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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

    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. 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

  5. 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. PMID:25710949

  6. 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. PMID:25680991

  7. Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation.

    PubMed

    Scheidegger, Milan; Henning, Anke; Walter, Martin; Lehmann, Mick; Kraehenmann, Rainer; Boeker, Heinz; Seifritz, Erich; Grimm, Simone

    2016-05-01

    Increased amygdala reactivity might lead to negative bias during emotional processing that can be reversed by antidepressant drug treatment. However, little is known on how N-methyl-d-aspartate (NMDA) receptor antagonism with ketamine as a novel antidepressant drug target might modulate amygdala reactivity to emotional stimulation. Using functional magnetic resonance imaging (fMRI) and resting-state fMRI (rsfMRI), we assessed amygdalo-hippocampal reactivity at baseline and during pharmacological stimulation with ketamine (intravenous bolus of 0.12 mg/kg, followed by a continuous infusion of 0.25 mg/kg/h) in 23 healthy subjects that were presented with stimuli from the International Affective Picture System (IAPS). We found that ketamine reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation. Reduced amygdala reactivity to negative pictures was correlated to resting-state connectivity to the pregenual anterior cingulate cortex. Interestingly, subjects experienced intensity of psychedelic alterations of consciousness during ketamine infusion predicted the reduction in neural responsivity to negative but not to positive or neutral stimuli. Our findings suggest that the pharmacological modulation of glutamate-responsive cerebral circuits, which is associated with a shift in emotional bias and a reduction of amygdalo-hippocampal reactivity to emotional stimuli, represents an early biomechanism to restore parts of the disrupted neurobehavioral homeostasis in MDD patients. Hum Brain Mapp 37:1941-1952, 2016. © 2016 Wiley Periodicals, Inc. PMID:26915535

  8. Intestinal Inflammation in Rats Induces Metallothionein in Colonic Submucosa

    PubMed Central

    Al-Gindan, Yasmin; Shawarby, Mohammed; Noto, Amy; Taylor, Carla G.

    2009-01-01

    The aim of the current study was to determine if induction of metallothionein (MT) via acute or chronic dietary zinc supplementation attenuates intestinal inflammation, and to investigate the relationship with site-specific intestinal MT determined by immunolocalization. Growing rats were assigned to zinc-deficient (ZD), acute zinc-treated (ZT), pair-fed, control or chronic Zn-supplemented (ZS) groups. Half the rats in each dietary group received 5% dextran sulphate sodium (DSS) in their drinking water for 4 days. DSS treatment produced acute intestinal inflammation in the colon only, however, dietary zinc deficiency, acute zinc treatment or chronic zinc supplementation did not alter the severity of ulceration. Serum zinc concentrations were attenuated in the DSS-challenged ZT and ZS groups suggesting that zinc was being utilized in some capacity in response to inflammation. DSS-challenge induced MT immunostaining in the colonic submucosa, however, MT was not associated with histological improvements in the present study. The site-specific MT induction in colonic submucosa during intestinal inflammation requires further clarification as a component of the host defense. PMID:19308267

  9. 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

  10. Unsuccessful alloplastic esophageal replacement with porcine small intestinal submucosa.

    PubMed

    Doede, Thorsten; Bondartschuk, Michail; Joerck, Carsten; Schulze, Eberhard; Goernig, Matthias

    2009-04-01

    In general, there is no perfect method for esophageal replacement under consideration of the numerous associated risks and complications. The aim of this study was to examine a new material--small intestinal submucosa (SIS)--in alloplastic esophageal replacement. We implanted tubular SIS prosthesis about 4 cm in length in the cervical esophagus of 14 piglets (weight 9-13 kg). For the first 10 days, the animals were fed parenterally, supplemented by free given water, followed by an oral feeding phase. Four weeks after surgery, the animals were sacrificed. Only 1 of the 14 animals survived the study period of 4 weeks. The other piglets had to be sacrificed prematurely because of severe esophageal stenosis. On postmortem exploration, the prosthesis could not be found either macroscopically or histologically. Sutures between the prosthesis and the cervical muscles did not improve the results. Until now, the use of alloplastic materials in esophageal replacement has failed irrespective of the kind of material. As well as in our experiments, severe stenosis had been reported in several animal studies. The reasons for this unacceptable high rate of stenosis after alloplastic esophageal replacement seem to be multifactorial. Possible solutions could be transanastomotic splints, less inert materials, the decrease of anastomotic tension by stay sutures, the use of adult stem cells, and tissue engineering. PMID:19335409

  11. BaroLoop: using a multichannel cuff electrode and selective stimulation to reduce blood pressure.

    PubMed

    Plachta, Dennis T T; Gierthmuehlen, Mortimer; Cota, Oscar; Boeser, Fabian; Stieglitz, Thomas

    2013-01-01

    The therapy of refractory hypertension is an increasing problem for health care systems and a frontend in research in both pharmacology and neuroelectronic engineering. Overriding the baroreceptive information of afferent nerve fibers, originating from pressure sensors in the aortic arch, can trigger the baroreflex, a systemic control system that lowers the blood pressure (BP) almost instantaneously. Using a multichannel cuff electrode, wrapped around a rat vagal nerve, we were able to regulate the BP using selective, tripolar stimulation. The tripolar stimulation was sufficiently selective to not trigger any unwanted side effects like bradycardia or bradypnea. The BP was reduced best with charge balanced stimulation amplitudes of 1 mA and pulse duration of 0.3 ms. The stimulation frequency had only a mild influence on the effectiveness of the stimulation and did work best at 40 Hz. We found that the BP took up to five times the stimulation period to recover to the value prior to stimulation. PMID:24109797

  12. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages

    PubMed Central

    Li, Wei; Zhu, Shu; Li, Jianhua; Assa, Andrei; Jundoria, Arvin; Xu, Jianying; Fan, Saijun; Eissa, N. Tony; Tracey, Kevin J.; Sama, Andrew E.; Wang, Haichao

    2011-01-01

    Historically, consumption of Green tea (Camellia sinensis) has been associated with health benefits against multiple diseases including cancer, atherosclerosis and cardiovascular disorders. Emerging evidence has suggested a pathogenic role for HMGB1, a newly identified “late” mediator of lethal systemic inflammation, in the aforementioned diseases. Here we demonstrated that a major ingredient of Green tea, EGCG, was internalized into HMGB1-containing LC3-positive cytoplasmic vesicles (likely autophagosomes) in macrophages, and induced HMGB1 aggregation in a time-dependent manner. Furthermore, EGCG stimulated LC3-II production and autophagosome formation, and inhibited LPS-induced HMGB1 up-regulation and extracellular release. The EGCG-mediated HMGB1 inhibitory effects were diminished by inhibition of class III phosphatidylinositol-3 kinase (with 3-methyladenine) or knockdown of an essential autophagy-regulating protein, beclin-1. Moreover, the EGCG-mediated protection against lethal sepsis was partly impaired by co-administration of an autophagy inhibitor, chloroquine. Taken together, the present study has suggested a possibility that EGCG inhibits HMGB1 release by stimulating its autophagic degradation. PMID:21371444

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Evaluation of small intestinal submucosa grafts for meniscal regeneration in a clinically relevant posterior meniscectomy model in dogs.

    PubMed

    Cook, James L; Fox, Derek B; Malaviya, Prasanna; Tomlinson, James L; Farr, Jack; Kuroki, Keiichi; Cook, Cristi Reeves

    2006-07-01

    Large meniscal defects are a common problem for which treatment options are limited. Successful meniscal regeneration has been achieved by using grafts of small intestinal submucosa in posterior, vascular meniscal defects in a dog model. This study investigates the long-term effects of a tibial tunnel fixation technique and a clinically based meniscectomy defect on meniscal regeneration using this model. Eight mongrel dogs underwent medial arthrotomy and partial meniscectomy. The dogs were divided into groups based on defect treatment: small intestinal submucosa (n = 4) or meniscectomy (n = 4). Dogs were scored for lameness by subjective scoring postoperatively, sacrificed at 6 months, and assessed for articular cartilage damage, gross and histologic appearance of the operated meniscus, amount of new tissue in the defect, and relative compressive stiffness of articular cartilage. Dogs in the meniscectomy group were significantly (P = .002) more lame than dogs treated with small intestinal submucosa. Small intestinal submucosa-treated joints had significantly (P = .01) less articular cartilage damage than meniscectomy joints. Small intestinal submucosa meniscal implants resulted in production of meniscal-like replacement tissue, which was consistently superior to meniscectomy in amount, type, and integration of new tissue, chondroprotection, and limb function during the study period. Small intestinal submucosa implants may be useful for treatment of large posterior vascular meniscal defects in humans. The tibial tunnel technique used for fixation may have clinical advantages and therefore warrants further investigation. PMID:16893153

  19. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

    PubMed Central

    Bonde, Ylva; Breuer, Olof; Lütjohann, Dieter; Sjöberg, Stefan; Angelin, Bo; Rudling, Mats

    2014-01-01

    Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. PMID:25172631

  20. 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

  1. Deep Brain Stimulation Reduces Neuronal Entropy in the MPTP-Primate Model of Parkinson's Disease

    PubMed Central

    Dorval, Alan D.; Russo, Gary S.; Hashimoto, Takao; Xu, Weidong; Grill, Warren M.; Vitek, Jerrold L.

    2008-01-01

    High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n ≥ 18 and P ≤ 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n ≥ 24 and P ≤ 10−4 in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit. PMID:18784271

  2. Transcranial direct current stimulation modulates ERP-indexed inhibitory control and reduces food consumption.

    PubMed

    Lapenta, Olivia Morgan; Sierve, Karina Di; de Macedo, Elizeu Coutinho; Fregni, Felipe; Boggio, Paulo Sérgio

    2014-12-01

    Food craving can be defined as the "urge to eat a specific food". Previous findings suggest impairment of inhibitory control, specifically a regulatory deficit in the lateral prefrontal circuitry that is associated with a compulsion for food. As demonstrated by three previous studies, bilateral transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) (anode right/cathode left) reduces food craving and caloric intake. We designed the present study to evaluate the neural mechanisms that underlie these effects. We replicated the design of one of these previous studies but included electroencephalographic assessments to register evoked potentials in a Go/No-go task that contained pictures of food and furniture (a control visual stimulus). We collected data from nine women (mean age = 23.4 ± 2 years) in a crossover experiment. We observed that active DLPFC tDCS (anode right/cathode left), compared with sham stimulation, reduced the frontal N2 component and enhanced the P3a component of responses to No-go stimuli, regardless of the stimulus condition (food or furniture). Active tDCS was also associated with a reduction in caloric intake. We discuss our findings in the context of cortico-subcortical processing of craving and tDCS effects on inhibitory control neural circuitry. PMID:25128836

  3. 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. PMID:22951732

  4. Surgical treatment of Peyronie's disease with small intestinal submucosa graft patch.

    PubMed

    Cosentino, M; Kanashiro, A; Vives, A; Sanchez, J; Peraza, M F; Moreno, D; Perona, J; De Marco, V; Ruiz-Castañe, E; Sarquella, J

    2016-05-01

    The objective of the study was to report our results using a porcine small intestinal submucosa graft (Surgisis ES, Cook Medical) for tunica albuginea substitution after plaque incision. We retrospectively evaluated patients surgically treated at our institution for Peyronie's disease (PD) by means of plaque incision and porcine small intestinal submucosa grafting (Surgisis) between 2009 and 2013. At the same time a literature review was conducted, searching for similar reports and results. Forty-four patients were identified who had been diagnosed with PD between 2009 and the beginning of 2013, and had been treated with corporoplasty, plaque incision and grafting with Surgisis for a severe curvature of the penis. Curvature of the penis was dorsal in 40 patients (90%) and laterally on the right in 4 patients (10%). Mean duration of surgery was 165 min (range 90-200). Mean size of the graft was 6.5 cm(2) and the mean follow-up was 19.2 months (range 11-48). In patients with severe curvature of the penis due to PD and the need for corporoplasty with plaque incision and graft placement, Surgisis represents a good option with a low risk of complications, below the rate described with previously investigated graft tissues. PMID:27030055

