that LF-EMF stimulation leads to a reduction both in the neural activity of LSG and in the incidence of ventricular arrhythmia. The obtained results suggested that inhibition of the LSG neural activity might be the causal of the reduction of ventricular arrhythmia since previous studies have shown that LSG hyperactivity may facilitate the incidence of ventricular arrhythmia. LF-EMF stimulation might be a novel noninvasive substitute for the existing implant device-based electrical stimulation or sympathectomy in the treatment of cardiac disorders. PMID:27470078

  13. Comparison of Porcine Small Intestinal Submucosa versus Polypropylene in Open Inguinal Hernia Repair: A Systematic Review and Meta-Analysis

    PubMed Central

    Nie, Xin; Xiao, Dongdong; Wang, Wenyue; Song, Zhicheng; Yang, Zhi; Chen, Yuanwen; Gu, Yan

    2015-01-01

    Background A systematic review and meta-analysis was performed in randomized controlled trials (RCTs) to compare porcine small intestinal submucosa (SIS) with polypropylene in open inguinal hernia repair. Method Electronic databases MEDLINE, Embase, and the Cochrane Library were used to compare patient outcomes for the two groups via meta-analysis. Result A total of 3 randomized controlled trials encompassing 200 patients were included in the meta-analysis. There was no significant difference in recurrence (P = 0.16), hematomas (P = 0.06), postoperative pain within 30 days (P = 0.45), or postoperative pain after 1 year (P = 0.12) between the 2 groups. The incidence of discomfort was significantly lower (P = 0.0006) in the SIS group. However, the SIS group experienced a significantly higher incidence of seroma (P = 0.03). Conclusions Compared to polypropylene, using SIS in open inguinal hernia repair is associated with a lower incidence of discomfort and a higher incidence of seroma. However, well-designed larger RCT studies with a longer follow-up period are needed to confirm these findings. PMID:26252895

  14. The Management of Diabetic Foot Ulcers with Porcine Small Intestine Submucosa Tri-Layer Matrix: A Randomized Controlled Trial

    PubMed Central

    Cazzell, Shawn M.; Lange, Darrell L.; Dickerson, Jaime E.; Slade, Herbert B.

    2015-01-01

    Objective: This study demonstrates that superior outcomes are possible when diabetic foot ulcers (DFU) are managed with tri-layer porcine small intestine submucosa (SIS). Approach: Patients with DFU from 11 centers participated in this prospective randomized controlled trial. Qualified subjects were randomized (1:1) to either SIS or standard care (SC) selected at the discretion of the Investigator and followed for 12 weeks or complete ulcer closure. Results: Eighty-two subjects (41 in each group) were evaluable in the intent-to-treat analysis. Ulcers managed with SIS had a significantly greater proportion closed by 12 weeks than for the Control group (54% vs. 32%, p=0.021) and this proportion was numerically higher at all visits. Time to closure for ulcers achieving closure was 2 weeks earlier for the SIS group than for SC. Median reduction in ulcer area was significantly greater for SIS at each weekly visit (all p values<0.05). Review of reported adverse events found no safety concerns. Innovation: These data support the use of tri-layer SIS for the effective management of DFU. Conclusion: In this randomized controlled trial, SIS was found to be associated with more rapid improvement, and a higher likelihood of achieving complete ulcer closure than those ulcers treated with SC. PMID:26634183

  15. Effects of fabrication on the mechanics, microstructure and micromechanical environment of small intestinal submucosa scaffolds for vascular tissue engineering.

    PubMed

    Sánchez-Palencia, Diana M; D'Amore, Antonio; González-Mancera, Andrés; Wagner, William R; Briceño, Juan C

    2014-08-22

    In small intestinal submucosa scaffolds for functional tissue engineering, the impact of scaffold fabrication parameters on success rate may be related to the mechanotransductory properties of the final microstructural organization of collagen fibers. We hypothesized that two fabrication parameters, 1) preservation (P) or removal (R) of a dense collagen layer present in SIS and 2) SIS in a final dehydrated (D) or hydrated (H) state, have an effect on scaffold void area, microstructural anisotropy (fiber alignment) and mechanical anisotropy (global mechanical compliance). We further integrated our experimental measurements in a constitutive model to explore final effects on the micromechanical environment inside the scaffold volume. Our results indicated that PH scaffolds might exhibit recurrent and large force fluctuations between layers (up to 195 pN), while fluctuations in RH scaffolds might be larger (up to 256 pN) but not as recurrent. In contrast, both PD and RD groups were estimated to produce scarcer and smaller fluctuations (not larger than 50 pN). We concluded that the hydration parameter strongly affects the micromechanics of SIS and that an adequate choice of fabrication parameters, assisted by the herein developed method, might leverage the use of SIS for functional tissue engineering applications, where forces at the cellular level are of concern in the guidance of new tissue formation.

  16. Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair.

    PubMed

    Liu, Zhengni; Feng, Xueyi; Wang, Huichun; Ma, Jun; Liu, Wei; Cui, Daxiang; Gu, Yan; Tang, Rui

    2014-01-01

    Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT) were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165). The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS) to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF-MWNT-PSIS) contributed to early vascularization from 2-12 weeks postimplantation and obtained more effective collagen deposition and exhibited improved tensile strength at 24 weeks postimplantation compared to PSIS or PSIS scaffolds, incorporating MWNT without VEGF165 loading (MWNT-PSIS).

  17. A Flexible Stent with Small Intestinal Submucosa Covering for Direct Intrahepatic Portocaval Shunt: Experimental Pilot Study in Swine

    SciTech Connect

    Niyyati, Mahtab; Petersen, Bryan D.; Pavcnik, Dusan Uchida, Barry T.; Timmermans, Hans A.; Hiraki, Takao; Wu Renghong; Brountzos, Elias; Keller, Frederick S.; Roesch, Josef

    2005-04-15

    The suitability of the flexible sandwich Zilver stent-graft (SZSG) with a biologically active tissue layer (small intestinal submucosa) for creation of the intravascular ultrasound (IVUS)-guided direct intrahepatic portocaval shunt (DIPS) was explored in six young swine in a search for a flexible system to replace the rigid polytetrafluoroethylene (PTFE) stent originally used by this group with limited success. The portal vein was punctured from the inferior vena cava through the caudate lobe of the liver using IVUS guidance. After balloon dilation of the puncture tract, DIPS was successfully created in all animals with use of an SZSG 9 mm in diameter and 6 cm or 8 cm long. Only one DIPS remained well patent at 14 days when the animal had to be killed because of encephalopathy. DIPS in the other five animals were found to be either severely stenosed (3 animals) or occluded (2 animals) at 4 weeks due to accelerated formation of neointimal hyperplasia (NIH) in the liver parenchymal portion of the shunt and superimposed thrombosis. The lack of high pressure in the portal system contributed to early endograft closure. The flexible stent and the covering fail badly. The reason for this could be due to either component. More work is required to find a reliable flexible system with long-term patency. Exploration of the IVUS-guided direct extrahepatic portocaval shunt is suggested.

  18. Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue.

    PubMed

    Karbowska, Joanna; Kochan, Zdzislaw

    2012-11-01

    Dehydroepiandrosterone (DHEA) reduces body fat in rodents and humans, and increases glycerol release from isolated rat epididymal adipocytes and human visceral adipose tissue explants. It suggests that DHEA stimulates triglyceride hydrolysis in adipose tissue; however, the mechanisms underlying this action are still unclear. We examined the effects of DHEA on the expression of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), the key enzymes of lipolysis, in rat epididymal white adipose tissue (eWAT). Male Wistar rats were fed a diet containing 0.6% DHEA for 2 weeks and eWAT was analyzed for mRNA and protein expression of ATGL and HSL, as well as mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ2) and its downstream target fatty acid translocase (FAT). Glycerol release from eWAT explants and serum free fatty acids (FFA) were also measured. Rats that received DHEA gained less weight, had 23% lower eWAT mass and 31% higher serum FFA levels than controls. Cultured explants of eWAT from DHEA-treated rats released 81% more glycerol than those from control rats. DHEA administration upregulated ATGL mRNA (1.62-fold, P<0.05) and protein (1.78-fold, P<0.05) expression as well as augmented HSL mRNA levels (1.36-fold, P<0.05) and Ser660 phosphorylation of HSL (2.49-fold, P<0.05). PPARγ2 and FAT mRNA levels were also increased in DHEA-treated rats (1.61-fold, P<0.05 and 2.16-fold, P<0.05; respectively). Moreover, ATGL, HSL, and FAT mRNA levels were positively correlated with PPARγ2 expression. This study demonstrates that DHEA promotes lipid mobilization in adipose tissue by increasing the expression and activity of ATGL and HSL. The effects of DHEA appear to be mediated, at least in part, via PPARγ2 activation, which in turn upregulates ATGL and HSL gene expression.

  19. Subthalamic Stimulation Reduces Vowel Space at the Initiation of Sustained Production: Implications for Articulatory Motor Control in Parkinson’s Disease

    PubMed Central

    Sidtis, John J.; Alken, Amy G.; Tagliati, Michele; Alterman, Ron; Van Lancker Sidtis, Diana

    2016-01-01

    Background: Stimulation of the subthalamic nuclei (STN) is an effective treatment for Parkinson’s disease, but complaints of speech difficulties after surgery have been difficult to quantify. Speech measures do not convincingly account for such reports. Objective: This study examined STN stimulation effects on vowel production, in order to probe whether DBS affects articulatory posturing. The objective was to compare positioning during the initiation phase with the steady prolongation phase by measuring vowel spaces for three “corner” vowels at these two time frames. Methods: Vowel space was measured over the initial 0.25 sec of sustained productions of high front (/i/), high back (/u/) and low vowels (/a/), and again during a 2 sec segment at the midpoint. Eight right-handed male subjects with bilateral STN stimulation and seven age-matched male controls were studied based on their participation in a larger study that included functional imaging. Mean values: age = 57±4.6 yrs; PD duration = 12.3±2.7 yrs; duration of DBS = 25.6±21.2 mos, and UPDRS III speech score = 1.6±0.7. STN subjects were studied off medication at their therapeutic DBS settings and again with their stimulators off, counter-balanced order. Results: Vowel space was larger in the initiation phase compared to the midpoint for both the control and the STN subjects off stimulation. With stimulation on, however, the initial vowel space was significantly reduced to the area measured at the mid-point. For the three vowels, the acoustics were differentially affected, in accordance with expected effects of front versus back position in the vocal tract. Conclusions: STN stimulation appears to constrain initial articulatory gestures for vowel production, raising the possibility that articulatory positions normally used in speech are similarly constrained. PMID:27003219

  20. Acupuncture transcutaneous electrical nerve stimulation reduces discomfort associated with barostat-induced rectal distension: A randomized-controlled study

    PubMed Central

    Leung, Wing-Wa; Jones, Alice YM; Ng, Simon SM; Wong, Cherry YN; Lee, Janet FY

    2013-01-01

    AIM: To explore the effectiveness of acupuncture transcutaneous electrical nerve stimulation (Acu-TENS), a non-invasive modality in reduction of rectal discomfort during barostat-induced rectal distension. METHODS: Forty healthy subjects were randomized to receive 45 min of either Acu-TENS or placebo-TENS (no electrical output) over acupuncture points Hegu (large-intestine 4), Neiguan (pericardium 6) and Zusanli (stomach 36). A balloon catheter attached to a dual-drive barostat machine was then inserted into the subjects’ rectum. A step-wise (4 mmHg) increase in balloon pressure was induced until maximal tolerable or 48 mmHg. Visual analogue scale and a 5-point subjective discomfort scale (no perception, first perception of distension, urge to defecate, discomfort/pain and extreme pain) were used to assess rectal discomfort at each distension pressure. Blood beta-endorphin levels were measured before, immediately after intervention, at 24 mmHg and at maximal tolerable distension pressure. RESULTS: There was no difference in the demographic data and baseline plasma beta-endorphin levels between the two groups. Perception threshold levels were higher in the Acu-TENS group when compared to the placebo group, but the difference reached statistical significance only at the sensations “urge to defecate” and “pain”. The distension pressures recorded at the “urge to defecate” sensation for the Acu-TENS and placebo-TENS groups were 28.0 ± 4.5 mmHg and 24.6 ± 5.7 mmHg, respectively (P = 0.043); and the pressures recorded for the “pain” sensation for these two groups were 36.0 ± 4.2 mmHg and 30.5 ± 4.3 mmHg respectively (P = 0.002). Compared to the placebo group, a higher number of participants in the Acu-TENS group tolerated higher distension pressures (> 40 mmHg) (65% in Acu-TENS vs 25% in placebo, P = 0.02). The plasma beta-endorphin levels of the Acu-TENS group were significantly higher than that of the placebo group at barostat inflation pressure of

  1. Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation.

    PubMed

    Dartt, Darlene A; Hodges, Robin R; Li, Dayu; Shatos, Marie A; Lashkari, Kameran; Serhan, Charles N

    2011-04-01

    The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are goblet cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased goblet cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival goblet cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT(1) and CysLT(2,) were present in rat conjunctiva and in rat and human cultured conjunctival goblet cells. All leukotrienes LTB(4), LTC(4), LTD(4), and LTE(4), as well as PGD(2), stimulated goblet cell secretion in rat goblet cells. LTD(4) and LTE(4) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), and LTD(4) activated ERK1/2. The CysLT(1) receptor antagonist MK571 significantly decreased LTD(4)-stimulated rat goblet cell secretion and the increase in [Ca(2+)](i). Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD(4)-stimulated goblet cell secretion in cultured rat goblet cells. LTD(4)-induced secretion from human goblet cells was blocked by RvD1. RvD1 and RvE1 prevented LTD(4)- and LTE(4)-stimulated increases in [Ca(2+)](i), as well as LTD(4) activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival goblet cell mucous secretion with LTD(4) using the CysLT(1) receptor. Stimulated secretion is terminated by preventing the increase in [Ca(2+)](i) and activation of ERK1/2 by RvD1 and RvE1.

  2. Development of hypoparathyroidism animal model and the feasibility of small intestinal submucosa application on the parathyroid autotransplantation.

    PubMed

    Park, Hae Sang; Jung, Soo Yeon; Kim, Ha Young; Kim, Da Yeon; Kim, Moon Suk; Chung, Sung Min; Rho, Young-Soo; Kim, Han Su

    2015-10-01

    The purpose of this study is to evaluate the feasibility of small intestinal submucosa (SIS) application on the parathyroid autotransplantation in a rat model of hypoparathyroidism. The rats were divided into four groups: NC (no procedure, n = 5), PTX (total parathyroidectomy, n = 6), PT (total parathyroidectomy and parathyroid autotransplantation, n = 10) and PT + SIS group (total parathyroidectomy and parathyroid autotransplantation with SIS, n = 10). The levels of parathyroid hormone (PTH), calcium, and phosphorous were measured on 0, 3, 7, 21, 56 and 84 days after surgery. PTH level was expressed as median (interquartile range) and histological and immunohistochemical examinations were performed. PTH levels were significantly decreased to "not detectable level" from day 3 in PTX group. PTH was not detected in both PT and PT + SIS groups on the 21st day. On the 56th day, PTH levels were increased in both groups: 3 out of 8 rats (37.5%) in the PT group, 6 out of 9 rats (66.7%) in the PT + SIS group. The PTH level was fully recovered to its preoperative range on the day 84 as 6 of 8 rats (75%) of the PT group and 7 of 9 rats (77.8%) of the PT + SIS group were recovered; the PTH levels were 117.84 and 178.36 pg/ml, respectively. The neo-vascularization was well observed around the parathyroid tissue, and the number of new vessels formed was higher in the PT + SIS group (15 vessels/high power field) as compared to the PT group (10 vessels/high power field). This study showed the feasibility and the treatment effect of SIS as the success rate of autotransplantation of parathyroid tissue was significantly increased without severe inflammatory response in hypothyroidism animal model.

  3. Endoluminal Treatment of Ruptured Abdominal Aortic Aneurysm with Small Intestinal Submucosa Sandwich Endografts: A Pilot Study in Sheep

    SciTech Connect

    Yamada, Katsuyuki; Pavcnik, Dusan; Uchida, Barry T.; Timmermans, Hans A.; Corless, Christopher L.; Yin, Qiang; Yamakado, Koichiro; Wha Park, Joong; Roesch, Josef; Keller, Frederick S.; Sato, Morio; Yamada, Ryusaku

    2001-03-15

    Purpose: To evaluate efficacy of small intestinal submucosa (SIS) Sandwich endografts for the treatment of acute rupture of abdominal aortic aneurysms (AAA) and to explore the short-term reaction of the aorta to this material.Methods: In eight adult sheep, an infrarenal AAA was created transluminally by dilation of a short Palmaz stent. In six sheep, the aneurysm was then ruptured by overdilation of the stent with a large angioplasty balloon. Two sheep with AAAs that were not ruptured served as controls. A SIS Sandwich endograft, consisting of a Z stent frame with 5 bodies and covered inside and out with SIS, was used to exclude the ruptured and non-ruptured AAAs. Follow-up aortography was done immediately after the procedure and before sacrifice at 4, 8, or 12 weeks. Autopsy and histologic studies followed.Results: Endograft placement was successful in all eight sheep. Both ruptured and non-ruptured AAAs were successfully excluded. Three animals with AAA rupture developed hind leg paralysis due to compromise of the arterial supply to the lower spinal cord and were sacrificed 1 day after the procedure. In five animals, three with rupture and two controls, follow-up aortograms revealed no aortic stenoses and no perigraft leaks. Gross and histologic studies revealed incorporation of the endografts into the aortic wall with replacement of SIS by dense neointima that was completely endothelialized in areas where the endograft was in direct contact with the aortic wall. In central portions of the endograft, in contact with the thrombosed aneurysm, endothelialization was incomplete even at 12 weeks.Conclusion: The SIS Sandwich endografts effectively excluded simple AAAs and ruptured AAAs. They were rapidly incorporated into the aortic wall. A detailed long-term study is warranted.

  4. INS-1 cell glucose-stimulated insulin secretion is reduced by the downregulation of the 67 kDa laminin receptor.

    PubMed

    Sabra, Georges; Dubiel, Evan A; Kuehn, Carina; Khalfaoui, Taoufik; Beaulieu, Jean-François; Vermette, Patrick

    2015-12-01

    Understanding β cell-extracellular matrix (ECM) interactions can advance our knowledge of the mechanisms that control glucose homeostasis and improve culture methods used in islet transplantation for the treatment of diabetes. Laminin is the main constituent of the basement membrane and is involved in pancreatic β cell survival and function, even enhancing glucose-stimulated insulin secretion. Most of the studies on cell responses towards laminin have focused on integrin-mediated interactions, while much less attention has been paid on non-integrin receptors, such as the 67 kDa laminin receptor (67LR). The specificity of the receptor-ligand interaction through the adhesion of INS-1 cells (a rat insulinoma cell line) to CDPGYIGSR-, GRGDSPC- or CDPGYIGSR + GRGDSPC-covered surfaces was evaluated. Also, the effects of the 67LR knocking down over glucose-stimulated insulin secretion were investigated. Culture of the INS-1 cells on the bioactive surfaces was improved compared to the low-fouling carboxymethyl dextran (CMD) surfaces, while downregulation of the 67LR resulted in reduced cell adhesion to surfaces bearing the CDPGYIGSR peptide. Glucose-stimulated insulin secretion was hindered by downregulation of the 67LR, regardless of the biological motif available on the biomimetic surfaces on which the cells were cultured. This finding illustrates the importance of the 67LR in glucose-stimulated insulin secretion and points to a possible role of the 67LR in the mechanisms of insulin secretion.

  5. Inhibition of pancreatic β-cell Ca2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance.

    PubMed

    Dadi, Prasanna K; Vierra, Nicholas C; Ustione, Alessandro; Piston, David W; Colbran, Roger J; Jacobson, David A

    2014-05-01

    Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is caused by Ca(2+) entry via voltage-dependent Ca(2+) channels. CaMKII is a key mediator and feedback regulator of Ca(2+) signaling in many tissues, but its role in β-cells is poorly understood, especially in vivo. Here, we report that mice with conditional inhibition of CaMKII in β-cells show significantly impaired glucose tolerance due to decreased GSIS. Moreover, β-cell CaMKII inhibition dramatically exacerbates glucose intolerance following exposure to a high fat diet. The impairment of islet GSIS by β-cell CaMKII inhibition is not accompanied by changes in either glucose metabolism or the activities of KATP and voltage-gated potassium channels. However, glucose-stimulated Ca(2+) entry via voltage-dependent Ca(2+) channels is reduced in islet β-cells with CaMKII inhibition, as well as in primary wild-type β-cells treated with a peptide inhibitor of CaMKII. The levels of basal β-cell cytoplasmic Ca(2+) and of endoplasmic reticulum Ca(2+) stores are also decreased by CaMKII inhibition. In addition, CaMKII inhibition suppresses glucose-stimulated action potential firing frequency. These results reveal that CaMKII is a Ca(2+) sensor with a key role as a feed-forward stimulator of β-cell Ca(2+) signals that enhance GSIS under physiological and pathological conditions.

  6. Reduced basal and stimulated (isoprenaline, Gpp(NH)p, forskolin) adenylate cyclase activity in Alzheimer's disease correlated with histopathological changes.

    PubMed

    Ohm, T G; Bohl, J; Lemmer, B

    1991-02-01

    Cyclic adenosine monophosphate (cAMP) is an adenylate cyclase borne second messenger involved in basic metabolic events. The beta-adrenoceptor sensitive adenylate cyclase was studied in post-mortem hippocampi of controls and Alzheimer patients. Virtually identical subsets of each hippocampus homogenate were stimulated by 100 mumol isoprenaline, Gpp(NH)p and forskolin, respectively, in presence of an ATP-regenerating system. The determination of cAMP formed was carried out by means of a radioassay. The observed significant 50% reduction in basal as well as in stimulated adenylate cyclase activity in Alzheimer's disease is negatively correlated with semiquantitative evaluations of amyloid plaques (P less than 0.05) but not with neuritic plaques, neurofibrillary tangles or neuropil threads. This reduction in enzyme activity is obviously not due to simple cell loss alone. It is likely that the crucial point of the observed functional disturbance is at the level of the catalytic unit of the adenylate cyclase, since the same degree of reduction is maintained at all steps of the signal cascade. PMID:2054615

  7. Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression

    PubMed Central

    Rapinesi, Chiara; Bersani, Francesco Saverio; Kotzalidis, Georgios D.; Imperatori, Claudio; Del Casale, Antonio; Di Pietro, Simone; Ferri, Vittoria R.; Serata, Daniele; Raccah, Ruggero N.; Zangen, Abraham; Angeletti, Gloria; Girardi, Paolo

    2015-01-01

    Introduction: Deep transcranial magnetic stimulation (dTMS) is a new form of TMS allowing safe stimulation of deep brain regions. The objective of this preliminary study was to assess the role of dTMS maintenance sessions in protecting patients with bipolar disorder (BD) or recurrent major depressive disorder (MDD) from developing depressive or manic relapses in a 12-month follow-up period. Methods: Twenty-four drug-resistant patients with a current depressive episode and a diagnosis of MDD or BD have been enrolled in the study. All the participants underwent daily dTMS sessions for 4 weeks. One group (maintenance – M group) received additional maintenance dTMS sessions weekly or twice a week. Results: After the first dTMS cycle, a significant reduction of Hamilton Depression Rating Scale (HDRS) scores was observed in all participants. Subsequently, the HDRS mean scores did not significantly change over time in the M group, while it significantly increased in the non-M-group after 6 and 12 months. Discussion: This study confirms previous evidence of a positive therapeutic effect of dTMS on depressive symptoms and suggests that, after recovery from acute episodes, maintenance dTMS sessions may be helpful in maintaining euthymia in a 12-month follow-up period. PMID:25709596

  8. Arginase inhibition reduces interleukin-1β-stimulated vascular smooth muscle cell proliferation by increasing nitric oxide synthase-dependent nitric oxide production

    SciTech Connect

    Yoon, Jeongyeon; Ryoo, Sungwoo

    2013-06-07

    Highlights: •Arginase inhibition suppressed proliferation of IL-1β-stimulated VSMCs in dose-dependent manner. •NO production from IL-1β-induced iNOS expression was augmented by arginase inhibition, reducing VSMC proliferation. •Incubation with cGMP analogues abolished IL-1β-dependent proliferation of VSMCs. -- Abstract: We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS) mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.

  9. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.

    PubMed

    Schaap, Frank G; Rensen, Patrick C N; Voshol, Peter J; Vrins, Carlos; van der Vliet, Hendrik N; Chamuleau, Robert A F M; Havekes, Louis M; Groen, Albert K; van Dijk, Ko Willems

    2004-07-01

    ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 10(8) plaqueforming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins.

  10. Resveratrol reduces prostaglandin E1-stimulated osteoprotegerin synthesis in osteoblasts: suppression of stress-activated protein kinase/c-Jun N-terminal kinase.

    PubMed

    Yamamoto, Naohiro; Otsuka, Takanobu; Kuroyanagi, Gen; Kondo, Akira; Kainuma, Shingo; Nakakami, Akira; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

    2015-01-01

    Resveratrol, a natural polyphenol mainly existing in red grapes and berries, possesses beneficial effects on human being. We have previously reported that prostaglandin E1 (PGE1) stimulates vascular endothelial growth factor synthesis via activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the PGE1-effect on osteoprotegerin (OPG) synthesis and the effect of resveratrol on the synthesis in MC3T3-E1 cells. PGE1 induced the expression levels of OPG mRNA and stimulated the OPG release. Resveratrol significantly reduced the PGE1-induced OPG release and the mRNA expression. SRT1720, an activator of SIRT1, suppressed the release of OPG. The protein levels of SIRT1 were not up-regulated by resveratrol with or without PGE1. Both SB203580 and SP600125, a specific p38 MAP kinase inhibitor and a specific SAPK/JNK inhibitor, respectively, but not PD98059, a specific MEK inhibitor, reduced the PGE1-stimulated OPG release. Resveratrol or SRT1720 failed to affect the phosphorylation of p38 MAP kinase. On the contrary, PGE1-induced phosphorylation of SAPK/JNK was significantly attenuated by both resveratrol and SRT1720. Our results strongly suggest that resveratrol inhibits PGE1-stimulated OPG synthesis via suppressing SAPK/JNK but not p38 MAP kinase in osteoblasts.

  11. Feeling worse to feel better: pain-offset relief simultaneously stimulates positive affect and reduces negative affect.

    PubMed

    Franklin, Joseph C; Lee, Kent M; Hanna, Eleanor K; Prinstein, Mitchell J

    2013-04-01

    Although pain itself induces negative affect, the removal (or offset) of pain induces a powerful state of relief. Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains a poorly understood emotion. In particular, some theorists associate relief with increased positive affect, whereas others associate relief with diminished negative affect. In the present study, we examined the affective nature of relief in a pain-offset paradigm with psychophysiological measures that were specific to negative valence (startle eyeblink reactivity) and positive valence (startle postauricular reactivity). Results revealed that pain offset simultaneously stimulates positive affect and diminishes negative affect for at least several seconds. Results also indicated that pain intensity differentially affects the positive and negative valence aspects of relief. These findings clarify the affective nature of relief and provide insight into why people engage in both normal and abnormal behaviors associated with relief.

  12. Constitutive spectral EEG peaks in the gamma range: suppressed by sleep, reduced by mental activity and resistant to sensory stimulation

    PubMed Central

    Grummett, Tyler S.; Fitzgibbon, Sean P.; Lewis, Trent W.; DeLosAngeles, Dylan; Whitham, Emma M.; Pope, Kenneth J.; Willoughby, John O.

    2014-01-01

    Objective: In a systematic study of gamma activity in neuro-psychiatric disease, we unexpectedly observed distinctive, apparently persistent, electroencephalogram (EEG) spectral peaks in the gamma range (25–100 Hz). Our objective, therefore, was to examine the incidence, distribution and some of the characteristics of these peaks. Methods: High sample-rate, 128-channel, EEG was recorded in 603 volunteers (510 with neuropsychiatric disorders, 93 controls), whilst performing cognitive tasks, and converted to power spectra. Peaks of spectral power, including in the gamma range, were determined algorithmically for all electrodes. To determine if peaks were stable, 24-h ambulatory recordings were obtained from 16 subjects with peaks. In 10 subjects, steady-state responses to stimuli at peak frequency were compared with off-peak-frequency stimulation to determine if peaks were a feature of underlying network resonances and peaks were evaluated with easy and hard versions of oddball tasks to determine if peaks might be influenced by mental effort. Results: 57% of 603 subjects exhibited peaks >2 dB above trough power at or above 25 Hz. Larger peaks (>5 dB) were present in 13% of subjects. Peaks were distributed widely over the scalp, more frequent centrally. Peaks were present through the day and were suppressed by slow-wave-sleep. Steady-state responses were the same with on- or off-peak sensory stimulation. In contrast, mental effort resulted in reductions in power and frequency of gamma peaks, although the suppression did not correlate with level of effort. Conclusions: Gamma EEG can be expressed constitutively as concentrations of power in narrow or wide frequency bands that play an, as yet, unknown role in cognitive activity. Significance: These findings expand the described range of rhythmic EEG phenomena. In particular, in addition to evoked, induced and sustained gamma band activity, gamma activity can be present constitutively in spectral peaks. PMID:25484861

  13. alpha1-Adrenoceptors stimulate a Galphas protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart.

    PubMed

    Gallego, Mónica; Setién, Raúl; Puebla, Lilian; Boyano-Adánez, María Del Carmen; Arilla, Eduardo; Casis, Oscar

    2005-03-01

    alpha(1)-Adrenoceptor stimulation prolongs the duration of the cardiac action potentials and leads to positive inotropic effects by inhibiting the transient outward K(+) current (I(to)). In the present study, we have examined the role of several protein kinases and the G protein involved in I(to) inhibition in response to alpha(1)-adrenoceptor stimulation in isolated adult rat ventricular myocytes. Our findings exclude the classic alpha(1)-adrenergic pathway: activation of the G protein G(alphaq), phospholipase C (PLC), and protein kinase C (PKC), because neither PLC, nor PKC, nor G(alphaq) blockade prevents the alpha(1)-induced I(to) reduction. To the contrary, the alpha(1)-adrenoceptor does not inhibit I(to) in the presence of protein kinase A (PKA), adenylyl cyclase, or G(alphas) inhibitors. In addition, PKA and adenylyl cyclase activation inhibit I(to) to the same extent as phenylephrine. Finally, we have shown a functional coupling between the alpha(1)-adrenoceptor and G(alphas) in a physiological system. Moreover, this coupling seems to be compartmentalized, because the alpha(1)-adrenoceptor increases cAMP levels only in intact cells, but not in isolated membranes, and the effect on I(to) disappears when the cytoskeleton is disrupted. We conclude that alpha(1)-adrenoceptor stimulation reduces the amplitude of the I(to) by activating a G(alphas) protein and the cAMP/PKA signaling cascade, which in turn leads to I(to) channel phosphorylation.

  14. Base-modified UDP-sugars reduce cell surface levels of P-selectin glycoprotein 1 (PSGL-1) on IL-1β-stimulated human monocytes

    PubMed Central

    Kanabar, Varsha; Tedaldi, Lauren; Jiang, Jingqian; Nie, Xiaodan; Panina, Irina; Descroix, Karine; Man, Francis; Pitchford, Simon C; Page, Clive P; Wagner, Gerd K

    2016-01-01

    P-selectin glycoprotein ligand-1 (PSGL-1, CD162) is a cell-surface glycoprotein that is expressed, either constitutively or inducibly, on all myeloid and lymphoid cell lineages. PSGL-1 is implicated in cell–cell interactions between platelets, leukocytes and endothelial cells, and a key mediator of inflammatory cell recruitment and transmigration into tissues. Here, we have investigated the effects of the β-1,4-galactosyltransferase inhibitor 5-(5-formylthien-2-yl) UDP-Gal (5-FT UDP-Gal, compound 1) and two close derivatives on the cell surface levels of PSGL-1 on human peripheral blood mononuclear cells (hPBMCs). PSGL-1 levels were studied both under basal conditions, and upon stimulation of hPBMCs with interleukin-1β (IL-1β). Between 1 and 24 hours after IL-1β stimulation, we observed initial PSGL-1 shedding, followed by an increase in PSGL-1 levels on the cell surface, with a maximal window between IL-1β-induced and basal levels after 72 h. All three inhibitors reduce PSGL-1 levels on IL-1β-stimulated cells in a concentration-dependent manner, but show no such effect in resting cells. Compound 1 also affects the cell surface levels of adhesion molecule CD11b in IL-1β-stimulated hPBMCs, but not of glycoproteins CD14 and CCR2. This activity profile may be linked to the inhibition of global Sialyl Lewis presentation on hPBMCs by compound 1, which we have also observed. Although this mechanistic explanation remains hypothetical at present, our results show, for the first time, that small molecules can discriminate between IL-1β-induced and basal levels of cell surface PSGL-1. These findings open new avenues for intervention with PSGL-1 presentation on the cell surface of primed hPBMCs and may have implications for anti-inflammatory drug development. PMID:27233805

  15. Intermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal BDNF-TrkB signaling in adult rats

    PubMed Central

    Garraway, Sandra M.; Turtle, Joel D.; Huie, J. Russell; Lee, Kuan H.; Hook, Michelle A.; Woller, Sarah A.; Grau, James W.

    2011-01-01

    Intermittent nociceptive stimulation following a complete transection or contused spinal cord injury (SCI) has been shown to exert several short and long lasting negative consequences. These include maladaptive spinal plasticity, enhanced mechanical allodynia and impaired functional recovery of locomotor and bladder functions. The neurotrophin, brain derived neurotrophic factor (BDNF) has been shown to play an important role in adaptive plasticity and also to restore functions following SCI. This suggests that the negative behavioral effects of shock are most likely related to corresponding changes in BDNF spinal levels. In this study we investigated the cellular effects of nociceptive stimulation in contused adult rats focusing on BDNF, its receptor, TrkB, and the subsequent downstream signaling system. The goal was to determine whether the behavioral effect of stimulation is associated with concomitant cellular changes induced during the initial post-injury period. Quantitative RT-PCR and western blotting were used to assess changes in the mRNA and/or protein levels of BDNF, TrkB and the downstream signaling proteins CAMKII and ERK1/2 at 1 hour, 24 hours and 7 days following administration of intermittent noxious shock to the tail of contused subjects. In addition, recovery of locomotor function (BBB score) was assessed daily for the first week post injury. The results showed that, while nociceptive stimulation failed to induce any changes in gene expression at 1 hour, it significantly reduced the expression of BDNF, TrkB, ERK2 and CAMKII, at 24 hours. In general, changes in gene expression were spatially localized to the dorsal spinal cord. In addition, locomotor recovery was impaired by shock. Evidence is also provided suggesting that shock engages a neuronal circuitry without having any negative effects on neuronal survival at 24 hours. These results suggest that nociceptive activity following SCI decreases BDNF and TrkB levels, which may significantly

  16. Stimulation of strontium accumulation in linoleate-enriched Saacharomyces cerevisiae is a result of reduced Sr{sup 2+} efflux

    SciTech Connect

    Avery, S.V.; Smith, S.L.; Ghazi, A.M.; Hoptroff, M.J.

    1999-03-01

    The influence of modified plasma membrane fatty acid composition on cellular strontium accumulation in Saccharomyces cerevisiae was investigated. Growth of S. cerevisiae in the presence of 1 mM linoleate (18:2) yielded cells that accumulated Sr{sup 2+} intracellularly at approximately twice the rate of S. cerevisiae grown without a fatty acid supplement. This effect was evident over a wide range of external Sr{sup 2+} concentrations and increased with the extent of cellular 18:2 incorporation. Stimulation of Sr{sup 2+} accumulation was not evident following enrichment of S. cerevisiae with either palmitoleate (16:1), linolenate (18:3) (n-3 and n-6 isomers), or eicosadienoate (20:2) (n-6 and n-9 isomers). Competition experiments revealed that Ca{sup 2+}- and Mg{sup 2+}-induced inhibition of Sr{sup 2+} accumulation did not differ between unsupplemented and 18:2-supplemented cells. Treatment with trifluoperazine (TFP) (which can act as a calmodulin antagonist and Ca{sup 2+}-ATPase inhibitor), at a low concentration that precluded nonspecific K{sup +} efflux, increased intracellular Sr{sup 2+} accumulation by approximately 3.6- and 1.4-fold in unsupplemented and 18:2-supplemented cells, respectively. Thus, TFP abolished the enhanced Sr{sup 2+} accumulation ability of 18:2 supplemented cells. Moreover, the rate of Sr{sup 2+} release from Sr{sup 2+}-loaded fatty acid-unsupplemented cells was found to be at least twice as great as that from Sr{sup 2+}-loaded 18:2-enriched cells. The influence of enrichment with other fatty acids on Sr{sup 2+} efflux was variable. The results reveal an enhanced Sr{sup 2+} accumulation ability of S. cerevisiae following 18:2-enrichment, which is attributed to diminished Sr{sup 2+} efflux activity in these cells.

  17. Probiotic Lactobacillus gasseri SBT2055 improves glucose tolerance and reduces body weight gain in rats by stimulating energy expenditure.

    PubMed

    Shirouchi, Bungo; Nagao, Koji; Umegatani, Minami; Shiraishi, Aya; Morita, Yukiko; Kai, Shunichi; Yanagita, Teruyoshi; Ogawa, Akihiro; Kadooka, Yukio; Sato, Masao

    2016-08-01

    Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055-containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055. PMID:27267802

  18. Stimulation of Wnt/beta-Catenin Signaling Pathway with Wnt Agonist Reduces Organ Injury after Hemorrhagic Shock

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Jacob, Asha; Khader, Adam; Giangola, Matthew; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2014-01-01

    Background Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need exist for effective therapy for hemorrhage victims. Wnt/β-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. Methods Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure (MAP) of 30 mmHg for 90 min, followed by resuscitation with crystalloid equal to two times the shed blood volume. After resuscitation, animals were infused with Wnt agonist (5 mg/kg) or Vehicle (20% DMSO in saline). Blood and tissue samples were collected 6 h after resuscitation for analysis. Results Hemorrhagic shock increased serum levels of AST, lactate, and LDH. Treatment with Wnt agonist significantly reduced these levels by 40%, 36%, and 77%, respectively. Wnt agonist also decreased BUN and creatinine by 34% and 56%, respectively. Treatment reduced lung myeloperoxidase activity and IL-6 mRNA by 55% and 68% respectively and, significantly improved lung histology. Wnt agonist treatment increased Bcl-2 protein to Sham values and decreased cleaved caspase-3 by 46% indicating attenuation of hemorrhage-induced apoptosis in the lungs. Hemorrhage resulted in significant reductions of β-catenin protein levels in the lungs as well as down-regulation of a Wnt target gene, Cyclin-D1, while Wnt agonist treatment preserved these levels. Conclusions The administration of Wnt agonist attenuated hemorrhage-induced organ injury, inflammation and apoptosis. This was correlated with preservation of the Wnt signaling pathway. Thus, Wnt/β-catenin activation could be protective

  19. Short UV-B Exposure Stimulated Enzymatic and Nonenzymatic Antioxidants and Reduced Oxidative Stress of Cold-Stored Mangoes.

    PubMed

    Jiang, Zhifang; Zheng, Yaoqi; Qiu, Rongrong; Yang, Yanjun; Xu, Mingfeng; Ye, Yu; Xu, Maojun

    2015-12-30

    The effects of UV-B irradiation on reactive oxygen species (ROS) levels, antioxidant compound contents, antioxidative enzyme activities, and oxidative damage of cold-stored mangoes were examined. Superoxide anion production rate, hydrogen peroxide concentration, ion leakage level and malondialdehyde content of the cold-stored fruit preradiated with 5 KJ m(-2) UV-B for 4 h were significantly decreased as compared with control fruit. The activities of ROS generating enzymes remained unchanged in UV-B-irradiated mangoes as compared to the control, but superoxide dismutase and catalase activities, ascorbate and polyphenol contents and antioxidant capacities of the cold-stored mangoes were significantly enhanced by UV-B. The UV-B-enhanced antioxidant compounds and antioxidative enzymes were highly correlated with the reduced-ROS levels in UV-B-irradiated mangoes. The data indicated that a short UV-B exposure reduced oxidative stress and alleviated oxidative damage of the cold-stored mangoes by triggering both enzymatic and nonenzymatic antioxidant systems although ROS generation in the fruit was not affected.

  20. The reduced state of the plastoquinone pool is required for chloroplast-mediated stomatal closure in response to calcium stimulation.

    PubMed

    Wang, Wen-Hua; He, En-Ming; Chen, Juan; Guo, Ying; Chen, Juan; Liu, Xiang; Zheng, Hai-Lei

    2016-04-01

    Besides their participation in photosynthesis, leaf chloroplasts function in plant responses to stimuli, yet how they direct stimulus-induced stomatal movement remains elusive. Here, we showed that over-reduction of the plastoquinone (PQ) pool by dibromothymoquinone (DBMIB) was closely associated with stomatal closure in plants which required chloroplastic H2O2 generation in the mesophyll. External application of H2 O2 reduced the PQ pool, whereas the cell-permeable reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) reversed the DBMIB-induced over-reduction of the PQ pool and stomatal closure. Mesophyll chloroplasts are key players of extracellular Ca(2+) (Ca(2+)o)-induced stomatal closure, but when treated with either 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) or NAC they failed to facilitate Ca(2+)o-induced stomatal closure due to the inhibition of chloroplastic H2 O2 synthesis in mesophyll. Similarly, the Arabidopsis electron transfer chain-related mutants npq4-1, stn7 and cas-1 exhibited diverse responses to Ca(2+)o or DBMIB. Transcriptome analysis also demonstrated that the PQ pool signaling pathway shared common responsive genes with the H2 O2 signaling pathway. These results implicated a mechanism for chloroplast-mediated stomatal closure involving the generation of mesophyll chloroplastic H2O2 based on the reduced state of the PQ pool, which is calcium-sensing receptor (CAS) and LHCII phosphorylation dependent.

  1. A Single Hot Event Stimulates Adult Performance but Reduces Egg Survival in the Oriental Fruit Moth, Grapholitha molesta

    PubMed Central

    Ma, Gang; Hoffmann, Ary A.; Ma, Chun-Sen

    2014-01-01

    Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures). These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h) of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, Grapholitha molesta. This hot event had no impact on the survival of G. molesta adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming. PMID:25551751

  2. Warming reduces tall fescue abundance but stimulates toxic alkaloid concentrations in transition zone pastures of the U.S.

    PubMed Central

    McCulley, Rebecca L.; Bush, Lowell P.; Carlisle, Anna E.; Ji, Huihua; Nelson, Jim A.

    2014-01-01

    Tall fescue pastures cover extensive acreage in the eastern half of the United States and contribute to important ecosystem services, including the provisioning of forage for grazing livestock. Yet little is known concerning how these pastures will respond to climate change. Tall fescue's ability to persist and provide forage under a warmer and wetter environment, as is predicted for much of this region as a result of climate change, will likely depend on a symbiotic relationship the plant can form with the fungal endophyte, Epichloë coenophiala. While this symbiosis can confer environmental stress tolerance to the plant, the endophyte also produces alkaloids toxic to insects (e.g., lolines) and mammals (ergots; which can cause “fescue toxicosis” in grazing animals). The negative animal health and economic consequences of fescue toxicosis make understanding the response of the tall fescue symbiosis to climate change critical for the region. We experimentally increased temperature (+3°C) and growing season precipitation (+30% of the long-term mean) from 2009–2013 in a mixed species pasture, that included a tall fescue population that was 40% endophyte-infected. Warming reduced the relative abundance of tall fescue within the plant community, and additional precipitation did not ameliorate this effect. Warming did not alter the incidence of endophyte infection within the tall fescue population; however, warming significantly increased concentrations of ergot alkaloids (by 30–40%) in fall-harvested endophyte-infected individuals. Warming alone did not affect loline alkaloid concentrations, but when combined with additional precipitation, levels increased in fall-harvested material. Although future warming may reduce the dominance of tall fescue in eastern U.S. pastures and have limited effect on the incidence of endophyte infection, persisting endophyte-infected tall fescue will have higher concentrations of toxic alkaloids which may exacerbate fescue

  3. Warming reduces tall fescue abundance but stimulates toxic alkaloid concentrations in transition zone pastures of the U.S.

    NASA Astrophysics Data System (ADS)

    Mcculley, Rebecca; Bush, Lowell; Carlisle, Anna; Ji, Huihua; Nelson, Jim

    2014-10-01

    Tall fescue pastures cover extensive acreage in the eastern half of the United States and contribute to important ecosystem services, including the provisioning of forage for grazing livestock. Yet little is known concerning how these pastures will respond to climate change. Tall fescue’s ability to persist and provide forage under a warmer and wetter environment, as is predicted for much of this region as a result of climate change, will likely depend on a symbiotic relationship the plant can form with the fungal endophyte, Epichloë coenophiala. While this symbiosis can confer environmental stress tolerance to the plant, the endophyte also produces alkaloids toxic to insects (e.g., lolines) and mammals (ergots; which can cause ‘fescue toxicosis’ in grazing animals). The negative animal health and economic consequences of fescue toxicosis make understanding the response of the tall fescue symbiosis to climate change critical for the region. We experimentally increased temperature (+3oC) and growing season precipitation (+30% of the long-term mean) from 2009 - 2013 in a mixed species pasture, that included a tall fescue population that was 40% endophyte-infected. Warming reduced the relative abundance of tall fescue within the plant community, and additional precipitation did not ameliorate this effect. Warming did not alter the incidence of endophyte infection within the tall fescue population; however, warming significantly increased concentrations of ergot alkaloids (by 30-40%) in fall-harvested endophyte-infected individuals. Warming alone did not affect loline alkaloid concentrations, but when combined with additional precipitation, levels increased in fall-harvested material. Although future warming may reduce the dominance of tall fescue in eastern U.S. pastures and have limited effect on the incidence of endophyte infection, persisting endophyte-infected tall fescue will have higher concentrations of toxic alkaloids which may exacerbate fescue

  4. Relationship between radiation dose and reduced X-ray sensitivity surrounding breast region using CR stimulable phosphor plate for mammography

    NASA Astrophysics Data System (ADS)

    Nishide, Hiroko; Kodera, Yoshie

    2015-03-01

    Computed radiography (CR) systems use a photostimulable phosphor plate (imaging plate ; IP) as a sensor for digital mammography. In clinical mammography, breast is almost exposed same region of IP, and therefor, direct x-ray regions surrounding suffer from reduced x-ray sensitivity. Consequently, the difference in x-ray sensitivity between the breast regions and the unattenuated x-ray region was obtained. However, radiation dose quantity that reduces x-ray sensitivity is not known. In this study, we imaged a breast phantom under fixed conditions, and subsequently, we investigated the pixel value differences between the breast region and the unattenuated x-ray regions. We measured the entrance air-kerma using 550 sensing elements of glass dosimeter, 22x25 lines, that were placed at the surface of the cassette including the IP. In order to measure the x-ray sensitivity, pre- and post-exposure breast phantom images were acquired after 500, 1,000, 1,350, and 1,500 trials. The pixel values were measured at four points; in the breast region and in the unattenuated x-ray region. The ratio of these pixel values was compared with the cumulative exposure dose. The ratio was nearly constant until 1,000 trials, but a significant reduction was observed after 1,350 trials. Further, in the image obtained after 1,500th trials, the shape of breast phantom could be observed. This image supports the fact that the x-ray sensitivity was lowered in the unattenuated x-ray region. The difference in the pixel value between the breast region and the unattenuated x-ray region was obtained over 1,000 exposures at 100,000 mAs.

  5. Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

    PubMed Central

    Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

    2011-01-01

    Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

  6. Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation

    PubMed Central

    Huang, Sin-Luo; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-01-01

    It has been shown that the blood-brain barrier (BBB) can be locally disrupted by focused ultrasound (FUS) in the presence of microbubbles (MB) while sustaining little damage to the brain tissue. Thus, the safety issue associated with FUS-induced BBB disruption (BBBD) needs to be investigated for future clinical applications. This study demonstrated the neuroprotective effects induced by low-intensity pulsed ultrasound (LIPUS) against brain injury in the sonicated brain. Rats subjected to a BBB disruption injury received LIPUS exposure for 5 min after FUS/MB application. Measurements of BBB permeability, brain water content, and histological analysis were then carried out to evaluate the effects of LIPUS. The permeability and time window of FUS-induced BBBD can be effectively modulated with LIPUS. LIPUS also significantly reduced brain edema, neuronal death, and apoptosis in the sonicated brain. Our results show that brain injury in the FUS-induced BBBD model could be ameliorated by LIPUS and that LIPUS may be proposed as a novel treatment modality for controllable release of drugs into the brain. PMID:26517350

  7. Aspirin-Triggered Lipoxin A4 Stimulates Alternative Activation of Microglia and Reduces Alzheimer Disease–Like Pathology in Mice

    PubMed Central

    Medeiros, Rodrigo; Kitazawa, Masashi; Passos, Giselle F.; Baglietto-Vargas, David; Cheng, David; Cribbs, David H.; LaFerla, Frank M.

    2014-01-01

    Microglia play an essential role in innate immunity, homeostasis, and neurotropic support in the central nervous system. In Alzheimer disease (AD), these cells may affect disease progression by modulating the buildup of β-amyloid (Aβ) or releasing proinflammatory cytokines and neurotoxic substances. Discovering agents capable of increasing Aβ uptake by phagocytic cells is of potential therapeutic interest for AD. Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory properties directly involved in inflammatory resolution, an active process essential for appropriate host responses, tissue protection, and the return to homeostasis. Herein, we demonstrate that aspirin-triggered LXA4 (15 μg/kg) s.c., twice a day, reduced NF-κB activation and levels of proinflammatory cytokines and chemokines, as well as increased levels of anti-inflammatory IL-10 and transforming growth factor-β. Such changes in the cerebral milieu resulted in recruitment of microglia in an alternative phenotype, as characterized by the up-regulation of YM1 and arginase-1 and the down-regulation of inducible nitric oxide synthase expression. Microglia in an alternative phenotype–positive cells demonstrated improved phagocytic function, promoting clearance of Aβ deposits and ultimately leading to reduction in synaptotoxicity and improvement in cognition. Our data indicate that activating LXA4 signaling may represent a novel therapeutic approach for AD. PMID:23506847

  8. PTEN permits acute increases in D3-phosphoinositide levels following TCR stimulation but inhibits distal signaling events by reducing the basal activity of Akt.

    PubMed

    Seminario, Maria-Cristina; Precht, Patricia; Bunnell, Stephen C; Warren, Sarah E; Morris, Christa M; Taub, Dennis; Wange, Ronald L

    2004-11-01

    Phosphoinositide 3-kinase (PI3K) is important in TCR signaling. PI3K generates phosphatidylinositol 3, 4, 5-trisphosphate (PI-3,4,5-P3), which regulates membrane localization and/or activity of multiple signaling proteins. PTEN (phosphatase and tensin homologue deleted on chromosome 10) opposes PI3K, reversing this reaction. Maintaining the balance between these two enzymes is important for normal T cell function. Here we use the PTEN-null Jurkat T cell line to address the role of PTEN in modulating proximal and distal TCR-signaling events. PTEN expression at levels that restored low basal Akt phosphorylation (an indicator of PI-3,4,5-P3 levels), but which were not themselves cytotoxic, had minimal effect on TCR-stimulated activation of phospholipase Cgamma1 and Ca2+ flux, but reduced the duration of extracellular signal-regulated kinase (Erk) activation. Distal signaling events, including nuclear factor of activated T cells (NFAT) activation, CD69 expression and IL-2 production, were all inhibited by PTEN expression. Notably, PTEN did not block TCR-stimulated PI-3,4,5-P3 accumulation. The effect of PTEN on distal TCR signaling events was strongly correlated with the loss of the constitutive Akt activation and glycogen synthase kinase-3 (GSK3) inhibition that is typical of Jurkat cells, and could be reversed by expression of activated Akt or pharmacologic inhibition of GSK3. These results suggest that PTEN acts in T cells primarily to control basal PI-3,4,5-P3 levels, rather than opposing PI3K acutely during TCR stimulation.

  9. A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants.

    PubMed

    Wee, Sunmee; Carroll, F Ivy; Woolverton, William L

    2006-02-01

    A slow onset of action has been hypothesized to weaken the reinforcing effects of drugs. The present study evaluated this hypothesis with slow-onset cocaine analogs, WIN 35428, RTI 31, and RTI 51. When cocaine or a cocaine analog was made available to rhesus monkeys (n = 4 or 5) for self-administration under a progressive-ratio (PR) schedule with a 1-h time-out between injections, all the drugs functioned as positive reinforcers. The maximum number of injections was in the order of cocaine > WIN 35428 > RTI 31 > RTI 51. In in vivo binding in rat striatum, equipotent doses of cocaine, WIN 35428, RTI 31, and RTI 51 were estimated to displace 25% of [(3)H]WIN 35428 binding at the dopamine transporters (DAT), respectively, 5.8, 22.4, 30.8, and 44.1 min after the intravenous injection. Further, relative reinforcing efficacy was correlated with rate of DAT binding such that slower displacement of [(3)H]WIN 35428 was associated with a weaker reinforcing effect. In in vitro binding in monkey brain tissue, the cocaine analogs had higher affinity for monoamine transporter sites, but similar affinity ratios of 5-HTT/DAT, compared to cocaine. Lastly, RTI 31 was shown to function as a positive reinforcer in drug-naïve rhesus monkeys under a fixed-ratio 1 schedule. Collectively, the data support the hypothesis that a slow onset at the DAT is associated with reduced reinforcing efficacy of DAT ligands. The data under both the PR and FR schedules, however, suggest that a slow onset at the DAT influence reinforcing effect only to a limited extent. PMID:15957006

  10. The SOD mimic MnTM-2-PyP(5+) reduces hyaluronan degradation-induced inflammation in mouse articular chondrocytes stimulated with Fe (II) plus ascorbate.

    PubMed

    Campo, Giuseppe M; Avenoso, Angela; D'Ascola, Angela; Scuruchi, Michele; Nastasi, Giancarlo; Micali, Antonio; Puzzolo, Domenico; Pisani, Antonina; Calatroni, Alberto; Campo, Salvatore

    2013-08-01

    In pathological conditions, oxidative burst generates hyaluronan (HA) fragmentation with a consequent increase in the number of small HA oligosaccharides. These fragments are able to stimulate an inflammatory response in different cell types by activating the CD44 and the toll-like receptors 4 (TLR-4) and 2 (TLR-2). The stimulation of CD44 and TLRs in turn activates the NF-kB which induces the production of several pro-inflammatory mediators that amplify and perpetuate inflammation. We aimed to study the antioxidant effect of the SOD mimic, synthetic manganese porphyrin, Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP(5+)) on preventing HA degradation in mouse articular chondrocytes stimulated with Fe (II) plus ascorbate. Fe (II) plus ascorbate stimulation induced oxidative burst confirmed by high levels of hydroxyl radical/peroxynitrite production, increased lipid peroxidation and HA degradation. HA fragments highly induced mRNA expression and the related protein production of CD44, TLR-4 and TLR-2, NF-kB activation and significantly up-regulated the inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and other pro-inflammatory mediators, i.e. matrix metalloprotease 13 (MMP-13) and inducible nitric oxide synthase (iNOS). Treatment of cells with MnTM-2-PyP(5+)was able to attenuate oxidative burst, HA degradation and NF-kB activation, and markedly decreased mRNA expression of CD44, and TLRs and the related protein synthesis, as well as the levels of up-regulated inflammatory mediators. Adding a specific HA-blocking peptide (PEP-1) to cells significantly reduced all the inflammatory parameters up-regulated by Fe (II) plus ascorbate, and increased MnTM-2-PyP(5+) activity. These findings suggest that HA degradation plays a key role in the initial inflammatory response of cartilage and antioxidants and could be a useful tool to prevent the propagation of this mechanism. PMID:23692848

  11. Shanzhiside methylester, the principle effective iridoid glycoside from the analgesic herb Lamiophlomis rotata, reduces neuropathic pain by stimulating spinal microglial β-endorphin expression.

    PubMed

    Fan, Hui; Li, Teng-Fei; Gong, Nian; Wang, Yong-Xiang

    2016-02-01

    Lamiophlomis rotata (L. rotata, Duyiwei) is an orally available Tibetan analgesic herb widely prescribed in China. Shanzhiside methylester (SM) is a principle effective iridoid glycoside of L. rotata and serves as a small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. This study aims to evaluate the signal mechanisms underlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactions between SM and morphine, or SM and β-endorphin, in anti-allodynia and anti-allodynic tolerance. Intrathecal SM exerted dose-dependent and long-lasting (>4 h) anti-allodynic effects in spinal nerve injury-induced neuropathic rats, with a maximal inhibition of 49% and a projected ED50 of 40.4 μg. SM and the peptidic GLP-1 receptor agonist exenatide treatments over 7 days did not induce self-tolerance to anti-allodynia or cross-tolerance to morphine or β-endorphin. In contrast, morphine and β-endorphin induced self-tolerance and cross-tolerance to SM and exenatide. In the spinal dorsal horn and primary microglia, SM significantly evoked β-endorphin expression, which was completely prevented by the microglial inhibitor minocycline and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. SM anti-allodynia was totally inhibited by the GLP-1 receptor antagonist exendin(9-39), minocycline, β-endorphin antiserum, μ-opioid receptor antagonist CTAP, and SB203580. SM and exenatide specifically activated spinal p38 MAPK phosphorylation. These results indicate that SM reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling. Stimulation of the endogenous β-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long-term treatment of chronic pain. PMID:26363192

  12. High-viscosity carboxymethylcellulose reduces carbachol-stimulated intestinal chloride secretion in weaned piglets fed a diet based on skimmed milk powder and maltodextrin.

    PubMed

    Lallès, Jean-Paul; Boudry, Gaëlle; Favier, Christine; Sève, Bernard

    2006-03-01

    High-viscosity carboxymethylcellulose (CMC) promotes gastrointestinal disorders, tissue alterations and bacterial overgrowth in pigs. The impact of CMC on intestinal absorptive and secretory physiology is not known. We hypothesised that CMC consumption alters intestinal Na-dependent glucose absorption and stimulates electrogenic chloride secretion. For testing this hypothesis, twenty-four piglets were weaned at 21 d of age and pair-fed for 13 d a starter diet based on skimmed milk powder and maltodextrin containing cellulose (control) or CMC. Body weight and faecal total aerobe and coliform counts were measured kinetically. At slaughter, digesta were weighed and characterised for viscosity and pH. Gastrointestinal tissues were weighed and sampled for physiology in Ussing chambers, morphometry and enzymology. Glucose absorption tended to be higher (P = 0.08) and carbachol-stimulated chloride secretion was lower (P = 0.01) with CMC in the small intestine, without changes in the colon. Aerobes were transiently higher at day 7 (P < 0.05) but coliform counts remained unchanged (P = 0.78) and beta-haemolitic Escherichia coli were virtually absent. Stomach and small-intestinal segments were heavier, and viscosity higher with CMC (0.001 < P < 0.05). The pH in the stomach was higher, and in the caecum and proximal colon lower with CMC (0.001 < P < 0.05). Jejunal villus area was slightly reduced with CMC (P < 0.05) without effects on enzyme activities (P > 0.10). In conclusion, CMC supplementation had pro-absorptive effects on the small intestine, possibly due to the absence of pathogenic E. coli in the present study.

  13. Costimulation with anti-cluster of differentiation 3 and anti-cluster of differentiation 28 reduces the activity of mucin 1-stimulated human mononuclear cells

    PubMed Central

    WRIGHT, STEPHEN E.; REWERS-FELKINS, KATHLEEN A.; QUINLIN, IMELDA; ZOHRA, FATEMA; AHMED, JEWEL

    2016-01-01

    Cytotoxic T-lymphocyte activation and extension of the cell life span is necessary in order to enable immunotherapy to perform effectively against cancer. In the present study, mucin 1 (MUC1)-stimulated human mononuclear cells (M1SHMCs) were costimulated with bead-attached monoclonal antibodies specific for cluster of differentiation (CD)3 and CD28 receptors. The study was undertaken to determine whether costimulation was capable of enhancing the killing of cancer cells in vitro and of protecting non-obese diabetic severe combined immunodeficient mice from tumor development. Lysis of MCF-7 tumor cells by M1SHMCs was reduced following costimulation with anti-CD3 and anti-CD28. Furthermore, costimulation with anti-CD3 and anti-CD28 eliminated the protective effects of M1SHMCs on MCF-7 breast cancer cell growth in the non-obese diabetic severe combined immunodeficient mice. The present study suggested that costimulation with anti-CD3 and anti-CD28 is not advisable following antigen activation of lymphocytes under the conditions used here. Using a lower anti-CD3/CD28 bead to T-cell ratio may prevent immune suppression, however, further studies are required to support this hypothesis. PMID:26870234

  14. Baicalein induces apoptosis and reduces inflammation in LPS-stimulated keratinocytes by blocking the activation of NF-κB: implications for alleviating oral lichen planus.

    PubMed

    Wang, J; Luo, H; Yang, L; Li, Y

    2016-01-01

    ic inflammatory diseases, including OLP, involves in the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Baicalein (BAI) is an alcohol soluble flavonoid known for its anti-inflammatory effect. However, its effectiveness on keratinocytes in OLP remains unclear. In the present study, we examined inflammation in oral mucosa tissue from OLP patients. Hematoxylin and eosin staining showed denser subepithelial lymphocytes infiltration compared to the normal oral mucosa epithelium. TNF-α and IL-6 were up-regulated in oral mucosa tissue of OLP patients. We next stimulated humans keratinocytes (HaCaT cells) with lipopolysaccharide (LPS) to create an inflammatory environment like that in the OLP tissue and assessed the effect of BAI on OLP and NF-κB signaling pathways. Our results showed that BAI treatment inhibited the level of TNF-α and IL-6 induced by LPS. However, the cells apoptosis was promoted after BAI treatment. Furthermore, BAI not only inhibited LPS-induced p38 MAPK and ERK1/2 phosphorylation, but also NF-κB activation by reducing IκBα phosphorylation and the nuclear translocation of NFκB-p65 and NFκB-p50 from cytoplasm to nucleus in keratinocytes. Our findings suggest that BAI inhibits the production of inflammatory cytokines by negatively regulating the NF-κB signaling pathway under LPS simulation in HaCaT cells. PMID:27453273

  15. Ginsenosides Have a Suppressive Effect on c-Fos Expression in Brain and Reduce Cardiovascular Responses Increased by Noxious Stimulation to the Rat Tooth

    PubMed Central

    Jung, Ji-Yeon; Seong, Kyung-Joo; Moon, In-Ohk; Cho, Jin-Hyoung; Kim, Sun-Hun

    2013-01-01

    The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth. PMID:23626473

  16. Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression.

    PubMed

    Ferreira, Fabiano; Filiputti, Eliane; Arantes, Vanessa C; Stoppiglia, Luis F; Araújo, Eliana P; Delghingaro-Augusto, Viviane; Latorraca, Márcia Q; Toyama, Marcos H; Boschero, Antonio C; Carneiro, Everardo M

    2003-03-01

    Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamylcholine (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmol/L) and CCh. Increasing concentrations of CCh (0.1-1000 micro mol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LP with a 50% effective concentration (EC(50)) of 2.15 +/- 0.7 and 4.64 +/- 0.1 micro mol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LP. Western blotting revealed that the protein kinase (PK)Calpha and phospholipase (PL)Cbeta(1) contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCalpha mRNA expression was reduced by 50% in islets from rats fed LP. In conclusion, a reduced expression of PKCalpha and PLCbeta(1) may be involved in the decreased insulin secretion by islets from LP rats after stimulation with CCh and PMA. PMID:12612139

  17. Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report.

    PubMed

    Reese, David; Shivapour, Ezzatolah T; Wahls, Terry L; Dudley-Javoroski, Shauna D; Shields, Richard

    2009-01-01

    Neuromuscular electrical stimulation has been used to aid musculoskeletal recovery. Excessive oxidative stress and excitoxicity are implicated in secondary progressive multiple sclerosis. A 52-year-old white female with SPMS had been scooter- and cane-dependent for 4 years. She requested and received a trial of neuromuscular electrical stimulation. Two months after initiating NMES the patient adopted several nutritional interventions to lower oxidative stress and excito-toxicity. During the first 2 months of neuromuscular electrical stimulation, the therapist observed modest gait improvements. Following the addition of nutritional interventions, more rapids gains in strength and endurance, including muscle groups not receiving neuromuscular electrical stimulation were observed by both the therapist and the patient. After 8 months of neuromuscular electrical stimulation (6 months of nutritional intervention) the patient's function had improved sufficiently that she no longer used a scooter or cane and rode her bicycle routinely 8 miles, including hills. PMID:19918474

  18. Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report

    PubMed Central

    Reese, David; Shivapour, Ezzatolah T; Dudley-Javoroski, Shauna D; Shields, Richard

    2009-01-01

    Neuromuscular electrical stimulation has been used to aid musculoskeletal recovery. Excessive oxidative stress and excitoxicity are implicated in secondary progressive multiple sclerosis. A 52-year-old white female with SPMS had been scooter- and cane-dependent for 4 years. She requested and received a trial of neuromuscular electrical stimulation. Two months after initiating NMES the patient adopted several nutritional interventions to lower oxidative stress and excito-toxicity. During the first 2 months of neuromuscular electrical stimulation, the therapist observed modest gait improvements. Following the addition of nutritional interventions, more rapids gains in strength and endurance, including muscle groups not receiving neuromuscular electrical stimulation were observed by both the therapist and the patient. After 8 months of neuromuscular electrical stimulation (6 months of nutritional intervention) the patient’s function had improved sufficiently that she no longer used a scooter or cane and rode her bicycle routinely 8 miles, including hills. PMID:19918474

  19. Optical Stimulation of Neurons

    PubMed Central

    Thompson, Alexander C.; Stoddart, Paul R.; Jansen, E. Duco

    2014-01-01

    Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential. PMID:26322269

  20. Chronic vagus nerve stimulation attenuates vascular endothelial impairments and reduces the inflammatory profile via inhibition of the NF-κB signaling pathway in ovariectomized rats.

    PubMed

    Li, Ping; Liu, Huaipu; Sun, Peng; Wang, Xiaoyu; Wang, Chen; Wang, Ling; Wang, Tinghuai

    2016-02-01

    Vagus nerve stimulation (VNS), a method for activating cholinergic anti-inflammatory pathways, could suppress endothelial activation and minimize tissue injury during inflammation. The aim of this study was to investigate the effects of chronic VNS on endothelial impairments and the inflammatory profile in ovariectomized (OVX) rats. Sprague-Dawley rats (7-8 months old) were randomly assigned to the following four groups: sham-OVX, OVX, OVX+sham-VNS, and OVX+VNS. Throughout the experimental period, the OVX+VNS group received VNS for 3h (20.0 Hz, 1.0 mA, and 10.00 ms pulse width) at the same time every other day. After 12 weeks of VNS, blood samples and thoracic aortas were collected for further analyses. Light microscopy and electron microscopy analyses showed that chronic VNS prevented endothelial swelling, desquamation and even necrosis in the OVX rats. In addition, it obviously improved endothelial function in the OVX rats by restoring the endothelial nitric oxide synthase (e-NOS) and serum endothelin-1 level. Increased expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) in the thoracic aortas and increases in the levels of circulating cytokines (TNF-α, IL-6, MCP-1, and CINC/KC) were also observed in the OVX rats. Chronic VNS significantly restored these detrimental changes partly by increasing the ACh concentrations in vascular walls and blocking NF-κB pathway activity. The results of this in vivo study have shown that the administration of chronic VNS during, in the early stage of estrogen deficiency, protects OVX rats from endothelial impairments and the inflammatory profile. These findings indicate that activation of the vagus nerve could be a promising supplemental therapy for reducing the risks of suffering from further CVDs in postmenopausal women. PMID:26692419

  1. Reduced input from foot sole skin through cooling differentially modulates the short latency and medium latency vestibular reflex responses to galvanic vestibular stimulation.

    PubMed

    Muise, Stephanie B; Lam, Chris K; Bent, Leah R

    2012-04-01

    Sensory afferent information from the skin of the foot sole and information from the vestibular system converge within the central nervous system; however, their mode of interaction remains unknown. The purpose of this study was to investigate the effect of reduced cutaneous foot sole information on the ability of the vestibular system to evoke short latency (SL) and medium latency (ML) lower limb muscle reflex responses. Galvanic vestibular stimulation (GVS; bipolar; binaural; 25 ms; 2 mA square-wave pulse) was applied to standing human subjects (four women, eight men, average age 21.1 ± 3.0 years) both before and after cooling the foot soles in 1°C ice water (15 min initially, followed by 5 min between blocks of 200 GVS pulses). Changes in soleus reflex amplitude were examined. Following ice water immersion, there was a 35.16% increase in the size of the ML response in the soleus muscle when expressed as a percentage of pre-stimulus electromyographic (EMG) activity (control 26.48 ± 4.91%; ice 36.16 ± 6.52%) with no change in size of the SL response (control 7.42 ± 1.12%; ice 8.72 ± 1.10%). These results support the previously proposed dissociation of the SL and ML responses with respect to their circuitry and functions. The results also suggest a greater role for cutaneous-vestibular interaction in the modulation of the ML than the SL response and at a location prior to the motoneuron pool.

  2. Warmer temperatures stimulate respiration and reduce net ecosystem productivity in a northern Great Plains grassland: Analysis of CO2 exchange in automatic chambers

    NASA Astrophysics Data System (ADS)

    Flanagan, L. B.

    2013-12-01

    The interacting effects of altered temperature and precipitation are expected to have significant consequences for ecosystem net carbon storage. Here I report the results of an experiment that evaluated the effects of elevated temperature and altered precipitation on ecosystem CO2 exchange in a northern Great Plains grassland, near Lethbridge, Alberta Canada. Open-top chambers were used to establish an experiment in 2012 with three treatments (control, warmed, warmed plus 50% of normal precipitation input). A smaller experiment with only the two temperature treatments (control and warmed) was conducted in 2013. Continuous half-hourly net CO2 exchange measurements were made using nine automatic chambers during May-October in both years. My objectives were to determine the sensitivity of the ecosystem carbon budget to temperature and moisture manipulations, and to test for direct and indirect effects of the environmental changes on ecosystem CO2 exchange. The experimental manipulations resulted primarily in a significant increase in air temperature in the warmed treatment plots. A cumulative net loss of carbon or negative net ecosystem productivity (NEP) occurred during May through September in the warmed treatment (NEP = -659 g C m-2), while in the control treatment there was a cumulative net gain of carbon (NEP = +50 g C m-2). An eddy covariance system that operated at the site, over a footprint region that was not influenced by the experimental treatments, also showed a net gain of carbon by the ecosystem. The reduced NEP was due to higher plant and soil respiration rates in the warmed treatment that appeared to be caused by a combination of: (i) higher carbon substrate availability indirectly stimulating soil respiration in the warmed relative to the control treatment, and (ii) a strong increase in leaf respiration likely caused by a shift in electron partitioning to the alternative pathway respiration in the warmed treatment, particularly when exposed to high

  3. Kupffer cell stimulation with Corynebacterium parvum reduces some cytochrome P450-dependent activities and diminishes acetaminophen and carbon tetrachloride-induced liver injury in the rat.

    PubMed

    Raiford, D S; Thigpen, M C

    1994-11-01

    -ethoxycoumarin. While sinusoidal efflux of GSH increased by 40% in rats pretreated with CP and cytosolic glutathione-S-transferase activity fell slightly, tissue GSH levels were unaffected. These data demonstrate that CP decreases microsomal cytochrome P450 content, reduces biotransformation of two P450IIE1 substrates, and diminishes ACET- and CCl4-induced hepatic injury. In contrast, hepatic injury due to the P450-independent toxin GLN was enhanced. Thus, chemical and immune stimulation of Kupffer cells may result in divergent effects on susceptibility to injury from individual hepatotoxins. PMID:7974494

  4. Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study.

    PubMed

    Baldursson, Baldur Tumi; Kjartansson, Hilmar; Konrádsdóttir, Fífa; Gudnason, Palmar; Sigurjonsson, Gudmundur F; Lund, Sigrún Helga

    2015-03-01

    A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care.

  5. Comparison of Small Intestinal Submucosa-Covered and Noncovered Nitinol Stents with PTFE Endografts in Injured Ovine Femoral Arteries: A Pilot Study

    SciTech Connect

    Nakata, Manabu; Pavcnik, Dusan Uchida, Barry T.; Van Alstine, William; Timmermans, Hans A.; Toyota, Naoyuki; Terada, Masaki; Brountzos, Elias; Kaufman, John A.; Keller, Frederick S.; Rosch, Josef

    2003-09-15

    The purpose of this study was to compare performance of small intestinal submucosa (SIS)-covered endografts (SCEs) to polytetra-fluoroethylene (PTFE)-covered endografts (PCEs) and to bare nitinol stents (BSs) in injured sheep femoral artery (FA). Bare Zilver 6 mm x 40 mm nitinol stents (n = 6), Zilver stents covered with SIS (n = 6), and Palmaz stents 6 mm x 37 mm covered with PTFE (n = 6) were implanted in the balloon-injured FAs of nine female sheep. Follow-up arteriograms were obtained before animal sacrifice at 1, 3 and 6 months, with three animals at each time point. The FAs with the implanted device were explanted for histologic studies and morphologic measurements. Stent implantation was technically successful in all sheep. All BS and SCEs were patent at each time point. Five BSs and five SCEs exhibited formation of progressive eccentric intimal hyperplasia (IH) that was more advanced in SCE at 6 months. Cross-sectional area narrowing averaged 60% for BSs and 67% for SCEs. One BS, one SCE and two patent PCEs exhibited mild-to-moderate formation of concentric IH. Four PCS occluded one at 1 month, two at 3 months and one at 6 months. Performance of the devices placed into sheep FAs depended on their relation to the curving peri-articular portion of the FA during extremity flexion. BSs and SCEs placed in this portion exhibited progressive growth of eccentric IH while PCEs placed in this portion occluded.

  6. Reduced Basal and LPS-Stimulated A1AR Expression in the Brain of NF-κB p50−/− Mice

    PubMed Central

    Jhaveri, Krishna A.; Reichensperger, Joel; Toth, Linda A.; Sekino, Yuko; Ramkumar, Vickram

    2007-01-01

    Adenosine promotes cytoprotection under condition of infection, ischemic preconditioning and oxidative stress. Previous studies from our laboratory indicate that the expression of the adenosine A1 receptor (A1AR) is induced by oxidative stress via activation of nuclear factor (NF)-κB. The prototypic transcription factor is comprised of homo- or heterodimers of p50 and p65 subunits. To determine the role of NF-κB in the regulation of the A1AR in vivo, we compared the A1AR RNA and protein levels in the brains of mice lacking the p50 subunit of NF-κB (p50−/− mice) and age-matched B6129PF2/J (F2) controls. Radioligand binding assays in the cortex revealed a significantly lower number of A1AR (Bmax) in the cortex of p50−/− mice (151 ± 62 fmol/mg protein) versus 479 ± 181 fmol/mg protein in the F2 (N=5 per strain, p < 0.05), but no change in Kd. Similar reductions in A1AR were measured in the hippocampus, brain stem and hypothalamus and in peripheral tissues, such as the adrenal gland, kidney and spleen. Estimation of the A1AR following purification by antibody affinity columns also indicated reduced A1AR in the p50−/− mice cortex, as compared to the F2 mice. A1AR immunocytochemistry indicates distinct neuronal labeling in the F2 cortex, which was substantially reduced in similar sections obtained from p50−/− mice. p50−/− mice expressed lower levels of A1AR mRNA than F2 mice, as determined by real time PCR. Quantitation of the A1AR transducing G proteins by Western blotting show significantly less Gαi3, no change in Gαi1, but higher levels of Gαo and Gβ in the cortices of p50−/−, as compared to F2 mice. Administration of bacterial lipopolysaccharide (LPS), an activator of NF-κB, increased A1AR expression in the cortices of F2 mice but not p50−/− mice. Cortical neurons cultures prepared from p50−/− mice showed a greater degree of apoptosis, compared to neurons from F2 mice. Activation of the A1AR reduced apoptosis with greater

  7. Antithrombin III, but not C1 esterase inhibitor reduces inflammatory response in lipopolysaccharide-stimulated human monocytes in an ex-vivo whole blood setting.

    PubMed

    Kellner, Patrick; Nestler, Frank; Leimert, Anja; Bucher, Michael; Czeslick, Elke; Sablotzki, Armin; Raspè, Christoph

    2014-12-01

    In order to examine the immunomodulatory effects of antithrombin III (AT-III) and C1 esterase inhibitor (C1-INH) in human monocytes, we investigated the intracellular expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in an ex-vivo laboratory study in a whole blood setting. Heparinized whole blood samples from 23 healthy male and female volunteers (mean age: 27±7years) were pre-incubated with clinically relevant concentrations of AT-III (n=11) and C1-INH (n=12), then stimulated with 0.2 ng/mL lipopolysaccharide (LPS) for 3h. After phenotyping CD14⁺ monocytes, intracellular expression of IL-6, IL-8, and TNF-α was assessed using flow cytometry. In addition, 12 whole blood samples (AT-III and C1-INH, n=6 each) were examined using hirudin for anticoagulation; all samples were processed in the same way. To exclude cytotoxicity effects, 7-amino-actinomycin D and Nonidet P40 staining were used to investigate probes. This study is the first to demonstrate the influence of C1-INH and AT-III on the monocytic inflammatory response in a whole blood setting, which mimics the optimal physiological setting. Cells treated with AT-III exhibited significant downregulation of the proportion of gated CD14⁺ monocytes for IL-6 and IL-8, in a dose-dependent manner; downregulation for TNF-α did not reach statistical significance. There were no significant effects on mean fluorescence intensity (MFI). In contrast, C1-INH did not significantly reduce the proportion of gated CD14⁺ monocytes or the MFI regarding IL-6, TNF-α, and IL-8. When using hirudin for anticoagulation, no difference in the anti-inflammatory properties of AT-III and C1-INH in monocytes occurs. Taken together, in contrast to TNF-α, IL-6 and IL-8 were significantly downregulated in monocytes in an ex-vivo setting of human whole blood when treated with AT-III. This finding implicates monocytes as an important point of action regarding the anti-inflammatory properties of AT-III in sepsis. C1

  8. Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum.

    PubMed

    Santamaría, Abel; Vázquez-Román, Beatriz; La Cruz, Verónica Pérez-De; González-Cortés, Carolina; Trejo-Solís, Ma Cristina; Galván-Arzate, Sonia; Jara-Prado, Aurelio; Guevara-Fonseca, Jorge; Ali, Syed F

    2005-12-15

    Quinolinate (QUIN) neurotoxicity has been attributed to degenerative events in nerve tissue produced by sustained activation of N-methyl-D-aspartate receptor (NMDAr) and oxidative stress. We have recently described the protective effects that selenium (Se), an antioxidant, produces on different markers of QUIN-induced neurotoxicity (Santamaría et al., 2003, J Neurochem 86:479-488.). However, the mechanisms by which Se exerts its protective actions remain unclear. Since some of these events are thought to be related with inhibition of deadly molecular cascades through the activation of antioxidant selenoproteins, in this study we investigated the effects of Se on QUIN-induced cell damage elicited by the nuclear factor kappaB (NF-kappaB) pathway, as well as the time-course response of striatal glutathione peroxidase (GPx) activity. Se (sodium selenite, 0.625 mg/kg/day, i.p.) was administered to rats for 5 days, and 120 min after the last administration, animals received a single striatal injection of QUIN (240 nmol/mul). Twenty-four hours later, their striata were tested for the expression of IkappaB-alpha (the NF-kappaB cytosolic binding protein), the immunohistochemical expression of NF-kappaB (evidenced as nuclear expression of P65), caspase-3-like activation, and DNA fragmentation. Additional groups were killed at 2, 6, and 24 h for measurement of GPx activity. Se reduced the QUIN-induced decrease in IkappaB-alpha expression, evidencing a reduction in its cytosolic degradation. Se also prevented the QUIN-induced increase in P65-immunoreactive cells, suggesting a reduction of NF-kappaB nuclear translocation. Caspase-3-like activation and DNA fragmentation produced by QUIN were also inhibited by Se. Striatal GPx activity was stimulated by Se at 2 and 6 h, but not at 24 h postlesion. Altogether, these data suggest that the protective effects exerted by Se on QUIN-induced neurotoxicity are partially mediated by the inhibition of proapoptotic events underlying Ikappa

  9. Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: Role of tumor necrosis factor alpha and apoptosis

    PubMed Central

    Woller, Sarah A.; Huie, J. Russell; Hartman, John J.; Hook, Michelle A.; Miranda, Rajesh C.; Huang, Yung-Jen; Ferguson, Adam R.; Grau, James W.

    2014-01-01

    We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered one day after SCI, on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days, post-treatment. In addition, because the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is implicated in numerous injury-induced processes including pain hypersensitivity, we assessed the temporal and spatial expression of TNFα, TNF receptors, and several downstream signaling targets after stimulation. Our results showed that unlike sham surgery or SCI only, nociceptive stimulation following SCI induced mechanical sensitivity by 24 hours. These behavioral changes were accompanied by increased expression of TNFα. Cellular assessments of downstream targets of TNFα revealed that nociceptive stimulation increased the expression of caspase 8 and the active subunit (12 kDa) of caspase 3 at a time point consistent with the onset of mechanical allodynia, indicative of active apoptosis. In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24 hours post-stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling. PMID:25180012

  10. Stimulant Treatment Reduces Lapses in Attention among Children with ADHD: The Effects of Methylphenidate on Intra-Individual Response Time Distributions

    ERIC Educational Resources Information Center

    Spencer, Sarah V.; Hawk, Larry W., Jr.; Richards, Jerry B.; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

    2009-01-01

    Recent research has suggested that intra-individual variability in reaction time (RT) distributions of children with ADHD is characterized by a particularly large rightward skew that may reflect lapses in attention. The purpose of the study was to provide the first randomized, placebo-controlled test of the effects of the stimulant methylphenidate…

  11. Assisting People with Attention Deficit Hyperactivity Disorder by Actively Reducing Limb Hyperactive Behavior with a Gyration Air Mouse through a Controlled Environmental Stimulation

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang

    2011-01-01

    The latest researches have adopted software technology turning the gyration air mouse into a high performance limb movement detector, and have assessed whether two persons with multiple disabilities would be able to control an environmental stimulation using limb movement. This study extends gyration air mouse functionality by actively reducing…

  12. Comparison of Small-Intestinal Submucosa and Expanded Polytetrafluoroethylene as a Vascular Conduit in the Presence of Gram-Positive Contamination

    PubMed Central

    Shell, Daniel H.; Croce, Martin A.; Cagiannos, Catherine; Jernigan, T Wright; Edwards, Norma; Fabian, Timothy C.

    2005-01-01

    Objective: As a vascular conduit, expanded polytetrafluoroethylene (ePTFE) is susceptible to graft infection with Gram-positive organisms. Biomaterials, such as porcine small-intestinal submucosa (SIS), have been successfully used clinically as tissue substitutes outside the vascular arena. Summary Background Data: In the present study, we compared a small-diameter conduit of SIS to ePTFE in the presence of Gram-positive contamination to evaluate infection resistance, incorporation and remodeling, morphometry, graft patency, and neointimal hyperplasia (NH) development. Methods: Adult male mongrel pigs were randomized to receive either SIS or ePTFE (3-cm length, 6-mm diameter) and further randomized to 1 of 3 groups: Control (no graft inoculation), Staphylococcus aureus, or mucin-producing S epidermidis (each graft inoculation with 108 colonies/mL). Pressure measurements were obtained proximal and distal to the graft to create the iliac/aorta pressure ratio. Morphometric analysis of the neointima and histopathologic examinations was performed. Other outcomes included weekly WBC counts, graft incorporation, and quantitative culture of explanted grafts. Results: Eighteen animals were randomized. All grafts were patent throughout the 6-week study period. Infected SIS grafts had less NH and little change in their iliac/aorta indices compared with infected ePTFE grafts. Quantitative cultures at euthanasia demonstrated no growth in either SIS group compared with 1.7 × 104 colonies for ePTFE S aureus and 6 × 102 for ePTFE S epi (each P < 0.001). All SIS grafts were incorporated. Histology demonstrated remodeling into host artery with smooth muscle and capillary ingrowth in all SIS groups. Scanning electron micrography illustrated smooth and complete endothelialization of all SIS grafts. Conclusions: Compared with ePTFE, SIS induces host tissue remodeling, exhibits a decreased neointimal response to infection, and is resistant to bacterial colonization. SIS may provide a

  13. The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury

    PubMed Central

    Chung, Yeun Goo; Algarrahi, Khalid; Franck, Debra; Tu, Duong D.; Adam, Rosalyn M.; Kaplan, David L.; Estrada, Carlos R.; Mauney, Joshua R.