  5. Myocardial regeneration after implantation of porcine small intestinal submucosa in the left ventricle

    PubMed Central

    Ramos, Cassiana Maria Garcez; Francisco, Julio César; Olandoski, Marcia; de Carvalho, Katherine Athayde Teixeira; Cunha, Ricardo; Erbano, Bruna Olandoski; Jorge, Lianna Ferrari; Baena, Cristina Pellegrino; do Amaral, Vivian Ferreira; Noronha, Lucia; de Macedo, Rafael Michel; Faria-Neto, José Rocha; Guarita-Souza, Luiz César

    2014-01-01

    Introduction Most cardiomyocytes do not regenerate after myocardial infarction. Porcine small intestinal submucosa has been shown to be effective in tissue repair. Objective To evaluate myocardial tissue regeneration and functional effects of SIS implantation in pigs after left ventriculotomy. Methods Fifteen pigs were assigned to two groups: porcine small intestinal submucosa (SIS) (N=10) and control (N=5). The SIS group underwent a mini sternotomy, left ventriculotomy and placement of a SIS patch. The control group underwent a sham procedure. Echocardiography was performed before and 60 days after the surgical procedure. Histological analysis was performed with hematoxylin-eosin stain and markers for actin 1A4, anti sarcomeric actin, connexin43 and factor VIII. Results Weight gain was similar in both groups. Echocardiography analysis revealed no difference between groups regarding end diastolic and systolic diameters and left ventricular ejection fraction, both pre (P=0.118, P=0.313, P=0.944) and post procedure (P=0.333, P=0.522, P=0.628). Both groups showed an increase in end diastolic (P<0,001 for both) and systolic diameter 60 days after surgery (P=0.005, SIS group and P=0.004, control group). New cardiomyocytes, blood vessels and inflammatory reactions were histologically identified in the SIS group. Conclusion SIS implantation in pigs after left ventriculotomy was associated with angiomuscular regeneration and no damage in cardiac function. PMID:25140470

  6. 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

  7. 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. PMID:24823330

  8. 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

  9. 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

  10. 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

  11. Spinal cord stimulation reduces mechanical hyperalgesia and glial cell activation in animals with neuropathic pain

    PubMed Central

    Sato, Karina L.; Johanek, Lisa M.; Sanada, Luciana S.; Sluka, Kathleen A.

    2015-01-01

    Spinal cord stimulation (SCS) is used to manage chronic intractable neuropathic pain. We examined parameters of SCS in rats with spared nerve injury by modulating frequency (4Hz vs. 60Hz), duration (30m vs. 6h), or intensity (50%, 75%, or 90% MT). To elucidate potential mechanisms modulated by SCS, we examined immunoreactivity glial markers in the spinal cord after SCS). An epidural SCS lead was implanted in the upper lumbar spinal cord. Animals were tested for mechanical withdrawal threshold (MWT) of the paw before and 2 weeks after SNI, before and after SCS daily for 4 days, and for 9 days after SCS. Seperate groups of animals were tested for glial immunoreactivity after 4 days of 6h SCS. All rats showed a decrease in MWT 2 weeks after nerve injury and an increase in glial activation. For frequency, 4Hz or 60Hz SCS reversed the MWT when compared to sham SCS. For duration, 6h of SCS showed a greater reduction in MWT when compared to 30 min. For intensity, 90% MT was greater than 75% MT and both were greater than 50% MT or sham SCS. SCS decreased glial activation (GFAP, MCP-1 and OX-42) in the spinal cord dorsal horn when compared to sham. In conclusion, 4Hz and 60Hz SCS for a 6h at 90% MT were the most effective parameters for reducing hyperalgesia, suggesting parameters of stimulation are important for effectiveness of SCS. SCS reduced glial activation at the level of the spinal cord suggesting reduction in central excitability. PMID:24361846

  12. 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

  13. Stimulation of 5-HT1B receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior

    PubMed Central

    Pentkowski, Nathan S.; Acosta, Jazmin I.; Browning, Jenny R.; Hamilton, Elizabeth C.; Neisewander, Janet L.

    2010-01-01

    Paradoxically, stimulation of 5-HT1B receptors (5-HT1BRs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT1BR agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3–10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0–1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT1BRs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT1BRs may be a novel target for developing medications for cocaine dependence. PMID:19650818

  14. Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

    PubMed

    Pentkowski, Nathan S; Acosta, Jazmin I; Browning, Jenny R; Hamilton, Elizabeth C; Neisewander, Janet L

    2009-09-01

    Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence. PMID:19650818

  15. 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.

  16. Use of canine small intestinal submucosa allograft for treating perineal hernias in two dogs

    PubMed Central

    Lee, A-Jin; Chung, Wook-Hun; Kim, Dae-Hyun; Lee, Kyung-Pil; Suh, Hyun Jung; Do, Sun Hee; Eom, Ki-dong

    2012-01-01

    Here, we describe two dogs in which canine small intestinal submucosa (SIS) was implanted as a biomaterial scaffold during perineal herniorrhaphy. Both dogs had developed severe muscle weakness, unilaterally herniated rectal protrusions, and heart problems with potential anesthetic risks. Areas affected by the perineal hernia (PH) located between the internal obturator and external anal sphincter muscles were reconstructed with naïve canine SIS sheets. In 12 months, post-operative complications such as wound infections, sciatic paralysis, rectal prolapse, or recurrence of the hernia were not observed. Symptoms of defecatory tenesmus also improved. Neither case showed any signs of rejection or specific immune responses as determined by complete and differential cell counts. Our findings demonstrate that canine SIS can be used as a biomaterial scaffold for PH repair in dogs. PMID:23000591

  17. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:25668514

  19. 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. PMID:26485286

  20. 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

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

    PubMed Central

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

    1996-01-01

    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. 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. PMID:25531112

  3. Electrical Stimulation over Bilateral Occipito-Temporal Regions Reduces N170 in the Right Hemisphere and the Composite Face Effect

    PubMed Central

    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. PMID:25531112

  4. Vagus Nerve Stimulation Reduces Body Weight and Fat Mass in Rats

    PubMed Central

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Marrosu, Francesco; Puligheddu, Monica; Floris, Gabriele; Asuni, Gino Paolo; Cappai, Angela Letizia; Deriu, Silvia; Follesa, Paolo

    2012-01-01

    Among the manifold effects of vagus nerve stimulation (VNS) delivered as an add-on treatment to patients with drug-resistant epilepsy, a moderate loss of body weight has been observed in some individuals. We have now investigated this effect in rats. Exposure of rats to VNS for 4 weeks reduced feed conversion efficiency as well as body weight gain (by ∼25%) and the amount of mesenteric adipose tissue (by ∼45%) in comparison with those in sham-operated control animals. A pair-fed experiment showed that both lower dietary intake and increase energy expenditure independently contributed to the reduction of body weight and mesenteric adipose tissue. Moreover, VNS increased the level of non-esterified fatty acids in plasma and mesenteric adipose tissue by ∼50 and 80%, respectively, without affecting that in the liver. In addition, VNS reduced the amounts of endocannabinoids and increased N-palmitoylethanolamide, an endogenous ligand of the transcription factor PPARα (peroxisome proliferator–activated receptor α) in mesenteric adipose tissue but not in the hypothalamus. These effects were accompanied by increased expression of the gene for brain-derived neurotrophic factor (BDNF) in the hypothalamus and up-regulation of the abundance of PPARα in the liver. Our results suggest that the reduction in body fat induced by VNS in rats may result from the action of both central and peripheral mediators. The reduced feed conversion efficiency associated with VNS may be mediated by hypothalamic BDNF, down-regulation of endocannabinoid tone in mesenteric adipose tissue and a PPARα-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure. PMID:23028630

  5. Preparation of a small intestinal submucosa modified polypropylene hybrid mesh via a mussel-inspired polydopamine coating for pelvic reconstruction.

    PubMed

    Ge, Liangpeng; Liu, Lubin; Wei, Haoche; Du, Lei; Chen, Shixuan; Huang, Yong; Huang, Renshu

    2016-04-01

    Pelvic organ prolapse (POP) is a serious health issue that affects many adult women. Surgical treatments for POP patients comprise a common strategy in which scaffold materials are used to reconstruct the prolapsed pelvic. However, the existing materials for pelvic reconstruction cannot meet clinical requirements in terms of biocompatibility, mechanics and immunological rejection. To address these concerns, polypropylene (PP) mesh was selected because of its strong mechanical properties. Small intestinal submucosa (SIS) was used to modify the PP mesh via a mussel-inspired polydopamine coating to enhance its biocompatibility. The scanning electron microscopy (SEM) and atomic force microscopy (AFM) results demonstrated that SIS was successfully conjugated on the surface of the PP mesh. Moreover, the cytotoxicity results indicated that the PP mesh and SIS-modified PP mesh were safe to use. Furthermore, in vivo tests demonstrated that the fibroplasia around the implanted site in the SIS-modified PP mesh group was significantly less than the fibroplasia around the PP mesh group. In addition, the immunohistochemistry staining results indicated that the expression of pro-inflammatory macrophages (M1) was substantially lower and that the expression of pro-healing macrophages (M2) was higher in the SIS-modified PP mesh group. Furthermore, ELISA detection indicated that the expression of IL-1β and IL-6 in the SIS-modified PP mesh group was reduced compared with the PP mesh group. These findings suggest that a SIS-modified polypropylene hybrid mesh via a mussel-inspired polydopamine coating is a promising approach in pelvic reconstruction. PMID:26801474

  6. 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

  7. 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

  8. Transcutaneous electric acupoint stimulation at Jiaji points reduce abdominal pain after colonoscopy: a randomized controlled trial

    PubMed Central

    Chen, Yanqing; Wu, Weilan; Yao, Yusheng; Yang, Yang; Zhao, Qiuyan; Qiu, Liangcheng

    2015-01-01

    Background: Transcutaneous electric acupoint stimulation (TEAS) at Jiaji acupuncture points has therapeutic potential for relieving viscera pain and opioid-related side effects. This prospective, randomized, triple-blinded, placebo-controlled trial was to investigate the efficacy of TEAS on abdominal pain after colonoscopy. Methods: Consecutive outpatients with American Society of Anesthesiologists (ASA) physical status I or II underwent selective colonoscopy were randomly assigned into two groups for either TEAS or sham pretreatment. The primary outcomes were the incidence of abdominal pain after colonoscopy. The secondary outcomes included the incidence of abdominal distension, postoperative nausea and vomiting (PONV), duration of PACU stay, and patient’s satisfaction and acceptance. Results: Among the 229 patients analyzed, fewer occurrence of post-procedural abdominal pain (11.4% vs 25.2%, P = 0.007) and distension (1.8% vs 7.8%, P = 0.032) were observed in TEAS group, when compared with the sham group. The duration of PACU stay was significant shortened in TEAS group (P < 0.001). Meanwhile, patients’ satisfaction score to medical service was higher (P < 0.001), and their acceptance to colonoscopy was improved (P = 0.011). Conclusion: Pretreatment with TEAS can reduce post-procedural discomfort, provide more efficient medical resources utilization, and improved patient’s satisfaction and colonoscopy acceptance. PMID:26131193

  9. Bisphenol A exposure reduces the estradiol response to gonadotropin stimulation during in vitro fertilization

    PubMed Central

    Bloom, Michael S.; Kim, Dongsul; vom Saal, Frederick S.; Taylor, Julia A.; Cheng, Gloria; Lamb, Julie D.; Fujimoto, Victor Y.