    2014-01-01

    Adverse side-effects associated with enterocystoplasty for neurogenic bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support bladder tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson’s trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial tissues in a neurogenic bladder model. PMID:24917031

  14. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.

    PubMed

    Bass, Caroline E; Grinevich, Valentina P; Gioia, Dominic; Day-Brown, Jonathan D; Bonin, Keith D; Stuber, Garret D; Weiner, Jeff L; Budygin, Evgeny A

    2013-01-01

    There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  15. G-quadruplex and G-rich sequence stimulate Pif1p-catalyzed downstream duplex DNA unwinding through reducing waiting time at ss/dsDNA junction

    PubMed Central

    Zhang, Bo; Wu, Wen-Qiang; Liu, Na-Nv; Duan, Xiao-Lei; Li, Ming; Dou, Shuo-Xing; Hou, Xi-Miao; Xi, Xu-Guang

    2016-01-01

    Alternative DNA structures that deviate from B-form double-stranded DNA such as G-quadruplex (G4) DNA can be formed by G-rich sequences that are widely distributed throughout the human genome. We have previously shown that Pif1p not only unfolds G4, but also unwinds the downstream duplex DNA in a G4-stimulated manner. In the present study, we further characterized the G4-stimulated duplex DNA unwinding phenomenon by means of single-molecule fluorescence resonance energy transfer. It was found that Pif1p did not unwind the partial duplex DNA immediately after unfolding the upstream G4 structure, but rather, it would dwell at the ss/dsDNA junction with a ‘waiting time’. Further studies revealed that the waiting time was in fact related to a protein dimerization process that was sensitive to ssDNA sequence and would become rapid if the sequence is G-rich. Furthermore, we identified that the G-rich sequence, as the G4 structure, equally stimulates duplex DNA unwinding. The present work sheds new light on the molecular mechanism by which G4-unwinding helicase Pif1p resolves physiological G4/duplex DNA structures in cells. PMID:27471032

  16. Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal–infant transmission

    PubMed Central

    Kuhn, L; Meddows-Taylor, S; Gray, G; Trabattoni, D; Clerici, M; Shearer, G M; Tiemessen, C

    2001-01-01

    T-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatment, but the effects of antiretroviral treatment, now widely used for prevention, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens would be affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV-infected mothers were not treated with any antiretroviral drugs. T-helper cell reactivity to HIV envelope peptides and other antigens was measured in vitro using a sensitive culture supernatant titration assay based on IL-2-dependent proliferation. Infants in the clinical trial were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4·5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detected 10-fold less frequently among those exposed to antiretroviral prophylaxis (2·4%) than among those unexposed (24·1%) (P = 0·007). Reductions in HIV-stimulated responses in cord blood occurred despite detectable HIV RNA (mean 3·38 standard deviation 0·76 log10 copies per ml) at delivery among treated women and occurred independent of treatment duration. Our results suggest that short-course antiretroviral treatment given to prevent maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate. PMID:11298132

  17. Generation of bioartificial heart tissue by combining a three-dimensional gel-based cardiac construct with decellularized small intestinal submucosa.

    PubMed

    Vukadinovic-Nikolic, Zlata; Andrée, Birgit; Dorfman, Suzanne E; Pflaum, Michael; Horvath, Tibor; Lux, Marco; Venturini, Letizia; Bär, Antonia; Kensah, George; Lara, Angelica Roa; Tudorache, Igor; Cebotari, Serghei; Hilfiker-Kleiner, Denise; Haverich, Axel; Hilfiker, Andres

    2014-02-01

    The in vitro generation of a bioartificial cardiac construct (CC) represents a promising tool for the repair of ischemic heart tissue. Several approaches to engineer cardiac tissue in vitro have been conducted. The main drawback of these studies is the insufficient size of the resulting construct for clinical applications. The focus of this study was the generation of an artificial three-dimensional (3D), contractile, and suturable myocardial patch by combining a gel-based CC with decellularized porcine small intestinal submucosa (SIS), thereby engineering an artificial tissue of 11 cm² in size. The alignment and morphology of rat neonatal cardiomyocytes (rCMs) in SIS-CC complexes were investigated as well as the re-organization of primary endothelial cells which were co-isolated in the rCM preparation. The ability of a rat heart endothelial cell line (RHE-A) to re-cellularize pre-existing vessel structures within the SIS or a biological vascularized matrix (BioVaM) was determined. SIS-CC contracted spontaneously, uniformly, and rhythmically with an average rate of 200 beats/min in contrast to undirected contractions observed in CC without SIS support. rCM exhibited an elongated morphology with well-defined sarcomeric structures oriented along the longitudinal axis in the SIS-CC, whereas round-shaped and random-arranged rCM were observed in CC. Electric coupling of rCM was demonstrated by microelectrode array measurements. A dense network of CD31⁺/eNOS⁺ cells was detected as permeating the whole construct. Superficial supplementation of RHE-A cells to SIS-CC led to the migration of these cells through the CC, resulting in the re-population of pre-existing vessel structures within the decelluarized SIS. By infusion of RHE-A cells into the BioVaM venous and arterial pedicles, a re-population of the BioVaM vessel bed as well as distribution of RHE-A cells throughout the CC was achieved. Rat endothelial cells within the CC were in contact with RHE-A cells

  18. pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1

    PubMed Central

    Lindner, Haley Buff; Felmly, Lloyd McPherson; Demcheva, Marina; Seth, Arun; Norris, Russell; Bradshaw, Amy D.; Vournakis, John; Muise-Helmericks, Robin C.

    2015-01-01

    Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity. pGlcNAc treated wounds exhibit decreased collagen content, increased collagen organization and decreased myofibroblast content. A fibrin gel assay was used to assess the regulation of fibroblast alignment in vitro. In this assay, fibrin lattice is formed with two pins that provide focal points upon which the gel can exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded fibroblasts results in cellular alignment as compared to untreated controls, by a process that is Akt1 dependent. We show that Akt1 is required in vivo for the pGlcNAc-induced increased tensile strength and elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing. PMID:25955155

  19. B cells from aged mice exhibit reduced apoptosis upon B-cell antigen receptor stimulation and differential ability to up-regulate survival signals.

    PubMed

    Montes, C L; Maletto, B A; Acosta Rodriguez, E V; Gruppi, A; Pistoresi-Palencia, M C

    2006-01-01

    During ageing, autoimmune disorders and the higher susceptibility to infectious have been associated with alterations in the humoral immune response. We report that splenic B lymphocytes from aged mice exhibit lower level of apoptosis induced by B-cell antigen receptor (BCR) ligation in vitro. Respect to B cells from young mice the anti-mu stimulated aged B cells show similar Bcl-2 and Bcl-xL expression but differential kinetic of A1 degradation and a higher level of cFLIP and FAIM. Even though B cells from aged mice show minor Fas expression they exhibit the same susceptibility to anti-Fas induced apoptosis. Aged B cells also present upon BCR stimulation, a higher proliferative response and similar level of activation markers expression than B cells from young mice. These data agree with the observation that aged mice exhibit an increment of T2 and mature B cell subset which rapidly enters cell cycle upon BCR engagement. The diminished apoptosis after activation in aged mice could compromise homeostatic mechanism allowing the persistence of self and non-self antigen specific B cells.

  20. Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

    SciTech Connect

    Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi . E-mail: aonoder@mail.ecc.u-tokyo.ac.jp

    2007-06-29

    Splenocytes of wild-type (Prnp {sup +/+}) and prion protein gene-deficient (Prnp {sup -/-}) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP{sup C}) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp {sup +/+} splenocytes. Rikn Prnp {sup -/-} splenocytes elicited lower cell proliferations than Prnp {sup +/+} or Zrch I Prnp {sup -/-} splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP{sup C} and PrPLP/Doppel.

  1. Propolis Reduces Phosphatidylcholine-Specific Phospholipase C Activity and Increases Annexin a7 Level in Oxidized-LDL-Stimulated Human Umbilical Vein Endothelial Cells

    PubMed Central

    Xuan, Hongzhuan; Li, Zhen; Wang, Jiying; Fu, Chongluo; Yuan, Jianlong; Hu, Fuliang

    2014-01-01

    To understand the mechanisms underlying the regulating dyslipidemia action of Chinese propolis and Brazilian green propolis, we investigated their effects on phosphatidylcholine-specific phospholipase C (PC-PLC) activity and annexin a7 (ANXA7) level which play crucial roles in the control of the progress of atherosclerosis. Furthermore, active oxygen species (ROS) levels, nuclear factor-KappaB p65 (NF-κB p65), and mitochondrial membrane potential (MMP) were also investigated in oxidized-LDL- (ox-LDL-) stimulated human umbilical vein endothelial cells (HUVECs). Our data indicated that the treatment of both types of propolis 12.5 μg/mL significantly increased cell viability and attenuated apoptosis rate, increased ANXA7 level, and decreased PC-PLC activity. Both types of propolis also inhibited ROS generation as well as the subsequent MMP collapse, and NF-κB p65 activation induced by ox-LDL in HUVECs. Our results also indicated that Chinese propolis and Brazilian green propolis had similar biological activities and prevented ox-LDL induced cellular dysfunction in HUVECs. PMID:24864152

  2. The group II metabotropic glutamate receptor agonist LY379268 reduces toluene-induced enhancement of brain-stimulation reward and behavioral disturbances

    PubMed Central

    Chan, Ming-Huan; Tsai, Yi-Ling; Lee, Mei-Yi; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien

    2015-01-01

    Toluene, a widely abused solvent with demonstrated addictive potential in humans, has been reported to negatively modulate N-methyl-D-aspartate receptors (NMDARs) and alter glutamatergic neurotransmission. The group II metabotropic glutamate receptor (mGluR) agonist LY379268 has been shown to regulate glutamate release transmission and NMDAR function and block toluene-induced locomotor hyperactivity. However, remaining unknown is whether group II mGluRs are involved in the toluene-induced reward-facilitating effect and other behavioral manifestations. The present study evaluated the effects of LY379268 on toluene-induced reward enhancement, motor incoordination, recognition memory impairment, and social interaction deficits. Our data demonstrated that LY379268 significantly reversed the toluene-induced lowering of intracranial self-stimulation (ICSS) thresholds and impairments in novel object recognition, rotarod performance, and social interaction with different potencies. These results indicate a negative modulatory role of group II mGluRs in acute toluene-induced reward-facilitating and behavioral effects and suggest that group II mGluR agonists may have therapeutic potential for toluene addiction and the prevention of toluene intoxication caused by occupational or intentional exposure. PMID:26044619

  3. Transcranial brain stimulation: closing the loop between brain and stimulation

    PubMed Central

    Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

    2016-01-01

    Purpose of review To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. Recent findings Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive transcranial brain stimulation. Priming interventions or paired associative stimulation can be used to ‘standardize’ the brain-state and hereby, homogenize the group response to stimulation. Neuroanatomical and neurochemical profiling based on magnetic resonance imaging and spectroscopy can capture trait-related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified rules. In contrast, adaptive closed-loop stimulation dynamically adjusts stimulation settings based on the occurrence of stimulation-induced state changes. Summary Approaches that take into account trait-related and state-related determinants of stimulation-induced plasticity bear considerable potential to establish noninvasive transcranial brain stimulation as interventional therapeutic tool. PMID:27224087

  4. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    PubMed

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa

    2015-08-01

    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (<2800 μA), TFS enhances and decreases the basal extracellular levels of GABA and glutamate, respectively. However, TFS did not modify the ADT. During the second microdialysis experiment, a group of animals was subjected to SE induced by pilocarpine administration (300 mg/kg, i.p.; SE group). The SE was associated with a significant rise of GABA and glutamate release (up to 120 and 182% respectively, 5h after pilocarpine injection) and the prevalence of high-voltage rhythmic spikes and increased spectral potency of delta, gamma, and theta bands. A group of animals (SE-TFS group) received TFS continuously during 2h at 100 μA, 5 min after the establishment of SE. This group showed a significant decrease in the expression of the convulsive activity and spectral potency in gamma and theta bands. The extracellular levels of GABA and glutamate in the hippocampus remained at basal conditions. These results suggest that TFS induces anticonvulsant effects when applied during the SE, an effect associated with lower amino acid release. This article is part of a Special Issue entitled "Status Epilepticus".

  5. Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans

    PubMed Central

    Wegrzyk, Jennifer; Fouré, Alexandre; Le Fur, Yann; Maffiuletti, Nicola A.; Vilmen, Christophe; Guye, Maxime; Mattei, Jean-Pierre; Place, Nicolas; Bendahan, David; Gondin, Julien

    2015-01-01

    Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit–at least in some subjects (i.e., responders)–a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI’s during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality–at least in this subgroup of subjects–by possibly exhibiting a muscle activation pattern similar to VOL contractions. PMID:26619330

  6. Stimulation of sulfate-reducing bacteria in lake water from a former open-pit mine through addition of organic wastes

    SciTech Connect

    Castro, J.M.; Wielinga, B.W.; Gannon, J.E.; Moore, J.N.

    1999-03-01

    A method to improve water quality in a lake occupying a former open-pit mine was evaluated in a laboratory-scale study. Untreated pit lake water contained high levels of sulfate, iron, and arsenic and was mildly acidic ({approximately} pH 6). Varying amounts of two locally available organic waste products were added to pit water and maintained in microcosms under anoxic conditions. In selected microcosms, populations of sulfate-reducing bacteria increased with time; sulfide was generated by sulfate reduction; sulfate, iron, and arsenic concentrations approached zero; and pH approached neutrality. Best results were obtained with intermediate amounts of waste potato skin.

  7. In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake.

    PubMed

    Huang, Dan Yang; Gao, Huanhuan; Boini, Krishna M; Osswald, Hartmut; Nürnberg, Bernd; Lang, Florian

    2010-06-01

    AMP-activated protein kinase (AMPK) is expressed in the apical membrane of cortical thick ascending limb, distal, and collecting tubules as well as macula densa cells of the kidneys. AMPK is an active modulator of epithelial Na(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, and the ATP-dependent potassium channel. The present experiments explored whether AMPK participates in the regulation of tubuloglomerular feedback (TGF) and renal tubular sodium handling. To this end, renal clearance and micropuncture experiments were performed in anesthetized rats. Under normal NaCl diet, neither TGF response nor renal fluid and sodium excretion were altered by pharmacological activation of AMPK in vivo. However, under high NaCl diet, the TGF response was significantly enhanced after intravenous or intratubular application of the AMPK activator AICAR. Moreover, AICAR application significantly increased fractional delivery of fluid and sodium to the end of the proximal tubule. High dietary NaCl intake increased the renal transcript levels encoding the AMPK-alpha1 subunit, while it decreased the expression of AMPK-beta1 and AMPK-gamma2 subunits. Immunoblots revealed that high dietary NaCl intake reduced renal expression of activated AMPK by about three times compared to normal NaCl diet whereas additional AICAR application increased AMPK activity. Our results suggest that AMPK regulates tubuloglomerular balance as well as tubular transport upon change of renal work load.

  8. Saccharomyces cerevisiae strain 905 reduces the translocation of Salmonella enterica serotype Typhimurium and stimulates the immune system in gnotobiotic and conventional mice.

    PubMed

    Martins, Flaviano S; Rodrigues, Ana Cristina P; Tiago, Fabiana C P; Penna, Francisco J; Rosa, Carlos A; Arantes, Rosa M E; Nardi, Regina M D; Neves, Maria J; Nicoli, Jacques R

    2007-03-01

    Previous results in the laboratory of the authors showed that Saccharomyces cerevisiae strain 905, isolated during 'cachaça' production, was able to colonize and survive in the gastrointestinal tract of germ-free and conventional mice, and to protect these animals against oral challenge with Salmonella enterica serotype Typhimurium or Clostridium difficile. In the present work, the effects of S. cerevisiae 905 on the translocation of Salm. Typhimurium (mesenteric lymph nodes, Peyer's patches, spleen, liver) as well as on the immune system (number of Küpffer cells, immunoglobulin production, clearance of Escherichia coli B41) were evaluated in gnotobiotic and/or conventional mice. The treatment with the yeast reduced significantly the translocation of Salm. Typhimurium to liver in gnotobiotic animals and to all the organs tested in conventional mice. The number of Küpffer cells per 100 hepatocytes in liver was significantly higher (P<0.05) in yeast mono-associated mice (52.9+/-15.7) than in germ-free controls (38.1+/-9.0). Probably as a consequence, clearance of E. coli B41 from the bloodstream was more efficient in yeast mono-associated animals when compared to germ-free mice. Higher levels (P<0.05) of secretory IgA in intestinal content and of IgA and IgM in serum were observed in yeast mono-associated mice when compared to germ-free group. Concluding, the protection against pathogenic bacteria observed in a previous study was probably due to a modulation of both local and systemic immunity of mice treated with S. cerevisiae 905.

  9. Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis.

    PubMed

    Liu, Wen-Sheng; Chu, Da-Chen; Chan, Hsiang-Lin; Li, Szu-Yuan; Liu, Chih-Kuang; Yang, Chih-Yu; Chen, Yu-Wei; Lee, Pui-Ching; Lai, Yen-Ting; Lin, Chih-Ching

    2016-10-01

    Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 months, 50 μg twice monthly for 2 months and then 100 μg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-α (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 × 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia.

  10. Cypermethrin Stimulates GSK3β-Dependent Aβ and p-tau Proteins and Cognitive Loss in Young Rats: Reduced HB-EGF Signaling and Downstream Neuroinflammation as Critical Regulators.

    PubMed

    Maurya, Shailendra Kumar; Mishra, Juhi; Abbas, Sabiya; Bandyopadhyay, Sanghamitra

    2016-03-01

    Pesticide exposure is recognized as a risk factor for Alzheimer's disease (AD). We investigated early signs of AD-like pathology upon exposure to a pyrethroid pesticide, cypermethrin, reported to impair neurodevelopment. We treated weanling rats with cypermethrin (10 and 25 mg/kg) and detected dose-dependent increase in the key proteins of AD, amyloid beta (Aβ), and phospho-tau, in frontal cortex and hippocampus as early as postnatal day 45. Upregulation of Aβ pathway involved an increase in amyloid precursor protein (APP) and its pro-amyloidogenic processing through beta-secretase (BACE) and gamma-secretase. Tau pathway entailed elevation in tau and glycogen-synthase kinase-3-beta (GSK3β)-dependent, phospho-tau. GSK3β emerged as a molecular link between the two pathways, evident from reduction in phospho-tau as well as BACE upon treating GSK3β inhibitor, lithium chloride. Exploring the mechanism revealed an attenuated heparin-binding epidermal growth factor (HB-EGF) signaling and downstream astrogliosis-mediated neuroinflammation to be responsible for inducing Aβ and phospho-tau. Cypermethrin caused a proximal reduction in HB-EGF, which promoted astrocytic nuclear factor kappa B signaling and astroglial activation close to Aβ and phospho-tau. Glial activation stimulated generation of interleukin-1 (IL-1), which upregulated GSK3β, and APP and tau as well, resulting in co-localization of Aβ and phospho-tau with IL-1 receptor. Intracerebral insertion of exogenous HB-EGF restored its own signaling and suppressed neuroinflammation and thereby Aβ and phospho-tau in cypermethrin-exposed rats, proving a central role of reduced HB-EGF signaling in cypermethrin-mediated neurodegeneration. Furthermore, cypermethrin stimulated cognitive impairments, which could be prevented by exogenous HB-EGF. Our data demonstrate that cypermethrin induces premature upregulation of GSK3β-dependent Aβ and tau pathways, where HB-EGF signaling and neuroinflammation serve as

  11. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    SciTech Connect

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  12. Assisting children with attention deficit hyperactivity disorder to reduce the hyperactive behavior of arbitrary standing in class with a Nintendo Wii remote controller through an active reminder and preferred reward stimulation.

    PubMed

    Shih, Ching-Hsiang; Wang, Shu-Hui; Wang, Yun-Ting

    2014-09-01

    Recent studies in the field of special education have shown that in combination with software technology, high-tech commercial products can be applied as useful assistive technology devices to help people with disabilities. This study extended this concept to turn a Nintendo Wii Remote Controller into a high-performance limb action detector, in order to evaluate whether two students with Attention Deficit Hyperactivity Disorder (ADHD) could reduce their hyperactive behavior through an active reminder and stimulation in the form of the participants' preferred rewards. This study focused on one particular hyperactive behavior common to both students: standing up arbitrarily during class. The active reminder was in the form of vibration feedback provided via the built-in function of the Wii Remote Controller, which was controlled and triggered by a control system to remind participants when they were engaging in standing behavior. This study was performed according to a multiple baseline design across participants. The results showed that both participants significantly improved their control over their hyperactive behavior during the intervention phase, and retained this effective performance in the maintenance phase. The practical and developmental implications of the findings are discussed.

  13. Electroacupuncture-Like Stimulation at the Baihui (GV20) and Dazhui (GV14) Acupoints Protects Rats against Subacute-Phase Cerebral Ischemia-Reperfusion Injuries by Reducing S100B-Mediated Neurotoxicity

    PubMed Central

    Cheng, Chin-Yi; Lin, Jaung-Geng; Tang, Nou-Ying; Kao, Shung-Te; Hsieh, Ching-Liang

    2014-01-01

    Objectives The purpose of this study was to evaluate the effects of electroacupuncture-like stimulation at the Baihui (GV20) and Dazhui (GV14) acupoints (EA at acupoints) during the subacute phase of cerebral ischemia-reperfusion (I/R) injury and to establish the neuroprotective mechanisms involved in the modulation of the S100B-mediated signaling pathway. Methods The experimental rats were subjected to middle cerebral artery occlusion (MCAo) for 15 min followed by 1 d or 7 d of reperfusion. EA at acupoints was applied 1 d postreperfusion then once daily for 6 consecutive days. Results We observed that 15 min of MCAo caused delayed infarct expansion 7 d after reperfusion. EA at acupoints significantly reduced the cerebral infarct and neurological deficit scores. EA at acupoints also downregulated the expression of the glial fibrillary acidic protein (GFAP), S100B, nuclear factor-κB (NF-κB; p50), and tumor necrosis factor-α (TNF-α), and reduced the level of inducible nitric oxide synthase (iNOS) and apoptosis in the ischemic cortical penumbra 7 d after reperfusion. Western blot analysis showed that EA at acupoints significantly downregulated the cytosolic expression of phospho-p38 MAP kinase (p-p38 MAP kinase), tumor necrosis factor receptor type 1-associated death domain (TRADD), Fas-associated death domain (FADD), cleaved caspase-8, and cleaved caspase-3 in the ischemic cortical penumbra 7 d after reperfusion. EA at acupoints significantly reduced the numbers of GFAP/S100B and S100B/nitrotyrosine double-labeled cells. Conclusion Our study results indicate that EA at acupoints initiated 1 d postreperfusion effectively downregulates astrocytic S100B expression to provide neuroprotection against delayed infarct expansion by modulating p38 MAP kinase-mediated NF-κB expression. These effects subsequently reduce oxidative/nitrative stress and inhibit the TNF-α/TRADD/FADD/cleaved caspase-8/cleaved caspase-3 apoptotic pathway in the ischemic cortical penumbra 7 d

  14. A light microscopy study of the migration of Naegleria fowleri from the nasal submucosa to the central nervous system during the early stage of primary amebic meningoencephalitis in mice.

    PubMed

    Jarolim, K L; McCosh, J K; Howard, M J; John, D T

    2000-02-01

    The migratory pathway of Naegleria fowleri from the nasal submucosa to the central nervous system (CNS) during the early stage of primary amebic meningoencephalitis (PAM) was investigated in mice. Twenty-one-day-old CD-1 mice were inoculated by intranasal instillation of 1 x 10(6) amebas. Animals were divided into 3 groups of 5 and, after being anesthetized, were killed at intervals of 24, 32, and 48 hr postinoculation by transcardial perfusion with formaldehyde, acetic acid, and methanol. The heads were decalcified, divided in the midsagittal plane, and the area of the cribriform plate removed and embedded in paraffin. Serial sections were cut at 8 microm and stained with a combination of celestin blue, Harris' hematoxylin, and acid fuchsin for light microscopy. Focal inflammation and amebas were observed in the submucosal nerve plexus, olfactory nerves penetrating the cribriform plate, and the olfactory bulb of the brain as early as 24 hr postinoculation. The time periods selected assured that the disease process would not obliterate soft tissue structures. Earlier studies used moribund mice in which the inflammation and the number of amebas were overwhelming. The present study provides convincing evidence that amebas gain initial access to the CNS through olfactory nerves within the cribriform plate during the early stages of PAM.

  15. Movement disorders induced by deep brain stimulation.

    PubMed

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-04-01

    Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders. PMID:26806438

  16. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine

    PubMed Central

    Bearson, Shawn M. D.; Bearson, Bradley L.; Loving, Crystal L.; Allen, Heather K.; Lee, InSoo; Madson, Darin; Kehrli, Marcus E.

    2016-01-01

    Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To develop an intervention strategy that is non-specific yet effective against diverse Salmonella serovars, we explored the prophylactic use of a cytokine to decrease Salmonella in swine by boosting the host’s innate immune system. Granulocyte-colony stimulating factor (G-CSF) is the major cytokine regulating the production, differentiation, function, and survival of neutrophils. Neutrophils play a critical role in the response to Salmonella; therefore, we evaluated the vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF (Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were intranasally inoculated with 1 × 107 colony forming unit (CFU) of Salmonella enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella, Ad5-G-CSF-treated pigs shed significantly less Salmonella (~103 CFU/g) in their feces than Ad5-empty-treated pigs (~104–105 CFU/g; P < 0.05). A significant 4-log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the Peyer’s patch region of the ileum exhibited a significant 0.5-log reduction in colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all challenged pigs was assessed by sequencing and analyzing the V1–V3 region of the 16S rRNA gene from fecal DNA samples. The microbial community structure of

  17. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine

    PubMed Central

    Bearson, Shawn M. D.; Bearson, Bradley L.; Loving, Crystal L.; Allen, Heather K.; Lee, InSoo; Madson, Darin; Kehrli, Marcus E.

    2016-01-01

    Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To develop an intervention strategy that is non-specific yet effective against diverse Salmonella serovars, we explored the prophylactic use of a cytokine to decrease Salmonella in swine by boosting the host’s innate immune system. Granulocyte-colony stimulating factor (G-CSF) is the major cytokine regulating the production, differentiation, function, and survival of neutrophils. Neutrophils play a critical role in the response to Salmonella; therefore, we evaluated the vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF (Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were intranasally inoculated with 1 × 107 colony forming unit (CFU) of Salmonella enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella, Ad5-G-CSF-treated pigs shed significantly less Salmonella (~103 CFU/g) in their feces than Ad5-empty-treated pigs (~104–105 CFU/g; P < 0.05). A significant 4-log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the Peyer’s patch region of the ileum exhibited a significant 0.5-log reduction in colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all challenged pigs was assessed by sequencing and analyzing the V1–V3 region of the 16S rRNA gene from fecal DNA samples. The microbial community structure of

  18. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine.

    PubMed

    Bearson, Shawn M D; Bearson, Bradley L; Loving, Crystal L; Allen, Heather K; Lee, InSoo; Madson, Darin; Kehrli, Marcus E

    2016-01-01

    Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To develop an intervention strategy that is non-specific yet effective against diverse Salmonella serovars, we explored the prophylactic use of a cytokine to decrease Salmonella in swine by boosting the host's innate immune system. Granulocyte-colony stimulating factor (G-CSF) is the major cytokine regulating the production, differentiation, function, and survival of neutrophils. Neutrophils play a critical role in the response to Salmonella; therefore, we evaluated the vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF (Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were intranasally inoculated with 1 × 10(7) colony forming unit (CFU) of Salmonella enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella, Ad5-G-CSF-treated pigs shed significantly less Salmonella (~10(3) CFU/g) in their feces than Ad5-empty-treated pigs (~10(4)-10(5) CFU/g; P < 0.05). A significant 4-log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the Peyer's patch region of the ileum exhibited a significant 0.5-log reduction in colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all challenged pigs was assessed by sequencing and analyzing the V1-V3 region of the 16S rRNA gene from fecal DNA samples. The microbial community structure of

  19. Stimulated rotational Raman scattering

    NASA Astrophysics Data System (ADS)

    Parazzoli, C. G.; Rafanelli, G. L.; Capps, D. M.; Drutman, C.

    1989-03-01

    The effect of Stimulated Rotational Raman Scattering (SRRS) processes on high energy laser directed energy weapon systems was studied. The program had 3 main objectives; achieving an accurate description of the physical processes involved in SRRS; developing a numerical algorithm to confidently evaluate SRRS-induced losses in the propagation of high energy laser beams in the uplink and downlink segments of the optical trains of various strategic defense system scenarios; and discovering possible methods to eliminate, or at least reduce, the deleterious effects of SRRS on the energy deposition on target. The following topics are discussed: the motivation for the accomplishments of the DOE program; the Semiclassical Theory of Non-Resonant SRRS for Diatomic Homonuclear Molecules; and then the following appendices; Calculation of the Dipole Transition Reduced Matrix Element, Guided Tour of Hughes SRRS Code, Running the Hughes SRRS Code, and Hughes SRRS Code Listing.

  20. Brefeldin A reduces tumor necrosis factor-α-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-κB pathways in human keratinocytes.

    PubMed

    Nam, Yoon Jeong; Lee, Chung Soo

    2016-09-01

    Keratinocytes may play an important role in the pathogenesis of inflammatory skin diseases. Brefeldin A has been shown to attenuate the production and secretion of chemical mediators involved in inflammation and immune responses. However, the effect of brefeldin A on the TNF-α-stimulated production of inflammatory mediators in keratinocytes has not been studied. We investigated the effect of brefeldin A on the TNF-α-stimulated production of inflammatory mediators using HaCaT cells and primary keratinocytes in relation to the Akt, mTOR, and NF-κB pathways, which regulates the transcription genes involved in immune and inflammatory responses. Brefeldin A, Akt inhibitor, Bay 11-7085 (an inhibitor of NF-κB activation), and rapamycin (mTOR inhibitor) inhibited the TNF-α-stimulated productions of inflammatory mediators, and activations of Akt, mTOR, and NF-κB in keratinocytes. The results show that brefeldin A appears to attenuate TNF-α-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of the Akt, mTOR, and NF-κB pathways. PMID:27198515

  1. Dorsal column stimulator applications

    PubMed Central

    Yampolsky, Claudio; Hem, Santiago; Bendersky, Damián

    2012-01-01

    Background: Spinal cord stimulation (SCS) has been used to treat neuropathic pain since 1967. Following that, technological progress, among other advances, helped SCS become an effective tool to reduce pain. Methods: This article is a non-systematic review of the mechanism of action, indications, results, programming parameters, complications, and cost-effectiveness of SCS. Results: In spite of the existence of several studies that try to prove the mechanism of action of SCS, it still remains unknown. The mechanism of action of SCS would be based on the antidromic activation of the dorsal column fibers, which activate the inhibitory interneurons within the dorsal horn. At present, the indications of SCS are being revised constantly, while new applications are being proposed and researched worldwide. Failed back surgery syndrome (FBSS) is the most common indication for SCS, whereas, the complex regional pain syndrome (CRPS) is the second one. Also, this technique is useful in patients with refractory angina and critical limb ischemia, in whom surgical or endovascular treatment cannot be performed. Further indications may be phantom limb pain, chronic intractable pain located in the head, face, neck, or upper extremities, spinal lumbar stenosis in patients who are not surgical candidates, and others. Conclusion: Spinal cord stimulation is a useful tool for neuromodulation, if an accurate patient selection is carried out prior, which should include a trial period. Undoubtedly, this proper selection and a better knowledge of its underlying mechanisms of action, will allow this cutting edge technique to be more acceptable among pain physicians. PMID:23230533

  2. Electrical stimulation and motor recovery.

    PubMed

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical

  3. Optogenetic stimulation of the auditory pathway

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Reuter, Kirsten; Jing, Zhizi; Jeschke, Marcus; Mendoza Schulz, Alejandro; Hoch, Gerhard; Bartels, Matthias; Vogt, Gerhard; Garnham, Carolyn W.; Yawo, Hiromu; Fukazawa, Yugo; Augustine, George J.; Bamberg, Ernst; Kügler, Sebastian; Salditt, Tim; de Hoz, Livia; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. PMID:24509078

  4. Transcranial direct current stimulation, implicit alcohol associations and craving.

    PubMed

    den Uyl, Tess E; Gladwin, Thomas E; Wiers, Reinout W

    2015-02-01

    Previous research has shown that stimulation of the left dorsolateral prefrontal cortex (DLPFC) enhances working memory (e.g. in the n-back task), and reduces craving for cigarettes and alcohol. Stimulation of the right inferior frontal gyrus (IFG) improves response inhibition. The underlying mechanisms are not clearly understood, nor is it known whether IFG stimulation also reduces craving. Here, we compared effects of DLPFC, IFG, and sham stimulation on craving in heavy drinkers in a small sample (n=41). We also tested effects of tDCS on overcoming response biases due to associations between alcohol and valence and alcohol and approach, using implicit association tests (IATs). Mild craving was reduced after DLPFC stimulation. Categorization of valence attribute words in the IAT was faster after DLPFC stimulation. We conclude that DLPFC stimulation can reduce craving in heavy drinkers, but found no evidence for tDCS induced changes in alcohol biases, although low power necessitates caution.

  5. Reducing exposure to long days from 75 to 30 days of extra-light treatment does not decrease the capacity of male goats to stimulate ovulatory activity in seasonally anovulatory females.

    PubMed

    Ponce, J L; Velázquez, H; Duarte, G; Bedos, M; Hernández, H; Keller, M; Chemineau, P; Delgadillo, J A

    2014-07-01

    The response of male goats exposed to different durations of long days (LD) during an extra-light treatment in autumn-winter, and their ability to induce ovulations in seasonally anovulatory goats were investigated in 2 experiments. In experiment 1, control males were exposed to natural photoperiod (n = 5), whereas 4 additional groups (n = 5/group) were exposed to 16 h of light per d during 75, 45, 30, or 15 d of LD. In the 4 groups, photoperiodic treatments ended on January 15th. Plasma concentrations of testosterone were determined in blood samples obtained once a week from October 15th to May 30th. The rise of testosterone levels occurred earlier in males from the 75-LD and 45-LD groups than in those from the 30-LD, 15-LD, and control groups (P < 0.05). In addition, the time during which levels of testosterone remained >5 ng/mL was longer in males from the 75-LD and 45-LD than in those from the 30-LD and 15-LD groups (P < 0.05). In experiment 2, a group of anovulatory goats (n = 13) was isolated from males, while 3 additional groups were put in contact during 15 d with males previously exposed to 75, 45, or 30 days of LD (n = 25, 27, and 26 females/group, respectively and n = 3 males per group). The proportion of goats that ovulated was higher in the 3 groups in contact with the photo-stimulated males (range: 88%-92%) than in the group isolated from them (0%; P < 0.05). The proportion of pregnant females did not differ between the 3 groups of does in contact with photo-stimulated males (range: 78%-92%; P > 0.05). We conclude that, in our experimental conditions, a photoperiodic treatment as short as 30 d of LD during autumn-winter, stimulated testosterone secretion of bucks during their period of sexual rest and rendered them able to induce ovulations in seasonal anestrous goats and to obtain pregnancies in these females.

  6. Strong Manual Acupuncture Stimulation of “Huantiao” (GB 30) Reduces Pain-Induced Anxiety and p-ERK in the Anterior Cingulate Cortex in a Rat Model of Neuropathic Pain

    PubMed Central

    Shao, Xiao-mei; Shen, Zui; Sun, Jing; Fang, Fang; Fang, Jun-fan; Wu, Yuan-yuan; Fang, Jian-qiao

    2015-01-01

    Persistent neuropathic pain is associated with anxiety. The phosphorylation of extracellular signal-regulated kinase (p-ERK) in the anterior cingulate cortex (ACC) plays an important role in pain-induced anxiety. Acupuncture is widely used for pain and anxiety. However, little is known about which acupuncture technique is optimal on pain-induced anxiety and the relationship between acupuncture effect and p-ERK. The rat model was induced by L5 spinal nerve ligation (SNL). Male adult SD rats were randomly divided into control, SNL, strong manual acupuncture (sMA), mild manual acupuncture (mMA), and electroacupuncture (EA) group. Bilateral “Huantiao” (GB 30) were stimulated by sMA, mMA, and EA, respectively. The pain withdrawal thresholds (PWTs) and anxiety behavior were measured, and p-ERK protein expression and immunoreactivity cells in ACC were detected. PWTs increased significantly in both sMA and EA groups. Meanwhile, anxiety-like behavior was improved significantly in the sMA and mMA groups. Furthermore, the overexpression of p-ERK induced by SNL was downregulated by strong and mild manual acupuncture. Therefore, strong manual acupuncture on bilateral “Huantiao” (GB 30) could be a proper therapy relieving both pain and pain-induced anxiety. The effect of different acupuncture techniques on pain-induced anxiety may arise from the regulation of p-ERK in ACC. PMID:26770252

  7. Peripheral nerve stimulation: definition.

    PubMed

    Abejón, David; Pérez-Cajaraville, Juan

    2011-01-01

    Recently, there has been a tremendous evolution in the field of neurostimulation, both from the technological point of view and from development of the new and different indications. In some areas, such as peripheral nerve stimulation, there has been a boom in recent years due to the variations in the surgical technique and the improved results documented by in multiple published papers. All this makes imperative the need to classify and define the different types of stimulation that are used today. The confusion arises when attempting to describe peripheral nerve stimulation and subcutaneous stimulation. Peripheral nerve stimulation, in its pure definition, involves implanting a lead on a nerve, with the aim to produce paresthesia along the entire trajectory of the stimulated nerve.

  8. Prophylactic administration of vector-encoded porcine granulocyte-colony stimulating factor reduces Salmonella shedding,tonsil colonization,& microbiota alterations of the gastrointestinal tract in Salmonella-challenged swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To d...

  9. Stimulant Use Disorders.

    PubMed

    Park, Taryn M; Haning, William F

    2016-07-01

    Compared with other illicit substances, stimulants are not commonly used by adolescents; however, they represent a serious concern regarding substance use among youths. This article uses methamphetamine as a model for stimulant use in adolescents; cocaine and prescription stimulants are also mentioned. Methamphetamine use among adolescents and young adults is a serious health concern with potentially long-term physical, cognitive, and psychiatric consequences. Brain development and the effects of misusing stimulants align such that usage in adolescents can more dangerous than during adulthood. It seems helpful to keep in mind the differences between adolescents and young adults when implementing interventions. PMID:27338967

  10. Cardiac Resynchronization Therapy Delivered Via a Multipolar Left Ventricular Lead is Associated with Reduced Mortality and Elimination of Phrenic Nerve Stimulation: Long‐Term Follow‐Up from a Multicenter Registry

    PubMed Central

    BEHAR, JONATHAN M.; BOSTOCK, JULIAN; ZHU LI, ADRIAN PO; CHIN, HUI MEN SELINA; JUBB, STEPHEN; LENT, EDWARD; GAMBLE, JAMES; FOLEY, PAUL W.X.; BETTS, TIM R.; RINALDI, CHRISTOPHER ALDO

    2015-01-01

    Lower Mortality and Eliminated PNS Associated with Quadripolar Leads Introduction Cardiac resynchronization therapy (CRT) using quadripolar left ventricular (LV) leads provides more pacing vectors compared to bipolar leads. This may avoid phrenic nerve stimulation (PNS) and allow optimal lead placement to maximize biventricular pacing. However, a long‐term improvement in patient outcome has yet to be demonstrated. Methods A total of 721 consecutive patients with conventional CRTD criteria implanted with quadripolar (n = 357) or bipolar (n = 364) LV leads were enrolled into a registry at 3 UK centers. Lead performance and mortality was analyzed over a 5‐year period. Results Patients receiving a quadripolar lead were of similar age and sex to those receiving a bipolar lead, although a lower proportion had ischemic heart disease (62.6% vs. 54.1%, P = 0.02). Both groups had similar rates of procedural success, although lead threshold, impedance, and procedural radiation dose were significantly lower in those receiving a quadripolar lead. PNS was more common in those with quadripolar leads (16.0% vs. 11.6%, P = 0.08), but was eliminated by switching pacing vector in all cases compared with 60% in the bipolar group (P < 0.001). Furthermore, LV lead displacement (1.7% vs. 4.6%, P = 0.03) and repositioning (2.0% vs. 5.2%, P = 0.03) occurred significantly less often in those with a quadripolar lead. All‐cause mortality was also significantly lower in the quadripolar compared to bipolar lead group in univariate and multivariate analysis (13.2% vs. 22.5%, P < 0.001). Conclusions In a large, multicenter experience, the use of quadripolar LV leads for CRT was associated with elimination of PNS and lower overall mortality. This has important implications for LV pacing lead choice. PMID:25631303

  11. Tactile stimulation lowers stress in fish.

    PubMed

    Soares, Marta C; Oliveira, Rui F; Ros, Albert F H; Grutter, Alexandra S; Bshary, Redouan

    2011-01-01

    In humans, physical stimulation, such as massage therapy, reduces stress and has demonstrable health benefits. Grooming in primates may have similar effects but it remains unclear whether the positive effects are due to physical contact or to its social value. Here we show that physical stimulation reduces stress in a coral reef fish, the surgeonfish Ctenochaetus striatus. These fish regularly visit cleaner wrasses Labroides dimidiatus to have ectoparasites removed. The cleanerfish influences client decisions by physically touching the surgeonfish with its pectoral and pelvic fins, a behaviour known as tactile stimulation. We simulated this behaviour by exposing surgeonfish to mechanically moving cleanerfish models. Surgeonfish had significantly lower levels of cortisol when stimulated by moving models compared with controls with access to stationary models. Our results show that physical contact alone, without a social aspect, is enough to produce fitness-enhancing benefits, a situation so far only demonstrated in humans. PMID:22086335

  12. Controlling illegal stimulants: a regulated market model

    PubMed Central

    Haden, Mark

    2008-01-01

    Prohibition of illegal drugs is a failed social policy and new models of regulation of these substances are needed. This paper explores a proposal for a post-prohibition, public health based model for the regulation of the most problematic drugs, the smokable and injectable stimulants. The literature on stimulant maintenance is explored. Seven foundational principles are suggested that could support this regulatory model of drug control that would reduce both health and social problems related to illegal stimulants. Some details of this model are examined and the paper concludes that drug policies need to be subject to research and based on evidence. PMID:18215317

  13. Passive Auditory Stimulation Improves Vision in Hemianopia

    PubMed Central

    Lewald, Jörg; Tegenthoff, Martin; Peters, Sören; Hausmann, Markus

    2012-01-01

    Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. Trial Registration DRKS00003577 PMID:22666311

  14. Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages

    PubMed Central

    2014-01-01

    Background Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined. Methods In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC’s effect on the nuclear factor-kappaB (NF-κB) signaling pathway. Results Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC’s inhibitory effects on inhibitor kappaB (IκB) degradation. Conclusions Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders. PMID:24628870

  15. [Electromagnetic urological stimulator].

    PubMed

    Zaslavskiĭ AOi; Markarov, G S; Gelis, Iu S

    1997-01-01

    The paper deals with an electromagnetic urological stimulator which generates a modulated low-frequency electromagnetic field of nonthermal intensity and its brief technical data. It presents a treatment regimen for urolithiasis and recommendations how to use the above therapeutical agent to stimulate urinary function in patients with urolithiasis in order to inoperatively eliminate urinary calculi and sand which form following extracorporeal shockwave lithotripsy.

  16. Stimulating your appetite.

    PubMed

    Whitfield, L

    1998-01-01

    A number of legal and illegal drugs can help stimulate appetite and are used for people with HIV to prevent wasting. Stimulating hunger is important because lower calorie intake and poor absorption of nutrients are associated with wasting. The uses and potential drawbacks of marijuana, thalidomide (Synovir), Marinol, and Megace are described. PMID:11365223

  17. Species-Dependent Phenotypes of Replication-Temperature-Sensitive trfA Mutants of Plasmid RK2: a Codon-Neutral Base Substitution Stimulates Temperature Sensitivity by Leading to Reduced Levels of trfA Expression

    PubMed Central

    Karunakaran, Ponniah; Blatny, Janet Martha; Ertesvåg, Helga; Valla, Svein

    1998-01-01

    TrfA is the only plasmid-encoded protein required for initiation of replication of the broad-host-range plasmid RK2. Here we describe the isolation of four trfA mutants temperature sensitive for replication in Pseudomonas aeruginosa. One of the mutations led to substitution of arginine 247 with cysteine. This mutant has been previously described to be temperature sensitive for replication, but poorly functional, in Escherichia coli. The remaining three mutants were identical, and each of them carried two mutations, one leading to substitution of arginine 163 with cysteine (mutation 163C) and the other a codon-neutral mutation changing the codon for glycine 235 from GGC to GGU (mutation 235). Neither of the two mutations caused a temperature-sensitive phenotype alone in P. aeruginosa, and the effect of the neutral mutation was caused by its ability to strongly reduce the trfA expression level. The double mutant and mutant 163C could not be stably maintained in E. coli, but mutant 235 could be established and, surprisingly, displayed a temperature-sensitive phenotype in this host. Mutation 235 strongly reduced the trfA expression level also in E. coli. The glycine 85 codon in trfA mRNA is GGU, and a change of this to GGC did not significantly affect expression. In addition, we found that wild-type trfA was expressed at much lower levels in E. coli than in P. aeruginosa, indicating that this level is a key parameter in the determination of the temperature-sensitive phenotypes in different species. The E. coli lacZ gene was translationally fused at the 3′ end and internally in trfA, in both cases leading to elimination of the effect of mutation 235 on expression. We therefore propose that this mutation acts through an effect on mRNA structure or stability. PMID:9683473

  18. Tissue stimulator enclosure welding fixture

    NASA Technical Reports Server (NTRS)

    Mcclure, S. R.

    1977-01-01

    It was demonstrated that the thickness of the stimulator titanium enclosure is directly related to the battery recharge time cycle. Reduction of the titanium enclosure thickness from approximately 0.37 mm (0.015 inch) to 0.05 mm (0.002 inch) significantly reduced the recharge time cycle and thereby patient inconvenience. However, fabrication of titanium enclosures from the thinner material introduced problems in forming, holding, and welding that required improvement in state of the art shop practices. The procedures that were utilized to resolve these fabrication problems are described.

  19. Computational modeling of epidural cortical stimulation

    NASA Astrophysics Data System (ADS)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2008-12-01

    Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

  20. Optically stimulated luminescence dosimetry

    NASA Astrophysics Data System (ADS)

    McKeever, Stephen W. S.

    2001-09-01

    Models and the conceptual framework necessary for an understanding of optically stimulated luminescence (OSL) are described. Examples of various OSL readout schemes are described, along with examples of the use of OSL in radiation dosimetry.

  1. Deep brain stimulation

    MedlinePlus

    ... the brain The neurostimulator, which puts out the electric current. The stimulator is similar to a heart pacemaker . It is usually placed under the skin near the collarbone, but may be ... pulses travel from the neurostimulator, along the extension ...

  2. ACTH stimulation test

    MedlinePlus

    ... Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 102. Chernecky CC, Berger BJ. ACTH stimulation test - diagnostic. In: ... . 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  3. Geothermal Well Stimulation

    SciTech Connect

    Campbell, D. A.; Morris, C. W.; Sinclair, A. R.; Hanold, R. J.; Vetter, O. J.

    1981-03-01

    The stimulation of geothermal wells presents some new and challenging problems. Formation temperatures in the 300-600 F range can be expected. The behavior of stimulation fluids, frac proppants, and equipment at these temperatures in a hostile brine environment must be carefully evaluated before performance expectations can be determined. In order to avoid possible damage to the producing horizon of the formation, high temperature chemical compatibility between the in situ materials and the stimulation materials must be verified. Perhaps most significant of all, in geothermal wells the required techniques must be capable of bringing about the production of very large amounts of fluid. This necessity for high flow rates represents a significant departure from conventional petroleum well stimulation and demands the creation of very high near-wellbore permeability and/or fractures with very high flow conductivity.

  4. Optogenetic stimulation of myelination (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yang, In Hong; Lee, Hae Ung; Thakor, Nitish V.

    2016-03-01

    Myelination is governed by axon-glia interaction which is modulated by neural activity. Currently, the effects of subcellular activation of neurons which induce neural activity upon myelination are not well understood. To identify if subcellular neuronal stimulation can enhance myelination, we developed a novel system for focal stimulation of neural activity with optogenetic in a compartmentalized microfluidic platform. In our systems, stimulation for neurons in restricted subcellular parts, such as cell bodies and axons promoted oligodendrocyte differentiation and the myelination of axons the just as much as whole cell activation of neurons did. The number of premature O4 positive oligodendrocytes was reduced and the numbers of mature and myelin basic protein-positive oligodendrocytes was increased both by subcellular optogenetic stimulation.

  5. Optogenetic stimulation of MCH neurons increases sleep.

    PubMed

    Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Zayachkivsky, Andrew; Liu, Meng; Uhde, Thomas; Glen, W Bailey; van den Pol, Anthony N; Mulholland, Patrick J; Shiromani, Priyattam J

    2013-06-19

    Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.

  6. Vagus Nerve Stimulation

    PubMed Central

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  7. New York Canyon Stimulation

    SciTech Connect

    Raemy, Bernard

    2012-06-21

    The New York Canyon Stimulation Project was to demonstrate the commercial application of Enhanced Geothermal System techniques in Buena Vista Valley area of Pershing County, Nevada. From October 2009 to early 2012, TGP Development Company aggressively implemented Phase I of Pre-Stimulation and Site/Wellbore readiness. This included: geological studies; water studies and analyses and procurement of initial permits for drilling. Oversubscription of water rights and lack of water needed for implementation of EGS were identified and remained primary obstacles. Despite extended efforts to find alternative solutions, the water supply circumstances could not be overcome and led TGP to determine a "No Go" decision and initiate project termination in April 2012.

  8. Muscle Stimulation Technology

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Under a Goddard Space Flight Center contract, Electrologic of America was able to refine the process of densely packing circuitry on personal computer boards, providing significant contributions to the closed-loop systems for the Remote Manipulator System Simulator. The microcircuitry work was then applied to the StimMaster FES Ergometer, an exercise device used to stimulate muscles suffering from paralysis. The electrical stimulation equipment was developed exclusively for V-Care Health Systems, Inc. Product still commercially available as of March 2002.

  9. Timeout as Reduced Environmental Stimulation (RES): Reply to Polsgrove.

    ERIC Educational Resources Information Center

    Smith, Donald E. P.

    1982-01-01

    D. Smith replies to L. Polsgrove's criticisms of Smith's earlier article (EC 133 830) on seclusionary timeout for children with emotional/behavioral problems. Smith suggests that in several studies timeout was seen by the children as a way of relieving the classroom's stimulus overload. (CL)

  10. Peptides having reduced toxicity that stimulate cholesterol efflux

    DOEpatents

    Bielicki, John K.; Johansson, Jan; Danho, Waleed

    2016-08-16

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  11. Safe neuromuscular electrical stimulator designed for the elderly.

    PubMed

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.

  12. Safe neuromuscular electrical stimulator designed for the elderly.

    PubMed

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials. PMID:21401669

  13. Evaluation of intradural stimulation efficiency and selectivity in a computational model of spinal cord stimulation.

    PubMed

    Howell, Bryan; Lad, Shivanand P; Grill, Warren M

    2014-01-01

    Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS, which, in turn

  14. What does galvanic vestibular stimulation stimulate?

    PubMed

    Wardman, Daniel L; Fitzpatrick, Richard C

    2002-01-01

    The technique of galvanic vestibular stimulation (GVS) has been used for a long time. The stimulus produces stereotyped automatic postural and ocular responses. The mechanisms underlying these responses are not understood although they are commonly attributed to altered otolith output. Based on animal studies, it seems reasonable to assume that vestibular afferents from the otoliths and semicircular canals are affected similarly by GVS. With this assumption, and anatomical knowledge of the vestibular apparatus, a model is developed to describe the expected responses of vestibular afferents to percutaneous GVS and the physiological implications of this altered sensory signal. Bilateral bipolar GVS, the most commonly used technique, should produce a canal signal consistent with a strong ear-down roll towards the cathodal side, a smaller nose-to-cathode yaw, but no pitch signal. Bilateral bipolar GVS should also produce an otolith signal consistent with tilt towards the cathodal side or a translational acceleration towards the anodal side. The expected responses for other configurations of GVS are also described. The model appears consistent with published data on the ocular and postural responses to GVS, and suggests other testable hypotheses concerning postural, ocular and perceptual responses to GVS.

  15. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  16. Optically stimulated luminescence dosimetry

    NASA Astrophysics Data System (ADS)

    McKeever, Stephen W.

    1999-02-01

    Optically Stimulated Luminescence (OSL) dosimetry is attractive to the health physics and dosimetry community due to its all-optical character, fast data acquisition and the avoidance of heating the detector. Until recently there was no luminescent material sensitive enough to radiation, and at the same time suitable for stimulation with visible light, for use in this application. However, anion-deficient aluminum oxide doped with carbon (Al2O3:C) appears to be not only an extremely sensitive thermoluminescence (TL) material, but is also well-suited to OSL applications. Several OSL readout protocols have been suggested, including cw-OSL, pulsed OSL (POSL), and 'delayed' OSL (DOSL). The paper discusses the physical mechanisms that give rise to the OSL signals and the dependence of these signals upon absorbed dose. Example applications of the use of OSL from Al2O3:C in environmental radiation and ultraviolet-B dosimetry are discussed.

  17. Sacral nerve stimulation.

    PubMed

    Matzel, K E; Stadelmaier, U; Besendörfer, M

    2004-01-01

    The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  18. Cognitive stimulation in brainstorming.

    PubMed

    Dugosh, K L; Paulus, P B; Roland, E J; Yang, H C

    2000-11-01

    Research on group brainstorming has demonstrated that it is less effective for generating large numbers of ideas than individual brainstorming, yet various scholars have presumed that group idea sharing should enhance cognitive stimulation and idea production. Three experiments examined the potential of cognitive stimulation in brainstorming. Experiments 1 and 2 used a paradigm in which individuals were exposed to ideas on audiotape as they were brainstorming, and Experiment 3 used the electronic brainstorming paradigm. Evidence was obtained for enhanced idea generation both during and after idea exposure. The attentional set of the participant and the content of the exposure manipulation (number of ideas, presence of irrelevant information) influenced this effect. These results are consistent with a cognitive perspective on group brainstorming.

  19. Stimulated Raman photoacoustic imaging

    PubMed Central

    Yakovlev, Vladislav V.; Zhang, Hao F.; Noojin, Gary D.; Denton, Michael L.; Thomas, Robert J.; Scully, Marlan O.

    2010-01-01

    Achieving label-free, molecular-specific imaging with high spatial resolution in deep tissue is often considered the grand challenge of optical imaging. To accomplish this goal, significant optical scattering in tissues has to be overcome while achieving molecular specificity without resorting to extrinsic labeling. We demonstrate the feasibility of developing such an optical imaging modality by combining the molecularly specific stimulated Raman excitation with the photoacoustic detection. By employing two ultrashort excitation laser pulses, separated in frequency by the vibrational frequency of a targeted molecule, only the specific vibrational level of the target molecules in the illuminated tissue volume is excited. This targeted optical absorption generates ultrasonic waves (referred to as stimulated Raman photoacoustic waves) which are detected using a traditional ultrasonic transducer to form an image following the design of the established photoacoustic microscopy. PMID:21059930

  20. Raft River well stimulation experiments: geothermal reservoir well stimulation program

    SciTech Connect

    Not Available

    1980-08-01

    The Geothermal Reservoir Well Stimulation Program (GRWSP) performed two field experiments at the Raft River KGRA in 1979. Wells RRGP-4 and RRGP-5 were selected for the hydraulic fracture stimulation treatments. The well selection process, fracture treatment design, field execution, stimulation results, and pre- and post-job evaluations are presented.

  1. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  2. Stochastic resonance in neuron models: Endogenous stimulation revisited

    NASA Astrophysics Data System (ADS)

    Plesser, Hans E.; Geisel, Theo

    2001-03-01

    The paradigm of stochastic resonance (SR)-the idea that signal detection and transmission may benefit from noise-has met with great interest in both physics and the neurosciences. We investigate here the consequences of reducing the dynamics of a periodically driven neuron to a renewal process (stimulation with reset or endogenous stimulation). This greatly simplifies the mathematical analysis, but we show that stochastic resonance as reported earlier occurs in this model only as a consequence of the reduced dynamics.

  3. Dynamics of stimulated L → H transitions

    SciTech Connect

    Miki, K.; Diamond, P. H.; Xiao, W. W.; Hahn, S.-H.; Gürcan, Ö. D.; Tynan, G. R.

    2013-08-15

    We report on model studies of stimulated L → H transitions [K. Miki et al., Phys. Rev. Lett. 110, 195002 (2013)]. These studies use a reduced mesoscale model. Model studies reveal that L → H transition can be triggered by particle injection into a subcritical state (i.e., Pstimulated transition. For low ambient heating, strong injection is predicted to trigger a transient turbulence collapse. Repetitive injection at a period less than the lifetime of the collapsed state can thus maintain the turbulence collapse and so sustain a driven H-mode-like state. The total number of particles required to induce a transition by either injection or gas puffing is estimated. Results indicate that the total number of injected particles required is much smaller than that required for a transition by gas puffing. We thus show that internal injection is more efficient than gas puffing of comparable strength. We also observe that zonal flows do not play a critical role in stimulated transitions. For spontaneous transitions, the spike of the Reynolds work of turbulence on the zonal flow precedes the spike in the mean electric field shear. In contrast, we show that the two are coincident for stimulated transitions, suggesting that there is no causal link between zonal and mean flows for stimulated transitions.

  4. High-Frequency Stimulation of Excitable Cells and Networks

    PubMed Central

    Weinberg, Seth H.

    2013-01-01

    High-frequency (HF) stimulation has been shown to block conduction in excitable cells including neurons and cardiac myocytes. However, the precise mechanisms underlying conduction block are unclear. Using a multi-scale method, the influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation alters the amplitude and frequency of repetitive firing in response to a constant applied current and increases the threshold to evoke a single action potential in response to a brief applied current pulse. Further, the excitable cells cannot evoke a single action potential or fire repetitively above critical values for the HF stimulation amplitude. Analytical expressions for the critical values and thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley model, it is shown that HF stimulation alters the dynamics of ionic current gating, shifting the steady-state activation, inactivation, and time constant curves, suggesting several possible mechanisms for conduction block. Finally, we demonstrate that HF stimulation of a network of neurons reduces the electrical activity firing rate, increases network synchronization, and for a sufficiently large HF stimulation, leads to complete electrical quiescence. In this study, we demonstrate a novel approach to investigate HF stimulation in biophysically-detailed ionic models of excitable cells, demonstrate possible mechanisms for HF stimulation conduction block in neurons, and provide insight into the influence of HF stimulation on neural networks. PMID:24278435

  5. Frequency dependence of behavioral modulation by hippocampal electrical stimulation

    PubMed Central

    La Corte, Giorgio; Wei, Yina; Chernyy, Nick; Gluckman, Bruce J.

    2013-01-01

    Electrical stimulation offers the potential to develop novel strategies for the treatment of refractory medial temporal lobe epilepsy. In particular, direct electrical stimulation of the hippocampus presents the opportunity to modulate pathological dynamics at the ictal focus, although the neuroanatomical substrate of this region renders it susceptible to altering cognition and affective processing as a side effect. We investigated the effects of three electrical stimulation paradigms on separate groups of freely moving rats (sham, 8-Hz and 40-Hz sine-wave stimulation of the ventral/intermediate hippocampus, where 8- and 40-Hz stimulation were chosen to mimic naturally occurring hippocampal oscillations). Animals exhibited attenuated locomotor and exploratory activity upon stimulation at 40 Hz, but not at sham or 8-Hz stimulation. Such behavioral modifications were characterized by a significant reduction in rearing frequency, together with increased freezing behavior. Logistic regression analysis linked the observed changes in animal locomotion to 40-Hz electrical stimulation independently of time-related variables occurring during testing. Spectral analysis, conducted to monitor the electrophysiological profile in the CA1 area of the dorsal hippocampus, showed a significant reduction in peak theta frequency, together with reduced theta power in the 40-Hz vs. the sham stimulation animal group, independent of locomotion speed (theta range: 4–12 Hz). These findings contribute to the development of novel and safe medical protocols by indicating a strategy to constrain or optimize parameters in direct hippocampal electrical stimulation. PMID:24198322

  6. Aromatase inhibitors in stimulated IVF cycles

    PubMed Central

    2011-01-01

    Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels PMID:21693033

  7. Stimulated parametric emission microscopy

    NASA Astrophysics Data System (ADS)

    Isobe, Keisuke; Kataoka, Shogo; Murase, Rena; Watanabe, Wataru; Higashi, Tsunehito; Kawakami, Shigeki; Matsunaga, Sachihiro; Fukui, Kiichi; Itoh, Kazuyoshi

    2006-01-01

    We propose a novel microscopy technique based on the four-wave mixing (FWM) process that is enhanced by two-photon electronic resonance induced by a pump pulse along with stimulated emission induced by a dump pulse. A Ti:sapphire laser and an optical parametric oscillator are used as light sources for the pump and dump pulses, respectively. We demonstrate that our proposed FWM technique can be used to obtain a one-dimensional image of ethanol-thinned Coumarin 120 solution sandwiched between a hole-slide glass and a cover slip, and a two-dimensional image of a leaf of Camellia sinensis.

  8. Central nervous system stimulants.

    PubMed

    George, A J

    2000-03-01

    Three major types of CNS stimulant are currently abused in sport: amphetamine, cocaine and caffeine. Each drug type has its own characteristic mechanism of action on CNS neurones and their associated receptors and nerve terminals. Amphetamine is widely abused in sports requiring intense anaerobic exercise where it prolongs the tolerance to anaerobic metabolism. It is addictive, and chronic abuse causes marked behavioural change and sometimes psychosis. Major sports abusing amphetamine are cycling, American football, ice-hockey and baseball. Cocaine increases tolerance to intense exercise, yet most of its chronic effects on energy metabolism are negative. Its greatest effects seem to be as a central stimulant and the enhancement of short-term anaerobic exercise. It is highly addictive and can cause cerebral and cardiovascular fatalities. Caffeine enhances fatty acid metabolism leading to glucose conservation, which appears to benefit long-distance endurance events such as skiing. Caffeine is also addictive, and chronic abuse can lead to cardiac damage. Social abuse of each of the three drugs is often difficult to distinguish from their abuse in sport.

  9. Reducing Dropouts.

    ERIC Educational Resources Information Center

    Timpane, Michael; And Others

    A group of three conference papers, all addressing the subject of effective programs to decrease the number of school dropouts, is presented in this document. The first paper, "Systemic Approaches to Reducing Dropouts" (Michael Timpane), asserts that dropping out is a symptom of failures in the social, economic, and educational systems. Dropping…

  10. Temporal Prediction in lieu of Periodic Stimulation

    PubMed Central

    Schroeder, Charles E.; Wyart, Valentin

    2016-01-01

    Predicting not only what will happen, but also when it will happen is extremely helpful for optimizing perception and action. Temporal predictions driven by periodic stimulation increase perceptual sensitivity and reduce response latencies. At the neurophysiological level, a single mechanism has been proposed to mediate this twofold behavioral improvement: the rhythmic entrainment of slow cortical oscillations to the stimulation rate. However, temporal regularities can occur in aperiodic contexts, suggesting that temporal predictions per se may be dissociable from entrainment to periodic sensory streams. We investigated this possibility in two behavioral experiments, asking human participants to detect near-threshold auditory tones embedded in streams whose temporal and spectral properties were manipulated. While our findings confirm that periodic stimulation reduces response latencies, in agreement with the hypothesis of a stimulus-driven entrainment of neural excitability, they further reveal that this motor facilitation can be dissociated from the enhancement of auditory sensitivity. Perceptual sensitivity improvement is unaffected by the nature of temporal regularities (periodic vs aperiodic), but contingent on the co-occurrence of a fulfilled spectral prediction. Altogether, the dissociation between predictability and periodicity demonstrates that distinct mechanisms flexibly and synergistically operate to facilitate perception and action. SIGNIFICANCE STATEMENT Temporal predictions are increasingly recognized as fundamental instruments for optimizing performance, enabling mammals to exploit regularities in the world. However, the notion of temporal predictions is often confounded with the idea of entrainment to periodic sensory inputs. At the behavioral level, it is also unclear whether perceptual sensitivity and reaction time improvements benefit the same way from temporal predictions and periodic stimulation. In two behavioral experiments on human

  11. A linearized current stimulator for deep brain stimulation.

    PubMed

    Shen, Ding-Lan; Chu, Yu-Jung

    2010-01-01

    This paper develops the front end of the stimulator which is applied in the implantable deep brain stimulation (DBS) for the therapy of Parkinson's disease. This stimulator adopts the low power switched-capacitor DAC accompanying with voltage-to-current transconductance amplifiers to obtain the adjustable output currents. The proposed distortion cancellation technique improves the linearity of the current stimulator. Multiple transconductance amplifiers sharing a single DAC save the circuit area. The biphasic stimulation waveform is generated from the bridge switching technique and the programmable pulse. This stimulation circuit provides the 0 approximately 165 microA current for a typical loading of 10 kΩ, 8 approximately 120 micros pulse width, and 126 approximately 244 Hz frequencies with a 0.35 microm CMOS technology at 3.3 V supply voltage. PMID:21096724

  12. Engagement Sensitive Visual Stimulation.

    PubMed

    Kumar, Deepesh; Dutta, Anirban; Das, Abhijit; Lahiri, Uttama

    2016-06-13

    Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one's performance. PMID:27478569

  13. Stimulated radiative laser cooling

    NASA Astrophysics Data System (ADS)

    Muys, P.

    2008-04-01

    Building a refrigerator based on the conversion of heat into optical energy is an ongoing engineering challenge. Under well-defined conditions, spontaneous anti-Stokes fluorescence of a dopant material in a host matrix is capable of lowering the host temperature. The fluorescence is conveying away a part of the thermal energy stored in the vibrational oscillations of the host lattice. In particular, applying this principle to the cooling of (solid-state) lasers opens up many potential device applications, especially in the domain of high-power lasers. In this paper, an alternative optical cooling scheme is outlined, leading to the radiative cooling of solid-state lasers. It is based on converting the thermal energy stored in the host into optical energy by means of a stimulated nonlinear process, rather than a spontaneous process. This should lead to better cooling efficiencies and a higher potential of applying the principle for device applications.

  14. Myeloperoxidase Stimulates Neutrophil Degranulation.

    PubMed

    Grigorieva, D V; Gorudko, I V; Sokolov, A V; Kostevich, V A; Vasilyev, V B; Cherenkevich, S N; Panasenko, O M

    2016-08-01

    Myeloperoxidase, heme enzyme of azurophilic granules in neutrophils, is released into the extracellular space in the inflammation foci. In neutrophils, it stimulates a dose-dependent release of lactoferrin (a protein of specific granules), lysozyme (a protein of specific and azurophilic granules), and elastase (a protein of azurophilic granules). 4-Aminobenzoic acid hydrazide, a potent inhibitor of peroxidase activity of myeloperoxidase, produced no effect on neutrophil degranulation. Using signal transduction inhibitors (genistein, methoxyverapamil, wortmannin, and NiCl2), we demonstrated that myeloperoxidase-induced degranulation of neutrophils resulted from enzyme interaction with the plasma membrane and depends on activation of tyrosine kinases, phosphatidylinositol 3-kinases (PI3K), and calcium signaling. Myeloperoxidase modified by oxidative/halogenation stress (chlorinated and monomeric forms of the enzyme) lost the potency to activate neutrophil degranulation. PMID:27597056

  15. Engagement Sensitive Visual Stimulation

    PubMed Central

    Kumar, Deepesh; Dutta, Anirban; Das, Abhijit; Lahiri, Uttama

    2016-01-01

    Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one’s performance. PMID:27478569

  16. Advanced waveforms and frequency with spinal cord stimulation: burst and high-frequency energy delivery.

    PubMed

    Pope, Jason E; Falowski, Steven; Deer, Tim R

    2015-07-01

    In recent years, software development has been key to the next generation of neuromodulation devices. In this review, we will describe the new strategies for electrical waveform delivery for spinal cord stimulation. A systematic literature review was performed using bibliographic databases, limited to the English language and human data, between 2010 and 2014. The literature search yielded three articles on burst stimulation and four articles on high-frequency stimulation. High-frequency and burst stimulation may offer advantages over tonic stimulation, as data suggest improved patient tolerance, comparable increase in function and possible success with a subset of patients refractory to tonic spinal cord stimulation. High-frequency and burst stimulation are new ways to deliver energy to the spinal cord that may offer advantages over tonic stimulation. These may offer new salvage strategies to mitigate spinal cord stimulation failure and improve cost-effectiveness by reducing explant rate.

  17. Electrical Stimulation for Drug-Resistant Epilepsy

    PubMed Central

    Chambers, A; Bowen, JM

    2013-01-01

    Objective The objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children. Data Sources A literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012. Review Methods Systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed. Results The search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children. Limitations We found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance. Conclusions Based on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as

  18. Spiral scan peripheral nerve stimulation.

    PubMed

    King, K F; Schaefer, D J

    2000-07-01

    Time-varying magnetic fields induce electric fields that can cause physiological stimulation. Stimulation has been empirically characterized as a function of dB/dt and duration based on experiments using trapezoidal and sinusoidal gradient waveforms with constant ramp time, amplitude, and direction. For two-dimensional (2D) spiral scans, the readout gradient waveforms are frequency- and amplitude-modulated sinusoids on two orthogonal axes in quadrature. The readout gradient waveform therefore rotates with amplitude and angular velocity that are generally not constant. It does not automatically follow that spiral stimulation thresholds can be predicted using available stimulation models. We scanned 18 normal volunteers with a 2D spiral scan and measured global thresholds for axial, sagittal, and coronal planes. We concluded that the stimulation model evaluated accurately predicts slew rate-limited spiral mean stimulation thresholds, if the effective ramp time is chosen to be the half-period at the end of the spiral readout.

  19. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

    PubMed Central

    Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

    2014-01-01

    Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

  20. Hydromechanical stimulation of bioluminescent plankton.

    PubMed

    Blaser, Stefan; Kurisu, Futoshi; Satoh, Hiroyasu; Mino, Takashi

    2002-01-01

    The response of the bioluminescent dinoflagellate Pyrocystis fusiformis was investigated for different hydraulic conditions ('hydromechanical stimulation'). Pipe flow and oscillating shear produced luminescence, whereas changes in hydrostatic pressure were not stimulating. More intense fluid motion led to higher intensity, mainly due to a higher probability of cell response. The organism was also able to emit light in a glucose-salt mixture. The experiments suggest that the cells are effectively stimulated if the flow conditions change in time.

  1. Optically stimulated differential impedance spectroscopy

    DOEpatents

    Maxey, Lonnie C; Parks, II, James E; Lewis, Sr., Samuel A; Partridge, Jr., William P

    2014-02-18

    Methods and apparatuses for evaluating a material are described. Embodiments typically involve use of an impedance measurement sensor to measure the impedance of a sample of the material under at least two different states of illumination. The states of illumination may include (a) substantially no optical stimulation, (b) substantial optical stimulation, (c) optical stimulation at a first wavelength of light, (d) optical stimulation at a second wavelength of light, (e) a first level of light intensity, and (f) a second level of light intensity. Typically a difference in impedance between the impedance of the sample at the two states of illumination is measured to determine a characteristic of the material.

  2. Electrical stimulation: a societal perspective.

    PubMed

    Gater, D R; McDowell, S M; Abbas, J J

    2000-01-01

    Societal perspective on functional electrical stimulation is colored by media influence, popular thought, and political climate as much as by the science that supports it. The purpose of this article is to examine how these influences facilitate or inhibit the application of electrical stimulation in today's world and to describe the challenges facing the use of electrical stimulation in the future. Emphasis will be placed on perceived need, cost, and available resources and how these factors must be addressed to utilize functional electrical stimulation successfully in society.

  3. Boosting brain excitability by transcranial high frequency stimulation in the ripple range

    PubMed Central

    Moliadze, Vera; Antal, Andrea; Paulus, Walter

    2010-01-01

    Alleviating the symptoms of neurological diseases by increasing cortical excitability through transcranial stimulation is an ongoing scientific challenge. Here, we tackle this issue by interfering with high frequency oscillations (80–250 Hz) via external application of transcranial alternating current stimulation (tACS) over the human motor cortex (M1). Twenty-one subjects participated in three different experimental studies and they received on separate days tACS at three frequencies (80 Hz, 140 Hz and 250 Hz) and sham stimulation in a randomized order. tACS with 140 Hz frequency increased M1 excitability as measured by transcranial magnetic stimulation-generated motor evoked potentials (MEPs) during and for up to 1 h after stimulation. Control experiments with sham and 80 Hz stimulation were without any effect, and 250 Hz stimulation was less efficient with a delayed excitability induction and reduced duration. After-effects elicited by 140 Hz stimulation were robust against inversion of test MEP amplitudes seen normally under activation. Stimulation at 140 Hz reduced short interval intracortical inhibition, but left intracortical facilitation, long interval cortical inhibition and cortical silent period unchanged. Implicit motor learning was not facilitated by 140 Hz stimulation. High frequency stimulation in the ripple range is a new promising non-invasive brain stimulation protocol to increase human cortical excitability during and after the end of stimulation. PMID:20962008

  4. Boosting brain excitability by transcranial high frequency stimulation in the ripple range.

    PubMed

    Moliadze, Vera; Antal, Andrea; Paulus, Walter

    2010-12-15

    Alleviating the symptoms of neurological diseases by increasing cortical excitability through transcranial stimulation is an ongoing scientific challenge. Here, we tackle this issue by interfering with high frequency oscillations (80–250 Hz) via external application of transcranial alternating current stimulation (tACS) over the human motor cortex (M1). Twenty-one subjects participated in three different experimental studies and they received on separate days tACS at three frequencies (80 Hz, 140 Hz and 250 Hz) and sham stimulation in a randomized order. tACS with 140 Hz frequency increased M1 excitability as measured by transcranial magnetic stimulation-generated motor evoked potentials (MEPs) during and for up to 1 h after stimulation. Control experiments with sham and 80 Hz stimulation were without any effect, and 250 Hz stimulation was less efficient with a delayed excitability induction and reduced duration. After-effects elicited by 140 Hz stimulation were robust against inversion of test MEP amplitudes seen normally under activation. Stimulation at 140 Hz reduced short interval intracortical inhibition, but left intracortical facilitation, long interval cortical inhibition and cortical silent period unchanged. Implicit motor learning was not facilitated by 140 Hz stimulation. High frequency stimulation in the ripple range is a new promising non-invasive brain stimulation protocol to increase human cortical excitability during and after the end of stimulation.

  5. Temporal Prediction in lieu of Periodic Stimulation.

    PubMed

    Morillon, Benjamin; Schroeder, Charles E; Wyart, Valentin; Arnal, Luc H

    2016-02-24

    Predicting not only what will happen, but also when it will happen is extremely helpful for optimizing perception and action. Temporal predictions driven by periodic stimulation increase perceptual sensitivity and reduce response latencies. At the neurophysiological level, a single mechanism has been proposed to mediate this twofold behavioral improvement: the rhythmic entrainment of slow cortical oscillations to the stimulation rate. However, temporal regularities can occur in aperiodic contexts, suggesting that temporal predictions per se may be dissociable from entrainment to periodic sensory streams. We investigated this possibility in two behavioral experiments, asking human participants to detect near-threshold auditory tones embedded in streams whose temporal and spectral properties were manipulated. While our findings confirm that periodic stimulation reduces response latencies, in agreement with the hypothesis of a stimulus-driven entrainment of neural excitability, they further reveal that this motor facilitation can be dissociated from the enhancement of auditory sensitivity. Perceptual sensitivity improvement is unaffected by the nature of temporal regularities (periodic vs aperiodic), but contingent on the co-occurrence of a fulfilled spectral prediction. Altogether, the dissociation between predictability and periodicity demonstrates that distinct mechanisms flexibly and synergistically operate to facilitate perception and action. PMID:26911682

  6. [Subcutaneous stimulation as additional therapy to spinal cord stimulation in a post-laminectomy syndrome patient].

    PubMed

    Akbaş, Mert; Yeğin, Mehmet Arif; Özdemir, İrem; Göksu, Ethem; Akyüz, Mahmut

    2016-01-01

    Spinal cord stimulation as treatment of chronic low back pain via neuromodulation has been frequently performed in recent years. The dorsal column is stimulated by an electrode placed at the epidural region. In the case presently described, subcutaneous lead was implanted in a patient with failed back syndrome after spinal cord stimulation was inadequate to treat back and gluteal pain. A 65-year-old male had undergone surgery to treat lumbar disc herniation, after which he received physical therapy and multiple steroid injections due to unrelieved pain. He was admitted to the pain clinic with pain radiating to right gluteal muscle and leg. Spinal cord stimulation was performed and, as pain was not relieved, subcutaneous lead was applied to the right cluneal nerve distribution. Following treatment, the patient scored 1-2 on visual analog scale. Pain had been reduced by over 80%. Octad electrode was placed between T8 and T10 vertebrae after Tuohy needle was introduced to intervertebral area between L1 and L2. Paresthesia occurred in the right extremity. Boundaries were determined by area of right gluteal region in which paresthesia did not occur. Octad electrode was placed subcutaneously after vertical line was drawn from center point. Paresthesia occurred throughout the region. Pulse wave was 390-450 msec; frequency was 10-30 Hz. Subcutaneous electrode replacement is effective additional therapy when pain is not relieved by spinal cord stimulation. PMID:27225614

  7. Introduction to the programming of deep brain stimulators.

    PubMed

    Volkmann, Jens; Herzog, Jan; Kopper, Florian; Deuschl, Güntner

    2002-01-01

    The clinical success of deep brain stimulation (DBS) for treating Parkinson's disease, tremor, or dystonia critically depends on the quality of postoperative neurologic management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to optimally adapt stimulation parameters and medication after implantation of a DBS system. In clinical practice, the infinite number of possible parameter settings in DBS can be reduced to few relevant combinations. In this article, the authors describe a general scheme of selecting stimulation parameters in DBS and provide clinical and neurophysiological arguments for such a standardized algorithm. They also describe noninvasive technical trouble shooting by using programming features of the commercially available neurostimulation devices.

  8. Effects of stimulant medication under varied motivational operations.

    PubMed

    Mace, F Charles; Prager, Kevin L; Thomas, Karen; Kochy, Jane; Dyer, Tim J; Perry, Lora; Pritchard, Duncan

    2009-01-01

    We evaluated the evocative effects of four conditions (high- and low-preference activities, low and divided attention) and stimulant medication on the behavior of a 16-year-old boy with attention deficit hyperactivity disorder and moderate mental retardation. All behavior (activity engagement, activity changes, inappropriate touching, rude behaviors, and physical aggression) improved with stimulant medication in most conditions, but undesirable behaviors were not reduced to acceptable levels in all conditions. This finding suggests that stimulant medication may be a valuable adjunct to function-based interventions. PMID:19721739

  9. Atomic oxygen stimulated outgassing

    NASA Technical Reports Server (NTRS)

    Linton, Roger C.; Reynolds, John M.

    1991-01-01

    The passive Long Duration Exposure Facility (LDEF) Experiment A0034, Atomic Oxygen Simulated Outgassing, consisted of two identical one-sixth tray modules, exposing selected thermal control coatings to atomic oxygen and the combined space environment on the leading edge and, for reference, to the relative wake environment on the trailing edge. Optical mirrors were included adjacent to the thermal coatings for deposition of outgassing products. Ultraviolet grade windows and metal covers were provided for additional assessment of the effects of the various environmental factors. Preliminary results indicate that orbital atomic oxygen is both a degrading and a optically restorative factor in the thermo-optical properties of selected thermal coatings. There is evidence of more severe optical degradation on collector mirrors adjacent to coatings that were exposed to the RAM-impinging atomic oxygen. This evidence of atomic oxygen stimulated outgassing is discussed in relation to alternative factors that could affect degradation. The general effects of the space environment on the experiment hardware as well as the specimens are discussed.

  10. EOR by stimulated microflora

    SciTech Connect

    Svarovskaya, L.I.; Altunina, L.K.; Rozhenkova, Z.A.; Bulavin, V.D.

    1995-12-31

    A combined microbiological and physico-chemical method for EOR has been developed for flooded West Siberia oil fields with formation temperature of 45{degrees}-95{degrees}C (318-365K). Formation water includes rich and various biocenoses numbering up to 2 x 10{sup 7} cells per ml. Representatives of genera, i.e, Pseudomonas, Bacillus, Actinomyces, Micrococcus, Mycobacterium, Sarcina, etc. were found to be the most widely distributed microorganisms. The method is based on injection of systems exhibiting high oil displacing capacity and at the same time being an additional nitrous nutrient for endemic populations of microorganisms. Their injection into formation water favors biomass growth by 4-6 orders and promotes syntheses of biosurfactants, biopolymers, acids, etc., and gaseous products. The features of residual oil displacement have been studied on laboratory models using a combined microbiological and physico-chemical method. A curve for the yield of residual oil is presented by two peaks. The first peak is stipulated by the washing action of oil displacement system, and the second one by the effect of metabolites produced at stimulation of biogenic processes. Oil displacement index increases by 15%-30%.

  11. Subliminal Stimulation: Hoax or Reality?

    ERIC Educational Resources Information Center

    Trank, Douglas M.

    Subliminal stimulation is defined as that which is perceived by an individual below the threshold of awareness or cognizance. This article traces the history of research in subliminal stimulation to illustrate that under certain circumstances and conditions, this behavioral phenomenon does occur. Although subliminal stimuli do affect human…

  12. Stimulating Language: Insights from TMS

    ERIC Educational Resources Information Center

    Devlin, Joseph T.; Watkins, Kate E.

    2007-01-01

    Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These…

  13. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas.

    PubMed

    van Dijk, A; Klanker, M; van Oorschot, N; Post, R; Hamelink, R; Feenstra, M G P; Denys, D

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  14. Nanomaterial-Enabled Neural Stimulation.

    PubMed

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  15. Nanomaterial-Enabled Neural Stimulation

    PubMed Central

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

  16. Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

    PubMed

    Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

    2015-02-01

    The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas.

  17. Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

    PubMed Central

    Kember, Guy; Ardell, Jeffrey L.; Armour, John A.; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity. PMID:25479368

  18. Gait ataxia in essential tremor is differentially modulated by thalamic stimulation.

    PubMed

    Fasano, Alfonso; Herzog, Jan; Raethjen, Jan; Rose, Franziska E M; Muthuraman, Muthuraman; Volkmann, Jens; Falk, Daniela; Elble, Rodger; Deuschl, Günther

    2010-12-01

    Patients with advanced stages of essential tremor frequently exhibit tandem gait ataxia with impaired balance control and imprecise foot placement, resembling patients with a cerebellar deficit. Thalamic deep brain stimulation, a surgical therapy for otherwise intractable cases, has been shown to improve tremor, but its impact on cerebellar-like gait difficulties remains to be elucidated. Eleven patients affected by essential tremor (five females; age 69.8 ± 3.9 years; disease duration 24.4 ± 11.2 years; follow-up after surgery 24.7 ± 20.3 months) were evaluated during the following conditions: stimulation off, stimulation on and supra-therapeutic stimulation. Ten age-matched healthy controls served as the comparison group. Locomotion by patients and controls was assessed with (i) overground gait and tandem gait; (ii) balance-assisted treadmill tandem gait and (iii) unassisted treadmill gait. The two treadmill paradigms were kinematically analysed using a 3D opto-electronic motion analysis system. Established clinical and kinesiological measures of ataxia were computed. During stimulation off, the patients exhibited ataxia in all assessment paradigms, which improved during stimulation on and worsened again during supra-therapeutic stimulation. During over ground tandem gait, patients had more missteps and slower gait velocities during stimulation off and supra-therapeutic stimulation than during stimulation on. During balance-assisted tandem gait, stimulation on reduced the temporospatial variability in foot trajectories to nearly normal values, while highly variable (ataxic) foot trajectories were observed during stimulation off and supra-therapeutic stimulation. During unassisted treadmill gait, stimulation on improved gait stability compared with stimulation off and supra-therapeutic stimulation, as demonstrated by increased gait velocity and ankle rotation. These improvements in ataxia were not a function of reduced tremor in the lower limbs or torso. In

  19. Electrical stimulation in exercise training

    NASA Technical Reports Server (NTRS)

    Kroll, Walter

    1994-01-01

    Electrical stimulation has a long history of use in medicine dating back to 46 A.D. when the Roman physician Largus found the electrical discharge of torpedo fishes useful in the treatment of pain produced by headache and gout. A rival Greek physician, Dioscorides, discounted the value of the torpedo fish for headache relief but did recommend its use in the treatment of hemorrhoids. In 1745, the Leyden jar and various sized electrostatic generators were used to treat angina pectoris, epilepsy, hemiplegia, kidney stones, and sciatica. Benjamin Franklin used an electrical device to treat successfully a young woman suffering from convulsive fits. In the late 1800's battery powered hydroelectric baths were used to treat chronic inflammation of the uterus while electrified athletic supporters were advertised for the treatment of male problems. Fortunately, such an amusing early history of the simple beginnings of electrical stimulation did not prevent eventual development of a variety of useful therapeutic and rehabilitative applications of electrical stimulation. Over the centuries electrical stimulation has survived as a modality in the treatment of various medical disorders with its primary application being in the rehabilitation area. Recently, a surge of new interest in electrical stimulation has been kindled by the work of a Russian sport scientist who reported remarkable muscle strength and endurance improvements in elite athletes. Yakov Kots reported his research on electric stimulation and strength improvements in 1977 at a Canadian-Soviet Exchange Symposium held at Concordia University in Montreal. Since then an explosion of new studies has been seen in both sport science and in medicine. Based upon the reported works of Kots and the present surge of new investigations, one could be misled as to the origin of electrical stimulation as a technique to increase muscle strength. As a matter of fact, electric stimulation has been used as a technique to improve

  20. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, J.W.