    2011-01-01

    Objective Investigate associations between serum BPA concentrations and follicular response to exogenous ovary stimulation. Design Fasting serum was prospectively collected on the day of oocyte retrieval and assessed for unconjugated BPA using high-performance liquid chromatography (HPLC) with Coularray detection. Multivariable linear regression and negative binomial regression were used to assess associations between concentrations of BPA and outcome measures. Models were adjusted for race/ethnicity, antral follicle count at baseline, and cigarette smoking. Setting A reproductive health center. Patients Forty-four women undergoing in vitro fertilization (IVF). Main outcome measures Peak-estradiol level (E2) and the number of oocytes retrieved during IVF. Results The median unconjugated serum BPA concentration is 2.53 ng/ml (range 0.3–67.36 ng/ml). Bisphenol A is inversely associated with E2 (β=−0.16; 95% confidence interval (CI) −0.32, 0.01), as well as with E2 normalized to the number of mature-sized follicles at the hCG trigger (β=−0.14; 95%CI −0.24, −0.03). No association is observed for BPA and the number of oocytes retrieved (adjusted risk ratio=0.95; 95%CI 0.82, 1.10). Conclusions Bisphenol A is associated with a reduced estradiol response during IVF. Although limited by the preliminary nature of this study, these results merit confirmation in a future comprehensive investigation. PMID:21813122

  10. 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

  11. 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

  12. 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

  13. 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

  14. Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa*

    PubMed Central

    Ninan, Lal; Stroshine, R L; Wilker, J.J.; Shi, Riyi

    2008-01-01

    An adhesive protein extracted from marine mussel (Mytilus edulis) was used to bond strips of connective tissue for the purpose of evaluating the use of curing agents to improve adhesive curing. Specifically, mussel adhesive protein solution (MAPS, 0.5 mM dihydroxyphenylalanine) was applied, with or without the curing agents, to the ends of two overlapping strips of porcine small intestinal submucosa. The bond strength of this lap joint was determined after curing for 1 h at room temperature (25°C). The strength of joints formed using only MAPS or with only the ethyl, butyl or octyl cyanoacrylate adhesives were determined. Although joints bonded using ethyl cyanoacrylate were strongest, those using MAPS were stronger than those using butyl and octyl cyanoacrylates. The addition of 25 mM solutions of the transition metal ions V5+, Fe3+ and Cr6+, which are all oxidants, increased the bond strength of the MAPS joints. The V5+ gave the strongest bonds and the Fe3+ the second strongest. In subsequent tests with V5+ and Fe3+ solutions, the bond strength increased with V5+ concentration, but it did not increase with Fe3+ concentration. Addition of 250 mM V5+ gave a very strong bond. PMID:17434815

  15. Small intestinal submucosa extracellular matrix (CorMatrix®) in cardiovascular surgery: a systematic review.

    PubMed

    Mosala Nezhad, Zahra; Poncelet, Alain; de Kerchove, Laurent; Gianello, Pierre; Fervaille, Caroline; El Khoury, Gebrine

    2016-06-01

    Extracellular matrix (ECM) derived from small intestinal submucosa (SIS) is widely used in clinical applications as a scaffold for tissue repair. Recently, CorMatrix® porcine SIS-ECM (CorMatrix Cardiovascular, Inc., Roswell, GA, USA) has gained popularity for 'next-generation' cardiovascular tissue engineering due to its ease of use, remodelling properties, lack of immunogenicity, absorbability and potential to promote native tissue growth. Here, we provide an overview of the biology of porcine SIS-ECM and systematically review the preclinical and clinical literature on its use in cardiovascular surgery. CorMatrix® has been used in a variety of cardiovascular surgical applications, and since it is the most widely used SIS-ECM, this material is the focus of this review. Since CorMatrix® is a relatively new product for cardiovascular surgery, some clinical and preclinical studies published lack systematic reporting of functional and pathological findings in sufficient numbers of subjects. There are also emerging reports to suggest that, contrary to expectations, an undesirable inflammatory response may occur in CorMatrix® implants in humans and longer-term outcomes at particular sites, such as the heart valves, may be suboptimal. Large-scale clinical studies are needed driven by robust protocols that aim to quantify the pathological process of tissue repair. PMID:26912574

  16. Heparinized poly(vinyl alcohol)--small intestinal submucosa composite membrane for coronary covered stents.

    PubMed

    Jiang, Tao; Wang, Guixue; Qiu, Juhui; Luo, Lailong; Zhang, Guoquan

    2009-04-01

    To develop a novel coating material for coronary covered stents, we prepared a kind of composite membrane which contains polyvinyl alcohol (PVA) and porcine small intestinal submucosa (SIS) powders crosslinked and heparinized by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The amount of immobilized heparin increased with increasing ratios of EDC:heparin, and the maximum amount was approximately 60 microg heparin per milligram SIS powder at a weight ratio of EDC:heparin of 2. Uniaxial tensile and balloon inflation testing suggested that the composite membrane crosslinked by lower EDC concentration is more flexible and elastic. The clotting time (APTT and PT) of the heparinized PVA-SIS membrane was longer than that of the unheparinized membrane. The number of adherent platelets on the heparinized PVA-SIS composite membrane was about 25% of the unheparininzed, and there was no sign of accumulation and almost no pseudopodium was observed. The endothelial cells were amicable with the heparinized and unheparinized PVA-SIS composite membranes. In in vivo implantation tests, we observed a thin capsule formed by several layers of fibroblasts surrounding the implants. These results showed that the heparinized PVA-SIS composite membrane has potential biomechanical and biological properties as a coating material for coronary covered stent. PMID:19258700

  17. Habituation of glomerular responses in the olfactory bulb following prolonged odor stimulation reflects reduced peripheral input

    PubMed Central

    Ogg, M. Cameron; Bendahamane, Mounir; Fletcher, Max L.

    2015-01-01

    Following prolonged odor stimulation, output from olfactory bulb (OB) mitral/tufted (M/T) cells is decreased in response to subsequent olfactory stimulation. Currently, it is unclear if this decrease is a function of adaptation of peripheral olfactory sensory neuron (OSN) responses or reflects depression of bulb circuits. We used wide-field calcium imaging in anesthetized transgenic GCaMP2 mice to compare excitatory glomerular layer odor responses before and after a 30-s odor stimulation. Significant habituation of subsequent glomerular odor responses to both the same and structurally similar odorants was detected with our protocol. To test whether depression of OSN terminals contributed to this habituation, olfactory nerve layer (ON) stimulation was used to drive glomerular layer responses in the absence of peripheral odor activation of the OSNs. Following odor habituation, in contrast to odor-evoked glomerular responses, ON stimulation-evoked glomerular responses were not habituated. The difference in response between odor and electrical stimulation following odor habituation provides evidence that odor response reductions measured in the glomerular layer of the OB are most likely the result of OSN adaptation processes taking place in the periphery. PMID:26441516

  18. Cranial Electrical Stimulation Potential Use in Reducing Sleep and Mood Disturbances in Persons With Dementia and Their Family Caregivers

    PubMed Central

    Rose, Karen M.; Taylor, Ann Gill; Bourguignon, Cheryl; Utz, Sharon W.; Goehler, Lisa E.

    2009-01-01

    Family caregivers of persons with dementia and their care recipients frequently experience sleep and mood disturbances throughout their caregiving and disease trajectories. Because conventional pharmacologic treatments of sleep and mood disturbances pose numerous risks and adverse effects to elderly persons, the investigation of other interventions is warranted. As older adults use complementary and alternative medicine interventions for the relief of sleep and mood disturbances, cranial electrical stimulation, an energy-based complementary and alternative medicine, may be a viable intervention. The proposed mechanism of action and studies that support cranial electrical stimulation as a modality to reduce distressing symptoms are reviewed. Directions for research are proposed. PMID:18552605

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Tissue engineered esophagus scaffold constructed with porcine small intestinal submucosa and synthetic polymers.

    PubMed

    Fan, Mei-Rong; Gong, Mei; Da, Lin-Cui; Bai, Lin; Li, Xiu-Qun; Chen, Ke-Fei; Li-Ling, Jesse; Yang, Zhi-Ming; Xie, Hui-Qi

    2014-02-01

    Acellular porcine small intestinal submucosa (SIS) has been successfully used for reconstructing esophagus with half circumferential defects. However, repairing full circumferential esophageal defects with SIS has been restricted due to the latter's poor mechanical properties. In the present study, synthetic polyesters biomaterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(lactide-co-glycolide) (PLGA) have been used to improve the mechanical properties of SIS. Feasibility of SIS/PHBHHx-PLGA composite material scaffold for esophageal tissue engineering has been assessed through a series of testing. The appropriate mixing ratio of PHBHHx and PLGA polymers has been determined as 5:5 by mechanical testing and in vitro degradation experiment. The morphology of constructed membranous and tubular scaffolds was also characterized. As confirmed by enzyme-linked immunosorbent assay, the contents of VEGF and TGF-β have respectively reached 657 ± 18 ng mL(-1) and 130 ± 4 pg mL(-1) within the SIS/PHBHHx-PLGA specimens. Biocompatibility of the SIS/PHBHHx-PLGA specimens with rat bone marrow mesenchymal stem cells (MSCs) was also evaluated by scanning electron microscopy and a live-dead cell viability assay. Actin filaments of MSCs on the composite materials were labeled. Biological safety of the extract from SIS/PHBHHx-PLGA specimens, measured as hemolysis rate, was all lower than 5%. Compared with SIS and SIS/PHBHHx-PLGA specimens, inflammatory reaction provoked by the PHBHHx-PLGA specimens in rats was however more severe. Our results have suggested that SIS/PHBHHx-PLGA composite material can offer a new approach for esophageal tissue engineering. PMID:24457267

  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. 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

  8. Reduced fMRI activity predicts relapse in patients recovering from stimulant dependence.

    PubMed

    Clark, Vincent P; Beatty, Gregory K; Anderson, Robert E; Kodituwakku, Piyadassa; Phillips, John P; Lane, Terran D R; Kiehl, Kent A; Calhoun, Vince D

    2014-02-01

    Relapse presents a significant problem for patients recovering from stimulant dependence. Here we examined the hypothesis that patterns of brain function obtained at an early stage of abstinence differentiates patients who later relapse versus those who remain abstinent. Forty-five recently abstinent stimulant-dependent patients were tested using a randomized event-related functional MRI (ER-fMRI) design that was developed in order to replicate a previous ERP study of relapse using a selective attention task, and were then monitored until 6 months of verified abstinence or stimulant use occurred. SPM revealed smaller absolute blood oxygen level-dependent (BOLD) response amplitude in bilateral ventral posterior cingulate and right insular cortex in 23 patients positive for relapse to stimulant use compared with 22 who remained abstinent. ER-fMRI, psychiatric, neuropsychological, demographic, personal and family history of drug use were compared in order to form predictive models. ER-fMRI was found to predict abstinence with higher accuracy than any other single measure obtained in this study. Logistic regression using fMRI amplitude in right posterior cingulate and insular cortex predicted abstinence with 77.8% accuracy, which increased to 89.9% accuracy when history of mania was included. Using 10-fold cross-validation, Bayesian logistic regression and multilayer perceptron algorithms provided the highest accuracy of 84.4%. These results, combined with previous studies, suggest that the functional organization of paralimbic brain regions including ventral anterior and posterior cingulate and right insula are related to patients' ability to maintain abstinence. Novel therapies designed to target these paralimbic regions identified using ER-fMRI may improve treatment outcome. PMID:23015512

  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. Reduced fMRI activity predicts relapse in patients recovering from stimulant dependence

    PubMed Central

    Clark, Vincent P.; Beatty, Gregory; Anderson, Robert E.; Kodituwakku, Piyadassa; Phillips, John; Lane, Terran D.R.; Kiehl, Kent A.; Calhoun, Vince D.