    1995-05-09

    A device is described for stimulating bone tissue by applying a low level alternating current signal directly to the patient`s skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures. 5 figs.

  1. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, James W.

    1995-01-01

    A device for stimulating bone tissue by applying a low level alternating current signal directly to the patient's skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures.

  2. Caloric vestibular stimulation modulates nociceptive evoked potentials.

    PubMed

    Ferrè, Elisa Raffaella; Haggard, Patrick; Bottini, Gabriella; Iannetti, Gian Domenico

    2015-12-01

    Vestibular stimulation has been reported to alleviate central pain. Clinical and physiological studies confirm pervasive interactions between vestibular signals and somatosensory circuits, including nociception. However, the neural mechanisms underlying vestibular-induced analgesia remain unclear, and previous clinical studies cannot rule out explanations based on alternative, non-specific effects such as distraction or placebo. To investigate how vestibular inputs influence nociception, we combined caloric vestibular stimulation (CVS) with psychophysical and electrocortical responses elicited by nociceptive-specific laser stimulation in humans (laser-evoked potentials, LEPs). Cold water CVS applied to the left ear resulted in significantly lower subjective pain intensity for experimental laser pain to the left hand immediately after CVS, relative both to before CVS and to 1 h after CVS. This transient reduction in pain perception was associated with reduced amplitude of all LEP components, including the early N1 wave reflecting the first arrival of nociceptive input to primary somatosensory cortex. We conclude that cold left ear CVS elicits a modulation of both nociceptive processing and pain perception. The analgesic effect induced by CVS could be mediated either by subcortical gating of the ascending nociceptive input, or by direct modulation of the primary somatosensory cortex.

  3. Magnetically stimulated fluid flow patterns

    ScienceCinema

    Martin, Jim; Solis, Kyle

    2016-07-12

    Sandia National Laboratories' Jim Martin and Kyle Solis explain research on the effects of magnetic fields on fluid flows and how they stimulate vigorous flows. Fluid flow is a necessary phenomenon in everything from reactors to cooling engines in cars.

  4. Demultiplexer circuit for neural stimulation

    DOEpatents

    Wessendorf, Kurt O; Okandan, Murat; Pearson, Sean

    2012-10-09

    A demultiplexer circuit is disclosed which can be used with a conventional neural stimulator to extend the number of electrodes which can be activated. The demultiplexer circuit, which is formed on a semiconductor substrate containing a power supply that provides all the dc electrical power for operation of the circuit, includes digital latches that receive and store addressing information from the neural stimulator one bit at a time. This addressing information is used to program one or more 1:2.sup.N demultiplexers in the demultiplexer circuit which then route neural stimulation signals from the neural stimulator to an electrode array which is connected to the outputs of the 1:2.sup.N demultiplexer. The demultiplexer circuit allows the number of individual electrodes in the electrode array to be increased by a factor of 2.sup.N with N generally being in a range of 2-4.

  5. Magnetically stimulated fluid flow patterns

    SciTech Connect

    Martin, Jim; Solis, Kyle

    2014-03-06

    Sandia National Laboratories' Jim Martin and Kyle Solis explain research on the effects of magnetic fields on fluid flows and how they stimulate vigorous flows. Fluid flow is a necessary phenomenon in everything from reactors to cooling engines in cars.

  6. Evoked response to taste stimulations.

    PubMed

    Wada, Masashi

    2005-01-01

    For the recording of gustatory evoked responses, the tip of a stimulator is pressed vertically on one side of the tongue until the trigger pulses are generated by a switch attached to the bottom of the stimulator. According to our results, no detectable response was observed in the absence of taste. The positive waves were distinguishable by using the technique of superimposition before averaging, and the positive wave was made clearer by averaging.

  7. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    The following are included: review of available data from previous fracturing stimulation operations, stimulation process variables, fracturing fluid design, hydraulic fracture design, stimulation case histories, and selected bibliography. (MHR)

  8. Anti-kindling Induced by Two-Stage Coordinated Reset Stimulation with Weak Onset Intensity

    PubMed Central

    Zeitler, Magteld; Tass, Peter A.

    2016-01-01

    Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR) stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing–dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e., unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies. PMID:27242500

  9. Electrical stimulation of mechanoreceptors

    NASA Astrophysics Data System (ADS)

    Echenique, A. M.; Graffigna, J. P.

    2011-12-01

    Within the field of Rehabilitation Engineering, this work is aimed at identifying the optimal parameters of electric current stimulus which activate the nervous axons of mecanoreceptors found in the fingertip, allowing, this way, to resemble tactile senses. These sensorial feelings can be used by aiding technological means, namely, the sensorial substitution technology, in an attempt to render information to blind people through the tactile sense. The physical pressure on sensorial areas (fingertips) used for reading activities through the Braille System is the main effect that is imitated and studied in this research work. An experimental aiding prototype for Braille reading research has been developed and tested with blinds and reduced vision people, with highly satisfactory results.

  10. 3D-printed wearable backpack stimulator for chronic in vivo aquatic stimulation.

    PubMed

    Unguez, Graciela; Duran, Craig; Valles-Rosales, Delia; Harris, Michael; Salazar, Evan; McDowell, Michael; Tang, Wei

    2015-08-01

    The neural mechanisms underlying changes in gene expression in the interconversion between skeletal muscle and the non-contractile electrogenic cells of the electric organ in electric fishes require several days to be manifested. It is extremely challenging to study these non-immediate forms of plasticity in reduced preparations in cell culture due to the time requirements. To address this experimental obstacle we developed a 3D-printed wearable backpack that allows chronic electrical stimulation of aquatic teleost fish. The backpack holds a biphasic simulator using a full H-bridge driver structure. Stimulation amplitude is adjusted with a current source controlled by a micro potentiometer whereas the stimulation waveform is reconfigurable through a micro-controller. A 3.7 V Lithium Ion Polymer battery powers the entire circuit. This backpack system will allow underwater chronic stimulation experiments aimed to study the role that neuronal input exerts on cell phenotypes in a vertebrate species with high tissue regeneration and cell trans-differentiation capabilities. PMID:26736714

  11. 95 stimulations in 63 wells

    SciTech Connect

    Horton, A.I.

    1982-02-01

    Since 1976, extensive studies on the nature of the Eastern gas shales and the production potential from stimulated shale wells have been conducted through joint efforts of industry and the Department of Energy (DOE). Prior to development of this project, the conventional method of stimulating the shales was borehole shooting, and conventional hydraulic fracturing of the shale was just beginning. DOE-industry investigations under the Eastern Gas Shales Project have experimented with other types of stimulations, including massive hydraulic fracturing, foam fracturing, cryogenic fracturing, chemical explosives, and novel treatments. Two of the latter have used (1) nitrogen and (2) oil assisted with nitrogen. Two other treatments, which were unsuccessful, were (1) an open hole packer-stage frac and (2) a kerosene frac. These were operational and conceptual failures. Details of the stimulations and production data, where available, have been complied and studied. The experience that has been gained may prove helpful to those considering stimulation technology in future well drilling ventures in the shale. However, the limited data available in regions of similar geologic factors preclude a thorough analysis of stimulation effectiveness.

  12. Brain Stimulation for Torsion Dystonia

    PubMed Central

    Fox, Michael D.; Alterman, Ron L.

    2016-01-01

    Dystonia is a heterogeneous neurological disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly utilized. Here we review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation. Strong (level B) evidence supports the use of deep brain stimulation (DBS) for the treatment of primary generalized or segmental dystonia, especially DYT-1, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer’s cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson’s disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques including epidural cortical stimulation and noninvasive brain stimulation have been investigated, but generally report smaller effect sizes in a more limited number of patients. Recent advances relevant to patient selection, surgical approach, DBS programming, and mechanism of action are discussed. PMID:25894231

  13. Theoretical investigation on the pumping effect of stimulated Brillouin scattering on stimulated Raman scattering in water

    NASA Astrophysics Data System (ADS)

    Shi, J.; Chen, X.; Ouyang, M.; Gong, W.; Su, Y.; Liu, D.

    2012-02-01

    The pumping effect of stimulated Brillouin scattering on stimulated Raman scattering is investigated theoretically through the coupled wave equations of stimulated Brillouin scattering and stimulated Raman scattering. The numerical simulations are in agreement with the experimental results. They indicate that the backward stimulated Raman scattering is excited and amplified collectively by both pump laser and stimulated Brillouin scattering.

  14. Emerging neural stimulation technologies for bladder dysfunctions.

    PubMed

    Lee, Jee Woong; Kim, Daejeong; Yoo, Sangjin; Lee, Hyungsup; Lee, Gu-Haeng; Nam, Yoonkey

    2015-03-01

    In the neural engineering field, physiological dysfunctions are approached by identifying the target nerves and providing artificial stimulation to restore the function. Neural stimulation and recording technologies play a central role in this approach, and various engineering devices and stimulation techniques have become available to the medical community. For bladder control problems, electrical stimulation has been used as one of the treatments, while only a few emerging neurotechnologies have been used to tackle these problems. In this review, we introduce some recent developments in neural stimulation technologies including microelectrode array, closed-loop neural stimulation, optical stimulation, and ultrasound stimulation.

  15. Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.

    2003-01-01

    Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

  16. High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low-responder patients for in vitro fertilization.

    PubMed

    Hofmann, G E; Toner, J P; Muasher, S J; Jones, G S

    1989-10-01

    Follicle-stimulating hormone (FSH) was used in high doses (6 ampoules/day:6FSH) for ovarian hyperstimulation for in vitro fertilization in women with a previous poor response to stimulation with the equivalent of "4FSH." Luteinizing hormone levels did not differ between stimulations, but both FSH and estradiol levels were higher in the 6FSH compared to the 4FSH cycle. There were fewer cancellations in the 6FSH cycle, but similar numbers of preovulatory oocytes were retrieved, fertilized, and transferred. The pregnancy rates per attempt and retrieval were higher in the 6FSH cycle. We conclude that raising and maintaining FSH levels during stimulation in low responders reduced cancellations and may improve in vitro fertilization outcome.

  17. Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

    PubMed Central

    Calatayud, S; Warner, T D; Mitchell, J A

    2002-01-01

    Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1β and TNF-α). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action. British Journal of Cancer (2002) 86, 1316–1321. DOI: 10.1038/sj/bjc/6600240 www.bjcancer.com © 2002 Cancer Research UK PMID:11953891

  18. Luminescent solar concentrator improvement by stimulated emission

    NASA Astrophysics Data System (ADS)

    Kaysir, Md Rejvi; Fleming, Simon; MacQueen, Rowan W.; Schmidt, Timothy W.; Argyros, Alexander

    2015-12-01

    Luminescent solar concentrators (LSCs) offer the prospect of reducing the cost of solar energy, and are a promising candidate for building integrated photovoltaic (PV) structures. However, the realization of commercially viable efficiency of LSCs is currently hindered by reabsorption losses. In this work, a method is introduced for reducing reabsorption as well as improving directional emission in LSCs by using stimulated emission. Light from a seed laser (potentially an inexpensive laser diode) passes through the entire length of the LSC panel, modifying the emission spectrum of excited dye molecules such that it is spectrally narrower, at wavelengths that minimize reabsorption, and directed by the seed laser towards a small target PV cell. A mathematical model of such a system is presented which identifies different physical parameters responsible for the power conversion efficiency and gives the net effective output power.

  19. Luminescent solar concentrators utilizing stimulated emission.

    PubMed

    Kaysir, Md Rejvi; Fleming, Simon; MacQueen, Rowan W; Schmidt, Timothy W; Argyros, Alexander

    2016-03-21

    Luminescent solar concentrators (LSCs) are an emerging technology that aims primarily to reduce the cost of solar energy, with great potential for building integrated photovoltaic (PV) structures. However, realizing LSCs with commercially viable efficiency is currently hindered by reabsorption losses. Here, we introduce an approach to reducing reabsorption as well as improving directional emission in LSCs by using stimulated emission. Light from a seed laser (potentially an inexpensive laser diode) passes through the entire area of the LSC panel, modifying the emission spectrum of excited dye molecules such that it is spectrally narrower, at wavelengths that minimize reabsorption to allow net gain in the system, and directed towards a small PV cell. A mathematical model, taking into account thermodynamic considerations, of such a system is presented which identifies key parameters and allows evaluation in terms of net effective output power. PMID:27136870

  20. Luminescent solar concentrators utilizing stimulated emission.

    PubMed

    Kaysir, Md Rejvi; Fleming, Simon; MacQueen, Rowan W; Schmidt, Timothy W; Argyros, Alexander

    2016-03-21

    Luminescent solar concentrators (LSCs) are an emerging technology that aims primarily to reduce the cost of solar energy, with great potential for building integrated photovoltaic (PV) structures. However, realizing LSCs with commercially viable efficiency is currently hindered by reabsorption losses. Here, we introduce an approach to reducing reabsorption as well as improving directional emission in LSCs by using stimulated emission. Light from a seed laser (potentially an inexpensive laser diode) passes through the entire area of the LSC panel, modifying the emission spectrum of excited dye molecules such that it is spectrally narrower, at wavelengths that minimize reabsorption to allow net gain in the system, and directed towards a small PV cell. A mathematical model, taking into account thermodynamic considerations, of such a system is presented which identifies key parameters and allows evaluation in terms of net effective output power.

  1. Cardiac electrophysiological effects of selective adrenoceptor stimulation and their possible roles in arrhythmias.

    PubMed

    Vaughan Williams, E M

    1985-01-01

    The selective alpha 1- and alpha 2-adrenoceptor agonists St 587 and BHT 933, respectively, and the antagonists prazosin (alpha 1) and WY 25309 (alpha 2) have been used in combination with the selective beta 2-adrenoceptor agonist pirbuterol, and the antagonists atenolol (beta 1) and ICI 118551 (beta 2), to analyse the effects of individual types of adrenoceptor stimulation in various parts of the rabbit heart. In the sinus node, beta 1-, but not beta 2-adrenoceptor stimulation increased the fast phase of depolarisation. Both beta 1- and beta 2-adrenoceptor stimulation increased the slope of the slow diastolic depolarisation, accelerated repolarisation, and increased maximum diastolic potential. Beta 1- and beta 2-adrenoceptor stimulation also accelerated repolarisation in Purkinje cells and papillary muscle. After blockade of both beta 1- and beta 2-adrenoceptors, alpha 1-adrenoceptor stimulation caused bradycardia, owing exclusively to delayed repolarisation. Alpha 2-adrenoceptor stimulation had no effect. Beta 1-, but not beta 2-adrenoceptor stimulation augmented peak contractions three- to fivefold, and reduced the time-to-peak tension. In contrast, alpha 1-adrenoceptor stimulation only moderately (up to 47%) increased peak tension, but increased time-to-peak and duration of contractions. The results would be consistent with beta 1-adrenoceptor stimulation increasing inward calcium current, and with stimulation of alpha 1-adrenoceptors delaying the decline of [Ca]i rather than increasing its magnitude. Both beta 1- and beta 2-stimulation increased repolarising current, but alpha 1-stimulation decreased it.

  2. Rapid assessment of gait and speech after subthalamic deep brain stimulation

    PubMed Central

    Farris, Sierra M.; Giroux, Monique L.

    2016-01-01

    Background: Describe a rapid assessment for patients with idiopathic Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus reporting worsening speech and/or gait problems. Methods: We retrospectively reviewed 29 patients that had improvement in gait and/or speech within 30 min after turning stimulation off. Clinical data analyzed include unified PD rating scale motor scores and stimulation parameters before and after adjusting stimulation. All patients received electrode efficacy and side effect threshold testing. Stimulation parameters were adjusted to maximize efficacy, avoid side effects, and maximize battery longevity. Results: Turning stimulation off revealed reversible speech and/or gait stimulation side effects within 30 min. Focusing on six factors revealed stimulation modifications that improved motor symptoms, eliminated stimulation side effects, and reduced battery drain. Primary stimulation parameters modified were cathode selection and pulse width reduction. Conclusions: Stimulation-induced side effects impacting gait and speech can be identified within 30 min. A systematic evaluation can distinguish disease progression from reversible stimulation side effects and improve motor outcomes over the long term. PMID:27583181

  3. Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study

    PubMed Central

    Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R.

    2016-01-01

    Background A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Methods Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Results Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. Conclusion The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. PMID:26508284

  4. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants.

    PubMed

    Weyandt, Lisa L; Oster, Danielle R; Marraccini, Marisa E; Gudmundsdottir, Bergljot Gyda; Munro, Bailey A; Zavras, Brynheld Martinez; Kuhar, Ben

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%-4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and characteristics such as sex, race, use of illicit drugs, and academic performance are associated with misuse of stimulant medications. Results also indicate that individuals both with and without ADHD are more likely to misuse short-acting agents

  5. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants

    PubMed Central

    Weyandt, Lisa L; Oster, Danielle R; Marraccini, Marisa E; Gudmundsdottir, Bergljot Gyda; Munro, Bailey A; Zavras, Brynheld Martinez; Kuhar, Ben

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%–4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and characteristics such as sex, race, use of illicit drugs, and academic performance are associated with misuse of stimulant medications. Results also indicate that individuals both with and without ADHD are more likely to misuse short-acting agents

  6. Effect of current focusing on the sensitivity of inferior colliculus neurons to amplitude-modulated stimulation.

    PubMed

    George, Shefin S; Shivdasani, Mohit N; Fallon, James B

    2016-09-01

    In multichannel cochlear implants (CIs), current is delivered to specific electrodes along the cochlea in the form of amplitude-modulated pulse trains, to convey temporal and spectral cues. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation and reduced channel interactions in the inferior colliculus (IC) compared with traditional monopolar (MP) stimulation, suggesting that focusing of stimulation could produce better transmission of spectral information. The present study explored the capability of IC neurons to detect modulated CI stimulation with FMP and TP stimulation compared with MP stimulation. The study examined multiunit responses of IC neurons in acutely deafened guinea pigs by systematically varying the stimulation configuration, modulation depth, and stimulation level. Stimuli were sinusoidal amplitude-modulated pulse trains (carrier rate of 120 pulses/s). Modulation sensitivity was quantified by measuring modulation detection thresholds (MDTs), defined as the lowest modulation depth required to differentiate the response of a modulated stimulus from an unmodulated one. Whereas MP stimulation showed significantly lower MDTs than FMP and TP stimulation (P values <0.05) at stimulation ≤2 dB above threshold, all stimulation configurations were found to have similar modulation sensitivities at 4 dB above threshold. There was no difference found in modulation sensitivity between FMP and TP stimulation. The present study demonstrates that current focusing techniques such as FMP and TP can adequately convey amplitude modulation and are comparable to MP stimulation, especially at higher stimulation levels, although there may be some trade-off between spectral and temporal fidelity with current focusing stimulation. PMID:27306672

  7. Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

    2015-06-01

    Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode

  8. Effect of current focusing on the sensitivity of inferior colliculus neurons to amplitude-modulated stimulation.

    PubMed

    George, Shefin S; Shivdasani, Mohit N; Fallon, James B

    2016-09-01

    In multichannel cochlear implants (CIs), current is delivered to specific electrodes along the cochlea in the form of amplitude-modulated pulse trains, to convey temporal and spectral cues. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation and reduced channel interactions in the inferior colliculus (IC) compared with traditional monopolar (MP) stimulation, suggesting that focusing of stimulation could produce better transmission of spectral information. The present study explored the capability of IC neurons to detect modulated CI stimulation with FMP and TP stimulation compared with MP stimulation. The study examined multiunit responses of IC neurons in acutely deafened guinea pigs by systematically varying the stimulation configuration, modulation depth, and stimulation level. Stimuli were sinusoidal amplitude-modulated pulse trains (carrier rate of 120 pulses/s). Modulation sensitivity was quantified by measuring modulation detection thresholds (MDTs), defined as the lowest modulation depth required to differentiate the response of a modulated stimulus from an unmodulated one. Whereas MP stimulation showed significantly lower MDTs than FMP and TP stimulation (P values <0.05) at stimulation ≤2 dB above threshold, all stimulation configurations were found to have similar modulation sensitivities at 4 dB above threshold. There was no difference found in modulation sensitivity between FMP and TP stimulation. The present study demonstrates that current focusing techniques such as FMP and TP can adequately convey amplitude modulation and are comparable to MP stimulation, especially at higher stimulation levels, although there may be some trade-off between spectral and temporal fidelity with current focusing stimulation.

  9. Deep brain stimulation: new techniques.

    PubMed

    Hariz, Marwan

    2014-01-01

    The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago. However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects. Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously. Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording. PMID:24262179

  10. Evoked Electromyographically Controlled Electrical Stimulation

    PubMed Central

    Hayashibe, Mitsuhiro

    2016-01-01

    Time-variant muscle responses under electrical stimulation (ES) are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications. Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES) are also well known source of time-varying characteristics coming from muscle response under ES. Therefore, it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favor of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG) signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm. PMID:27471448

  11. Laser stimulation for pain research

    NASA Astrophysics Data System (ADS)

    Clark, Stuart; Dickinson, Mark R.; King, Terence A.; Jones, Anthony; Chen, Andrew; Derbyshire, Stuart; Townsend, D. W.; Kinahan, Paul E.; Mintun, M. A.; Nichols, T.

    1996-01-01

    Pain is a serious medical problem; it inflicts huge economic loss and personal suffering. Pain signals are conducted via small, non- and partially myelinated A-delta and C nerve fibers and lasers are particularly well suited to stimulating these fibers. Large myelinated fibers convey touch and vibration information and these fibers are also discharged when contact thermodes and other touch pain stimuli are used and this would give a more muddled signal for functional imaging experiments. The advantages of lasers over conventional methods of pain stimulation are good temporal resolution, no variable parameters are involved such as contact area and they give very reproducible results. Accurate inter-stimulus changes can be achieved by computer control of the laser pulse duration, pulse height and repetition rate and this flexibility enables complex stimulation paradigms to be realized. We present a flexible carbon dioxide laser system designed to generate these stimuli for the study of human cerebral pain responses. We discuss the advantages within research of this system over other methods of pain stimulation such as thermal, electrical and magnetic. The stimulator is used in conjunction with functional magnetic resonance imaging, positron emission tomography and electrophysiological methods of imaging the brain's activity. This combination is a powerful tool for the study of pain-induced activity in different areas of the brain. An accurate understanding of the brain's response to pain will help in research into the areas of rheumatoid arthritis and chronic back pain.

  12. Synergistic combination of near-infrared irradiation and targeted gold nanoheaters for enhanced photothermal neural stimulation.

    PubMed

    Eom, Kyungsik; Im, Changkyun; Hwang, Seoyoung; Eom, Seyoung; Kim, Tae-Seong; Jeong, Hae Sun; Kim, Kyung Hwan; Byun, Kyung Min; Jun, Sang Beom; Kim, Sung June

    2016-04-01

    Despite a potential of infrared neural stimulation (INS) for modulating neural activities, INS suffers from limited light confinement and bulk tissue heating. Here, a novel methodology for an advanced optical stimulation is proposed by combining near-infrared (NIR) stimulation with gold nanorods (GNRs) targeted to neuronal cell membrane. We confirmed experimentally that in vitro and in vivo neural activation is associated with a local heat generation based on NIR stimulation and GNRs. Compared with the case of NIR stimulation without an aid of GNRs, combination with cell-targeted GNRs allows photothermal stimulation with faster neural response, lower delivered energy, higher stimulation efficiency and stronger behavior change. Since the suggested method can reduce a requisite radiant exposure level and alleviate a concern of tissue damage, it is expected to open up new possibilities for applications to optical neuromodulations for diverse excitable tissues and treatments of neurological disorders. PMID:27446678

  13. Synergistic combination of near-infrared irradiation and targeted gold nanoheaters for enhanced photothermal neural stimulation

    PubMed Central

    Eom, Kyungsik; Im, Changkyun; Hwang, Seoyoung; Eom, Seyoung; Kim, Tae-Seong; Jeong, Hae Sun; Kim, Kyung Hwan; Byun, Kyung Min; Jun, Sang Beom; Kim, Sung June

    2016-01-01

    Despite a potential of infrared neural stimulation (INS) for modulating neural activities, INS suffers from limited light confinement and bulk tissue heating. Here, a novel methodology for an advanced optical stimulation is proposed by combining near-infrared (NIR) stimulation with gold nanorods (GNRs) targeted to neuronal cell membrane. We confirmed experimentally that in vitro and in vivo neural activation is associated with a local heat generation based on NIR stimulation and GNRs. Compared with the case of NIR stimulation without an aid of GNRs, combination with cell-targeted GNRs allows photothermal stimulation with faster neural response, lower delivered energy, higher stimulation efficiency and stronger behavior change. Since the suggested method can reduce a requisite radiant exposure level and alleviate a concern of tissue damage, it is expected to open up new possibilities for applications to optical neuromodulations for diverse excitable tissues and treatments of neurological disorders. PMID:27446678

  14. Wireless magnetothermal deep brain stimulation.

    PubMed

    Chen, Ritchie; Romero, Gabriela; Christiansen, Michael G; Mohr, Alan; Anikeeva, Polina

    2015-03-27

    Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors. PMID:25765068

  15. Technology for Peripheral Nerve Stimulation.

    PubMed

    Parker, John L; Cameron, Tracy

    2015-01-01

    Peripheral nerve stimulation (PNS) has been in use for over 50 years to treat patients suffering from chronic pain who have failed conservative treatments. Despite this long history, the devices being used have changed very little. In fact, current PNS technology was developed specifically for spinal cord stimulation. The use of technology developed for other applications in PNS has led to an unnecessary number of device complications and the limited adoption of this promising therapy. The following chapter provides an overview of PNS technology throughout the years, outlining both the benefits and limitations. We will briefly explore the electrophysiology of PNS stimulation, with an emphasis on technology and indication-specific devices. Finally, design and technical requirements of an ideal PNS device will be discussed.

  16. Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release.

    PubMed

    Melchior, James R; Ferris, Mark J; Stuber, Garret D; Riddle, David R; Jones, Sara R

    2015-09-01

    terminals (blue) reduces the cholinergic and GABAergic modulatory effects on stimulated dopamine release.

  17. The Electrical Stimulation Modifies the Cerebral Function

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa Lilia; López-Meraz, María Leonor; Cuéllar-Herrera, Manola; Neri-Bazán., Leticia

    2002-08-01

    Electrical stimulation has been used for therapeuthic purposes. In this review, we present the clinical and scientific bases for using electrical stimulation as a treatment for pharmacological refractory epilepsy. We also describe results in receptors of inhibitory neurotransmitters obtained in rat brain with or without epilepsy, undergoing brain stimulation. Brain electrical stimulation may improve our understanding of brain function and neuroplasticity.

  18. Reduced innervation in the human pharynx in patients with obstructive sleep apnea.

    PubMed

    de Carlos, Félix; Cobo, Juan; Macías, Emilio; Feito, Jorge; González, Mónica; Cobo, Teresa; Fernández-Mondragón, María P; García-Suárez, Olivia; Vega, José A

    2015-07-01

    Obstructive sleep apnea is a disease characterized by repetitive breathing during sleep that lead to reduced oxygen saturation and sleep disturbance among other symptoms. Obstructive sleep apnea is caused by blockade of the upper respiratory airway, although the pathogenic mechanism underlying this occlusion remains unknown. In these studies we explored the hypothesis that alterations in the innervation, especially mechanosensory innervation, of the pharynx may contribute to obstructive sleep apnea. We tested this hypothesis by analyzing the innervation of the human pharynx in normal individuals and in subjects clinically diagnosed with obstructive sleep apnea. Using immunohistochemistry for axon and Schwann cells, as well as for two putative mechanoproteins (ASIC2 and TRPV4), we observed a significant reduction in the density of nerve fibers in the submucosa of patients with obstructive sleep apnea as well as morphological abnormalities in mechanosensory corpuscles. Importantly, while ASIC2 and TRPV4 expression was regularly found in the axons of mechanosensory corpuscles distributed throughout the muscular layer in the control subjects, it was absent in patients with obstructive sleep apnea. These findings support that neurological alterations are important contributors to the pathogenesis of obstructive sleep apnea.

  19. Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Tokuda, Takashi; Asano, Ryosuke; Sugitani, Sachie; Taniyama, Mari; Terasawa, Yasuo; Nunoshita, Masahiro; Nakauchi, Kazuaki; Fujikado, Takashi; Tano, Yasuo; Ohta, Jun

    2008-04-01

    The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

  20. Exploiting pallidal plasticity for stimulation in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Lourens, Marcel A. J.; Schwab, Bettina C.; Nirody, Jasmine A.; Meijer, Hil G. E.; van Gils, Stephan A.

    2015-04-01

    Objective. Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson’s disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Here, we present a methodology to exploit the plasticity of GABAergic synapses inside the external globus pallidus (GPe) for the optimization of DBS. Approach. Assuming the existence of spike-timing-dependent plasticity (STDP) at GABAergic GPe-GPe synapses, we simulate neural activity in a network model of the subthalamic nucleus and GPe. In particular, we test different DBS protocols in our model and quantify their influence on neural synchrony. Main results. In an exemplary set of biologically plausible model parameters, we show that STDP in the GPe has a direct influence on neural activity and especially the stability of firing patterns. STDP stabilizes both uncorrelated firing in the healthy state and correlated firing in the parkinsonian state. Alternative stimulation protocols such as coordinated reset stimulation can clearly profit from the stabilizing effect of STDP. These results are widely independent of the STDP learning rule. Significance. Once the model settings, e.g., connection architectures, have been described experimentally, our model can be adjusted and directly applied in the development of novel stimulation protocols. More efficient stimulation leads to both minimization of side effects and savings in battery power.

  1. An implant for chronic selective stimulation of nerves.

    PubMed

    Bugbee, M; Donaldson, N N; Lickel, A; Rijkhoff, N J; Taylor, J

    2001-01-01

    An implantable stimulator system has been developed for nerve stimulation. The system is capable of stimulating selectively, either by fibre position, fibre size or by sending action potentials in one direction only, based on the use of nerve cuffs. The stimulator produces either quasi-trapezoidal current pulses, to allow anodal blocking, or conventional rectangular-shaped current pulses, of amplitude 20 microA to 5 mA (in 20 microA steps) with duration of 16 micros to 1 ms (in 8 micros steps). For safety, both active and passive charge balancing is used. The amplitude of the active charge-balancing phase can be varied between 1/7 and 1/47 of the pulse amplitude. During manufacture, each implant is customised so as to drive either 6 quasi-tripolar (dipolar), 4 tripolar or 2 pentapolar cuffs. Possible applications of the device are: improved defaecation and bladder voiding after spinal cord injury, by stimulation of the sacral motor roots; neuromodulation to reduce hyperreflexia without concomitant muscle contractions; in stroke patients, to enable balanced inversion-eversion while dorsiflexing the ankle by stimulating the peroneal nerve. It may also be used in chronic animal experiments.This paper describes the implant system, its hardware and communication protocol, and shows results from in vitro tests of the device and the first acute anodal-blocking experiments in pigs. PMID:11344005

  2. Facilitate Insight by Non-Invasive Brain Stimulation

    PubMed Central

    Chi, Richard P.; Snyder, Allan W.

    2011-01-01

    Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement. PMID:21311746

  3. Spinal cord stimulation in multiple sclerosis: clinical results.

    PubMed Central

    Illis, L S; Sedgwick, E M; Tallis, R C

    1980-01-01

    Clinical results of spinal cord stimulation by means of epidural electrodes are reported in 19 patients with multiple sclerosis. On temporary stimulation with percutaneous electrodes, significant improvement in mobility occurred in 27.7% of 18 patients and the same number showed improved sensory function. Only one of 13 patients with severe upper limb ataxia improved. The major response, both in terms of the percentage of patients responding and the extent of the responses seen was in bladder function: 75% of 16 patients with bladder symptoms improved and seven of the 11 patients with severe bladder disturbance (Kurtzke grade 3 or more) improved. Four of these seven patients had before and after cystometry and 3 showed reduced detrusor hyperreflexia. Altogether, 10 patients had a worthwhile clinical response in one or more aspects of the disease and of these, nine have so far gone on to permanent stimulation. Medium-term results (up to two years) show that, with one exception, improvement in bladder function has been maintained as long as stimulation has been continued and at least 50% of improvement in mobility has been maintained. A favourable response depends not upon the fact of stimulation but upon the type of stimulation received. This, along with other evidence, indicates that the response is not caused either by a placebo effect or by the natural fluctuation of the disease. PMID:7354351

  4. External Dentin Stimulation Induces ATP Release in Human Teeth.

    PubMed

    Liu, X; Wang, C; Fujita, T; Malmstrom, H S; Nedergaard, M; Ren, Y F; Dirksen, R T

    2015-09-01

    ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation-dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation-induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation-induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain. PMID:26130258

  5. Chemosensory stimulation during sleep - Arousal responses to gustatory stimulation.

    PubMed

    Stuck, B A; Moutsis, T T; Bingel, U; Sommer, J U

    2016-05-13

    The processing of nociceptive, visual, vibrotactile, thermal and acoustic stimuli during sleep has been extensively investigated in the past. Recently, interest has focused on the impact of olfactory stimulation on sleep. In contrast to all other sensory systems, olfactory stimulation does not lead to an increased arousal frequency, regardless of hedonicity and concentration. The impact of the second chemosensory system, gustation, on sleep however has not been investigated to date. Twenty-one normosmic and normogeusic volunteers of both genders, aged 19-33 years, participated in the trial. Stimulation was performed with a gustometer using the following aqueous solutions: saccharose 20% (sweet), sodium chloride (NaCl) 7.5% (salty), citrate 5% (sour), and quinine 0.02% (bitter). A tasteless solution was used as negative control. Capsaicin, a strong trigeminal stimulus, served as positive control. Primary outcome was arousal frequency per stimulus in each sleep stage, as assessed with polysomnography. The frequency of arousals decreased in deeper sleep stages (N1: 211 arousals of 333 stimuli=63%, N2: 676/2728=25%, N3: 43/1378=3%, REM: 57/1010=6%). Statistically significant differences in terms of arousal frequency were found in N2 between the negative control and NaCl 100 μl (p<0.001), saccharose 100 μl, citrate 50 μl & 100 μl, and quinine 100 μl (p<0.05). Capsaicin led to complete awakenings in 94% of stimuli (30/32). These results demonstrate that gustatory stimulation during sleep induces arousals depending on stimulus intensity and sleep stage, which is different to olfactory stimulation and may be related to differences in central processing of the two chemosensory systems. PMID:26921652

  6. Newberry Well 55-29 Stimulation Data 2014

    DOE Data Explorer

    Trenton T. Cladouhos

    2015-09-03

    The Newberry Volcano EGS Demonstration in central Oregon, a 5 year project begun in 2010, tests recent technological advances designed to reduce the cost of power generated by EGS in a hot, dry well (NWG 55-29) drilled in 2008. First, the stimulation pumps used were designed to run for weeks and deliver large volumes of water at moderate well-head pressure. Second, to stimulate multiple zones, AltaRock developed thermo-degradable zonal isolation materials (TZIMs) to seal off fractures in a geothermal well to stimulate secondary and tertiary fracture zones. The TZIMs degrade within weeks, resulting in an optimized injection/ production profile of the entire well. Third, the project followed a project-specific Induced Seismicity Mitigation Plan (ISMP) to evaluate, monitor for, and mitigate felt induced seismicity. An initial stimulation was conducted in 2012 and continued for 7 weeks, with over 41,000 m3 of water injected. Further analysis indicated a shallow casing leak and an unstable formation in the open hole. The well was repaired with a shallow casing tieback and perforated liner in the open hole and re-stimulated in 2014. The second stimulation started September 23rd, 2014 and continued for 3 weeks with over 9,500 m3 of water injected. The well was treated with several batches of newly tested TZIM diverter materials and a newly designed Diverter Injection Vessel Assembly (DIVA), which was the main modification to the original injection system design used in 2012. A second round of stimulation that included two perforation shots and additional batches of TZIM was conducted on November 11th, 2014 for 9 days with an additional 4,000 m3 of water injected. The stimulations resulted in a 3-4 fold increase in injectivity, and PTS data indicates partial blocking and creation of flow zones near the bottom of the well.

  7. [Programmed stimulation for in vitro fertilization].

    PubMed

    Imthurn, B; Macas, E; Hotz, E; Keller, P J

    1992-01-01

    A programmed stimulation protocol for in vitro fertilisation was evaluated in order to perform oocytes aspiration from Tuesday to Friday only. For this purpose, norethisterone acetate (Primolut-Nor) was given in a daily dose of 10 mg for 10-25 days, starting on the 2nd day of the preceding cycle and ending on a Monday. The stimulation was started on the following Friday by administering daily 0.1 mg D-Trp-6-LHRH s. c. (Decapeptyl). In group A (preliminary study) the treatment with HMG 150 IU/d (Pergonal) was initiated two days later. In group B the treatment with HMG was individualised with respect to the initial dose and the starting point. 10 ultrasonographic, needle-guided, transvaginal aspirations were performed from January to March 1990 in Group A, 29 aspirations from April to December 1990 in Group B. Indication for IVF in all patients was tubal infertility. All aspirations were possible from Tuesday to Friday. In Group A 5 of 15 cycles (33%) had to be cancelled. A total of 53 oocytes (5.3 +/- 2.3 per aspiration) were retrieved. Cleavage per oocyte took place in 62%. There was no pregnancy. In Group B, the cancellation rate could be reduced to 3% (1/30 cycles; p less than 0.025). 227 oocytes were recovered (7.8 +/- 3.1 per aspiration; p less than 0.05) and there was a higher cleavage rate (74%, n.s.). The clinical pregnancy rate (with allowance for progressive introduction of freezing) increased to 30% per stimulation cycle (9/30, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Infant Stimulation Curriculum. Revised Edition.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Herschel W. Nisonger Center.

    Presented is the Infant Stimulation Curriculum (developed by the Developmentally Delayed Infant Outreach Project) for parents and teachers to use with children who are developmentally between birth and 36 months of age. Published in a card format at a sixth grade readability level, the curriculum includes introductory cards providing information…

  9. Activities to Stimulate Critical Thinking.

    ERIC Educational Resources Information Center

    Haynes, Thomas B.; Schroeder, Connie

    1989-01-01

    Describes sample vocational activities that stimulate critical thinking: (1) setting up an accounting system (business education); (2) developing a marketing plan (marketing education); (3) developing a fertilizer application plan (agricultural education); (4) making the best purchase (home economics); (5) planning a repair/remodeling project…

  10. Aversive Stimulation -- Criteria for Application.

    ERIC Educational Resources Information Center

    O'Donnell, Patrick A.; Ohlson, Glenn A.

    Criteria for applying aversive stimulation with severely handicapped children are examined, and practical and ethical issues are considered. Factors seen to influence punishment outcomes include timing, intensity, and schedule of reinforcement. Suggested is the need for further research on the comparative effectiveness of positive and negative…

  11. Thalidomide inhibits granulocyte responses in healthy humans after ex vivo stimulation with bacterial antigens.

    PubMed

    Juffermans, N P; Verbon, A; Schultz, M J; Hack, C E; van Deventer, S J; Speelman, P; van der Poll, T

    2001-05-01

    Ingestion of thalidomide was associated with a reduction in the upregulation of the granulocyte activation marker CD11b and a reduced capacity to release elastase and lactoferrin after stimulation with lipopolysaccharide or lipoteichoic acid. A single oral dose of thalidomide attenuates neutrophil activation upon ex vivo stimulation with bacterial antigens.

  12. Stimulation of phagocytosis by sulforaphane

    SciTech Connect

    Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

    2011-02-04

    Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  13. Optically seeded stimulated Raman scattering of aqueous sulfate microdroplets

    NASA Astrophysics Data System (ADS)

    Pasternack, Louise; Fleming, James W.; Owrutsky, Jeffrey C.

    1996-07-01

    Optically seeded, stimulated Raman scattering is demonstrated for 25- mu m -radius water droplets containing sulfate. Frequency-doubled Nd:YAG laser-excited Stokes radiation from the 3450- cm -1 O-H-stretching vibration of water provides the seed for morphology-dependent stimulated Raman scattering from the nu 1 vibration of sulfate that is excited by a dye laser. Seeding enhances the otherwise weaker signal for low concentrations of the anion, thereby reducing the solute detection limit, by a method that does not require changing of the droplet composition.

  14. Enhanced stimulated Raman scattering in temperature controlled liquid water

    NASA Astrophysics Data System (ADS)

    Ganot, Yuval; Shrenkel, Shmuel; Barmashenko, Boris D.; Bar, Ilana

    2014-08-01

    The dependence of single pass stimulated Raman scattering (SRS) in liquid water on temperature was investigated. Thermal self-defocusing and competition with backward stimulated Brillouin scattering were found to be the major limiting factors for forward SRS (FSRS) generation. Experiments were performed to show that water cooling reduces these factors, resulting in significant enhancement of the FSRS and leading to a maximum conversion efficiency of 35% for pump energy of 120 mJ/pulse and for water at a temperature of 4 °C. Computer simulations of the involved waves resulted in FSRS efficiencies agreeing well with the experimental ones.

  15. The effect of optokinetic stimulation on daytime sleepiness

    NASA Technical Reports Server (NTRS)

    Leslie, K. R.; Stickgold, R.; Dizio, P.; Lackner, J. R.; Hobson, J. A.

    1997-01-01

    This study examined the effect of optokinetic stimulation on objective sleepiness, as measured by the Multiple Sleep Latency Test (MSLT). The Nightcap, a portable sleep monitor, was used in a novel way to perform MSLTs, as well as record sleep in the home. Subjects wore the Nightcap for seven consecutive nights. On days 3 and 5 of the protocol, subjects came into the lab for an MSLT. On the experimental day, subjects underwent 10 minutes optokinetic stimulation (OKS), resulting in moderate motion sickness prior to each MSLT trial. Although subjects in the OKS condition reported significantly more drowsiness than controls, this did not result in significantly reduced sleep latencies.

  16. Deep brain stimulation for major depression.

    PubMed

    Schlaepfer, T E; Bewernick, B H

    2013-01-01

    A third of patients suffering from major depression cannot be helped by conventional treatment methods. These patients face reduced quality of life, high risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). Long-term antidepressant effects, augmentation of social functioning, and normalization of brain metabolism have been shown in about 50% of patients. Cognitive safety regarding attention, learning, and memory has been reported. Adverse events were wound infection, suicide, and hypomania, amongst others. Larger studies are under way to confirm these preliminary encouraging results. New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. The application of DBS for other psychiatric diseases (e.g., bipolar disorder, alcohol dependency, opioid addiction, schizophrenia) is debated and single case studies are under way. Standards are needed for study registration, target selection, patient inclusion and monitoring, and publication of results to guarantee safety for the patients and scientific exchange.

  17. Network effects of deep brain stimulation

    PubMed Central

    Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

    2015-01-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

  18. Deep Brain Electrical Stimulation in Epilepsy

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa L.

    2008-11-01

    The deep brain electrical stimulation has been used for the treatment of neurological disorders such as Parkinson's disease, chronic pain, depression and epilepsy. Studies carried out in human brain indicate that the application of high frequency electrical stimulation (HFS) at 130 Hz in limbic structures of patients with intractable temporal lobe epilepsy abolished clinical seizures and significantly decreased the number of interictal spikes at focus. The anticonvulsant effects of HFS seem to be more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss. In addition, experiments using models of epilepsy indicate that HFS (pulses of 60 μs width at 130 Hz at subthreshold current intensity) of specific brain areas avoids the acquisition of generalized seizures and enhances the postictal seizure suppression. HFS is also able to modify the status epilepticus. It is concluded that the effects of HFS may be a good strategy to reduce or avoid the epileptic activity.

  19. Subliminal stimulation and somatosensory signal detection.

    PubMed

    Ferrè, Elisa Raffaella; Sahani, Maneesh; Haggard, Patrick

    2016-10-01

    Only a small fraction of sensory signals is consciously perceived. The brain's perceptual systems may include mechanisms of feedforward inhibition that protect the cortex from subliminal noise, thus reserving cortical capacity and conscious awareness for significant stimuli. Here we provide a new view of these mechanisms based on signal detection theory, and gain control. We demonstrated that subliminal somatosensory stimulation decreased sensitivity for the detection of a subsequent somatosensory input, largely due to increased false alarm rates. By delivering the subliminal somatosensory stimulus and the to-be-detected somatosensory stimulus to different digits of the same hand, we show that this effect spreads across the sensory surface. In addition, subliminal somatosensory stimulation tended to produce an increased probability of responding "yes", whether the somatosensory stimulus was present or not. Our results suggest that subliminal stimuli temporarily reduce input gain, avoiding excessive responses to further small inputs. This gain control may be automatic, and may precede discriminative classification of inputs into signals or noise. Crucially, we found that subliminal inputs influenced false alarm rates only on blocks where the to-be-detected stimuli were present, and not on pre-test control blocks where they were absent. Participants appeared to adjust their perceptual criterion according to a statistical distribution of stimuli in the current context, with the presence of supraliminal stimuli having an important role in the criterion-setting process. These findings clarify the cognitive mechanisms that reserve conscious perception for salient and important signals.

  20. Network effects of deep brain stimulation.

    PubMed

    Alhourani, Ahmad; McDowell, Michael M; Randazzo, Michael J; Wozny, Thomas A; Kondylis, Efstathios D; Lipski, Witold J; Beck, Sarah; Karp, Jordan F; Ghuman, Avniel S; Richardson, R Mark

    2015-10-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies.

  1. ATF3 inhibits PDX-1-stimulated transactivation.

    PubMed

    Kim, Won-Ho; Jang, Min Kyung; Kim, Choi Hee; Shin, Hwa Kyoung; Jung, Myeong Ho

    2011-11-01

    Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. However, the exact mechanisms by which ER stress reduces PDX-1 activity in pancreatic β-cells are unclear. Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress.

  2. Subliminal stimulation and somatosensory signal detection.

    PubMed

    Ferrè, Elisa Raffaella; Sahani, Maneesh; Haggard, Patrick

    2016-10-01

    Only a small fraction of sensory signals is consciously perceived. The brain's perceptual systems may include mechanisms of feedforward inhibition that protect the cortex from subliminal noise, thus reserving cortical capacity and conscious awareness for significant stimuli. Here we provide a new view of these mechanisms based on signal detection theory, and gain control. We demonstrated that subliminal somatosensory stimulation decreased sensitivity for the detection of a subsequent somatosensory input, largely due to increased false alarm rates. By delivering the subliminal somatosensory stimulus and the to-be-detected somatosensory stimulus to different digits of the same hand, we show that this effect spreads across the sensory surface. In addition, subliminal somatosensory stimulation tended to produce an increased probability of responding "yes", whether the somatosensory stimulus was present or not. Our results suggest that subliminal stimuli temporarily reduce input gain, avoiding excessive responses to further small inputs. This gain control may be automatic, and may precede discriminative classification of inputs into signals or noise. Crucially, we found that subliminal inputs influenced false alarm rates only on blocks where the to-be-detected stimuli were present, and not on pre-test control blocks where they were absent. Participants appeared to adjust their perceptual criterion according to a statistical distribution of stimuli in the current context, with the presence of supraliminal stimuli having an important role in the criterion-setting process. These findings clarify the cognitive mechanisms that reserve conscious perception for salient and important signals. PMID:27387873

  3. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    PubMed

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery. PMID:23002940

  4. Nanoparticles: A Challenging Vehicle for Neural Stimulation

    PubMed Central

    Colombo, Elisabetta; Feyen, Paul; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio

    2016-01-01

    Neurostimulation represents a powerful and well-established tool for the treatment of several diseases affecting the central nervous system. Although, effective in reducing the symptoms or the progression of brain disorders, the poor accessibility of the deepest areas of the brain currently hampers the possibility of a more specific and controlled therapeutic stimulation, depending on invasive surgical approaches and long-term stability, and biocompatibility issues. The massive research of the last decades on nanomaterials and nanoscale devices favored the development of new tools to address the limitations of the available neurostimulation approaches. This mini-review focuses on the employment of nanoparticles for the modulation of the electrophysiological activity of neuronal networks and the related transduction mechanisms underlying the nanostructure-neuron interfaces. PMID:27047327

  5. Effects of deep pressure stimulation on physiological arousal.

    PubMed

    Reynolds, Stacey; Lane, Shelly J; Mullen, Brian

    2015-01-01

    Deep pressure stimulation has been used in therapeutic practice because of the assumption that it changes physiological arousal. The purpose of this study was to test the effects of deep pressure stimulation, applied with a Vayu Vest (Therapeutic Systems), on both autonomic arousal and performance in a normative adult sample. A repeated-measures, repeated-baseline design was used with participants completing a performance test before and after deep pressure application. A convenience sample of 50 adults participated in the study. Results showed that wearing the Vayu Vest for even short periods of time reduced sympathetic arousal and non-stimulus-driven electrical occurrences. Concomitant increases in parasympathetic arousal were found. Performance improvements were noted after wearing the Vayu Vest, potentially because of changes in arousal. We conclude that deep pressure stimulation is capable of eliciting changes in autonomic arousal and may be a useful modality in diagnostic groups seen by occupational therapy practitioners. PMID:25871605

  6. Mitigating Simulator Adaptation Syndrome by means of tactile stimulation.

    PubMed

    Gálvez-García, Germán; Albayay, Javier; Rehbein, Lucio; Tornay, Francisco

    2017-01-01

    Some drivers experience Simulator Adaptation Syndrome (SAS), a condition in which nausea, disorientation, dizziness, headache, and difficulty focusing, are exhibited when driving in a simulator. To reduce this syndrome, we investigated the efficacy of tactile stimulation (TS) on mitigating Simulator Adaptation Syndrome (SAS) in a driving simulation. Fifteen drivers (eight women; mean age = 24.07 years) participated in this experiment. We compared the total scores of the Simulator Sickness Questionnaire (SSQ) across two stimulation conditions (TS condition and no stimulation condition as a baseline measure). The experimental outcomes revealed that TS seemed to decrease SAS due to attentional distraction from the symptoms and not because of an improvement in balance ability. PMID:27633193

  7. The rationale for deep brain stimulation in Alzheimer's disease.

    PubMed

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

  8. Electrical stimulation of the hypoglossal nerve: a potential therapy.

    PubMed

    Schwartz, Alan R; Smith, Philip L; Oliven, Arie

    2014-02-01

    Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse, which result from a decrease in pharyngeal dilator muscle tone. The genioglossus is a major pharyngeal dilator that maintains airway patency during sleep. Early studies in animal and humans have demonstrated that electrical stimulation of this muscle reduces pharyngeal collapsibility, increases airflow, and mitigates obstructive sleep apnea. These findings impelled the development of fully implantable hypoglossal nerve stimulating systems (HGNS), for which feasibility trial results are now available. These pilot studies have confirmed that hypoglossal nerve stimulation can prevent pharyngeal collapse without arousing patients from sleep. Potentially, a substantial segment of the patient population with obstructive sleep apnea can be treated with this novel approach. Furthermore, the feasibility trial findings suggest that the therapeutic potential of HGNS can be optimized by selecting patients judiciously, titrating the stimulus intensity optimally, and characterizing the underlying function and anatomy of the pharynx. These strategies are currently being examined in ongoing pivotal trials of HGNS.

  9. A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

    PubMed Central

    Cole, Michael H.; Graepel, Cara L.; Hyam, Jonathan A.; Jenkinson, Ned; Brittain, John-Stuart; Coyne, Terry J.; Silburn, Peter A.; Aziz, Tipu Z.; Kerr, Graham; Brown, Peter

    2012-01-01

    Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait

  10. Oxygen radicals as second messengers for expression of the monocyte chemoattractant protein, JE/MCP-1, and the monocyte colony-stimulating factor, CSF-1, in response to tumor necrosis factor-alpha and immunoglobulin G. Evidence for involvement of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase.

    PubMed

    Satriano, J A; Shuldiner, M; Hora, K; Xing, Y; Shan, Z; Schlondorff, D

    1993-09-01

    The potential involvement of reactive oxygen species in the expression of genes involved in immune response was examined in mesangial cells. Tumor necrosis factor (TNF-alpha) and aggregated (aggr.) IgG increased mRNA levels for the monocyte chemoattractant protein, JE/MCP-1, and the colony-stimulating factor, CSF-1. Scavengers for free radicals such as di- and tetra-methylthiourea (DMTU and TMTU) attenuated the increase in mRNA levels in response to TNF-alpha and aggr. IgG. Generation of superoxide anion by xanthine oxidase and hypoxanthine increased mRNA levels of these genes, but exogenous H2O2 did not. Addition of NADPH to activate a membrane-bound NADPH-oxidase generated superoxide and caused a dose-dependent increase in mRNA levels and further enhanced the stimulation by TNF-alpha or aggr. IgG. An inhibitor of NADPH-dependent oxidase 4'-hydroxy-3'-methoxy-acetophenone attenuated the rise in mRNA levels in response to TNF-alpha and aggr. IgG. By nuclear run-on experiments TNF-alpha, aggr. IgG and NADPH increased the transcription rates for JE/MCP-1 and CSF-1, effects inhibited by TMTU. We conclude that generation of reactive oxygen species, possibly by NADPH-dependent oxidase, are involved in the induction of the JE/MCP-1 and CSF-1 genes by TNF-alpha and IgG complexes. The concerted expression of leukocyte-directed cytokines represents a general response to tissue injury.

  11. Somato stimulation and acupuncture therapy.

    PubMed

    Zhao, Jing-Jun; Rong, Pei-Jing; Shi, Li; Ben, Hui; Zhu, Bing

    2016-05-01

    Acupuncture is an oldest somato stimulus medical technique. As the most representative peripheral nerve stimulation therapy, it has a complete system of theory and application and is applicable to a large population. This paper expounds the bionic origins of acupuncture and analyzes the physiological mechanism by which acupuncture works. For living creatures, functionally sound viscera and effective endurance of pain are essential for survival. This paper discusses the way in which acupuncture increases the pain threshold of living creatures and the underlying mechanism from the perspective of bionics. Acupuncture can also help to adjust visceral functions and works most effectively in facilitating the process of digestion and restraining visceral pain. This paper makes an in-depth overview of peripheral nerve stimulation therapy represented by acupuncture. We look forward to the revival of acupuncture, a long-standing somato stimulus medicine, in the modern medical systems.

  12. Multisensory stimulation in stroke rehabilitation.

    PubMed

    Johansson, Barbro Birgitta

    2012-01-01

    The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, and various kinds of music therapy. Non-invasive brain stimulation has showed promising preliminary results in aphasia and neglect. Patient heterogeneity and the interaction of age, gender, genes, and environment are discussed. Randomized controlled longitudinal trials starting earlier post-stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation. It is proposed that we should pay more attention to age, gender, and laterality in clinical studies.

  13. Multisensory Stimulation in Stroke Rehabilitation

    PubMed Central

    Johansson, Barbro Birgitta

    2012-01-01

    The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, and various kinds of music therapy. Non-invasive brain stimulation has showed promising preliminary results in aphasia and neglect. Patient heterogeneity and the interaction of age, gender, genes, and environment are discussed. Randomized controlled longitudinal trials starting earlier post-stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation. It is proposed that we should pay more attention to age, gender, and laterality in clinical studies. PMID:22509159

  14. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    PubMed

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. PMID:25194209

  15. Stimulated Superconductivity at Strong Coupling

    SciTech Connect

    Bao, Ning; Dong, Xi; Silverstein, Eva; Torroba, Gonzalo; /Stanford U., ITP /Stanford U., Phys. Dept. /SLAC

    2011-08-12

    Stimulating a system with time dependent sources can enhance instabilities, thus increasing the critical temperature at which the system transitions to interesting low-temperature phases such as superconductivity or superfluidity. After reviewing this phenomenon in non-equilibrium BCS theory (and its marginal fermi liquid generalization) we analyze the effect in holographic superconductors. We exhibit a simple regime in which the transition temperature increases parametrically as we increase the frequency of the time-dependent source.

  16. Interleukin-6 stimulates defective angiogenesis

    PubMed Central

    Gopinathan, Ganga; Milagre, Carla; Pearce, Oliver M.T.; Reynolds, Louise E.; Hodivala-Dilke, Kairbaan; Leinster, David A.; Zhong, Haihong; Hollingsworth, Robert E.; Thompson, Richard; Whiteford, James R.; Balkwill, Frances

    2015-01-01

    The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here we show that IL-6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL-6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared to VEGF-stimulated vessels. The mechanism of IL-6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as Angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL-6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies there was an association between levels of IL-6mRNA, Jagged1 and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL-6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease and stroke. PMID:26081809

  17. Gastric stimulation for weight loss.

    PubMed

    Mizrahi, Meir; Ben Ya'acov, Ami; Ilan, Yaron

    2012-05-21

    The prevalence of obesity is growing to epidemic proportions, and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss. Behavior and lifestyle therapy are safe treatments for obesity in the short term, but the durability of the weight loss is limited. Although promising obesity drugs are in development, the currently available drugs lack efficacy or have unacceptable side effects. Surgery leads to long-term weight loss, but it is associated with morbidity and mortality. Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders. GES is a promising, minimally invasive, safe, and effective method for treating obesity. External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time. In addition, data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES. This may involve alteration of secretion of hormones associated with hunger or satiety. Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome. Here, we review the current status, potential mechanisms of action, and possible future applications of gastric stimulation for obesity. PMID:22654422

  18. High and low frequency transcutaneous electrical nerve stimulation inhibits nociceptive responses induced by CO2 laser stimulation in humans.

    PubMed

    de Tommaso, Marina; Fiore, Pietro; Camporeale, Alfonso; Guido, Marco; Libro, Giuseppe; Losito, Luciana; Megna, Marisa; Puca, Francomichele; Megna, Gianfranco

    2003-05-15

    The aim of the study was to evaluate the effects of transcutaneous electric nerve stimulation (TENS) on CO(2) laser evoked potentials (LEPs) in 16 normal subjects. The volar side of the forearm was stimulated by 10 Hz TENS in eight subjects and by 100 Hz TENS in the remainder; the skin of the forearm was stimulated by CO(2) laser and the LEPs were recorded in basal conditions and soon after and 15 min after TENS. Both low and high frequency TENS significantly reduced the subjective rating of heat stimuli and the LEPs amplitude, although high frequency TENS appeared more efficacious. TENS seemed to exert a mild inhibition of the perception and processing of pain induced by laser Adelta fibres activation; the implications of these effects in the clinical employment of TENS remain to be clarified. PMID:12727307

  19. High and low frequency transcutaneous electrical nerve stimulation inhibits nociceptive responses induced by CO2 laser stimulation in humans.

    PubMed

    de Tommaso, Marina; Fiore, Pietro; Camporeale, Alfonso; Guido, Marco; Libro, Giuseppe; Losito, Luciana; Megna, Marisa; Puca, Francomichele; Megna, Gianfranco

    2003-05-15

    The aim of the study was to evaluate the effects of transcutaneous electric nerve stimulation (TENS) on CO(2) laser evoked potentials (LEPs) in 16 normal subjects. The volar side of the forearm was stimulated by 10 Hz TENS in eight subjects and by 100 Hz TENS in the remainder; the skin of the forearm was stimulated by CO(2) laser and the LEPs were recorded in basal conditions and soon after and 15 min after TENS. Both low and high frequency TENS significantly reduced the subjective rating of heat stimuli and the LEPs amplitude, although high frequency TENS appeared more efficacious. TENS seemed to exert a mild inhibition of the perception and processing of pain induced by laser Adelta fibres activation; the implications of these effects in the clinical employment of TENS remain to be clarified.

  20. Microwave-stimulated superconductivity due to presence of vortices

    PubMed Central

    Lara, Antonio; Aliev, Farkhad G.; Silhanek, Alejandro V.; Moshchalkov, Victor V.

    2015-01-01

    The response of superconducting devices to electromagnetic radiation is a core concept implemented in diverse applications, ranging from the currently used voltage standard to single photon detectors in astronomy. Suprisingly, a sufficiently high power subgap radiation may stimulate superconductivity itself. The possibility of stimulating type II superconductors, in which the radiation may interact also with vortex cores, remains however unclear. Here we report on superconductivity enhanced by GHz radiation in type II superconducting Pb films in the presence of vortices. The stimulation effect is more clearly observed in the upper critical field and less pronounced in the critical temperature. The magnetic field dependence of the vortex related microwave losses in a film with periodic pinning reveals a reduced dissipation of mobile vortices in the stimulated regime due to a reduction of the core size. Results of numerical simulations support the validy of this conclusion. Our findings may have intriguing connections with holographic superconductors in which the possibility of stimulation is under current debate. PMID:25778446

  1. Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse

    PubMed Central

    Howell, Leonard L.; Negus, S. Stevens

    2015-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters in general, and dopamine transporters in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability, and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  2. Monoamine transporter inhibitors and substrates as treatments for stimulant abuse.

    PubMed

    Howell, Leonard L; Negus, S Stevens

    2014-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters, in general, and dopamine transporters, in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination, and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  3. Opening Hemichannels in Nonjunctional Membrane Stimulates Gap Junction Formation

    PubMed Central

    Beahm, Derek L.; Hall, James E.

    2004-01-01

    We studied gap junction formation in pairs of Xenopus laevis oocytes expressing connexins that form functional hemichannels and found no correlation between junctional conductance (Gj) and whole-cell hemichannel conductances (Ghemi) within the first few hours of pairing. However, opening hemichannels to a threshold current stimulated a rapid Gj increase. Moreover, cx46 hemichannel current stimulated cx40 Gj even though cx40 and cx46 do not form heteromeric or heterotypic gap junctions. Initial growth rate and final steady-state level of stimulated Gj were proportional to the product of hemichannel conductances. External calcium affected the growth rate of stimulated Gj but not the final steady-state value. Time constants of formation were short in low [Ca2+]out (3 min in 200 μM Ca2+) and long in high [Ca2+]out (15 min in 1 mM Ca2+), but in oocyte pairs pretreated with lectins to reduce steric hindrance imposed by large membrane glycoproteins the time constant was short and Ca2+-independent. We suggest that hemichannel activity stimulates Gj by collapsing the extracellular volume between membranes to allow the end-to-end binding between hemichannels. These studies suggest the possibility that functional hemichannels could trigger or enhance junctional formation in vivo in response to appropriate stimuli. PMID:14747314

  4. Short-interval intracortical inhibition is modulated by high-frequency peripheral mixed nerve stimulation.

    PubMed

    Murakami, Takenobu; Sakuma, Kenji; Nomura, Takashi; Nakashima, Kenji

    2007-06-01

    Cortical excitability can be modulated by manipulation of afferent input. We investigated the influence of peripheral mixed nerve stimulation on the excitability of the motor cortex. Motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the right abductor pollicis brevis (APB), extensor carpi radialis (ECR) and first dorsal interosseous (FDI) muscles were evaluated using paired-pulse transcranial magnetic stimulation (TMS) before and after high-frequency peripheral mixed nerve stimulation (150 Hz, 30 min) over the right median nerve at the wrist. The MEP amplitude and SICI of the APB muscle decreased transiently 0-10 min after the intervention, whereas the ICF did not change. High-frequency peripheral mixed nerve stimulation reduced the excitability of the motor cortex. The decrement in the SICI, which reflects the function of GABA(A)ergic inhibitory interneurons, might compensate for the reduced motor cortical excitability after high-frequency peripheral mixed nerve stimulation.

  5. Cathodal transcranial direct current stimulation in children with dystonia: a sham-controlled study.

    PubMed

    Young, Scott J; Bertucco, Matteo; Sanger, Terence D

    2014-02-01

    Increased motor cortex excitability is a common finding in dystonia, and transcranial direct current stimulation can reduce motor cortex excitability. In an earlier study, we found that cathodal direct-current stimulation decreased motor overflow for some children with dystonia. To investigate this observation further, we performed a sham-controlled, double-blind, crossover study of 14 children with dystonia. We found a significant reduction in overflow following real stimulation, when participants performed the experimental task with the hand contralateral to the cathode. While these results suggest that cathodal stimulation may help some children to reduce involuntary overflow, the size of the effect is small. Further research will need to investigate ways to increase the magnitude of the effect of cathodal transcranial direct current stimulation. PMID:23760989

  6. Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation

    PubMed Central

    Salimpour, Yousef; Mari, Zoltan K.

    2015-01-01

    In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via

  7. Deep Brain Stimulation Tested for Early Alzheimer's

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160137.html Deep Brain Stimulation Tested for Early Alzheimer's Although treatment seems ... 2016 THURSDAY, July 28, 2016 (HealthDay News) -- Deep brain stimulation appears safe for people with early Alzheimer's ...

  8. Neuromuscular Electrical Stimulation for Skeletal Muscle Function

    PubMed Central

    Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

    2012-01-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

  9. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

    PubMed Central

    Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

    2005-01-01

    Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

  10. Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine

    PubMed Central

    de Tommaso, Marina; Trotta, Gabriele; Vecchio, Eleonora; Ricci, Katia; Van de Steen, Frederik; Montemurno, Anna; Lorenzo, Marta; Marinazzo, Daniele; Bellotti, Roberto; Stramaglia, Sebastiano

    2015-01-01

    In previous studies, migraine patients showed abnormalities in pain-related evoked responses, as reduced habituation to repetitive stimulation. In this study, we aimed to apply a novel analysis of EEG bands synchronization and directed dynamical influences under painful stimuli in migraine patients compared to non-migraine healthy volunteers. Thirty-one migraine without aura outpatients (MIGR) were evaluated and compared to 19 controls (CONT). The right hand was stimulated by means of 30 consecutive CO2 laser stimuli. EEG signal was examined by means of Morlet wavelet, synchronization entropy (SE), and Granger causality (GC), and the statistically validated results were mapped on the corresponding scalp locations. The vertex complex of averaged laser-evoked responses (LEPs) showed reduced habituation compared to CONT. In the prestimulus phase, enhanced SE in the 0, 5–30 Hz range was present in MIGR and CONT between the bilateral temporal–parietal and the frontal regions around the midline. Migraine patients showed an anticipation of EEG changes preceding the painful stimulation compared to CONT. In the poststimulus phase, the same cortical areas were more connected in MIGR vs CONT. In both groups of patients and CONT, the habituation index was negatively correlated with the GC scores. A different pattern of cortical activation after painful stimulation was present in migraine. The increase in cortical connections during repetitive painful stimulation may subtend the phenomenon of LEPs reduced habituation. Brain network analysis may give an aid in understanding subtle changes of pain processing under laser stimuli in migraine patients. PMID:26635589

  11. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    PubMed

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  12. Purchase decision-making is modulated by vestibular stimulation

    PubMed Central

    Preuss, Nora; Mast, Fred W.; Hasler, Gregor

    2014-01-01

    Purchases are driven by consumers’ product preferences and price considerations. Using caloric vestibular stimulation (CVS), we investigated the role of vestibular-affective circuits in purchase decision-making. CVS is an effective noninvasive brain stimulation method, which activates vestibular and overlapping emotional circuits (e.g., the insular cortex and the anterior cingulate cortex (ACC)). Subjects were exposed to CVS and sham stimulation while they performed two purchase decision-making tasks. In Experiment 1 subjects had to decide whether to purchase or not. CVS significantly reduced probability of buying a product. In Experiment 2 subjects had to rate desirability of the products and willingness to pay (WTP) while they were exposed to CVS and sham stimulation. CVS modulated desirability of the products but not WTP. The results suggest that CVS interfered with emotional circuits and thus attenuated the pleasant and rewarding effect of acquisition, which in turn reduced purchase probability. The present findings contribute to the rapidly growing literature on the neural basis of purchase decision-making. PMID:24600365

  13. Gamma Frequency–Range Abnormalities to Auditory Stimulation in Schizophrenia

    PubMed Central

    Kwon, Jun Soo; O’Donnell, Brian F.; Wallenstein, Gene V.; Greene, Robert W.; Hirayasu, Yoshio; Nestor, Paul G.; Hasselmo, Michael E.; Potts, Geoffrey F.; Shenton, Martha E.; McCarley, Robert W.

    2010-01-01

    Background Basic science studies at the neuronal systems level have indicated that gamma-range (30–50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing g-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. Methods Synchronization of the electroencephalogram (EEG) to different rates (20–40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. Results Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. Conclusions These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks. PMID:10565499

  14. Transcapillary fluid dynamics during ovarian stimulation for in vitro fertilization.

    PubMed

    Tollan, A; Holst, N; Forsdahl, F; Fadnes, H O; Oian, P; Maltau, J M

    1990-02-01

    Transcapillary fluid dynamics were studied in 10 women during ovarian stimulation for in vitro fertilization. The examinations were done on the first day of stimulation (day 3 of the menstrual cycle, mean serum estradiol concentration 0.2 nmol/L), and the day before oocyte aspiration (day 10 to 12, mean serum estradiol concentration 6.8 nmol/L). Interstitial colloid osmotic pressure was measured on the thorax at heart level by the "wick" method, and interstitial hydrostatic pressure by the "wick-in-needle" method. Plasma colloid osmotic pressure decreased (mean, 2.0 mm Hg; p less than 0.002) and interstitial colloid osmotic pressure increased (mean, 1.0 mm Hg; p less than 0.02) during hormonal stimulation. This implies a reduced transcapillary colloid osmotic gradient (plasma colloid osmotic pressure--interstitial colloid osmotic pressure), probably because of increased capillary permeability to plasma proteins. Hemoglobin and hematocrit were significantly reduced, and body weight and foot volume significantly increased. These results demonstrate that during ovarian stimulation there are both water retention and augmented filtration of fluid from the vascular to the interstitial compartment. This may be of significance for the pathophysiologic condition in the ovarian hyperstimulation syndrome.

  15. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    Each of the following types of well stimulation techniques are summarized and explained: hydraulic fracturing; thermal; mechanical, jetting, and drainhole drilling; explosive and implosive; and injection methods. Current stimulation techniques, stimulation techniques for geothermal wells, areas of needed investigation, and engineering calculations for various techniques. (MHR)

  16. Modeling and Field Results from Seismic Stimulation

    SciTech Connect

    Majer, E.; Pride, S.; Lo, W.; Daley, T.; Nakagawa, Seiji; Sposito, Garrison; Roberts, P.

    2006-05-30

    Modeling the effect of seismic stimulation employing Maxwell-Boltzmann theory shows that the important component of stimulation is mechanical rather than fluid pressure effects. Modeling using Biot theory (two phases) shows that the pressure effects diffuse too quickly to be of practical significance. Field data from actual stimulation will be shown to compare to theory.

  17. Infant Habituation to Visual and Auditory Stimulation.

    ERIC Educational Resources Information Center

    Dunn, Jane; Haskins, Ron

    A total of 14 infants participated in this study of the recovery of visual orienting by crossmodal stimulation when no new visual information was present. The locus of the crossmodal stimulation (auditory stimulation) was discriminable to the subject. Infants in three age groups were tested on three occasions each separated by 30 days. No…

  18. Vomiting Center reanalyzed: An electrical stimulation study

    NASA Technical Reports Server (NTRS)

    Miller, A. D.; Wilson, V. J.

    1982-01-01

    Electrical stimulation of the brainstem of 15 decerebrate cats produced stimulus-bound vomiting in only 4 animals. Vomiting was reproducible in only one cat. Effective stimulating sites were located in the solitary tract and reticular formation. Restricted localization of a vomiting center, stimulation of which evoked readily reproducible results, could not be obtained.

  19. Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Shivdasani, Mohit N.; Shepherd, Robert K.; Fallon, James B.

    2014-12-01

    Objective. The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. Approach. The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. Main results. FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. Significance. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

  20. Brain stimulation and inhibitory control.

    PubMed

    Juan, Chi-Hung; Muggleton, Neil G

    2012-04-01

    Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control. PMID:22494830

  1. Brain stimulation and inhibitory control.

    PubMed

    Juan, Chi-Hung; Muggleton, Neil G

    2012-04-01

    Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control.

  2. Stimulated Parametric Emission Microscope Systems

    NASA Astrophysics Data System (ADS)

    Itoh, Kazuyoshi; Isobe, Keisuke

    2006-10-01

    We present a novel microscopy technique based on the fourwave mixing (FWM) process that is enhanced by two-photon electronic resonance induced by a pump pulse along with stimulated emission induced by a dump pulse. A Ti:sapphire laser and an optical parametric oscillator are used as light sources for the pump and dump pulses, respectively. We demonstrate that our FWM technique can be used to obtain two-dimensional microscopic images of an unstained leaf of Camellia sinensis and an unlabeled tobacco BY2 Cell.

  3. Stimulated Brillouin Scattering Microscopic Imaging

    PubMed Central

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue. PMID:26691398

  4. Transcranial magnetic stimulation in neurology

    PubMed Central

    Eldaief, Mark C.; Press, Daniel Z.

    2013-01-01

    Summary Transcranial magnetic stimulation (TMS) is a neurophysiologic technique to noninvasively induce a controlled current pulse in a prespecified cortical target. This can be used to transiently disrupt the function of the targeted cortical region and explore causal relations to behavior, assess cortical reactivity, and map out functionally relevant brain regions, for example during presurgical assessments. Particularly when applied repetitively, TMS can modify cortical excitability and the effects can propagate trans-synaptically to interconnected cortical, subcortical, and spinal cord regions. As such, TMS can be used to assess the functional integrity of neural circuits and to modulate brain activity with potential therapeutic intent. PMID:24353923

  5. Multicolor stimulated Raman scattering microscopy

    NASA Astrophysics Data System (ADS)

    Lu, Fa-Ke; Ji, Minbiao; Fu, Dan; Ni, Xiaohui; Freudiger, Christian W.; Holtom, Gary; Xie, X. Sunney

    2012-08-01

    Stimulated Raman scattering (SRS) microscopy has opened up a wide range of biochemical imaging applications by probing a particular Raman-active molecule vibrational mode in the specimen. However, the original implementation with picosecond pulse excitation can only realize rapid chemical mapping with a single Raman band. Here we present a novel SRS microscopic technique using a grating-based pulse shaper for excitation and a grating-based spectrograph for detection to achieve simultaneous multicolor SRS imaging with high sensitivity and high acquisition speeds. In particular, we use a linear combination of the measured CH2 and CH3 stretching signals to map the distributions of protein and lipid contents simultaneously.

  6. Stimulated Brillouin Scattering Microscopic Imaging.

    PubMed

    Ballmann, Charles W; Thompson, Jonathan V; Traverso, Andrew J; Meng, Zhaokai; Scully, Marlan O; Yakovlev, Vladislav V

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  7. Stimulated Brillouin Scattering Microscopic Imaging

    NASA Astrophysics Data System (ADS)

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-12-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  8. Pumping effect of stimulated Brillouin scattering on stimulated Raman scattering in water

    NASA Astrophysics Data System (ADS)

    Liu, Dahe; Shi, Jinwei; Ouyang, Min; Chen, Xudong; Liu, Juan; He, Xingdao

    2009-09-01

    It is investigated experimentally that stimulated Raman scattering (SRS) can be enhanced by stimulated Brillouin scattering (SBS). Two physical mechanisms of these phenomena were analyzed. These phenomena show that not only the competition between SBS and SRS exists, the pumping effect of stimulated Brillouin scattering on back-stimulated Raman scattering is also a commonly existing rule regardless of the experimental conditions.

  9. Pharmacovigilance in practice: erythropoiesis-stimulating agents.

    PubMed

    Hedenus, Michael; Ludwig, Heinz; Henry, David H; Gasal, Eduard

    2014-10-01

    Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or other problems related to medical products after they have been licensed for marketing. The purpose of PV is to advance the safe use of marketed medical products. Regulatory agencies and license holders collaborate to collect data reported by health care providers, patients, and the public as well as data from systematic reviews, meta-analyses, and individual clinical and nonclinical studies. They validate and analyze the data to determine whether safety signals exist, and if warranted, develop an action plan to mitigate the identified risk. Erythropoiesis-stimulating agents (ESAs) provide an example of how PV is applied in reality. Among other approved indications, ESAs may be used to treat anemia in patients with chemotherapy-induced anemia. ESAs increase hemoglobin levels and reduce the need for transfusions; they are also associated with a known increased risk of thromboembolic events. Starting in 2003, emerging data suggested that ESAs might reduce survival. As a result of PV activities by regulatory agencies and license holders, labeling for ESAs addresses these risks. Meta-analyses and individual clinical studies have confirmed that ESAs increase the risk of thromboembolic events, but when used as indicated, ESAs have not been shown to have a significant effect on survival or disease progression. Ongoing safety studies will provide additional data in the coming years to further clarify the risks and benefits of ESAs.

  10. Pharmacovigilance in practice: erythropoiesis-stimulating agents.

    PubMed

    Hedenus, Michael; Ludwig, Heinz; Henry, David H; Gasal, Eduard

    2014-10-01

    Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or other problems related to medical products after they have been licensed for marketing. The purpose of PV is to advance the safe use of marketed medical products. Regulatory agencies and license holders collaborate to collect data reported by health care providers, patients, and the public as well as data from systematic reviews, meta-analyses, and individual clinical and nonclinical studies. They validate and analyze the data to determine whether safety signals exist, and if warranted, develop an action plan to mitigate the identified risk. Erythropoiesis-stimulating agents (ESAs) provide an example of how PV is applied in reality. Among other approved indications, ESAs may be used to treat anemia in patients with chemotherapy-induced anemia. ESAs increase hemoglobin levels and reduce the need for transfusions; they are also associated with a known increased risk of thromboembolic events. Starting in 2003, emerging data suggested that ESAs might reduce survival. As a result of PV activities by regulatory agencies and license holders, labeling for ESAs addresses these risks. Meta-analyses and individual clinical studies have confirmed that ESAs increase the risk of thromboembolic events, but when used as indicated, ESAs have not been shown to have a significant effect on survival or disease progression. Ongoing safety studies will provide additional data in the coming years to further clarify the risks and benefits of ESAs. PMID:24890561

  11. Bubble stimulation efficiency of dinoflagellate bioluminescence.

    PubMed

    Deane, Grant B; Stokes, M Dale; Latz, Michael I

    2016-02-01

    Dinoflagellate bioluminescence, a common source of bioluminescence in coastal waters, is stimulated by flow agitation. Although bubbles are anecdotally known to be stimulatory, the process has never been experimentally investigated. This study quantified the flash response of the bioluminescent dinoflagellate Lingulodinium polyedrum to stimulation by bubbles rising through still seawater. Cells were stimulated by isolated bubbles of 0.3-3 mm radii rising at their terminal velocity, and also by bubble clouds containing bubbles of 0.06-10 mm radii for different air flow rates. Stimulation efficiency, the proportion of cells producing a flash within the volume of water swept out by a rising bubble, decreased with decreasing bubble radius for radii less than approximately 1 mm. Bubbles smaller than a critical radius in the range 0.275-0.325 mm did not stimulate a flash response. The fraction of cells stimulated by bubble clouds was proportional to the volume of air in the bubble cloud, with lower stimulation levels observed for clouds with smaller bubbles. An empirical model for bubble cloud stimulation based on the isolated bubble observations successfully reproduced the observed stimulation by bubble clouds for low air flow rates. High air flow rates stimulated more light emission than expected, presumably because of additional fluid shear stress associated with collective buoyancy effects generated by the high air fraction bubble cloud. These results are relevant to bioluminescence stimulation by bubbles in two-phase flows, such as in ship wakes, breaking waves, and sparged bioreactors.

  12. Infrared neural stimulation in the cochlea

    PubMed Central

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2014-01-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed. PMID:25075260

  13. Infrared neural stimulation in the cochlea.

    PubMed

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2013-03-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed. PMID:25075260

  14. Seizure Suppression Efficacy of Closed-Loop Versus Open-Loop Deep Brain Stimulation in a Rodent Model of Epilepsy.

    PubMed

    Salam, M Tariqus; Perez Velazquez, Jose Luis; Genov, Roman

    2016-06-01

    We assess and compare the effects of both closed-loop and open-loop neurostimulation of the rat hippocampus by means of a custom low-power programmable therapeutic neurostimulation device on the suppression of spontaneous seizures in a rodent model of epilepsy. Chronic seizures were induced by intraperitoneal kainic acid injection. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to the custom-built programmable therapeutic neurostimulation device that can trigger an electrical stimulation either in a periodic manner or upon detection of the intracerebral electroencephalographic (icEEE) seizure onset. This device includes a microchip consisting of a 256-channel icEEG recording system and a 64-channel stimulator, and a programmable seizure detector implemented in a field-programmable gate array (FPGA). The neurostimulator was used to evaluate seizure suppression efficacy in ten epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the no-stimulation group and the stimulation group. The no-stimulation group did not receive stimulation. The stimulation group received, first, closed-loop stimulation and, next, open-loop stimulation. The no-stimulation and stimulation groups had a similar seizure frequency baseline, averaging five seizures per day. Closed-loop stimulation reduced seizure frequency by 90% and open-loop stimulation reduced seizure frequency by 17%, both in the stimulation group as compared to the no-stimulation group. PMID:26571534

  15. Paired associative transspinal and transcortical stimulation produces plasticity in human cortical and spinal neuronal circuits.

    PubMed

    Dixon, Luke; Ibrahim, Mohamed M; Santora, Danielle; Knikou, Maria

    2016-08-01

    Anatomical, physiological, and functional connectivity exists between the neurons of the primary motor cortex (M1) and spinal cord. Paired associative stimulation (PAS) produces enduring changes in M1, based on the Hebbian principle of associative plasticity. The present study aimed to establish neurophysiological changes in human cortical and spinal neuronal circuits by pairing noninvasive transspinal stimulation with transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40 min at precise interstimulus intervals, with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor threshold, and reduced the soleus Hoffmann's reflex (H-reflex) low frequency-mediated homosynaptic depression. Transcortical-transspinal PAS did not affect intracortical circuits, decreased M1 excitability, and reduced the soleus H-reflex-paired stimulation pulses' mediated postactivation depression. Both protocols affected the excitation threshold of group Ia afferents and motor axons. These findings clearly indicate that the pairing of transspinal with transcortical stimulation produces cortical and spinal excitability changes based on the timing interval and functional network interactions between the two associated inputs. This new PAS paradigm may constitute a significant neuromodulation method with physiological impact, because it can be used to alter concomitantly excitability of intracortical circuits, corticospinal neurons, and spinal inhibition in humans. PMID:27281748

  16. Deep Brain Stimulation for Obesity

    PubMed Central

    Sussman, Eric S; Zhang, Michael; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-01-01

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer’s disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain. PMID:26180683

  17. Braille line using electrical stimulation

    NASA Astrophysics Data System (ADS)

    Puertas, A.; Purés, P.; Echenique, A. M.; Ensinck, J. P. Graffigna y. G.