    2012-01-01

    Relapse presents a major problem for patients recovering from stimulant dependence. Here we examined the hypothesis that patterns of brain function obtained at an early stage of abstinence differentiates patients who later relapse vs. those who remain abstinent. Forty-five recently abstinent stimulant-dependent patients were tested using a randomized event-related functional MRI (ER-fMRI) design that was developed in order to replicate a previous ERP study of relapse using a selective attention task, and were then monitored until 6 months of verified abstinence or stimulant use occurred. SPM revealed smaller absolute BOLD response amplitude in bilateral ventral posterior cingulate and right insular cortex in 23 patients positive for relapse to stimulant use compared with 22 who remained abstinent. ER-fMRI data was compared with psychiatric, neuropsychological, demographic, personal- and family- history of drug use in order to form predictive models, and was found to predict abstinence with higher accuracy than any other single measure obtained in this study. Logistic regression using fMRI amplitude in right posterior cingulate and insular cortex predicted abstinence with 77.8% accuracy, which increased to 89.9% accuracy when history of mania was included. Using 10-fold cross-validation, Bayesian logistic regression and multilayer perceptron algorithms provided the highest accuracy of 84.4%. These results, combined with previous studies, suggest that the functional organization of paralimbic brain regions including ventral anterior and posterior cingulate and right insula are related to patients’ ability to maintain abstinence. Novel therapies designed to target these paralimbic regions identified using ER-fMRI may improve treatment outcome. PMID:23015512

  11. Bi-frontal transcranial alternating current stimulation in the ripple range reduced overnight forgetting

    PubMed Central

    Ambrus, Géza Gergely; Pisoni, Alberto; Primaßin, Annika; Turi, Zsolt; Paulus, Walter; Antal, Andrea

    2015-01-01

    High frequency oscillations in the hippocampal structures recorded during sleep have been proved to be essential for long-term episodic memory consolidation in both animals and in humans. The aim of this study was to test if transcranial Alternating Current Stimulation (tACS) of the dorsolateral prefrontal cortex (DLPFC) in the hippocampal ripple range, applied bi-frontally during encoding, could modulate declarative memory performance, measured immediately after encoding, and after a night's sleep. An associative word-pair learning test was used. During an evening encoding phase, participants received 1 mA 140 Hz tACS or sham stimulation over both DLPFCs for 10 min while being presented twice with a list of word-pairs. Cued recall performance was investigated 10 min after training and the morning following the training session. Forgetting from evening to morning was observed in the sham condition, but not in the 140 Hz stimulation condition. 140 Hz tACS during encoding may have an effect on the consolidation of declarative material. PMID:26441544

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

    PubMed

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

    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

  13. 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

  14. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

    PubMed Central

    Stanton, Bruce A.; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

    2015-01-01

    Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials. PMID:26018799

  15. Investing in the future: stimulation of the medial prefrontal cortex reduces discounting of delayed rewards.

    PubMed

    Cho, Sang Soo; Koshimori, Yuko; Aminian, Kelly; Obeso, Ignacio; Rusjan, Pablo; Lang, Anthony E; Daskalakis, Zafiris J; Houle, Sylvain; Strafella, Antonio P

    2015-02-01

    Generally, rewards that are received sooner are often preferred over future rewards, and the time between the choice and the reception of the reward is an important factor that influences our decisions, a phenomenon called delay discounting (DD). In DD, the medial prefrontal cortex (MePFC) and striatal dopamine neurotransmission both play an important role. We used repetitive transcranial magnetic stimulation (rTMS) to transiently activate the MePFC to evaluate its behavioral effect on the DD paradigm, and subsequently to measure its effect on striatal dopamine. Twenty-four right-handed young healthy subjects (11 females; age: 22.1±2.9 years) underwent DD following 10 Hz-rTMS of the MePFC and vertex stimulation (control condition). Thereafter, 11 subjects (5 females; age: 22.2±2.87 years) completed the PET study at rest using [(11)C]-(+)-PHNO following 10 Hz-rTMS of the MePFC and vertex. Modulation of the MePFC excitability influenced the subjective level of DD for delayed rewards and interfered with synaptic dopamine level in the striatum. The present study yielded findings that might reconcile the role of these areas in inter-temporal decision making and dopamine modulation, suggesting that the subjective sense of time and value of reward are critically controlled by these important regions. PMID:25168685

  16. 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

  17. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    PubMed

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. PMID:27012610

  18. 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. PMID:22295102

  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. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke

    PubMed Central

    2012-01-01

    Background Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this. PMID:22676920

  1. Zinc directly stimulates cholecystokinin secretion from enteroendocrine cells and reduces gastric emptying in rats.

    PubMed

    Nakajima, Shingo; Hira, Tohru; Iwaya, Hitoshi; Hara, Hiroshi

    2016-07-15

    Zinc, an essential mineral element, regulates various physiological functions such as immune responses and hormone secretion. Cholecystokinin (CCK), a gut hormone, has a role in protective immunity through the regulation of gastrointestinal motility, appetite, and inflammatory response. Here, we examined the effect of zinc on CCK secretion in STC-1 cells, an enteroendocrine cell line derived from murine duodenum, and in rats. Extracellular zinc triggered CCK secretion accompanied with increased intracellular Ca(2+) and Zn(2+) mobilization in STC-1 cells. Zinc-induced CCK secretion was abolished in the absence of intracellular Zn(2+) or extracellular calcium. Upon inhibition of transient receptor potential ankyrin 1 (TRPA1), extracellular zinc failed to increase intracellular Ca(2+) and subsequent CCK secretion. In rats, oral zinc administration decreased gastric emptying through the activation of CCK signaling. These results suggest that zinc is a novel stimulant for CCK secretion through the activation of TRPA1 related to intracellular Zn(2+) and Ca(2+) mobilization. PMID:27107934

  2. Congruent tactile stimulation reduces the strength of visual suppression during binocular rivalry

    PubMed Central

    Lunghi, Claudia; Alais, David

    2015-01-01

    Presenting different images to each eye triggers ‘binocular rivalry’ in which one image is visible and the other suppressed, with the visible image alternating every second or so. We previously showed that binocular rivalry between cross-oriented gratings is altered when the fingertip explores a grooved stimulus aligned with one of the rivaling gratings: the matching visual grating's dominance duration was lengthened and its suppression duration shortened. In a more robust test, we here measure visual contrast sensitivity during rivalry dominance and suppression, with and without exploration of the grooved surface, to determine if rivalry suppression strength is modulated by touch. We find that a visual grating undergoes 45% less suppression when observers touch an aligned grating, compared to a cross-oriented one. Touching an aligned grating also improved visual detection thresholds for the ‘invisible’ suppressed grating by 2.4 dB, relative to a vision-only condition. These results show that congruent haptic stimulation prevents a visual stimulus from becoming deeply suppressed in binocular rivalry. Moreover, because congruent touch acted on the phenomenally invisible grating, this visuo-haptic interaction must precede awareness and likely occurs early in visual processing. PMID:25797534

  3. Congruent tactile stimulation reduces the strength of visual suppression during binocular rivalry.

    PubMed

    Lunghi, Claudia; Alais, David

    2015-01-01

    Presenting different images to each eye triggers 'binocular rivalry' in which one image is visible and the other suppressed, with the visible image alternating every second or so. We previously showed that binocular rivalry between cross-oriented gratings is altered when the fingertip explores a grooved stimulus aligned with one of the rivaling gratings: the matching visual grating's dominance duration was lengthened and its suppression duration shortened. In a more robust test, we here measure visual contrast sensitivity during rivalry dominance and suppression, with and without exploration of the grooved surface, to determine if rivalry suppression strength is modulated by touch. We find that a visual grating undergoes 45% less suppression when observers touch an aligned grating, compared to a cross-oriented one. Touching an aligned grating also improved visual detection thresholds for the 'invisible' suppressed grating by 2.4 dB, relative to a vision-only condition. These results show that congruent haptic stimulation prevents a visual stimulus from becoming deeply suppressed in binocular rivalry. Moreover, because congruent touch acted on the phenomenally invisible grating, this visuo-haptic interaction must precede awareness and likely occurs early in visual processing. PMID:25797534

  4. 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.

  5. 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 ...

  6. Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7.

    PubMed

    Haasters, Florian; Docheva, Denitsa; Gassner, Christoph; Popov, Cvetan; Böcker, Wolfgang; Mutschler, Wolf; Schieker, Matthias; Prall, Wolf Christian

    2014-09-12

    Fractures to the osteoporotic bone feature a delay in callus formation and reduced enchondral ossification. Human mesenchymal stem cells (hMSC), the cellular source of fracture healing, are recruited to the fracture site by cytokines, such as BMP-2 and BMP-7. Aim of the study was to scrutinize hMSC for osteoporosis associated alterations in BMP mediated migration and invasion as well as in extracellular matrix (ECM) binding integrin expression. HMSC were isolated from 18 healthy or osteoporotic donors. Migration was assessed using a collagen IV coated micro-slide linear gradient chamber and time-lapse microscopy. Invasion was analyzed utilizing an ECM coated transmembrane invasion assay. Quantitative real-time RT PCR was performed for the ECM binding integrins α1, α2, α3, α4, α5, α11, αv and β1. HMSC from osteoporotic patients showed a significant increase of migration upon BMP-2 or FCS stimulation, as well as a significant increase of invasion upon BMP-2, BMP-7 or FCS stimulation. Nevertheless, the migration and invasion capacity was significantly decreased compared to healthy controls. Out of all integrins analyzed, collagen binding integrin α2 was significantly downregulated in hMSC from osteoporotic patients. In conclusion, we here demonstrate for the first time osteoporosis associated alterations in BMP mediated hMSC recruitment. These findings may underlie the reduced healing of osteoporotic fractures. Nevertheless, the maintained migration and invasion response upon BMP stimulation illustrates the therapeutic potential of these clinically approved substances in the treatment of osteoporotic fractures. Another therapeutic target may be the downregulation of the collagen binding integrin α2 in hMSC from osteoporotic patients. PMID:25152406

  7. Stimulated Osteogenic Differentiation of Human Mesenchymal Stem Cells by Reduced Graphene Oxide.

    PubMed

    Jin, Linhua; Lee, Jong Ho; Jin, Oh Seong; Shin, Yong Cheol; Kim, Min Jeong; Hong, Suck Won; Lee, Mi Hee; Park, Jong-Chul; Han, Dong-Wook

    2015-10-01

    Osteoprogenitor cells play a significant role in the growth or repair of bones, and have great potential as cell sources for regenerative medicine and bone tissue engineering, but control of their specific differentiation into bone cells remains a challenge. Graphene-based nanomaterials are attractive candidates for biomedical applications as substrates for stem cell (SC) differentiation, scaffolds in tissue engineering, and components of implant devices owing to their biocompatible, transferable and implantable properties. This study examined the enhanced osteogenic differentiation of human mesenchymal stem cells (hMSCs) by reduced graphene oxide (rGO) nanoparticles (NPs), and rGO NPs was prepared by reducing graphene oxide (GO) with a hydrazine treatment followed by annealing in argon and hydrogen. The cytotoxicity profile of each particle was examined using a water-soluble tetrazolium-8 (WST-8) assay. At different time-points, a WST-8 assay, alkaline phosphatase (ALP) activity assay and alizarin red S (ARS) staining were used to determine the effects of rGO NPs on proliferation, differentiation and mineralization, respectively. The results suggest that graphene-based materials have potential as a platform for stem cells culture and biomedical applications. PMID:26726448

  8. Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation

    PubMed Central

    Kremer-Tal, Sigal; Narla, Goutham; Chen, Yingbei; Hod, Eldad; DiFeo, Analisa; Yea, Steven; Lee, Ju-Seog; Schwartz, Myron; Thung, Swan N.; Fiel, Isabel M.; Banck, Michaela; Zimran, Eran; Thorgeirsson, Snorri S.; Mazzaferro, Vincenzo; Bruix, Jordi; Martignetti, John A.; Llovet, Josep M.; Friedman, Scott L.

    2012-01-01

    Background/Aims Hepatocellular carcinoma (HCC) has the most rapidly rising cancer incidence in the US and Europe. The KLF6 tumor suppressor is frequently inactivated in HCC by loss-of-heterozygosity (LOH) and/or mutation. Methods Here we have analyzed 33 HBV- and 40 HCV-related HCCs for mRNA expression of wildtype KLF6 (wtKLF6) as well as the KLF6 variant 1 (SV1), a truncated, growth-promoting variant that antagonizes wtKLF6 function. The HCV-related tumors analyzed represented the full histologic spectrum from cirrhosis and dysplasia to metastatic cancer. Results Expression of KLF6 mRNA is decreased in 73% of HBV-associated HCCs compared to matched surrounding tissue (ST), with reductions of ~80% in one-third of the patients. KLF6 mRNA expression is also reduced in dysplastic nodules from patients with HCV compared to cirrhotic livers (p < 0.005), with an additional, marked decrease in the very advanced, metastatic stage (p < 0.05). An increased ratio of KLF6SV1/wt KLF6 is present in a subset (6/33, 18%) of the HBV-related HCCs compared to matched ST. Reconstituting KLF6 in HepG2 cells by retroviral infection decreased proliferation and related markers including cyclin D1 and beta-catenin, increased cellular differentiation based on induction of albumin, E-cadherin, and decreased alpha fetoprotein. Conclusions We conclude that reduced KLF6 expression is common in both HBV- and HCV-related HCCs and occurs at critical stages during cancer progression. Effects of KLF6 are attributable to regulation of genes controlling hepatocyte growth and differentiation. PMID:17196295

  9. Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice.

    PubMed

    Liu, Ying; Palanivel, Rengasamy; Rai, Esther; Park, Min; Gabor, Tim V; Scheid, Michael P; Xu, Aimin; Sweeney, Gary

    2015-01-01

    Numerous studies have characterized the antidiabetic effects of adiponectin, yet the precise cellular mechanisms in skeletal muscle, in particular, changes in autophagy, require further clarification. In the current study, we used a high-fat diet (HFD) to induce obesity and insulin resistance in wild-type (WT) or adiponectin knockout (Ad-KO) mice with and without adiponectin replenishment. Temporal analysis of glucose tolerance and insulin sensitivity using hyperinsulinemic-euglycemic clamp and muscle insulin receptor substrate and Akt phosphorylation demonstrated exaggerated and more rapid HFD-induced insulin resistance in skeletal muscle of Ad-KO mice. Superoxide dismutase activity, the reduced glutathione-to-glutathione disulfide ratio, and lipid peroxidation indicated that HFD-induced oxidative stress was corrected by adiponectin. Gene array analysis implicated several antioxidant enzymes, including Gpxs, Prdx, Sod, and Nox4, in mediating this effect. Adiponectin also attenuated palmitate-induced reactive oxygen species production in cultured myotubes and improved insulin-stimulated glucose uptake in primary muscle cells. Increased LC3-II and decreased p62 expression suggested that HFD induced autophagy in muscle of WT mice; however, these changes were not observed in Ad-KO mice. Replenishing adiponectin in Ad-KO mice increased LC3-II and Beclin1 and decreased p62 protein levels, induced fibroblast growth factor-21 expression, and corrected HFD-induced decreases in LC3, Beclin1, and ULK1 gene expression. In vitro studies examining changes in phospho-ULK1 (Ser555), LC3-II, and lysosomal enzyme activity confirmed that adiponectin directly induced autophagic flux in cultured muscle cells in an AMPK-dependent manner. We overexpressed an inactive mutant of Atg5 to create an autophagy-deficient cell model, and together with pharmacological inhibition of autophagy, demonstrated reduced insulin sensitivity under these conditions. In summary, adiponectin stimulated

  10. 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

  11. Transcranial direct current stimulation (tDCS) reduces the cost of performing a cognitive task on gait and postural control

    PubMed Central

    Zhou, Junhong; Hao, Ying; Wang, Ye; Jor’dan, Azizah; Pascual-Leone, Alvaro; Zhang, Jue; Fang, Jing; Manor, Brad

    2014-01-01

    This proof-of-concept, double-blind study is designed to determine the effects of transcranial direct current stimulation (tDCS) on the “cost” of performing a secondary cognitive task on gait and postural control in healthy young adults. Twenty adults aged 22±2yrs completed two separate double-blind visits in which gait and postural control were assessed immediately before and after a 20-minute session of either real or sham tDCS (1.5 mA) targeting the left dorsolateral prefrontal cortex. Gait speed and stride duration variability, along with standing postural sway speed and area, were recorded under normal conditions and while simultaneously performing a serial-subtraction cognitive task. Dual task cost was calculated as the percent change in each outcome from normal to dual task conditions. tDCS was well-tolerated by all subjects. Stimulation did not alter gait or postural control under normal conditions. As compared to sham stimulation, real tDCS led to increased gait speed (p=0.006), as well as decreased standing postural sway speed (p=0.01) and area (p=0.01), when performing serial-subtraction task. Real tDCS also diminished (p<0.01) the dual task cost on each of these outcomes. No effects of tDCS were observed for stride duration variability. A single session of tDCS targeting the left dorsolateral prefrontal cortex improved the ability to adapt one’s gait and postural control to a concurrent cognitive task and reduced the cost normally associated with such dual tasking. These results highlight the involvement of cortical brain networks in gait and posture control, and implicate the modulation of prefrontal cortical excitability as a potential therapeutic intervention. PMID:24443958

  12. Transcranial direct current stimulation reduces the cost of performing a cognitive task on gait and postural control.

    PubMed

    Zhou, Junhong; Hao, Ying; Wang, Ye; Jor'dan, Azizah; Pascual-Leone, Alvaro; Zhang, Jue; Fang, Jing; Manor, Brad

    2014-04-01

    This proof-of-concept, double-blind study was designed to determine the effects of transcranial direct current stimulation (tDCS) on the 'cost' of performing a secondary cognitive task on gait and postural control in healthy young adults. Twenty adults aged 22 ± 2 years completed two separate double-blind visits in which gait and postural control were assessed immediately before and after a 20 min session of either real or sham tDCS (1.5 mA) targeting the left dorsolateral prefrontal cortex. Gait speed and stride duration variability, along with standing postural sway speed and area, were recorded under normal conditions and while simultaneously performing a serial-subtraction cognitive task. The dual task cost was calculated as the percent change in each outcome from normal to dual task conditions. tDCS was well tolerated by all subjects. Stimulation did not alter gait or postural control under normal conditions. As compared with sham stimulation, real tDCS led to increased gait speed (P = 0.006), as well as decreased standing postural sway speed (P = 0.01) and area (P = 0.01), when performing the serial-subtraction task. Real tDCS also diminished (P < 0.01) the dual task cost on each of these outcomes. No effects of tDCS were observed for stride duration variability. A single session of tDCS targeting the left dorsolateral prefrontal cortex improved the ability to adapt gait and postural control to a concurrent cognitive task and reduced the cost normally associated with such dual tasking. These results highlight the involvement of cortical brain networks in gait and postural control, and implicate the modulation of prefrontal cortical excitability as a potential therapeutic intervention. PMID:24443958

  13. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    PubMed

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  14. 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

  15. p62/IMP2 stimulates cell migration and reduces cell adhesion in breast cancer

    PubMed Central

    Li, Yang; Francia, Giulio; Zhang, Jian-Ying

    2015-01-01

    p62/IMP2 is an oncofetal protein that is overexpressed in several types of cancer, and is a member of the family of insulin-like growth factor 2 mRNA binding proteins. We previously reported that high levels of p62/IMP2 autoantibody are present in sera from cancer patients, compared to healthy individuals. Here, we report the overexpression of p62/IMP2 in tumor tissues of 72 out of 104 cases of human breast cancer, and high levels of p62/IMP2 autoantibody in patients’ sera (in 63 out of 216 cases). To explore the role of p62/IMP2 in breast cancer progression, we generated p62/IMP2 transfected variants of two human breast cancer cell lines: MDA-MB-231 and LM2-4. Using in vitro assays we found that overexpression of p62/IMP2 can increase cell migration, and reduce cell adhesion to extracellular matrix (ECM) proteins. A Human Extracellular Matrix and Adhesion Molecules qPCR array was performed with our generated variants, and it identified a group of mRNAs whose expression was altered with p62/IMP2 overexpression, including connective tissue growth factor (CTGF) mRNA – which we show to be a p62/IMP2 binding partner. Overall, our results provide new insights into the molecular mechanism by which p62/IMP2 can contribute to breast cancer progression. PMID:26416451

  16. 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

  17. 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

  18. 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

  19. 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

  20. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    PubMed Central

    Anderson, Collin J.; Sheppard, Daylan T.; Huynh, Rachel; Anderson, Daria Nesterovich; Polar, Christian A.; Dorval, Alan D.

    2015-01-01

    The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson’s disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms. PMID:26217192

  1. Rice protein hydrolysates stimulate GLP-1 secretion, reduce GLP-1 degradation, and lower the glycemic response in rats.

    PubMed

    Ishikawa, Yuki; Hira, Tohru; Inoue, Daisuke; Harada, Yukikazu; Hashimoto, Hiroyuki; Fujii, Mikio; Kadowaki, Motoni; Hara, Hiroshi

    2015-08-01

    Rice has historically been consumed in Asia as a major source of carbohydrates, however, little is known regarding the functional roles of rice proteins as dietary factors. In the present study, we investigated whether peptides derived from rice proteins could stimulate GLP-1 secretion, which results in reducing glycemia via the incretin effect in normal rats. Hydrolysates were prepared from the protein fraction of rice endosperm or rice bran, and the effects of these hydrolysates on GLP-1 secretion were examined in a murine enteroendocrine cell line GLUTag. Plasma was collected after oral administration of the rice protein hydrolysates, under anesthesia, or during glucose tolerance tests in rats. In anesthetized rats, plasma dipeptidyl peptidase-IV (DPP-IV) activity was measured after ileal administration of the rice protein hydrolysates. GLP-1 secretion from GLUTag cells was potently stimulated by the rice protein hydrolysates, especially by the peptic digest of rice endosperm protein (REPH) and that of rice bran protein (RBPH). Oral administration of REPH or RBPH elevated plasma GLP-1 concentrations, which resulted in the reduction of glycemia under the intraperitoneal glucose tolerance test. In addition, the plasma DPP-IV activity was attenuated after ileal administration of REPH or RBPH, which resulted in a higher ratio of intact (active) GLP-1 to total GLP-1 in the plasma. These results demonstrate that rice proteins exert potent stimulatory effects on GLP-1 secretion, which could contribute to the reduction of postprandial glycemia. The inhibitory effect of these peptides on the plasma DPP-IV activity may potentiate the incretin effect of GLP-1. PMID:26107658

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Gastric submucosa is inferior to the liver as transplant site for autologous islet transplantation in pancreatectomized diabetic Beagles.