    2007-11-01

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  18. Role of diacylglycerol in adrenergic-stimulated sup 86 Rb uptake by proximal tubules

    SciTech Connect

    Baines, A.D.; Drangova, R.; Ho, P. )

    1990-05-01

    We used rat proximal tubule fragments purified by Percoll centrifugation to examine the role of diacylglycerol (DAG) in noradrenergic-stimulated Na+ reabsorption. Tubular DAG concentration and ouabain-inhibitable 86Rb uptake increased within 30 s after adding norepinephrine (NE) and remained elevated for at least 5 min. NE (1 microM) increased DAG content 17% and ouabain-inhibitable 86Rb uptake 23%. Cirazoline-stimulated 86Rb uptake was not inhibited by BaCl, quinidine, or bumetanide (1-10 microM) or by the omission of HCO3- or Cl- from the medium, but it was completely inhibited by ouabain and furosemide. Oleoyl-acetyl glycerol, L-alpha-1,2-dioctanoylglycerol, and L-alpha-1,2-dioleoylglycerol (DOG) increased total 86Rb uptake 8-11%. 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 nM) increased uptake by only 4%. Staurosporine at 5 nM inhibited DOG stimulation completely, whereas 50 nM staurosporine was required to inhibit NE stimulation completely. Sphingosine inhibited DOG stimulation by 66% but did not inhibit NE stimulation. Amiloride (1 mM) completely blocked DOG stimulation. Monensin increased 86Rb uptake 31% and completely blocked the DOG effect but reduced the NE effect by only 26% (P = 0.08). In tubules from salt-loaded rats, NE did not increase DAG concentration, but NE-stimulated 86Rb uptake was reduced by only 23% (P = 0.15). Thus DAG released by NE may stimulate Na+ entry through Na(+)-H+ exchange. NE predominantly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) by activating a protein kinase that is insensitive to DAG and TPA and is inhibited by staurosporine but not by sphingosine. NE may also stimulate K+ efflux through a BaCl-insensitive K+ channel that is inhibited by millimolar furosemide.

  19. Low and high frequency acupuncture stimulation inhibits mental stress-induced sweating in humans via different mechanisms.

    PubMed

    Ogata, Akihiro; Sugenoya, Junichi; Nishimura, Naoki; Matsumoto, Takaaki

    2005-03-31

    The effects of acupuncture stimulation at 5 Hz and 100 Hz on mental stress-induced sweating were analyzed, and the mechanisms involved were examined using the rate of sweat expulsion as an estimate of central sudomotor outflow. Mental arithmetic was imposed on 25 young healthy volunteers for 2 min before, during and after the stimulation. Acupuncture stimulation was delivered to either the Zusanli (leg) or Hegu (hand) acupoint, and the sweat rate was measured quantitatively during mental arithmetic on the palm or the sole, respectively. When stimulation at 5 Hz was applied to the Zusanli acupoint, the palmar sweat rate (paSR), rate of sweat expulsion (Fsw) and paSR/Fsw were reduced during the stimulation, whereas when it was applied to the Hegu acupoint, plantar SR (plSR) and Fsw were reduced, but plSR/Fsw was not altered. When stimulation at 100 Hz was applied to Zusanli, paSR and paSR/Fsw were reduced, but Fsw was unchanged whereas when it was applied to Hegu, neither plSR, Fsw nor plSR/Fsw was altered. The results suggest that acupuncture stimulation at 5 Hz affects both the supraspinal rhythm-generating mechanism and the mechanisms situated below (probably the spinal cord), whereas stimulation at 100 Hz only affects the mechanisms below the rhythm-generating mechanism. Thus, acupuncture stimulation at 5 Hz and at 100 Hz may reduce mental stress-induced sweating through different mechanisms.

  20. Multiday Transcranial Direct Current Stimulation Causes Clinically Insignificant Changes in Childhood Dystonia: A Pilot Study.

    PubMed

    Bhanpuri, Nasir H; Bertucco, Matteo; Young, Scott J; Lee, Annie A; Sanger, Terence D

    2015-10-01

    Abnormal motor cortex activity is common in dystonia. Cathodal transcranial direct current stimulation may alter cortical activity by decreasing excitability while anodal stimulation may increase motor learning. Previous results showed that a single session of cathodal transcranial direct current stimulation can improve symptoms in childhood dystonia. Here we performed a 5-day, sham-controlled, double-blind, crossover study, where we measured tracking and muscle overflow in a myocontrol-based task. We applied cathodal and anodal transcranial direct current stimulation (2 mA, 9 minutes per day). For cathodal transcranial direct current stimulation (7 participants), 3 subjects showed improvements whereas 2 showed worsening in overflow or tracking error. The effect size was small (about 1% of maximum voluntary contraction) and not clinically meaningful. For anodal transcranial direct current stimulation (6 participants), none showed improvement, whereas 5 showed worsening. Thus, multiday cathodal transcranial direct current stimulation reduced symptoms in some children but not to a clinically meaningful extent, whereas anodal transcranial direct current stimulation worsened symptoms. Our results do not support transcranial direct current stimulation as clinically viable for treating childhood dystonia.

  1. Combined Spinal Cord Stimulation and Peripheral Nerve Stimulation for Brachial Plexopathy: A Case Report.

    PubMed

    Choi, Ji Hye; Choi, Shu Chung; Kim, Dong Kyu; Sung, Choon Ho; Chon, Jin Young; Hong, Sung Jin; Lee, Ji Young; Moon, Ho Sik

    2016-03-01

    Brachial plexopathy usually results from an iatrogenic brachial plexus injury and can sometimes cause severe chronic pain and disability. There are a number of possible treatments for this condition, including medication, physical therapy, nerve blocks, and neuromodulation, but they are not always successful. Recently, combined spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been tried for various chronic pain diseases because of their different mechanisms of action.Here, we describe the case of a 54-year-old man who was diagnosed with brachial plexopathy 8 years ago. He underwent video-assisted thoracoscopic surgery to remove a superior mediastinal mass. However, his brachial plexus was damaged during the surgery. Although he had received various treatments, the pain did not improve. For the management of intractable severe pain, he underwent SCS 2 years ago, which initially reduced his pain from numeric rating scale (NRS) 10/10 to NRS 4 - 5/10, but the pain then gradually increased, reaching NRS 8/10, 6 months ago. At that time, he was refractory to other treatments, and we therefore applied PNS in combination with SCS. The PNS electrode was positioned on the radial nerve under ultrasound guidance. After combined PNS and SCS, his background pain disappeared, although a breakthrough pain (NRS 3 - 4/10) was caused intermittently by light touch. Furthermore, the patient's need for analgesics decreased, and he was satisfied with the outcome of this combined treatment. We concluded that combined SCS and PNS is a very useful treatment modality, which can stimulate the target nerve both directly and indirectly, and hence, relieve pain from brachial plexopathy. PMID:27008302

  2. Blood pressure control with selective vagal nerve stimulation and minimal side effects

    NASA Astrophysics Data System (ADS)

    Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

    2014-06-01

    Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

  3. Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats.

    PubMed

    Lyon, Timothy D; Ferroni, Matthew C; Kadow, Brian T; Slater, Richard C; Zhang, Zhaocun; Chang, Victor; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-02-15

    This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under α-chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective β-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P < 0.05) reduced the amplitude and area under the curve of the bladder contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a β-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders. PMID:26676253

  4. The effect of single-pulse transcranial magnetic stimulation and peripheral nerve stimulation on complexity of EMG signal: fractal analysis.

    PubMed

    Cukic, M; Oommen, J; Mutavdzic, D; Jorgovanovic, N; Ljubisavljevic, M

    2013-07-01

    The aim of this study was to examine whether single-pulse transcranial magnetic stimulation (spTMS) affects the pattern of corticospinal activity once voluntary drive has been restored after spTMS-induced EMG silence. We used fractal dimension (FD) to explore the 'complexity' of the electromyography (EMG) signal, and median frequency of the spectra (MDF) to examine changes in EMG spectral characteristics. FD and MDF of the raw EMG epochs immediately before were compared with those obtained from epochs after the EMG silence. Changes in FD and MDF after spTMS were examined with three levels of muscle contraction corresponding to weak (20-40%), moderate (40-60%) and strong (60-80% of maximal voluntary contraction) and three intensities of stimulation set at 10, 20 and 30% above the resting motor threshold. FD was calculated using the Higuchi fractal dimension algorithm. Finally, to discern the origin of FD changes between the CNS and muscle, we compared the effects of spTMS with the effects of peripheral nerve stimulation (PNS) on FD and MDF. The results show that spTMS induced significant decrease in both FD and MDF of EMG signal after stimulation. PNS did not have any significant effects on FD nor MDF. Changes in TMS intensity did not have any significant effect on FD or MDF after stimulation nor had the strength of muscle contraction. However, increase in contraction strength decreased FD before stimulation but only between weak and moderate contraction. The results suggest that the effects of spTMS on corticospinal activity, underlying voluntary motor output, outlast the TMS stimulus. It appears that the complexity of the EMG signal is reduced after spTMS, suggesting that TMS alters the dynamics of the ongoing corticospinal activity most likely temporarily synchronizing the neural network activity. Further studies are needed to confirm whether observed changes after TMS occur at the cortical level. PMID:23652725

  5. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  6. Vestibular stimulation by magnetic fields

    PubMed Central

    Ward, Bryan K.; Roberts, Dale C.; Della Santina, Charles C.; Carey, John P.; Zee, David S.

    2015-01-01

    Individuals working next to strong static magnetic fields occasionally report disorientation and vertigo. With the increasing strength of magnetic fields used for magnetic resonance imaging (MRI) studies, these reports have become more common. It was recently learned that humans, mice and zebrafish all demonstrate behaviors consistent with constant peripheral vestibular stimulation while inside a strong, static magnetic field. The proposed mechanism for this effect involves a Lorentz force resulting from the interaction of a strong static magnetic field with naturally occurring ionic currents flowing through the inner ear endolymph into vestibular hair cells. The resulting force within the endolymph is strong enough to displace the lateral semicircular canal cupula, inducing vertigo and the horizontal nystagmus seen in normal mice and in humans. This review explores the evidence for interactions of magnetic fields with the vestibular system. PMID:25735662

  7. Electrode array for neural stimulation

    DOEpatents

    Wessendorf, Kurt O.; Okandan, Murat; Stein, David J.; Yang, Pin; Cesarano, III, Joseph; Dellinger, Jennifer

    2011-08-16

    An electrode array for neural stimulation is disclosed which has particular applications for use in a retinal prosthesis. The electrode array can be formed as a hermetically-sealed two-part ceramic package which includes an electronic circuit such as a demultiplexer circuit encapsulated therein. A relatively large number (up to 1000 or more) of individually-addressable electrodes are provided on a curved surface of a ceramic base portion the electrode array, while a much smaller number of electrical connections are provided on a ceramic lid of the electrode array. The base and lid can be attached using a metal-to-metal seal formed by laser brazing. Electrical connections to the electrode array can be provided by a flexible ribbon cable which can also be used to secure the electrode array in place.

  8. Acupuncture stimulation and neuroendocrine regulation.

    PubMed

    Yu, Jung-Sheng; Zeng, Bai-Yun; Hsieh, Ching-Liang

    2013-01-01

    Acupuncture has been used to treat different conditions for at least 3000 years in China and has gained increasing acceptance worldwide. The acupuncture needle inserted into the muscle layer at the acupoint produces the so-called obtaining qi sensation that causes the excitation of A-δ and C-fibers of the muscle tissue, resulting in afferent signals. The afferent signals pass through the dorsal horn cells of the spinal cord ascending to the brain, such as the hypothalamus, enhancing the release of neuropeptides and hormones, and these afferent signals in the spinal segment may innervate the visceral organ, inducing effect on visceral function. Here, we reviewed the effect of acupuncture stimulation on neuropeptides and hormones, including β-endorphin, serotonin, oxytocin, adrenocorticotropic hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, cholecystokinin, and acetylcholine, as well as insulin sensitivity, immunomodulation (anti-inflammation), and autonomic nerve activity. PMID:24215920

  9. [Use of erythropoiesis stimulating agents].

    PubMed

    Lapierre, A; Souquet, P-J

    2014-02-01

    Anemia is fairly common in lung neoplasms and adequate management can influence both the prognosis and the quality of life of patients. Anemia can stem from diverse mechanisms, and its management must include the search for correctable causes (iron deficiency, inflammation, disease- or treatment-related), and their subsequent treatment. Use of erythropoiesis stimulating agents, namely recombinant erythropoietin, results in hemoglobin increase, fewer blood transfusions, and better quality of life. However, there is also a significant increase in thromboembolic risk associated with this treatment, and their effect on overall survival is still debated. Thus, their use must be restricted to patients treated with palliative intent, receiving chemotherapy but no radiotherapy, with a baseline hemoglobin level under 100 g/L, and target hemoglobin level must not exceed 120 g/L.

  10. Low frequency chronic electrical stimulation of normal and dystrophic chicken muscle.

    PubMed Central

    Barnard, E A; Barnard, P J; Jarvis, J C; Lai, J

    1986-01-01

    The fast-twitch posterior latissimus dorsi muscle of normal and genetically dystrophic chickens was subjected to continuous indirect electrical stimulation at 10 Hz for periods of 4-8 weeks. To sustain this in vivo nerve stimulation an internally implantable miniature stimulator device was designed. This regime of stimulation caused complete fatigue of the normal muscle within 5 min of its initiation. The dystrophic muscles maintained a very small degree of contractile activity during this initial phase. Tangible twitching of the muscle returned in 5 week birds between 3 and 5 days and in 10 week birds between 11 and 16 days after implantation. After 4 weeks of stimulation, no significant change was measured in the time-to-peak of the isometric twitch response, nor in the half-relaxation time. The resistance to fatigue was significantly increased in the stimulated muscles when tested with a series of tetani at 40 Hz. The mean fibre area was decreased, in all muscles stimulated for longer than 3 weeks, in comparison to their contralateral controls, except where fibre splitting in dystrophic birds abnormally reduced the control value. The majority fibre type of the muscle was changed from type IIB to IIA. The histochemical reactions for both NADH-linked oxidation and phosphorylase were distinctly increased in the stimulated muscles. In normal muscle, stimulation increased somewhat the number of nuclei per unit area and changed their intracellular distribution, so that a greater proportion was found adjacent to the sarcolemma. The normal posterior latissimus dorsi muscle responded to chronic stimulation with increases of 3-6-fold in its acetylcholinesterase (AChE) activity. The maximum change in AChE occurred after 2 weeks stimulation; a steady level, 3 times that of the control unstimulated muscle, persisted at later times. Chronic stimulation suppressed the over-production of AChE that is characteristic of dystrophic chicken fast-twitch muscle, to attain a level

  11. Pattern-onset stimulation boosts central multifocal VEP responses.

    PubMed

    Hoffmann, Michael B; Straube, Sirko; Bach, Michael

    2003-01-01

    Multifocal visual evoked potentials (VEP) allow one to assess whether stimulation at specific visual field locations elicits cortical activity; it might therefore enable us to conduct objective visual field perimetry. However, due to the cortical folding, which differs markedly between subjects, a particular electroencephalogram generator may fail to project signal on some recording electrodes. This may lead to false alarms for potential scotomata. Here we compare pattern-reversal and pattern-onset stimulation in their efficacy to activate the visual cortex and recorded mfVEPs to 60 locations comprising a visual field of 44 degrees diameter. We report three main findings: (1) Pattern-onset compared to pattern-reversal enhances the amplitude by 30% for stimulation of the central visual field (<10 degrees radius), while evoking 30% less response in the periphery (>15 degrees ). (2) Although pattern-onset and pattern-reversal responses differ markedly in their eccentricity dependence, they have a similar topographical distribution. (3) By combining both stimuli, the number of false positives was reduced to less than 1.5% of the visual field locations tested. We conclude that pattern-onset and pattern-reversal activate identical visual cortical areas but target different neural mechanisms within these areas. Furthermore, pattern-onset stimulation greatly increases the sensitivity of the mfVEP to assess the cortical representation of the central 10 degrees of the visual field. PMID:12901714

  12. Neuroendocrine regulation of thyroid-stimulating hormone secretion in amphibians.

    PubMed

    Okada, Reiko; Kobayashi, Tetsuya; Yamamoto, Kazutoshi; Nakakura, Takashi; Tanaka, Shigeyasu; Vaudry, Hubert; Kikuyama, Sakae

    2009-04-01

    The hypothalamic peptides thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and corticotropin-releasing factor (CRF), which have been postulated as acting as thyroid-stimulating hormone (TSH)-releasing hormone in amphibians, were tested for their activity by employing a recently developed radioimmunoassay for bullfrog (Rana catesbeiana) TSH. CRF markedly stimulated the release of TSH from both adult and larval bullfrog pituitary cells. Both TRH and GnRH moderately stimulated the release of TSH from adult pituitary cells but not from larval ones. The release of TSH was also enhanced by bullfrog hypothalamic extracts. The hypothalamic extract-evoked release of TSH was markedly reduced by a CRF receptor antagonist, suggesting that CRF and/or CRF-related peptides are the main TSH-releasing factors occurring in the bullfrog hypothalamus. Experiments using CRF receptor agonists and antagonists revealed that CRF acts through the type 2 receptor. With regard to other hypothalamic substances that influence the release of TSH, pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide were found to be potent stimulators and somatostatin an inhibitor of TSH release. Thus, it becomes clear that the main regulatory peptides controlling TSH secretion in amphibians are different from those in mammals. Triiodothyronine did not affect the basal release of TSH from the pituitary of either larval or adult bullfrogs but suppressed the CRF-induced release of TSH, suggesting that negative feedback by thyroid hormone is functioning both in larvae and adults.

  13. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences.

    PubMed

    Fauser, Bart C J M; Devroey, Paul

    2003-07-01

    Most clinicians working in in vitro fertilization (IVF) centers worldwide have taken for granted for more than a decade the paradigm of so-called 'controlled' ovarian hyperstimulation, using maximum stimulation by exogenous gonadotropins, together with the gonadotropin-releasing hormone (GnRH) agonist long-protocol. Potential detrimental effects of this approach with regard to oocyte quality, corpus luteum function and endometrial receptivity have been largely ignored. These factors might by themselves have a major impact on IVF outcome and should therefore be considered seriously. The recent introduction of GnRH antagonists along with the current emphasis on the need for transfer of a reduced number of embryos enables a careful re-evaluation of current IVF strategies. We can now render stimulation protocols simpler, starting with a spontaneous menstrual cycle, allowing for more subtle interference with single dominant follicle selection. Here, we discuss recent approaches to ovarian stimulation, the induction of oocyte maturation, and effects of these altered follicular phase interventions on corpus luteum function following ovarian stimulation.

  14. Modeling of a Segmented Electrode for Desynchronizing Deep Brain Stimulation

    PubMed Central

    Buhlmann, J.; Hofmann, L.; Tass, P. A.; Hauptmann, C.

    2011-01-01

    Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders like Parkinson’s disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates nerve fibers and cell bodies in the vicinity. Even though the different target nuclei display considerable differences in their anatomical structure, only few types of electrodes are currently commercially available. It is desirable to adjust the electric field and in particular the volume of tissue activated around the electrode with respect to the corresponding target nucleus in a such way that side effects can be reduced. Furthermore, a more selective and partial activation of the target structure is desirable for an optimal application of novel stimulation strategies, e.g., coordinated reset neuromodulation. Hence we designed a DBS electrode with a segmented design allowing a more selective activation of the target structure. We created a finite element model (FEM) of the electrode and analyzed the volume of tissue activated for this electrode design. The segmented electrode activated an area in a targeted manner, of which the dimension and position relative to the electrode could be controlled by adjusting the stimulation parameters for each electrode contact. According to our computational analysis, this directed stimulation might be superior with respect to the occurrence of side effects and it enables the application of coordinated reset neuromodulation under optimal conditions. PMID:22163220

  15. A Computational Framework for Electrical Stimulation of Vestibular Nerve.

    PubMed

    Marianelli, Prisca; Capogrosso, Marco; Bassi Luciani, Lorenzo; Panarese, Alessandro; Micera, Silvestro

    2015-09-01

    The vestibular organs are very important to generate reflexes critical for stabilizing gaze and body posture. Vestibular diseases significantly reduce the quality of life of people who are affected by them. Some research groups have recently started developing vestibular neuroprostheses to mitigate these symptoms. However, many scientific and technological issues need to be addressed to optimise their use in clinical trials. We developed a computational model able to mimic the response of human vestibular nerves and which can be exploited for "in-silico" testing of new strategies to design implantable vestibular prostheses. First, a digital model of the vestibular system was reconstructed from anatomical data. Monopolar stimulation was delivered at different positions and distances from ampullary nerves. The electrical potential induced by the injected current was computed through finite-element methods and drove extra-cellular stimulation of fibers in the vestibular, facial, and cochlear nerves. The electrical activity of vestibular nerves and the resulting eye movements elicited by different stimulation protocols were investigated. A set of electrode configurations was analyzed in terms of selectivity at increasing injected current. Electrode position along the nerve plays a major role in producing undesired activity in other nontargeted nerves, whereas distance from the fiber does not significantly affect selectivity. Indications are provided to minimize misalignment in nonoptimal electrode locations. Eye movements elicited by the different stimulation protocols are calculated and compared to experimental values, for the purpose of model validation. PMID:25751868

  16. Transcranial magnetic stimulation in patients with cerebellar stroke.

    PubMed

    Cruz-Martínez, A; Arpa, J

    1997-01-01

    Conduction time of the central motor pathways (CMCT) by transcranial magnetic stimulation (TMS) was performed within the first two weeks in 7 patients with isolated hemicerebellar lesions after stroke. Cerebellar infarcts were small (< 2 cm in diameter) in 5 patients and no brainstem structure was involved in CT studies. The threshold (3 cases) and CMCT (4 cases) were abnormal or asymmetric by stimulation of the motor cortex contralateral to the impaired hemicerebellum. The follow-up study in 2 patients revealed electrophysiological improvement closely related to clinical cerebellar recovery rate. CMCT was significantly longer by cortex stimulation contralateral to the impaired hemicerebellum than by ipsilateral stimulation. Prolonged CMCT was significantly correlated with the rated severity of cerebellar signs. Increased threshold may be due to depressed facilitating action of the deep cerebellar nuclei on contralateral motor cortex. Abnormal CMCT might result in reduced size and increased dispersion of the efferent volleys. Recovery of electrophysiological results could represent in part true potentially reversible functional deficit. Whichever the pathophysiological mechanisms involved, our results demonstrate that the cerebellum dysfunction plays a role in the abnormalities of CMCT elicited by TMS.

  17. Acetylation mediates Cx43 reduction caused by electrical stimulation

    PubMed Central

    Meraviglia, Viviana; Azzimato, Valerio; Colussi, Claudia; Florio, Maria Cristina; Binda, Anna; Panariti, Alice; Qanud, Khaled; Suffredini, Silvia; Gennaccaro, Laura; Miragoli, Michele; Barbuti, Andrea; Lampe, Paul D.; Gaetano, Carlo; Pramstaller, Peter P.; Capogrossi, Maurizio C.; Recchia, Fabio A.; Pompilio, Giulio; Rivolta, Ilaria; Rossini, Alessandra

    2015-01-01

    Communication between cardiomyocytes depends upon Gap Junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylases (HAT) and deacetylases (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 hours significantly reduced Connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43. PMID:26264759

  18. Foamed sand provides improved stimulation results from Devonian Shale

    SciTech Connect

    Strang, D.L.; Norton, J.L.

    1983-11-01

    Generally, water saturations in the Devonian Shale are low. Production records indicate minimal, if any, water in the areas producing gas or gas and oil. This low water saturation appears to be the key to stimulating the shale, especially in the oil-producing areas. The introduction of water in the stimulation fluid appears to reduce the permeability to oil, which is reflected in poorer production. The relative permeability reduction seems to be more of a problem than particle migration or clay swelling and could explain the good initial results from straight nitrogen treatments. However, the lack of a proppant, even with low closure stress, leads to very rapid declines. Water-base stimulation fluids appear to increase water saturation in the Devonian Shale. Use of 90+ quality foam with sand should provide a method of minimizing saturation changes while creating a propped fracture. Initial results indicate this technique provides better sustained production increases in the Devonian Shale. This paper defines areas of production, describes the geology and presents physical data of the Devonian Shale. It also compares results of several types of treatments that have been used in the Devonian Shale. These results indicate 90+ quality foam with sand should provide an improved stimulation technique for this formation.

  19. Mimicking muscle activity with electrical stimulation

    NASA Astrophysics Data System (ADS)

    Johnson, Lise A.; Fuglevand, Andrew J.

    2011-02-01

    Functional electrical stimulation is a rehabilitation technology that can restore some degree of motor function in individuals who have sustained a spinal cord injury or stroke. One way to identify the spatio-temporal patterns of muscle stimulation needed to elicit complex upper limb movements is to use electromyographic (EMG) activity recorded from able-bodied subjects as a template for electrical stimulation. However, this requires a transfer function to convert the recorded (or predicted) EMG signals into an appropriate pattern of electrical stimulation. Here we develop a generalized transfer function that maps EMG activity into a stimulation pattern that modulates muscle output by varying both the pulse frequency and the pulse amplitude. We show that the stimulation patterns produced by this transfer function mimic the active state measured by EMG insofar as they reproduce with good fidelity the complex patterns of joint torque and joint displacement.

  20. Increased skin temperature during transcutaneous electrical stimulation.

    PubMed

    Abram, S E; Asiddao, C B; Reynolds, A C

    1980-01-01

    Conflicting reports have appeared in the literature concerning the effects of transcutaneous electrical nerve stimulation on skin temperature. This report studied 33 patients with chronic pain involving one extremity (13 upper, 20 lower) to determine whether changes in sympathetic tone, as reflected in skin temperature, occurred in response to electrical stimulation of painful areas. Stimulation was carried out for 20 to 45 minutes. Skin temperatures were measured from the thumbs or great toes of stimulated and contralateral extremities before and during stimulation. Skin temperature rose 2.5 +/- 0.7 (mean +/- SEM) in both the ipsilateral and contralateral extremity in patients who experienced relief of pain during stimulation. There was no significant change in skin temperature in patients who experienced no relief.

  1. Electrical carotid sinus stimulation: chances and challenges in the management of treatment resistant arterial hypertension.

    PubMed

    Chobanyan-Jürgens, Kristine; Jordan, Jens

    2015-09-01

    Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

  2. Distributed clock gating for power reduction of a programmable waveform generator for neural stimulation.

    PubMed

    Noorsal, Emilia; Sooksood, Kriangkrai; Bihr, Ulrich; Becker, Joachim; Ortmanns, Maurits

    2012-01-01

    This paper describes how to employ distributed clock gating to achieve an overall low power design of a programmable waveform generator intended for a neural stimulator. The power efficiency is enabled using global timing control combined with local amplitude distribution over a bus to the local stimulator frontends. This allows the combination of local and global clock gating for complete sub-blocks of the design. A counter and a shifter employed at the local digital stimulator reduce the design complexity for the waveform generation and thus the overall power consumptions. The average power results indicate that 63% power can be saved for the global stimulator control unit and 89-96% power can be saved for the local digital stimulator by using the proposed approach. The circuit has been implemented and successfully tested in a 0.35 µm AMS HVCMOS technology.

  3. Stimulation of the periaqueductal gray matter of the rat produces a preferential ipsilateral antinociception.

    PubMed

    Levine, R; Morgan, M M; Cannon, J T; Liebeskind, J C

    1991-12-13

    The few studies analyzing somatotopic organization of stimulation-produced antinociception (SPA) from the periaqueductal gray matter (PAG) have reported contradictory results. In the present study, the distribution of SPA on the hindquarters was assessed by measuring the threshold for inhibition of withdrawal reflexes to noxious heat applied to the hindpaws and tail in pentobarbital-anesthetized rats. Of the 3 body regions tested, the hindpaw contralateral to the stimulating electrode required the highest level of PAG stimulation to inhibit withdrawal. Reducing the intensity of the heat stimulus applied to the hindpaws caused a concomitant reduction in SPA threshold. As before, a higher stimulation current was needed to inhibit the withdrawal reflex in the contralateral than in the ipsilateral paw. These data indicate the antinociception from PAG stimulation is not equally distributed throughout the body, and that the intensity of the noxious stimulus influences the threshold for SPA. PMID:1815821

  4. Electrical stimulation therapy improves sleep respiratory parameters in obstructive sleep apnea syndrome: a meta-analysis.

    PubMed

    Tan, Jie-wen; Qi, Wei-wei; Ye, Rui-xin; Wu, Yuan-yuan

    2013-10-01

    Recent clinical trials have shown that electrical stimulation has beneficial effects in obstructive sleep apnea syndrome (OSAS). The purpose of this study was to evaluate the efficacy of electrical stimulation therapy for OSAS with a meta-analysis. The meta-analysis of all relative studies was performed through searching international literature, including PUBMED, CNKI, and EMBASE databases. This literature analysis compared all patients undergoing electrical stimulation therapy with respect to the respiratory disturbance index (RDI) and changes in sleep structure. Six studies were selected involving a total of 91 patients. The meta-analysis indicated that electrical stimulation therapy reduced RDI, longest apnea time, and improved the minimum SaO2. Based on the evidence found, electrical stimulation may be a potential therapy for OSAS, warranting further clinical trials.

  5. Analysis of Facial Expression by Taste Stimulation

    NASA Astrophysics Data System (ADS)

    Tobitani, Kensuke; Kato, Kunihito; Yamamoto, Kazuhiko

    In this study, we focused on the basic taste stimulation for the analysis of real facial expressions. We considered that the expressions caused by taste stimulation were unaffected by individuality or emotion, that is, such expressions were involuntary. We analyzed the movement of facial muscles by taste stimulation and compared real expressions with artificial expressions. From the result, we identified an obvious difference between real and artificial expressions. Thus, our method would be a new approach for facial expression recognition.

  6. A Microcomputer-Based Neurophysiological Stimulator

    PubMed Central

    Halter, John

    1979-01-01

    A neurophysiological stimulator is presented which utilizes TTL hardware controlled by a microcomputer. Up to four channels of stimulation are provided, each of which consists of a TTL-Based Pulse Generator. Operating parameters are entered into the stimulator via a front panel in a format familiar to the clinician. Operating parameters may be investigated and modified at any time by another computer, thereby enabling the implementation of more complex clinical procedures. ImagesFigure 1Figure 4

  7. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    A literature search on reservoir and/or well stimulation techniques suitable for application in geothermal fields is presented. The literature on stimulation techniques in oil and gas field applications was also searched and evaluated as to its relevancy to geothermal operations. The equivalent low-temperature work documented in the open literature is cited, and an attempt is made to evaluate the relevance of this information as far as high-temperature stimulation work is concerned. Clays play an important role in any stimulation work. Therefore, special emphasis has been placed on clay behavior anticipated in geothermal operations. (MHR)

  8. Transcranial Direct Current Stimulation in Stroke Recovery

    PubMed Central

    Schlaug, Gottfried; Renga, Vijay; Nair, Dinesh

    2009-01-01

    TDCS - Transcranial Direct Current Stimulation - is an emerging technique of non-invasive brain stimulation that has been found useful in examining cortical function in normal subjects and in facilitating treatments of various neurological disorders. A better understanding of adaptive as well as maladaptive post-stroke neuroplasticity and its modulation through non-invasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We will review TDCS’s role as a facilitator of stroke recovery, the different modes of transcranial direct current stimulation, and the potential mechanisms underlying the neural effects of TDCS. PMID:19064743

  9. External Dentin Stimulation Induces ATP Release in Human Teeth

    PubMed Central

    Wang, C.; Fujita, T.; Malmstrom, H.S.; Nedergaard, M.; Ren, Y.F.; Dirksen, R.T.

    2015-01-01

    ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation-dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation–induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation–induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain. PMID:26130258

  10. Influence of transcranial magnetic stimulation on spike-wave discharges in a genetic model of absence epilepsy.

    PubMed

    Godlevsky, Leonid S; Kobolev, Evgeniy V; van Luijtelaar, Egidius L J M; Coenen, Antony M L; Stepanenko, Konstantin I; Smirnov, Igor V

    2006-12-01

    Transcranial magnetic stimulation (TMS) impulses, (0.5 Hz, 3 impulses) were presented at threshold intensity to male WAG/Rij rats. One group received stimuli, which involved motor responses of hindlimbs, rats of the second group received sham stimulation. Electrocorticograms (ECoG) were recorded before and up to 2 hr from the moment of transcranial magnetic stimulation. It was established that such stimulation engendered a reduction of spike-wave discharge (SWD) bursts duration. This effect was most pronounced in 30 min from the moment of cessation of stimulation, when a decrease of 31.4% was noted in comparison with sham-stimulated control group. The number of bursts of spike-wave discharges was reduced, but did not reach significant difference when compared both with pre-stimulative base-line level and with sham-stimulated control rats. Bursts of spike-wave discharges restored up to pre-stimulative level in 90-150 minutes from the moment of cessation of transcranial stimulation. It can be concluded that transcranical magnetic stimulation possessed an ability to engender short-time suppression of bursts of spike-wave discharges in WAG/Rij rats. PMID:17176666

  11. American Society of Clinical Oncology guidelines for the use of hematopoietic colony-stimulating factors.

    PubMed

    Ozer, H

    1996-01-01

    The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce the likelihood of neutropenic complications due to chemotherapy. Clinical benefit has been shown, but the high cost of colony-stimulating factors has led to concern about their appropriate use. The American Society of Clinical Oncology has established evidence-based, clinical practice guidelines for the use of colony-stimulating factors in patients who are not enrolled in clinical trials. An expert multidisciplinary panel reviewed the clinical data documenting the activity of colony-stimulating factors. For each common clinical situation, the panel formulated a guideline to encourage reasonable use of colony-stimulating factors to preserve effectiveness but discourage excess use when little marginal benefit is anticipated. Outcomes considered in evaluating colony stimulating factor benefit included duration of neutropenia, incidence of febrile neutropenia, incidence and duration of antibiotic use, frequency and duration of hospitalization, infectious mortality, chemotherapy dose intensity, chemotherapy efficacy, quality of life, colony-stimulating factor toxicity, and economic impact. To the extent that these data were available, the panel placed greatest value on survival benefit, reduction in rates of febrile neutropenia, decreased hospitalization, and reduced costs. Lesser value was placed on alterations in absolute neutrophil counts.

  12. Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea.

    PubMed Central

    Hida, W.; Okabe, S.; Miki, H.; Kikuchi, Y.; Taguchi, O.; Takishima, T.; Shirato, K.

    1994-01-01

    BACKGROUND--It has previously been reported that short term submental stimulation can reduce the frequency of apnoea and improve sleep architecture in patients with obstructive sleep apnoea. The effects of submental stimulation during consecutive nights on apnoea or on daytime sleepiness have not, however, been studied. METHODS--Patients with obstructive sleep apnoea were studied by polysomnography on a control night, for five consecutive nights of submental stimulation, and on three following nights (n = 8). A multiple sleep latency test (MSLT) (n = 8) and measurement of the upper airway resistance (n = 5) were performed during the day after the polysomnographic study, on the control night, and on the fifth stimulation night. In an additional five patients with obstructive sleep apnoea, matched for age, sex, and weight, the effects of two nights of stimulation were examined for comparison. Submental stimulation began when an apnoea lasted for five seconds and stopped with the resumption of breathing as detected by oronasal flow. RESULTS--The apnoea index, the number of times per hour that SaO2 dropped below 85% (SaO2 < 85%/hour), and the total apnoea duration expressed as a percentage of total sleep time during stimulation nights decreased to approximately 50% of the corresponding values on the control night. This improvement persisted for at least two nights after the five consecutive stimulation nights, but not after the two consecutive stimulation nights. Sleep architecture and MSLT following the stimulation nights improved but upper airway resistance did not change. CONCLUSIONS--Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing. PMID:8016764

  13. Transcutaneous spinal cord direct current stimulation inhibits the lower limb nociceptive flexion reflex in human beings.

    PubMed

    Cogiamanian, Filippo; Vergari, Maurizio; Schiaffi, Elena; Marceglia, Sara; Ardolino, Gianluca; Barbieri, Sergio; Priori, Alberto

    2011-02-01

    Aiming at developing a new, noninvasive approach to spinal cord neuromodulation, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in the central pain pathways in human beings. A double-blind crossover design was used to investigate the effects of anodal direct current (2mA, 15min) applied on the skin overlying the thoracic spinal cord on the lower-limb flexion reflex in a group of 11 healthy volunteers. To investigate whether transcutaneous spinal cord DC stimulation (tsDCS) acts indirectly on the nociceptive reflex by modulating excitability in mono-oligosynaptic segmental reflex pathways, we also evaluated the H-reflex size from soleus muscle after tibial nerve stimulation. In our healthy subjects, anodal thoracic tsDCS reduced the total lower-limb flexion reflex area by 40.25% immediately after stimulation (T0) and by 46.9% 30min after stimulation offset (T30). When we analyzed the 2 lower-limb flexion reflex components (RII tactile and RIII nociceptive) separately, we found that anodal tsDCS induced a significant reduction in RIII area with a slight but not significant effect on RII area. After anodal tsDCS, the RIII area decreased by 27% at T0 and by 28% at T30. Both sham and active tsDCS left all the tested H-reflex variables unchanged. None of our subjects reported adverse effects after active stimulation. These results suggest that tsDCS holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain. Thoracic transcutaneous direct current stimulation induces depression of nociceptive lower limb flexion reflex in human beings that persists after stimulation offset; this form of stimulation holds promise as a tool that is complementary or alternative to drugs and invasive spinal cord electrical stimulation for managing pain.

  14. Unilateral Subthalamic Nucleus Stimulation Has a Measurable Ipsilateral Effect on Rigidity And Bradykinesia in Parkinson Disease

    PubMed Central

    Tabbal, Samer D.; Ushe, Mwiza; Mink, Jonathan W.; Revilla, Fredy J.; Wernle, Angie R.; Hong, Minna; Karimi, Morvarid; Perlmutter, Joel S.

    2008-01-01

    Background Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. Methods In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity (n= 42), bradykinesia (n= 38), and gait speed (n= 45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. Results All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. Conclusions Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS. These findings suggest that unilateral STN DBS alters pathways that affect rigidity and bradykinesia bilaterally but do not support the clinical use of unilateral STN DBS since bilateral DBS clearly provides greater benefit. PMID:18329019

  15. Draft Genome Sequence of Pelosinus fermentans JBW45, Isolated during In Situ Stimulation for Cr(VI) Reduction

    PubMed Central

    Bowen De León, Kara; Young, Mary Lynn; Camilleri, Laura B.; Brown, Steven D.; Skerker, Jeffrey M.; Deutschbauer, Adam M.; Arkin, Adam P.

    2012-01-01

    Pelosinus fermentans JBW45 is an anaerobic, lactate-fermenting bacterium isolated from Cr(VI)-contaminated groundwater at the Hanford Nuclear Reservation 100-H site (Washington) that was collected after stimulation with a polylactate compound. The genome sequence of this organism will provide insight into the metabolic potential of a predominant population during stimulation for metal-reducing conditions. PMID:22965085

  16. Ovarian stimulation in patients with breast cancer.

    PubMed

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  17. Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADP.

    PubMed

    Bao, Haiying; Kasten, Shane A; Yan, Xiaohua; Hiromasa, Yasuaki; Roche, Thomas E

    2004-10-26

    Pyruvate dehydrogenase kinase 2 (PDK2) activity is stimulated by NADH and NADH plus acetyl-CoA via the reduction and reductive acetylation of the lipoyl groups of the dihydrolipoyl acetyltransferase (E2) component. Elevated K(+) and Cl(-) were needed for significant stimulation. Stimulation substantially increased both k(cat) and the K(m) for ATP; the fractional stimulation increased with the level of ATP. With an E2 structure lacking the pyruvate dehydrogenase (E1) binding domain, stimulation of PDK2 was retained, the K(m) for E1 decreased, and the equilibrium dissociation constant for ATP increased but remained much lower than the K(m) for ATP. Stimulation of PDK2 activity greatly reduced the fraction of bound ADP. These results fit an ordered reaction mechanism with ATP binding before E1 and stimulation increasing the rate of dissociation of ADP. Conversion of all of the lipoyl groups in the E2 60mer to the oxidized form (E2(ox)) greatly reduced k(cat) and the K(m) of PDK2 for ATP. Retention over an extended period of time of a low portion of reduced lipoyl groups maintains E2 in a state that supported much higher PDK2 activity than short-term (5 min) reduction of a large portion of lipoyl groups of E2(ox), but reduction of E2(ox) produced a larger fold stimulation. Reduction and to a greater extent reductive acetylation increased PDK2 binding to E2; conversion to E2(ox) did not significantly hinder binding. We suggest that passing even limited reducing equivalents among lipoyl groups maintains E2 lipoyl domains in a conformation that aids kinase function. PMID:15491151

  18. Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions.

    PubMed

    Makovac, Elena; Garfinkel, Sarah N; Bassi, Andrea; Basile, Barbara; Macaluso, Emiliano; Cercignani, Mara; Calcagnini, Giovanni; Mattei, Eugenio; Agalliu, Daniela; Cortelli, Pietro; Caltagirone, Carlo; Bozzali, Marco; Critchley, Hugo

    2015-06-01

    Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets. PMID:25578794

  19. A monolithic integrated low-voltage deep brain stimulator with wireless power and data transmission

    NASA Astrophysics Data System (ADS)

    Zhang, Zhang; Ye, Tan; Jianmin, Zeng; Xu, Han; Xin, Cheng; Guangjun, Xie

    2016-09-01

    A monolithic integrated low-voltage deep brain stimulator with wireless power and data transmission is presented. Data and power are transmitted to the stimulator by mutual inductance coupling, while the in-vitro controller encodes the stimulation parameters. The stimulator integrates the digital control module and can generate the bipolar current with equal amplitude in four channels. In order to reduce power consumption, a novel controlled threshold voltage cancellation rectifier is proposed in this paper to provide the supply voltage of the stimulator. The monolithic stimulator was fabricated in a SMIC 0.18 μm 1-poly 6-metal mixed-signal CMOS process, occupying 0.23 mm2, and consumes 180 μW on average. Compared with previously published stimulators, this design has advantages of large stimulated current (0–0.8 mA) with the double low-voltage supply (1.8 and 3.3 V), and high-level integration. Project supported by the National Natural Science Foundation of China (Nos. 61404043, 61401137), the Key Laboratory of Infrared Imaging Materials and Detectors, Shanghai Institute of Technical Physics, Chinese Academy of Sciences (Nos. IIMDKFJJ-13-06, IIMDKFJJ-14-03), and the Fundamental Research Funds for the Central Universities (No. 2015HGZX0026).