    PubMed

    Yin, Zhu-Zeng; Wang, Shu-Sen; Li, Qiang; Huang, Ying; Chen, Li; Chen, Gang; Liu, Rong; Wang, Xi-Mo

    2016-08-01

    Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5). Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation (mean survival time, 7.16±0.69 days). However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group (mean survival time, 120±28.58 days; P<0.01 vs. GS group). The results of intravenous glucose tolerance test (IVGTT) confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles. PMID:27465328

  8. The study of a light-activated albumin protein solder to bond layers of porcine small intestinal submucosa.

    PubMed

    Ware, Mark H; Buckley, Christine A

    2003-01-01

    This study investigated the feasibility of bonding layers of porcine small intestinal submucosa (SIS, Cook Biotech, Inc.) with a light-activated protein solder. SIS is an acellular, collagen-based extracellular matrix material that is approximately 100 microns thick. The solder consists of bovine serum albumin and indocyanine green dye (ICG) in deionized water. The solder is activated by an 808 nm diode laser, which denatures the albumin, causing the albumin to bond with the collagen of the tissue. The predictable absorption and thermal energy diffusion rates of ICG increase the chances of reproducible results. To determine the optimal condition for laser soldering SIS, the following parameters were varied: albumin concentration (from 30-45% (w/v) in increments of 5%), the concentration of ICG (from 0.5-2.0 mg/ml H2O) and the irradiance of the laser (10-64 W/cm2). While many of the solder compositions and laser irradiance combinations resulted in no bonding, a solder composition of 45% albumin, ICG concentration of 0.5 mg/ml H2O, and a laser irradiance of 21 W/cm2 did produce a bond between two pieces of SIS. The average shear strength of this bond was 29.5 +/- 17.1 kPa (n = 14). This compares favorably to our previous work using fibrin glue as an adhesive, in which the average shear strength was 27 +/- 15.8 kPa (n = 40). PMID:12724859

  9. 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

  10. Central dysmyelination reduces the temporal fidelity of synaptic transmission and the reliability of postsynaptic firing during high-frequency stimulation.

    PubMed

    Kim, Sei Eun; Turkington, Karl; Kushmerick, Christopher; Kim, Jun Hee

    2013-10-01

    Auditory brain stem circuits rely on fast, precise, and reliable neurotransmission to process auditory information. To determine the fundamental role of myelination in auditory brain stem function, we examined the evoked auditory brain stem response (ABR) from the Long Evans shaker (LES) rat, which lacks myelin due to a genetic deletion of myelin basic protein. In control rats, the ABR evoked by a click consisted of five well-defined waves (denoted waves I-V). In LES rats, waves I, IV, and V were present, but waves II and III were undetectable, indicating disrupted function in the earliest stages of central nervous system auditory processing. In addition, the developmental shortening of the interval between waves I and IV that normally occurs in control rats was arrested and resulted in a significant increase in the central conduction time in LES rats. In brain stem slices, action potential transmission between the calyx of Held terminals and the medial nucleus of the trapezoid body (MNTB) neurons was delayed and less reliable in LES rats, although the resting potential, threshold, input resistance, and length of the axon initial segment of the postsynaptic MNTB neurons were normal. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) and the degree of synaptic depression during high-frequency stimulation were not different between LES rats and controls, but LES rats exhibited a marked slow component to the EPSC decay and a much higher rate of presynaptic failures. Together, these results indicate that loss of myelin disrupts brain stem auditory processing, increasing central conduction time and reducing the reliability of neurotransmission. PMID:23843435

  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. Consumption of residue containing cucurbitacin feeding stimulant and reduced rates of carbaryl insecticide by western corn rootworm (Coleoptera: Chrysomelidae).

    PubMed

    Behle, R W

    2001-12-01

    Application of insecticide at a reduced rate with a cucurbitacin-based feeding stimulant is a viable alternative to a broadcast insecticide application for control of adult western corn rootworms, Diabrotica virgifera virgifera, LeConte. Because of the small amount of material applied, it is conceivable that a high density of beetles could consume all of the spray residue before economic control is achieved. A laboratory experiment was conducted to determine the amount of cucurbitacin-based spray residue consumed by beetles. Dried residue of four treatments were exposed to three groups of 10 rootworm beetles for 1 h each. Treatments consisted of a cucurbitacin-based adjuvant (Cidetrak CRW, Trécé, Salinas, CA) with carbaryl insecticide (Sevin XLR Plus, Rhone Poulenc, Research Triangle Park, NC) mixed at 0, 0.12, 1.2, and 12 g (AI)/liter. For the treatment with cucurbitacin adjuvant only (no insecticide), beetles consumed 0.029 mg beetle(-1) h(-1) of exposure. Approximately 54% of the beetles were recorded as feeding at any given time during the 60-min feeding period. However, when the spray residue contained carbaryl, no weight loss of treatment residue was measured, though the beetles were observed to feed from the residue during the first few minutes of exposure. When residue included insecticide, beetles quickly ceased feeding (within 20 min), and toxicity behavior was observed 30 min after initial exposure for up to 75% of the beetles, which were classified as moribund (unable to stand upright). Beetle mortality was recorded 24 h after exposure and demonstrated that male beetles (53% dead for three insecticide treatments) were more susceptible to carbaryl toxicity than female beetles (28% dead for three insecticide treatments). Regression analysis showed a significant positive relationship between mortality of female beetles and ovarian development. Based on the measurements of this experiment, it is unlikely that realistic beetle densities would consume

  13. GLP-1 receptor stimulation of the lateral parabrachial nucleus reduces food intake: neuroanatomical, electrophysiological, and behavioral evidence.

    PubMed

    Richard, Jennifer E; Farkas, Imre; Anesten, Fredrik; Anderberg, Rozita H; Dickson, Suzanne L; Gribble, Fiona M; Reimann, Frank; Jansson, John-Olov; Liposits, Zsolt; Skibicka, Karolina P

    2014-11-01

    The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN. PMID:25116706

  14. Tc-99m-labeled RGD-conjugated alpha-melanocyte stimulating hormone hybrid peptides with reduced renal uptake

    PubMed Central

    Yang, Jianquan; Hu, Chien-An

    2015-01-01

    The purpose of this study was to examine whether the replacement of the positively-charged Lys or Arg linker with a neutral linker could reduce the renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3–13 {(Arg11)CCMSH} through the neutral βAla or Ahx {aminohexanoic acid} linker (replacing the Lys or Arg linker) to generate novel RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH hybrid peptides. The receptor binding affinity and cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma cells. The melanoma targeting and imaging properties of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The replacement of the Lys or Arg linker with the βAla or Ahx linker retained nanomolar receptor binding affinities and remarkable cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH. The receptor binding affinities of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were 0.8 and 1.3 nM. Three-hour incubation with 0.1 µM of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH decreased the survival percentages of B16/F1 cells by 71 and 67% as compared to the untreated control cells five days post the treatment. The replacement of the Arg linker with the βAla or Ahx linker reduced the non-specific renal uptake of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH by 62% and 61% at 2 h post-injection. 99mTc-RGD-βAla-(Arg11)CCMSH displayed higher melanoma uptake than 99mTc-RGD-Ahx-(Arg11)CCMSH at 0.5, 2, 4 and 24 h post-injection. Enhanced tumor to kidney uptake ratio of 99mTc-RGD-βAla-(Arg11)CCMSH warranted the further evaluation of 188Re-labeled RGD-βAla-(Arg11)CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future. PMID:25557051

  15. 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

  16. 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. PMID:22951290

  17. 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.

  18. 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

  19. Does audiovisual stimulation with music and nature sights (MuViCure) reduce pain and discomfort during placement of a femoral nerve block?

    PubMed

    Nikolajsen, Lone; Lyndgaard, Kirsten; Schriver, Nina B; Moller, Jytte F

    2009-02-01

    MuViCure (Photobia ApS, Copenhagen, Denmark) is a new program for audiovisual stimulation. We hypothesized that audiovisual stimulation would reduce pain and discomfort and improve patients' well-being during placement of a femoral nerve block. Fifty-five outpatients scheduled for anterior cruciate ligament reconstruction were randomly allocated into three groups: the first group received audiovisual stimulation (MuViCure), the second group received audio stimulation (MusiCure, Gefion Records ApS, Virum, Denmark), and the third group received no intervention (control). Ten of the 55 patients underwent a qualitative in-depth interview 1-2 days after surgery. Pain and discomfort during the procedure were more prominent in the MuViCure group when compared with the other two groups. Despite these negative results, 14 of the 19 patients in the MuViCure group answered that MuViCure had a positive effect on their well-being. The qualitative interviews revealed that a number of factors other than the audiovisual stimulation had a significant impact on the patients' experience. The use of MuViCure may be more appropriate in other settings. PMID:19185817

  20. Ingramon, a Peptide Inhibitor of MCP-1 Chemokine, Reduces Migration of Blood Monocytes Stimulated by Glioma-Conditioned Medium.

    PubMed

    Krasnikova, T L; Arefieva, T I; Pylaeva, E A; Sidorova, M V

    2016-02-01

    Malignant gliomas are most common and fatal primary brain tumors. In addition to neoplastic cells, the tumor tissue contains microglial cells and monocyte-derived macrophages. It is an established fact that monocyte recruiting promotes the tumor growth and dissemination. Monocyte chemotactic protein-1 (MCP-1) is the major attractant for monocytes. We have previously synthesized an MCP-1 antagonist ingramon, a synthetic peptide fragment (65-76) of this chemokine. In the present study, we demonstrated that glioma-conditioned medium contains MCP-1 and stimulates migration of blood monocytes. Ingramon inhibited the effect of glioma-conditioned medium on monocyte migration. PMID:26906197

  1. 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

  2. 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.

  3. Reduced levodopa-induced complications after 5 years of subthalamic stimulation in Parkinson's disease: a second honeymoon.

    PubMed

    Simonin, Clemence; Tir, M; Devos, D; Kreisler, A; Dujardin, K; Salleron, J; Delval, A; Blond, S; Defebvre, L; Destée, A; Krystkowiak, P

    2009-10-01

    The purpose of this paper is to describe the effect of 5 years of subthalamic nucleus deep brain stimulation (STN DBS) on levodopa-induced complications, both in everyday life and during an acute challenge with levodopa. Thirty three patients were evaluated during an acute levodopa challenge before surgery and then 1 and 5 years afterwards (both off stim and on stim), using the UPDRS III scale and the CAPSIT-PD scales for dystonia and peak-dose dyskinesia. The UPDRS IV scale was used to assess motor complications in everyday life. The levodopa daily dose and DBS parameters were also recorded. Levodopa-induced complications in everyday life (UPDRS IV) and during an acute levodopa challenge had improved markedly after 1 year (both on and off stim) and still further at 5 years. Peak-dose dyskinesia decreased between the 1- and 5-year measurements. STN DBS decreases levodopa-induced motor complications over the long term. This phenomenon may be explained by (a) overall stabilization of the basal ganglia network and (b) striatal synaptic changes. Our results suggest that DBS leads to both qualitative and quantitative modulations in the corticostriatal loops. PMID:19536584

  4. Cathodal transcranial direct current stimulation of the posterior parietal cortex reduces steady-state postural stability during the effect of light touch.

    PubMed

    Ishigaki, Tomoya; Imai, Ryota; Morioka, Shu

    2016-09-28

    Touching a stable object with a fingertip using slight force (<1 N) stabilizes standing posture independent of mechanical support, which is referred to as the effect of light touch (LT). In the neural mechanism of the effect of LT, the specific contribution of the cortical brain activity toward the effect of LT remains undefined, particularly the contribution toward steady-state postural sway. The aim of the present study was to investigate the cortical region responsible for the reduction of postural sway in response to the effect of LT. Active LT was applied with the right fingertip and transcranial direct current stimulation (sham or cathodal) was applied to the left primary sensorimotor cortex or the left posterior parietal cortex in the two groups. The experiments were conducted using a single-blind sham-controlled crossover design. Steady-state postural sway was compared with the factors of transcranial direct current stimulation (sham or cathodal) and time (pre or post). In the results, the effect of LT reduced postural stability in the mediolateral direction after cathodal transcranial direct current stimulation of the left posterior parietal cortex. No effect was observed after stimulation of the left primary sensorimotor cortex. This indicates that the left posterior parietal cortex is partly responsible for the effect of LT when touching a fixed point with the right fingertip during suprapostural tasks, where posture is adjusted according to the precision requirements. Cortical processing of sensory integration for voluntary postural orientation in response to touch occurs in the posterior parietal cortex. PMID:27495219

  5. 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

  6. Reduced ex vivo stimulated IL-6 response in infants randomized to fish oil from 9 to 18 months, especially among PPARG2 and COX2 wild types.

    PubMed

    Harsløf, Laurine B S; Damsgaard, Camilla T; Andersen, Anders D; Aakjær, Ditte L; Michaelsen, Kim F; Hellgren, Lars I; Frøkiær, Hanne; Vogel, Ulla; Lauritzen, Lotte

    2015-03-01

    We investigated whether n-3 LCPUFA affected immune function in late infancy and explored effect-modification by single nucleotide polymorphisms (SNPs) and links to intestinal microbiota. Infants (n=105) were randomized to fish oil (FO, 1.2g/d n-3 LCPUFA) or sunflower oil (SO)-supplements from age 9-18 months. Immune function was assessed by ex vivo cytokine production in stimulated blood and plasma immunoglobulin E (IgE). We genotyped functional SNPs in PPARG2 and COX2 and analyzed fecal microbiota by 16S-rRNA terminal restriction fragment length polymorphism. FO compared to SO reduced Lactobacillus paracasei-stimulated IL-6 at 18 months (P=0.03, n=104). This effect was most pronounced among infants wild-type for PPARG2-Pro12Ala and/or COX2-T8473C (P<0.05). Predominant bacterial fragments were associated with 18 months IgE in all infants (P=0.004) (bp100) and with IL-6 production among infants weaned before 9 months (P=0.047) (bp102). Thus, FO reduced IL-6 in a genotype-modified manner. The microbiota was partly linked to IL-6 and IgE, not directly to FO. PMID:25498245

  7. 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

  8. 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. PMID:26641945

  9. 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. PMID:26945669

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Serotonin interferes with Ca2+ and PKC signaling to reduce gonadotropin-releasing hormone-stimulated GH secretion in goldfish pituitary cells.

    PubMed

    Yu, Yi; Wong, Anderson O L; Chang, John P

    2008-10-01

    In goldfish, two endogenous gonadotropin-releasing hormones (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), are thought to stimulate growth hormone (GH) release via protein kinase C (PKC) and subsequent increases in intracellular Ca(2+) levels ([Ca(2+)](i)). In contrast, the signaling mechanism for serotonin (5-HT) inhibition of GH secretion is still unknown. In this study, whether 5-HT inhibits GH release by actions at sites along the PKC and Ca(2+) signal transduction pathways leading to hormone release were examined in primary cultures of goldfish pituitary cells. Under static incubation and column perifusion conditions, 5-HT reduced basal, as well as sGnRH- and cGnRH-II-stimulated, GH secretion. 5-HT also suppressed GH responses to two PKC activators but had no effect on the GH-releasing action of the Ca(2+) ionophore ionomycin. Ca(2+)-imaging studies with identified somatotropes revealed that 5-HT did not alter basal [Ca(2+)](i) but attenuated the magnitude of the [Ca(2+)](i) responses to the two GnRHs. Prior treatment with 5-HT and cGnRH-II reduced the magnitude of the [Ca(2+)](i) responses induced by depolarizing levels of K(+). Similar inhibition, however, was not observed with prior treatment of 5-HT and sGnRH. These results suggest that 5-HT, by direct actions at the somatotrope level, interferes with PKC and Ca(2+) signaling pathways to reduce the GH-releasing effect of GnRH. 5-HT action may occur at the level of PKC activation or its downstream signaling events prior to the subsequent rise in [Ca(2+)](i.). The differential Ca(2+) responses by depolarizing doses of K(+) is consistent with our previous findings that sGnRH and cGnRH-II are coupled to overlapping and yet distinct Ca(2+)-dependent mechanisms. PMID:18723020

  15. Peripheral blood mononuclear cell supernatants from asymptomatic dogs immunized and experimentally challenged with Leishmania chagasi can stimulate canine macrophages to reduce infection in vitro.

    PubMed

    Rodrigues, Cleusa Alves Theodoro; Batista, Luís Fábio da Silva; Teixeira, Márcia Cristina Aquino; Pereira, Andréa Mendes; Santos, Patrícia Oliveira Meira; de Sá Oliveira, Geraldo Gileno; de Freitas, Luiz Antônio Rodrigues; Veras, Patrícia Sampaio Tavares

    2007-02-28

    Leishmania chagasi is the causative agent of visceral leishmaniasis in both humans and dogs in the New World. The dog is the main domestic reservoir and its infection displays different clinical presentations, from asymptomatic to severe disease. Macrophages play an important role in the control of Leishmania infection. Although it is not an area of intense study, some data suggest a role for canine macrophages in parasite killing by a NO-dependent mechanism. It has been proposed that control of human disease could be possible with the development of an effective vaccine against canine visceral leishmaniasis. Development of a rapid in vitro test to predict animal responses to Leishmania infection or vaccination should be helpful. In this study, an in vitro model was established to test whether peripheral blood mononuclear cell (PBMC) supernatants from dogs immunized with promastigote lysates and infected with L. chagasi promastigotes could stimulate macrophages from healthy dogs in order to control parasite infection. PBMC from a majority of the immunized and experimentally infected dogs expressed IFN-gamma mRNA and secreted IFN-gamma when stimulated with soluble L. chagasi antigen (SLA) in vitro. Additionally, the supernatants from stimulated PBMC were able to reduce the percentage of infected donor macrophages. The results also indicate that parasite killing in this system is dependent on NO, since aminoguanidine (AMG) reversed this effect. This in vitro test appears to be useful for screening animal responses to parasite inoculation as well as studying the lymphocyte effector mechanisms involved in pathogen killing by canine macrophages. PMID:17045743

  16. [Characterization of Cr (VI) removal and total Cr equilibrium adsorption by sulfate reducing granular sludge in stimulant wastewater].

    PubMed

    Luo, Jun; Pang, Zhi-Hua; Hu, Yong-You; Zhong, Hai-Tao; Chen, Jian-Yu; Lin, Fang-Min

    2010-11-01

    Sulfate reducing granular sludge (SRGS) cultivated in small scale EGSB reactor was used for Cr (VI) removing. Characterization of Cr (VI) removal and total Cr equilibrium adsorption was studied, and the adsorption isotherm was fitted. Results showed that removal of Cr (VI) was in connection with the structure and chemical composition of SRGS and several environmental factors. The Cr (VI) removal rate increased with the dosage of granular sludge; the increasing of oscillation speed and temperature could enhance Cr (VI) removal and total Cr adsorption, but while the oscillation speed reached 150 r x min(-1) or the temperature came to 40 degrees C, the physical structure of granular sludge would be affected and the granular sludge discrete, and total Cr equilibrium adsorption decreased; lower pH value caused higher Cr (VI) removal rate, however the sulfate on the surface of granular sludge was affected by lower pH value easily and would translate into H2S, then total Cr adsorption rate decreased. Cr (VI) removal would be influenced by physical, chemical and biological factors, and the process included reduction and adsorption mainly. The maximum adsorption of total Cr by granular sludge was 6.84 mg x g(-1), and the total Cr adsorbing process fitted in with Langmuir adsorption isotherm. PMID:21250453

  17. 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

  18. Reduced cerebral and cardiovascular hemodynamics during sustained affective stimulation in young women with chronic low blood pressure.

    PubMed

    Cellini, Nicola; de Zambotti, Massimiliano; Covassin, Naima; Gallicchio, Germano; Stegagno, Luciano; Sarlo, Michela

    2015-05-01

    Although low blood pressure has been associated with lower affect and higher depressive symptoms in the elderly, the presence of possible impairment in emotional reactivity in chronic hypotensive individuals in early adulthood remains largely unexplored. Using a combination of transcranial Doppler sonography, beat-to-beat blood pressure recording and impedance cardiography we assessed central and peripheral hemodynamic changes in 15 undergraduate women with chronic hypotension (Age: 23.9 ± 2.7 years) and 15 normotensive controls (Age: 23.7 ± 3.1 years) during sustained exposure to pleasant, unpleasant and neutral pictures. Overall, systolic blood pressure (SBP) increased in normotensives and decreased in hypotensives during picture viewing as compared to baseline. Also, compared to normotensives, in hypotensives mean cerebral blood flow velocity increased to a lesser extent during the viewing of pleasant pictures and the magnitude of this increase was negatively associated with subjective emotional arousal. In addition, in hypotensives screening SBP was positively associated with valence rating of pleasant contents. These findings indicate a close association between chronic low blood pressure and reduced processing of pleasant stimuli in young adulthood. PMID:25727023

  19. 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

  20. 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

  1. Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells

    PubMed Central

    Liu, Xueqing; Sun, Wenjia; Zhao, Yanyang; Chen, Beidong; Wu, Wei; Bao, Li; Qi, Ruomei

    2015-01-01

    Aim. To investigate the effect of ginkgolide B on junction proteins and the reduction of monocyte migration in oxidized low-density lipoprotein- (ox-LDL-) treated endothelial cells. Methods. Human umbilical vein endothelial cells (HUVECs) were used in the present study. Immunofluorescence and Western blot were performed to determine the expression of junctional adhesion molecule-A (JAM-A), connexin 43 (Cx43), and vascular endothelial cadherin (VE-cadherin). Monocyte migration was detected by the Transwell assay. Results. ox-LDL stimulation increased JAM-A expression by 35%, Cx43 expression by 24%, and VE-cadherin expression by 37% in HUVECs. Ginkgolide B (0.2, 0.4, and 0.6 mg/mL) dose-dependently abolished the expression of these junction proteins. The monocyte transmigration experiments showed that the level of monocyte migration was sixfold higher in the ox-LDL-treated group than in the control group. Ginkgolide B (0.6 mg/mL) nearly completely abolished monocyte migration. Both ginkgolide B and LY294002 suppressed Akt phosphorylation and the expression of these junction proteins in ox-LDL-treated endothelial cells. These results suggest that the ginkgolide B-induced inhibition of junction protein expression is associated with blockade of the PI3K/Akt pathway. Conclusion. Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis. PMID:26246869

  2. 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

  3. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms.