  20. Effects of subthalamic nucleus stimulation and levodopa on the autonomic nervous system in Parkinson's disease

    PubMed Central

    Ludwig, Janne; Remien, Piet; Guballa, Christoph; Binder, Andreas; Binder, Sabine; Schattschneider, Jörn; Herzog, Jan; Volkmann, Jens; Deuschl, Günther; Wasner, Gunnar; Baron, Ralf

    2007-01-01

    Dysfunctions of the autonomic nervous system (ANS) are common in Parkinson's disease (PD). Regarding motor disability, deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option in long lasting PD. The aims of this study were to examine whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and breathing‐induced cutaneous sympathetic vasoconstriction (CVC) were tested in 14 PD patients treated with STN stimulation during “ON” and “OFF” condition of the stimulator. The effects of a single dose of levodopa on ANS were tested in 15 PD patients without DBS. STN stimulation had no influence on cardiovascular ANS functions, whereas CVC was significantly increased. In contrast, levodopa significantly lowered BP and HR at rest and enhanced orthostatic hypotension. Further, HRV, skin perfusion and temperature increased after administration of levodopa. Our results suggest that in contrast to levodopa, STN stimulation has only minor effects on autonomic functions. Since less pharmacotherapy is needed after STN stimulation, reduced levodopa intake results in relative improvement of autonomic function in deep brain stimulated PD patients. PMID:17371906

  1. Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges

    PubMed Central

    Kubera, Katharina M.; Barth, Anja; Hirjak, Dusan; Thomann, Philipp A.; Wolf, Robert C.

    2015-01-01

    This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes. PMID:26528145

  2. Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

    PubMed Central

    Makovac, Elena; Garfinkel, Sarah N; Bassi, Andrea; Basile, Barbara; Macaluso, Emiliano; Cercignani, Mara; Calcagnini, Giovanni; Mattei, Eugenio; Agalliu, Daniela; Cortelli, Pietro; Caltagirone, Carlo; Bozzali, Marco; Critchley, Hugo

    2015-01-01

    Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets. PMID:25578794

  3. Field stimulation of the carotid baroreceptor complex does not compromise baroreceptor function in spontaneously hypertensive rats.

    PubMed

    Kouchaki, Zahra; Georgakopoulos, Dimitrios; Butlin, Mark; Avolio, Alberto P

    2014-01-01

    Field stimulation of the carotid baroreceptors has been successfully used to induce a long-term reduction in blood pressure. However, baroreceptor stimulation may interfere with or compromise the beneficial short-term blood pressure regulation function of the baroreceptors. This study aims to quantify the baroreceptor function before and during acute, unilateral field stimulation of the carotid baroreceptors. Spontaneously Hypertensive Rats (n=7) were anaesthetised and instrumented to measure heart rate and mean arterial pressure (MAP), aortic pulse wave velocity (a surrogate measure of arterial stiffness), abdominal aortic flow and renal artery flow. A custom made field stimulation device was fitted to the left common carotid artery. Baroreceptor function was measured by quantifying heart rate response to MAP change induced by bolus injection of phenylephrine. Field stimulation of the baroreceptors reduced heart rate by 20 bpm (p=0.003) with MAP reduction of 18 mmHg (p=0.008). Maximal barorecep-tor gain without stimulation was -1.20±0.41 bpm/mmHg and during stimulation -1.41±0.52 bpm/mmHg (p=0.59). The MAP at which maximal gain occurred also did not change (152±11, 160±9 mmHg respectively, p=0.22). This study indicates that unilateral field stimulation of the carotid baroreceptor complex, while causing a sustained reduction of arterial pressure, does not alter acute baroreceptor function peak gain. PMID:25570608

  4. Automatic electrical stimulation of abdominal wall muscles increases tidal volume and cough peak flow in tetraplegia.

    PubMed

    Gollee, H; Hunt, K J; Allan, D B; Fraser, M H; McLean, A N

    2008-01-01

    Paralysis of the respiratory muscles in people with tetraplegia affects their ability to breathe and contributes to respiratory complications. Surface functional electrical stimulation (FES) of abdominal wall muscles can be used to increase tidal volume (V_{T}) and improve cough peak flow (CPF) in tetraplegic subjects who are able to breathe spontaneously. This study aims to evaluate the feasibility and effectiveness of a novel abdominal FES system which generates stimulation automatically, synchronised with the subjects' voluntary breathing activity. Four subjects with complete tetraplegia (C4-C6), breathing spontaneously, were recruited. The automatic stimulation system ensured that consistent stimulation was achieved. We compared spirometry during unassisted and FES-assisted quiet breathing and coughing, and measured the effect of stimulation on end-tidal CO_2 (EtCO_2) during quiet breathing. The system dependably recognised spontaneous respiratory effort, stimulating appropriately, and was well tolerated by patients. Significant increases in V_T during quiet breathing (range 0.05-0.23 L) and in CPF (range 0.04-0.49 L/s) were observed. Respiratory rate during quiet breathing decreased in all subjects when stimulated, whereas minute ventilation increased by 1.05-2.07 L/min. The changes in EtCO_2 were inconclusive. The automatic stimulation system augmented spontaneous breathing and coughing in tetraplegic patients and may provide a potential means of respiratory support for tetraplegic patients with reduced respiratory capacity.

  5. Measurement of evoked potentials during thalamic deep brain stimulation

    PubMed Central

    Kent, Alexander R.; Swan, Brandon D.; Brocker, David T.; Turner, Dennis A.; Gross, Robert E.; Grill, Warren M.

    2014-01-01

    Background Deep brain stimulation (DBS) treats the symptoms of several movement disorders, but optimal selection of stimulation parameters remains a challenge. The evoked compound action potential (ECAP) reflects synchronized neural activation near the DBS lead, and may be useful for feedback control and automatic adjustment of stimulation parameters in closed-loop DBS systems. Objectives Determine the feasibility of recording ECAPs in the clinical setting, understand the neural origin of the ECAP and sources of any stimulus artifact, and correlate ECAP characteristics with motor symptoms. Methods The ECAP and tremor response were measured simultaneously during intraoperative studies of thalamic DBS, conducted in patients who were either undergoing surgery for initial lead implantation or replacement of their internal pulse generator. Results There was large subject-to-subject variation in stimulus artifact amplitude, which model-based analysis suggested may have been caused by glial encapsulation of the lead, resulting in imbalances in the tissue impedance between the contacts. ECAP recordings obtained from both acute and chronically implanted electrodes revealed that specific phase characteristics of the signal varied systematically with stimulation parameters. Further, a trend was observed in some patients between the energy of the initial negative and positive ECAP phases, as well as secondary phases, and changes in tremor from baseline. A computational model of thalamic DBS indicated that direct cerebellothalamic fiber activation dominated the clinically measured ECAP, suggesting that excitation of these fibers is critical in DBS therapy. Conclusions This work demonstrated that ECAPs can be recorded in the clinical setting and may provide a surrogate feedback control signal for automatic adjustment of stimulation parameters to reduce tremor amplitude. PMID:25457213

  6. Target structures in the cochlea for infrared neural stimulation (INS)

    NASA Astrophysics Data System (ADS)

    Young, Hunter; Tan, Xiaodong; Richter, Claus-Peter

    2014-03-01

    Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also result in the generation of a stress relaxation wave causing mechanical stimulation of hair cells in the cochlea, creating an optoacoustic response. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

  7. [Deep brain stimulation in schizophrenia].

    PubMed

    Kuhn, J; Bodatsch, M; Sturm, V; Lenartz, D; Klosterkötter, J; Uhlhaas, P J; Winter, C; Gründler, T O J

    2011-11-01

    Deep brain stimulation (DBS) has successfully advanced our treatment options for putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation, more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially, schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here, we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronisation. In conclusion, the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might hinder the use of DBS for schizophrenia at this point in time.

  8. Transcranial Magnetic Stimulation for Schizophrenia.

    PubMed

    Dougall, Nadine; Maayan, Nicola; Soares-Weiser, Karla; McDermott, Lisa M; McIntosh, Andrew

    2015-11-01

    People with schizophrenia typically experience auditory hallucinations or delusions during acute episodes. Although effective drug treatments are available, many have intractable symptoms that do not recover between acute episodes. One proposed alternative to drug treatments is transcranial magnetic stimulation (TMS). To date, many research trials to assess effectiveness of TMS for people with symptoms of schizophrenia have been conducted worldwide. However, there is a lack of consensus on whether TMS should be recommended to be adopted in routine clinical practice. We conducted a systematic review of the literature for all relevant randomized controlled trials (RCTs) comparing TMS with sham or standard treatment. Forty-one trials (1473 participants) survived eligibility criteria and had extractable data. We found significant differences in favor of temporoparietal TMS compared with sham TMS for global state (7 RCTs, n = 224, MD: -0.5, 95% CI: -0.76 to -0.23) and for positive symptoms measured on the Positive and Negative Syndrome Scale (5 RCTs, n = 127, MD: -6.09, 95% CI: -10.95 to -1.22). However, we also found that the quality of trial reporting was frequently suboptimal and the risks of bias were strong or unascertainable for many trial aspects; this led to many results being graded as very low-quality evidence. On that basis, we were unable to definitively support or refute the routine use of TMS in clinical practice. Future definitive trials of TMS with rigorous processes and high-quality reporting are needed.

  9. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, J.W.

    1993-01-01

    The present invention relates to the electrical treatment of biological tissue. In particular, the present invention discloses a device that produces discrete electrical pulse trains for treating osteoporosis and accelerating bone growth. According to its major aspects and broadly stated, the present invention consists of an electrical circuit configuration capable of generating Bassett-type waveforms shown with alternative signals provide for the treatment of either fractured bones or osteoporosis. The signal generator comprises a quartz clock, an oscillator circuit, a binary divider chain, and a plurality of simple, digital logic gates. Signals are delivered efficiently, with little or no distortion, and uniformly distributed throughout the area of injury. Perferably, power is furnished by widely available and inexpensive radio batteries, needing replacement only once in several days. The present invention can be affixed to a medical cast without a great increase in either weight or bulk. Also, the disclosed stimulator can be used to treat osteoporosis or to strengthen a healing bone after the cast has been removed by attaching the device to the patient`s skin or clothing.

  10. Hyperthermia Stimulates HIV-1 Replication

    PubMed Central

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42–45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38–40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity. PMID:22807676

  11. Three-dimensional visual stimulator

    NASA Astrophysics Data System (ADS)

    Takeda, Tsunehiro; Fukui, Yukio; Hashimoto, Keizo; Hiruma, Nobuyuki

    1995-02-01

    We describe a newly developed three-dimensional visual stimulator (TVS) that can change independently the directions, distances, sizes, luminance, and varieties of two sets of targets for both eyes. It consists of liquid crystal projectors (LCP's) that generate the flexible images of targets, Badal otometers that change target distances without changing the visual angles, and relay-lens systems that change target directions. A special control program is developed for real-time control of six motors and two LCP's in the TVS together with a three-dimensional optometer III that simultaneously measures eye movement, accommodation, pupil diameter, and head movement. distance, 0 to -20 D; direction, 16 horizontally and 15 vertically; size, 0-2 deg visual angle; and luminance, 10-2-10 2 cd/m2. The target images are refreshed at 60 Hz and speeds with which the target makes a smooth change (ramp stimuli) are size, 10 deg/s. A simple application demonstrates the performance.

  12. Improved Pain Relief With Burst Spinal Cord Stimulation for Two Weeks in Patients Using Tonic Stimulation: Results From a Small Clinical Study

    PubMed Central

    Courtney, Peter; Espinet, Anthony; Mitchell, Bruce; Russo, Marc; Muir, Andrew; Verrills, Paul

    2015-01-01

    Objectives Conventional spinal cord stimulation (SCS) delivers a tonic waveform with consistent stream of pulses; burst delivers groups of pulses separated by short pulse‐free periods. The current study compared the short‐term safety and efficacy of burst with tonic stimulation in subjects already receiving SCS. Materials and Methods At 4 IRB‐approved sites, 22 subjects previously implanted with an SCS device for intractable, chronic pain gave informed consent and received burst stimulation for 14 days. Subjects reported average daily Visual Analog Scale (VAS) for overall, trunk, and limb pain using tonic stimulation and after 7 and 14 days of burst stimulation. Thoughts about pain were assessed using the Pain Catastrophizing Scale. Areas of paresthesia were assessed during tonic and burst stimulation using body maps. Assessment of patient satisfaction and preferred stimulation occurred after 14 days of burst. Results Average daily overall VAS reduced 46% from a mean of 53.5 (±20.2) mm during tonic SCS to 28.5 (±18.1) mm during burst (p < 0.001); trunk and limb VAS scores were also reduced by 33% and 51%, respectively. During burst, 16 subjects (73%) reported no paresthesia, 5 (23%) reported a reduction, and 1 (4%) reported increased paresthesia. After 14 days, 21 subjects (95%) reported being very satisfied or satisfied with burst. Burst was preferred by 20 subjects (91%), tonic by 1 (5%), and 1 (5%) reported no preference. Better pain relief was the most common reason cited for preference. Conclusions A majority of subjects reported improved pain relief using burst compared with tonic stimulation. Most subjects experienced less paresthesia during burst and preferred burst citing better pain relief. PMID:25879884

  13. Electrocutaneous stimulation system for Braille reading.

    PubMed

    Echenique, Ana Maria; Graffigna, Juan Pablo; Mut, Vicente

    2010-01-01

    This work is an assistive technology for people with visual disabilities and aims to facilitate access to written information in order to achieve better social inclusion and integration into work and educational activities. Two methods of electrical stimulation (by current and voltage) of the mechanoreceptors was tested to obtain tactile sensations on the fingertip. Current and voltage stimulation were tested in a Braille cell and line prototype, respectively. These prototypes are evaluated in 33 blind and visually impaired subjects. The result of experimentation with both methods showed that electrical stimulation causes sensations of touch defined in the fingertip. Better results in the Braille characters reading were obtained with current stimulation (85% accuracy). However this form of stimulation causes uncomfortable sensations. The latter feeling was minimized with the method of voltage stimulation, but with low efficiency (50% accuracy) in terms of identification of the characters. We concluded that electrical stimulation is a promising method for the development of a simple and unexpensive Braille reading system for blind people. We observed that voltage stimulation is preferred by the users. However, more experimental tests must be carry out in order to find the optimum values of the stimulus parameters and increase the accuracy the Braille characters reading.

  14. Stimulated Cherenkov emission in gas dynamics

    SciTech Connect

    Kuzelev, M. V. Rukhadze, A. A.

    2008-11-15

    A linear theory is developed for stimulated Cherenkov emission from planar and cylindrical gas flows in gaseous environments. An analogy is demonstrated between Cherenkov emission in gas dynamics and stimulated Cherenkov electromagnetic emission from a charged particle beam in a medium.

  15. [MRI compatibility of deep brain stimulator].

    PubMed

    Zhang, Yujing

    2013-07-01

    Deep brain stimulation (DBS) therapy develops rapidly in clinical application. The structures of deep brain stimulator and magnetic resonance imaging (MRI) equipment are introduced, the interactions are analyzed, and the two compatible problems of radio frequency (RF) heating and imaging artifact are summarized in this paper.

  16. Stimulation Activities: Age Birth to Five Years.

    ERIC Educational Resources Information Center

    Bloomgarden, Dave

    This handbook provides a collection of stimulation activities that encourage a child's physical and mental growth from birth to five years of age. Emphasis is placed on making stimulation aids that are inexpensive or can be made from scrap materials. Advice is given about ways to carry out designated activities. All activities have been tried and…

  17. Pseudomonas putida Stimulates Primordia on Agaricus bitorquis.

    PubMed

    Colauto, Nelson B; Fermor, Terry R; Eira, Augusto F; Linde, Giani A

    2016-04-01

    Casing layer is one step of Agaricus bisporus cultivation where there is a competitive environment with a high number of microorganisms and diversity interacting with mycelia. It is suggested that a minimal community of these microorganisms would be necessary to stimulate fructification. However, A. bisporus is not able to produce primordia in sterile casing layers or Petri dishes. Thus, the objective of this study was to characterize bacterial microbiota of casing layers from A. bisporus cultivation, isolate, identify and characterize the bacteria responsible for the stimulation of primordium and their action mechanism using Agaricus bitorquis as a primordium stimulation model. Bacterial and Pseudomonas spp. communities of different casing layers of A. bisporus cultivation were collected and quantified. It was concluded that Pseudomonas spp. corresponds to 75-85% of bacterial population of the casing layers in A. bisporus cultivation and among those 12% are Pseudomonas putida. Four biochemical assays were used to identify P. putida. In vitro primordium stimulation of living P. putida and non-living bacterial suspensions, after chemical or physical treatments, was tested using A. bitorquis as a primordium stimulation model. Primordium stimulation assay was registered by photographs, and micrographs of vertical cut of primordium were registered by scanning electron microscope. Interaction of living P. putida with A. bitorquis mycelia is capable of stimulating primordial instead of non-living bacterial suspensions. Stimulation of A. bitorquis primordia does not imply or is related to mycelial growth inhibition, but a hierarchical relation of primordium succession and development is suggested. PMID:26742772

  18. Ultraviolet Light: Some Considerations for Vision Stimulation.

    ERIC Educational Resources Information Center

    Knowlton, Marie

    1986-01-01

    The article examines evidence of visual impairment caused by excessive amounts of ultraviolet (UV) light. Among considerations when using a source of UV light for vision stimulation are the position of the child and teacher, use of window glass filters or protective glasses, and careful recordkeeping of all UV stimulation. (Author/JW)[

  19. Repeated electrical stimulation of reward-related brain regions affects cocaine but not "natural" reinforcement.

    PubMed

    Levy, Dino; Shabat-Simon, Maytal; Shalev, Uri; Barnea-Ygael, Noam; Cooper, Ayelet; Zangen, Abraham

    2007-12-19

    Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction. PMID:18094257

  20. Mechanisms for chelator stimulation of microbial Fe(III) -oxide reduction

    USGS Publications Warehouse

    Lovley, D.R.; Woodward, J.C.

    1996-01-01

    The mechanisms by which nitrilotriacetic acid (NTA) stimulated Fe(III) reduction in sediments from a petroleum-contaminated aquifer were investigated in order to gain insight into how added Fe(III) chelators stimulate the activity of hydrocarbon-degrading, Fe(III)-reducing microorganisms in these sediments, and how naturally occurring Fe(III) chelators might promote Fe(III) reduction in aquatic sediments. NTA solubilized Fe(III) from the aquifer sediments. NTA stimulation of microbial Fe(III) reduction did not appear to be the result of making calcium, magnesium, potassium, or trace metals more available to the microorganisms. Stimulation of Fe(III) reduction could not be attributed to NTA serving as a source of carbon or fixed nitrogen for Fe(III)-reducing bacteria as NTA was not degraded in the sediments. Studies with the Fe(III)-reducing microorganism, Geobacter metallireducens, and pure Fe(III)-oxide forms, demonstrated that NTA stimulated the reduction of a variety of Fe(III) forms, including highly crystalline Fe(III)-oxides such as goethite and hematite. The results suggest that NTA solubilization of insoluble Fe(III)-oxide is an important mechanism for the stimulation of Fe(III) reduction by NTA in aquifer sediments.

  1. Neural origin of evoked potentials during thalamic deep brain stimulation.

    PubMed

    Kent, Alexander R; Grill, Warren M

    2013-08-01

    Closed-loop deep brain stimulation (DBS) systems could provide automatic adjustment of stimulation parameters and improve outcomes in the treatment of Parkinson's disease and essential tremor. The evoked compound action potential (ECAP), generated by activated neurons near the DBS electrode, may provide a suitable feedback control signal for closed-loop DBS. The objectives of this work were to characterize the ECAP across stimulation parameters and determine the neural elements contributing to the signal. We recorded ECAPs during thalamic DBS in anesthetized cats and conducted computer simulations to calculate the ECAP of a population of thalamic neurons. The experimental and computational ECAPs were similar in shape and had characteristics that were correlated across stimulation parameters (R(2) = 0.80-0.95, P < 0.002). The ECAP signal energy increased with larger DBS amplitudes (P < 0.0001) and pulse widths (P < 0.002), and the signal energy of secondary ECAP phases was larger at 10-Hz than at 100-Hz DBS (P < 0.002). The computational model indicated that these changes resulted from a greater extent of neural activation and an increased synchronization of postsynaptic thalamocortical activity, respectively. Administration of tetrodotoxin, lidocaine, or isoflurane abolished or reduced the magnitude of the experimental and computational ECAPs, glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonopentanoic acid (APV) reduced secondary ECAP phases by decreasing postsynaptic excitation, and the GABAA receptor agonist muscimol increased the latency of the secondary phases by augmenting postsynaptic hyperpolarization. This study demonstrates that the ECAP provides information about the type and extent of neural activation generated during DBS, and the ECAP may serve as a feedback control signal for closed-loop DBS.

  2. Neurologic Complications of Psychomotor Stimulant Abuse.

    PubMed

    Sanchez-Ramos, Juan

    2015-01-01

    Psychomotor stimulants are drugs that act on the central nervous system (CNS) to increase alertness, elevate mood, and produce a sense of well-being. These drugs also decrease appetite and the need for sleep. Stimulants can enhance stamina and improve performance in tasks that have been impaired by fatigue or boredom. Approved therapeutic applications of stimulants include attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. These agents also possess potent reinforcing properties that can result in excessive self-administration and abuse. Chronic use is associated with adverse effects including psychosis, seizures, and cerebrovascular accidents, though these complications usually occur in individuals with preexisting risk factors. This chapter reviews the adverse neurologic consequences of chronic psychomotor stimulant use and abuse, with a focus on two prototypical stimulants methamphetamine and cocaine. PMID:26070756

  3. Relief of pain by transcutaneous stimulation.

    PubMed

    Loeser, J D; Black, R G; Christman, A

    1975-03-01

    A series of 198 patients with chronic pain of diverse etiology was carefully analyzed for epidemiologic and descriptive factors which might influence the response to transcutaneous stimulation. The overall series included 12 1/2% with long-term success, and 68% with partial or short-term relief. There were no consistent specific diagnoses, or epidemiologic or descriptive factors that made good results from stimulation predictable. Stimulation of the painful area itself was not always necessary for pain relief. Favorable responses to transcutaneous stimulation were usually correlated with the continued existence of significant sensory input from the painful region. The authors conclude that transcutaneous stimulation is a valuable therapeutic modality for some patients with chronic pain.

  4. Optical nerve stimulation for a vestibular prosthesis

    NASA Astrophysics Data System (ADS)

    Harris, David M.; Bierer, Steven M.; Wells, Jonathon D.; Phillips, James O.

    2009-02-01

    Infrared Nerve Stimulation (INS) offers several advantages over electrical stimulation, including more precise spatial selectivity and improved surgical access. In this study, INS and electrical stimulation were compared in their ability to activate the vestibular branch of the VIIIth nerve, as a potential way to treat balance disorders. The superior and lateral canals of the vestibular system of Guinea pigs were identified and approached with the aid of precise 3-D reconstructions. A monopolar platinum stimulating electrode was positioned near the ampullae of the canals, and biphasic current pulses were used to stimulate vestibular evoked potentials and eye movements. Thresholds and input/output functions were measured for various stimulus conditions. A short pulsed diode laser (Capella, Lockheed Martin-Aculight, Inc., Bothell WA) was placed in the same anatomical position and various stimulus conditions were evaluated in their ability to evoke similar potentials and eye movements.

  5. Advances in functional electrical stimulation (FES).

    PubMed

    Popović, Dejan B

    2014-12-01

    This review discusses the advancements that are needed to enhance the effects of electrical stimulation for restoring or assisting movement in humans with an injury/disease of the central nervous system. A complex model of the effects of electrical stimulation of peripheral systems is presented. The model indicates that both the motor and sensory systems are activated by electrical stimulation. We propose that a hierarchical hybrid controller may be suitable for functional electrical stimulation (FES) because this type of controller acts as a structural mimetic of its biological counterpart. Specific attention is given to the neural systems at the periphery with respect to the required electrodes and stimulators. Furthermore, we note that FES with surface electrodes is preferred for the therapy, although there is a definite advantage associated with implantable technology for life-long use. The last section of the review discusses the potential need to combine FES and robotic systems to provide assistance in some cases. PMID:25287528

  6. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles.

    PubMed

    Kolnes, Anders J; Birk, Jesper B; Eilertsen, Einar; Stuenæs, Jorid T; Wojtaszewski, Jørgen F P; Jensen, Jørgen

    2015-02-01

    Epinephrine increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown, and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or epinephrine (0.02 mg/100 g rat) was injected subcutaneously in Wistar rats (∼130 g) with low (24-h-fasted), normal (normal diet), and high glycogen content (fasted-refed), and epitrochlearis muscles were removed after 3 h and incubated ex vivo, eliminating epinephrine action. Epinephrine injection reduced glycogen content in epitrochlearis muscles with high (120.7 ± 17.8 vs. 204.6 ± 14.5 mmol/kg, P < 0.01) and normal glycogen (89.5 ± 7.6 vs. 152 ± 8.1 mmol/kg, P < 0.01), but not significantly in muscles with low glycogen (90.0 ± 5.0 vs. 102.8 ± 7.8 mmol/kg, P = 0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b, and 1b was higher and GS activity lower in muscles with high compared with low glycogen. GS sites 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where epinephrine decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where epinephrine injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independently of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where epinephrine injection decreased glycogen content. In conclusion, epinephrine stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low, glycogen content. Epinephrine-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content.

  7. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

    PubMed

    Talbot, Sébastien; Abdulnour, Raja-Elie E; Burkett, Patrick R; Lee, Seungkyu; Cronin, Shane J F; Pascal, Maud A; Laedermann, Cedric; Foster, Simmie L; Tran, Johnathan V; Lai, Nicole; Chiu, Isaac M; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M; Kuchroo, Vijay K; Bean, Bruce P; Levy, Bruce D; Woolf, Clifford J

    2015-07-15

    Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  8. Silencing nociceptor neurons reduces allergic airway inflammation

    PubMed Central

    Talbot, Sébastien; Abdulnour, Raja-Elie E.; Burkett, Patrick R.; Lee, Seungkyu; Cronin, Shane J.F.; Pascal, Maud A.; Laedermann, Cedric; Foster, Simmie L.; Tran, Johnathan V.; Lai, Nicole; Chiu, Isaac M.; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M.; Kuchroo, Vijay K.; Bean, Bruce P.; Levy, Bruce D.; Woolf, Clifford J.

    2015-01-01

    Summary Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large pore ion channels to specifically block nociceptors, substantially reduced ovalbumin or house dust mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  9. Stimulation at dorsal and ventral electrode contacts targeted at the subthalamic nucleus has different effects on motor and emotion functions in Parkinson's disease.

    PubMed

    Greenhouse, Ian; Gould, Sherrie; Houser, Melissa; Hicks, Gayle; Gross, James; Aron, Adam R

    2011-02-01

    Motor and emotion processing depend on different fronto-basal ganglia circuits. Distinct sub-regions of the subthalamic nucleus (STN) may modulate these circuits. We evaluated whether stimulation targeted at separate territories in the STN region would differentially affect motor and emotion function. In a double-blind design, we studied twenty Parkinson's disease patients who had deep brain stimulation (DBS) electrodes implanted bilaterally in the STN. We stimulated either dorsal or ventral contacts of the STN electrodes on separate days in each patient and acquired behavioral measures. Dorsal contact stimulation improved motor function by reducing scores on the Unified Parkinson's Disease Rating Scale and by reducing both reaction time and reaction time variability compared to ventral contact stimulation. By contrast, ventral contact stimulation led to an increase in positive emotion compared to dorsal contact stimulation. These results support the hypothesis that different territories within the STN region implement motor and emotion functions. PMID:21184765

  10. Simulation of functional neuromuscular stimulation assisted sit-to-stand movements.

    PubMed

    Gillette, Jason C; Hartman, Eric C

    2003-01-01

    Functional neuromuscular stimulation (FNS) has the potential to enhance the capability for individuals with a spinal cord injury (SCI) to perform activities of daily living. Individuals with SCI have successfully used FNS to stand, but the transition from sitting to standing is often awkward and may require excessive amounts of arm support. The long-term goal of this research project is to provide stimulation patterns that reduce the demands on an FNS user's arms and provide a smooth, stable sit-to-stand transition. A multi-segment, dynamic model has been developed to simulate different combinations of stimulated muscles and stimulation patterns. The model includes individualized anthropometric parameters, active and passive muscle and joint mechanics, and arm support forces (experimentally measured or an assumed pattern). Stimulated muscle properties were derived using SIMM software (Musculographics, Chicago, IL), and the simulations were run in Matlab (Mathworks, Natick, MA). Initial simulation results have estimated that ramped stimulation of the vastus lateralis and semimembranosus muscles reduces the peak vertical arm support forces from 91% to 42% of body weight as compared to unassisted sit-to-stand. Kinematic results also suggested that the hand support forces remained excessive due to a lack of joint coordination and insufficient ankle joint stiffness. In further simulations, additional muscles will be stimulated to increase joint stiffness and stimulation patterns will be designed to mimic able-bodied sit-to-stand motions. This model will be validated and improved using results of sit-to-stand experiments with FNS users once an optimized set of muscles and stimulation patterns has been determined.

  11. Repetitive transcranial magnetic stimulation in anorexia nervosa: a pilot study.

    PubMed

    Van den Eynde, F; Guillaume, S; Broadbent, H; Campbell, I C; Schmidt, U

    2013-02-01

    The search for new treatments to improve outcome in people with anorexia nervosa continues. This pilot study investigated whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex reduces eating disorder related symptoms following exposure to visual and real food stimuli. Safety and tolerability were also assessed. Ten right-handed people with anorexia nervosa underwent one session of rTMS. Subjective experiences related to the eating disorder (e.g. urge to restrict, feeling full etc.) were assessed before and after rTMS. Non-parametric repeated measures tests were used. rTMS was safe and well-tolerated, and resulted in reduced levels of feeling full, feeling fat and feeling anxious. Thus, rTMS may reduce core symptoms of anorexia nervosa. Future research should establish the therapeutic potential of rTMS in anorexia nervosa. PMID:21880470

  12. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    PubMed Central

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-01-01

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

  13. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation.

    PubMed

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-07-16

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  14. Shaping the effects of transcranial direct current stimulation of the human motor cortex.

    PubMed

    Nitsche, M A; Doemkes, S; Karaköse, T; Antal, A; Liebetanz, D; Lang, N; Tergau, F; Paulus, W

    2007-04-01

    Transcranial DC stimulation (tDCS) induces stimulation polarity-dependent neuroplastic excitability shifts in the human brain. Because it accomplishes long-lasting effects and its application is simple, it is used increasingly. However, one drawback is its low focality, caused by 1) the large stimulation electrode and 2) the functionally effective reference electrode, which is also situated on the scalp. We aimed to increase the focality of tDCS, which might improve the interpretation of the functional effects of stimulation because it will restrict its effects to more clearly defined cortical areas. Moreover, it will avoid unwanted reversed effects of tDCS under the reference electrode, which is of special importance in clinical settings, when a homogeneous shift of cortical excitability is needed. Because current density (current strength/electrode size) determines the efficacy of tDCS, increased focality should be accomplished by 1) reducing stimulation electrode size, but keeping current density constant; or 2) increasing reference electrode size under constant current strength. We tested these hypotheses for motor cortex tDCS. The results show that reducing the size of the motor cortex DC-stimulation electrode focalized the respective tDCS-induced excitability changes. Increasing the size of the frontopolar reference electrode rendered stimulation over this cortex functionally inefficient, but did not compromise the tDCS-generated motor cortical excitability shifts. Thus tDCS-generated modulations of cortical excitability can be focused by reducing the size of the stimulation electrode and by increasing the size of the reference electrode. For future applications of tDCS, such paradigms may help to achieve more selective tDCS effects.

  15. Magnesium-dependent stimulation of protein synthesis by the insulin mimic, pervanadate.

    PubMed

    Barnes, D M; Sykes, D B; Smith, J J; Miller, D S

    1995-08-01

    The insulin mimic, peroxide of vanadate (pervanadate), stimulated 35S-methionine incorporation into Xenopus oocyte protein in a Mg(2+)-dependent manner. Reducing the extracellular Mg2+ concentration from 1.0 to 0.1 mM decreased the pervanadate-stimulated component of incorporation by 35%; with 0.01 mM Mg2+ or lower, the pervanadate-stimulated component was abolished. In addition, reducing extracellular Mg2+ to 0.01 mM inhibited about 50% of the insulin-stimulated component of methionine incorporation. Mg2+ depletion had no effects on incorporation in controls or when protein synthesis was stimulated by Zn2+ or bovine growth hormone. Thus, not all substances that stimulated protein synthesis showed a dependence on extracellular Mg2+. Reducing extracellular Ca2+ had no effects on methionine incorporation in control cells or in cells stimulated by pervanadate or insulin. When oocytes maintained in a paraffin oil medium were brought into contact with a 0.5 microliter droplet of buffer containing the Mg2+ indicator dye, mag-fura-2, and pervanadate, apparent droplet Mg2+ decreased rapidly, indicating net uptake by the cells. Insulin also caused a net uptake of Mg2+. In contrast, apparent extracellular Mg2+ was constant when cells were in contact with droplets containing no effectors. Together, these data indicate that extracellular Mg2+, but not Ca2+, is involved in the stimulation of protein synthesis by pervanadate, and to a lesser extent by insulin. Pervanadate appears to induce a net uptake of Mg2+, and this change in membrane transport may be an early event in signalling the increase in translation.

  16. Electrical stimulation to accelerate wound healing

    PubMed Central

    Thakral, Gaurav; LaFontaine, Javier; Najafi, Bijan; Talal, Talal K.; Kim, Paul; Lavery, Lawrence A.

    2013-01-01

    Background There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. PMID:24049559

  17. A fully implantable rodent neural stimulator

    NASA Astrophysics Data System (ADS)

    Perry, D. W. J.; Grayden, D. B.; Shepherd, R. K.; Fallon, J. B.

    2012-02-01

    The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

  18. Numerical dosimetry of transcranial magnetic stimulation coils

    NASA Astrophysics Data System (ADS)

    Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique capable of stimulating neurons by means of electromagnetic induction. TMS can be used to map brain function and shows promise for the diagnosis and treatment of neurological and psychiatric disorders. Calculation of fields induced in the brain are necessary to accurately identify stimulated neural tissue during TMS. This allows the development of novel TMS coil designs capable of stimulating deeper brain regions and increasing the localization of stimulation that can be achieved. We have performed numerical calculations of magnetic and electric field with high-resolution anatomically realistic human head models to find these stimulated brain regions for a variety of proposed TMS coil designs. The realistic head models contain heterogeneous tissue structures and electrical conductivities, yielding superior results to those obtained from the simplified homogeneous head models that are commonly employed. The attenuation of electric field as a function of depth in the brain and the localization of stimulating field have been methodically investigated. In addition to providing a quantitative comparison of different TMS coil designs the variation of induced field between subjects has been investigated. We also show the differences in induced fields between adult, adolescent and child head models to preemptively identify potential safety issues in the application of pediatric TMS.

  19. Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers

    PubMed Central

    Advokat, Claire; Scheithauer, Mindy

    2013-01-01

    Recent increases in attention deficit hyperactivity disorder (ADHD) diagnoses, and the escalation of stimulant prescriptions, has raised concern about diversion and abuse of stimulants, as well as the ethics of using these drugs as “cognitive enhancers.”Such concern appears misplaced in the face of substantial evidence that stimulant drugs do not improve the academic performance of ADHD-diagnosed students. Moreover, numerous studies have found little or no benefit of stimulants on neuropsychological tests of ADHD-diagnosed as well as normal, individuals. This paper examines the apparent paradox: why don't drugs that improve “attention,” produce better academic outcomes in ADHD-diagnosed students? We found that stimulant drugs significantly improved impairment of episodic memory in ADHD-diagnosed undergraduate students. Nevertheless, we also found consistent academic deficits between ADHD students and their non-ADHD counterparts, regardless of whether or not they used stimulant medications. We reviewed the current literature on the behavioral effects of stimulants, to try to find an explanation for these conflicting phenomena. Across a variety of behavioral tasks, stimulants have been shown to reduce emotional reactions to frustration, improve the ability to detect errors, and increase effortful behavior. However, all of these effects would presumably enhance academic performance. On the other hand, the drugs were also found to promote “risky behavior” and to increase susceptibility to environmental distraction. Such negative effects, including the use of drugs to promote wakefulness for last minute study, might explain the lack of academic benefit in the “real world,” despite their cognitive potential. Like many drugs, stimulants influence behavior in multiple ways, depending on the environmental contingencies. Depending on the circumstances, stimulants may, or may not, enhance cognition. PMID:23754970

  20. Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers.

    PubMed

    Advokat, Claire; Scheithauer, Mindy

    2013-01-01

    Recent increases in attention deficit hyperactivity disorder (ADHD) diagnoses, and the escalation of stimulant prescriptions, has raised concern about diversion and abuse of stimulants, as well as the ethics of using these drugs as "cognitive enhancers."Such concern appears misplaced in the face of substantial evidence that stimulant drugs do not improve the academic performance of ADHD-diagnosed students. Moreover, numerous studies have found little or no benefit of stimulants on neuropsychological tests of ADHD-diagnosed as well as normal, individuals. This paper examines the apparent paradox: why don't drugs that improve "attention," produce better academic outcomes in ADHD-diagnosed students? We found that stimulant drugs significantly improved impairment of episodic memory in ADHD-diagnosed undergraduate students. Nevertheless, we also found consistent academic deficits between ADHD students and their non-ADHD counterparts, regardless of whether or not they used stimulant medications. We reviewed the current literature on the behavioral effects of stimulants, to try to find an explanation for these conflicting phenomena. Across a variety of behavioral tasks, stimulants have been shown to reduce emotional reactions to frustration, improve the ability to detect errors, and increase effortful behavior. However, all of these effects would presumably enhance academic performance. On the other hand, the drugs were also found to promote "risky behavior" and to increase susceptibility to environmental distraction. Such negative effects, including the use of drugs to promote wakefulness for last minute study, might explain the lack of academic benefit in the "real world," despite their cognitive potential. Like many drugs, stimulants influence behavior in multiple ways, depending on the environmental contingencies. Depending on the circumstances, stimulants may, or may not, enhance cognition. PMID:23754970

  1. A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants.

    PubMed

    Xu, Jiansong; Healy, Stephen M; Truong, Dennis Q; Datta, Abhishek; Bikson, Marom; Potenza, Marc N

    2015-09-01

    Transcranial direct current stimulation (tDCS) studies often use one anode to increase cortical excitability in one hemisphere. However, mental processes may involve cortical regions in both hemispheres. This study's aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study. PMID:26339204

  2. A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants.

    PubMed

    Xu, Jiansong; Healy, Stephen M; Truong, Dennis Q; Datta, Abhishek; Bikson, Marom; Potenza, Marc N

    2015-09-01

    Transcranial direct current stimulation (tDCS) studies often use one anode to increase cortical excitability in one hemisphere. However, mental processes may involve cortical regions in both hemispheres. This study's aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study.

  3. A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants

    PubMed Central

    Xu, Jiansong; Healy, Stephen M.; Truong, Dennis Q.; Datta, Abhishek; Bikson, Marom; Potenza, Marc N.

    2015-01-01

    Transcranial direct current stimulation (tDCS) studies often use one anode to increase cortical excitability in one hemisphere. However, mental processes may involve cortical regions in both hemispheres. This study’s aim was to assess the safety and possible effects on affect and working memory of tDCS using two anodes for bifrontal stimulation. A group of healthy subjects participated in two bifrontal tDCS sessions on two different days, one for real and the other for sham stimulation. They performed a working memory task and reported their affect immediately before and after each tDCS session. Relative to sham, real bifrontal stimulation did not induce significant adverse effects, reduced decrement in vigor-activity during the study session, and did not improve working memory. These preliminary findings suggest that bifrontal anodal stimulation is feasible and safe and may reduce task-related fatigue in healthy participants. Its effects on neuropsychiatric patients deserve further study. PMID:26339204

  4. Proteasome proteolysis supports stimulated platelet function and thrombosis

    PubMed Central

    Gupta, Nilaksh; Li, Wei; Willard, Belinda; Silverstein, Roy L.; McIntyre, Thomas M.

    2014-01-01

    Objective Proteasome inhibitors are in use to treat hematologic cancers, but also reduce thrombosis. Whether the proteasome participates in platelet activation or function is opaque since little is known of the proteasome in these terminally differentiated cells. Approach and Results Platelets displayed all three primary proteasome protease activities, which MG132 and bortezomib (Velcade®) inhibited. Proteasome substrates are marked by ubiquitin, and platelets contained a functional ubiquitination system that modified the proteome by mono- and poly-ubiquitination. Systemic MG132 strongly suppressed formation of occlusive, platelet-rich thrombi in FeCl3-damaged carotid arteries. Transfusion of platelets treated ex vivo with MG132 and washed prior to transfusion into thrombocytopenic mice also reduced carotid artery thrombosis. Proteasome inhibition reduced platelet aggregation by low thrombin concentrations and ristocetin-stimulated agglutination through the GPIb-IX-V complex. This receptor was not appropriately internalized after proteasome inhibition in stimulated platelets, and spreading and clot retraction after MG132 exposure also were decreased. The effects of proteasome inhibitors were not confined to a single receptor as MG132 suppressed thrombin-, ADP-, and LPS-stimulated microparticle shedding. Proteasome inhibition increased ubiquitin decoration of cytoplasmic proteins, including the cytoskeletal proteins Filamin A and Talin-1. Mass spectrometry revealed a single MG132-sensitive tryptic cleavage after R1745 in an extended Filamin A loop, which would separate its actin-binding domain from its carboxy terminal GPIbα binding domain. Conclusions Platelets contain a ubiquitin/proteasome system that marks cytoskeletal proteins for proteolytic modification to promote productive platelet-platelet and platelet-wall interactions. PMID:24177323

  5. Reducing Artifacts in TMS-Evoked EEG

    NASA Astrophysics Data System (ADS)

    Fuertes, Juan José; Travieso, Carlos M.; Álvarez, A.; Ferrer, M. A.; Alonso, J. B.

    Transcranial magnetic stimulation induces weak currents within the cranium to activate neuronal firing and its response is recorded using electroencephalography in order to study the brain directly. However, different artifacts contaminate the results. The goal of this study is to process these artifacts and reduce them digitally. Electromagnetic, blink and auditory artifacts are considered, and Signal-Space Projection, Independent Component Analysis and Wiener Filtering methods are used to reduce them. These last two produce a successful solution for electromagnetic artifacts. Regarding the other artifacts, processed with Signal-Space Projection, the method reduces the artifact but modifies the signal as well. Nonetheless, they are modified in an exactly known way and the vector used for the projection is conserved to be taken into account when analyzing the resulting signals. A system which combines the proposed methods would improve the quality of th