    PubMed

    Villegas-Bastida, Albino; Torres-Rosas, Rafael; Arriaga-Pizano, Lourdes Andrea; Flores-Estrada, Javier; Gustavo-Acosta, Altamirano; Moreno-Eutimio, Mario Adan

    2014-01-01

    Electrical vagus nerve (VN) stimulation during sepsis attenuates tumor necrosis factor (TNF) production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36) on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP). The septic rats were subsequently treated with EA-ST36 (CLP+ST36), and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P < 0.05), and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms. PMID:25057275

  4. Reducing The Cost of Transport and Increasing Walking Distance After Stroke: A Randomized Controlled Trial on Fast Locomotor Training Combined With Functional Electrical Stimulation.

    PubMed

    Awad, Louis N; Reisman, Darcy S; Pohlig, Ryan T; Binder-Macleod, Stuart A

    2016-08-01

    Background Neurorehabilitation efforts have been limited in their ability to restore walking function after stroke. Recent work has demonstrated proof-of-concept for a functional electrical stimulation (FES)-based combination therapy designed to improve poststroke walking by targeting deficits in paretic propulsion. Objectives To determine the effects on the energy cost of walking (EC) and long-distance walking ability of locomotor training that combines fast walking with FES to the paretic ankle musculature (FastFES). Methods Fifty participants >6 months poststroke were randomized to 12 weeks of gait training at self-selected speeds (SS), fast speeds (Fast), or FastFES. Participants' 6-minute walk test (6MWT) distance and EC at comfortable (EC-CWS) and fast (EC-Fast) walking speeds were measured pretraining, posttraining, and at a 3-month follow-up. A reduction in EC-CWS, independent of changes in speed, was the primary outcome. Group differences in the number of 6MWT responders and moderation by baseline speed were also evaluated. Results When compared with SS and Fast, FastFES produced larger reductions in EC (Ps ≤.03). FastFES produced reductions of 24% and 19% in EC-CWS and EC-Fast (Ps <.001), respectively, whereas neither Fast nor SS influenced EC. Between-group 6MWT differences were not observed; however, 73% of FastFES and 68% of Fast participants were responders, in contrast to 35% of SS participants. Conclusions Combining fast locomotor training with FES is an effective approach to reducing the high EC of persons poststroke. Surprisingly, differences in 6MWT gains were not observed between groups. Closer inspection of the 6MWT and EC relationship and elucidation of how reduced EC may influence walking-related disability is warranted. PMID:26621366

  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. 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

  7. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell

    PubMed Central

    Wilden, Jessica A.; Qing, Kurt Y.; Hauser, Sheketha R.; McBride, William J.; Irazoqui, Pedro P.; Rodd, Zachary A.

    2015-01-01

    Object There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. Methods In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of γ–aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8–10 rats/group), after which the animals were placed in operant chambers containing 2 levers—one used to administer water and the other to administer 15% EtOH—to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat’s left AcbSh. The animals then received 100 or 200 μA (3–4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. Results In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 μA of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Conclusions Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism. PMID:24460492

  8. 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

  9. 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

  10. Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.

    PubMed

    Cook, J L; Tomlinson, J L; Arnoczky, S P; Fox, D B; Reeves Cook, C; Kreeger, J M

    2001-06-01

    Porcine small intestinal submucosa (SIS) was used to replace large, avascular defects in the medial menisci of dogs. Twelve dogs received SIS grafts and 3 dogs were left untreated as controls. Dogs were evaluated at 4, 8, and 12 weeks by means of lameness scoring and ultrasonography. Dogs were sacrificed at 1, 6, or 12 weeks after implantation, and the tissue at the site of meniscal resection was evaluated for gross and histologic appearance, cross-sectional and surface area, and collagen types I and II. The femoral and tibial condyles were assessed for articular cartilage damage. Control dogs were significantly more lame than grafted dogs 8 and 12 weeks after instrumentation. Grafted dogs' replacement tissue appeared meniscal-like when evaluated grossly and ultrasonographically 12 weeks after instrumentation. The amount of replacement tissue was significantly greater in both cross-sectional and surface area for grafted dogs than for controls at all time points. Histologically, the SIS biomaterial could be identified in all grafted dogs at 1 week post-implantation, but in none at 6 weeks post-implantation. Subjectively, grafted dogs' replacement tissue was histologically superior to that of controls with respect to tissue type, organization, and architecture. Collagen types I and II immunoreactivity in grafted menisci were similar to that of normal menisci. Control dogs had significantly more articular cartilage damage than grafted dogs. SIS appears to induce regeneration of meniscal-like tissue in large, avascular meniscal defects in dogs, resulting in superior clinical function and articular cartilage protection compared to ungrafted controls. PMID:11429152

  11. 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

  12. 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

  13. 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

  14. 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

  15. Both short intense and prolonged moderate in vitro stimulation reduce the mRNA expression of calcium-regulatory proteins in rat skeletal muscle.

    PubMed

    Mänttäri, Satu; Ørtenblad, Niels; Madsen, Klavs; Pilegaard, Henriette

    2013-01-01

    Sarcoplasmic and t-tubule membrane proteins regulating sarcoplasmic Ca(2+) concentration exhibit fibre-type-dependent isoform expression, and play central roles in muscle contraction and relaxation. The purpose of this study was to evaluate the effects of in vitro electrical stimulation on the mRNA expression of components involved in Ca(2+) regulation in oxidative and glycolytic skeletal muscle. The mRNA level of Ca(2+)-ATPase (SERCA1, 2), calsequestrin (CASQ1, 2), ryanodine receptor (RyR1), and dihydropyridine receptor (Cacna1) was assessed in rat extensor digitorum longus (EDL) and soleus (SOL) muscles at 4 h of recovery following in vitro stimulations (either short intensive (SHO) 60 Hz, 5 min, or prolonged moderate (PRO) 20 Hz, 40 min). Stimulation induced acute regulation of the mRNA level of Ca(2+)-regulating proteins in a manner that does not follow typical fibre-type-specific transitions. In general, stimulation decreased mRNA content of all proteins studied. Most prominent down-regulation was observed for Cacna1 (26 and 32 % after SHO and PRO, respectively, in SOL; 19 % after SHO in EDL). SERCA1, SERCA2, CASQ1, CASQ2, and RyR1 mRNA content also decreased significantly in both muscles relative to resting control. Of notice is that hexokinase II mRNA content was increased in EDL and unchanged in SOL underlining the specificity of the down-regulation of mRNA of Ca(2+) regulatory proteins. The results demonstrate contraction-induced down-regulation of mRNAs for the main components of Ca(2+)-regulating system in skeletal muscle. The down-regulation of both isoforms of SERCA and CASQ after a single electrical stimulation session suggests that adaptations to repeated stimulation involve further regulatory mechanisms in addition to acute mRNA responses. PMID:23111891

  16. 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…

  17. 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…

  18. Reduced cortical vasodilatory response to stimulation of the nucleus basalis of Meynert in the aged rat and evidence for a control of the cerebral circulation.

    PubMed

    Lacombe, P; Sercombe, R; Vaucher, E; Seylaz, J

    1997-09-26

    In earlier studies we showed that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large increases in cerebral blood flow, mainly through cholinergic mechanisms. We then investigated the effect of aging on this influence by measuring cortical blood flow (CoBF) and tissue gas partial pressures (PtO2, PtCO2) in the conscious young adult and aged rat. NBM stimulation increased frontal (+101%) and parietal (+29%) CoBF in young rats. The effects were halved in aged rats. Moreover, PtO2 was significantly increased in young but not in aged rats. By contrast, the corticovascular reactivity to hypercapnia did not differ between young and aged rats, nor did the potentiating vasodilator effect of physostigmine. In combined autoradiographic measurements of cerebral blood flow and cerebral glucose utilization, we recently found that the cortical circulatory response to NBM stimulation was not accompanied by significant metabolic change. Thus, the blood flow changes observed in the cortex cannot be ascribed to increased metabolic activity. The distribution of this uncoupling coincides with that of cholinergic NBM projections directly impinging on cortical microvessels. These data support the cortical microcirculation and suggest the possible involvement of NBM dysfunction in the pathology of cortical microcirculation. PMID:9329714

  19. Blocking T cell co-stimulation using a CD80 blocking small molecule reduces delayed type hypersensitivity responses in rhesus monkeys

    PubMed Central

    Haanstra, K G; Endell, J; Estévâo, D; Kondova, I; Jonker, M

    2009-01-01

    Blockade of co-stimulation signals between T cells and antigen-presenting cells could be an important approach for treatment of autoimmune diseases and transplant rejection. Recently a series of small compound inhibitors which bind human CD80 (B7-1) and inhibit T cell co-stimulation has been described. To investigate their potency for clinical use, one of these compounds, RhuDex™, was evaluated for reactivity with rhesus monkey CD80. The in vitro biological effect on rhesus monkey lymphocytes, the potency for suppression of an inflammatory recall response and the protein-induced delayed type hypersensitivity (DTH) response in the skin were studied. In a rhesus monkey T cell co-stimulation assay RhuDex™ inhibited proinflammatory cytokine release and cellular proliferation with micromolar potency. Systemic administration of RhuDex™ to rhesus monkeys inhibited the DTH response significantly, indicating that this compound may inhibit autoimmune mediated inflammatory processes where the target, CD80, is up-regulated. PMID:19737235

  20. 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

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

    PubMed

    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

  2. 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.

  3. Cyclophosphamide and IL-12-transduced DCs enhance the antitumor activity of tumor antigen-stimulated DCs and reduce Tregs and MDSCs number.

    PubMed

    Rossowska, Joanna; Pajtasz-Piasecka, Elżbieta; Anger, Natalia; Wojas-Turek, Justyna; Kicielińska, Jagoda; Piasecki, Egbert; Duś, Danuta

    2014-01-01

    A hostile tumor microenvironment, characterized by an abundance of T regulatory cells and myeloid-derived suppressor cells (MDSCs), considerably limits the efficacy of dendritic cell (DC)-based vaccines. The intention of this study was to enhance the antitumor activity of vaccines consisting of bone marrow-derived DCs stimulated with TAg (BMDC/TAg) via single administration of cyclophosphamide and multiple injections of interleukin (IL)-12-transduced DCs (BMDC/IL-12). The combined chemoimmunotherapy was applied in the treatment of mice with subcutaneously (SC) growing, advanced MC38 colon carcinoma. The highest level of tumor growth inhibition, accompanied by high cytotoxic activity of effector cells, and their increased influx into tumor tissue, was observed after application of cyclophosphamide in combination with BMDC/TAg and BMDC/IL-12. The effect was probably associated with the elimination of T regulatory cells from spleens and tumors, but most of all with changes in the number and differentiation stage of MDSCs. After the therapy, the percentage of granulocytic and monocytic MDSCs in spleens was significantly lower than in the control group. Moreover, MDSCs derived from spleens and tumors showed increased expression of MHC class II, which may indicate the higher maturation stage of the myeloid cells as well as their enhanced capacity toward antigen presentation. The obtained data indicate that the optimal composition of antitumor vaccines able to limit the suppressor activity of MDSCs is essential to enhance the elimination of tumor cells and to achieve an optimal therapeutic effect. PMID:25304726

  4. Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously.

    PubMed Central

    Honkoop, A. H.; Hoekman, K.; Wagstaff, J.; van Groeningen, C. J.; Vermorken, J. B.; Boven, E.; Pinedo, H. M.

    1996-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a haematopoietic growth factor with a wide variety of applications in the clinic. In early phase I studies the continuous intravenous (c.i.) route of administration was often used. Later it was shown that subcutaneous (s.c.) administration was also effective. The optimal route of administration remains, however, poorly defined, and no studies have made a direct comparison between these two routes of administration. We treated patients with advanced breast cancer with moderately high-dose doxorubicin and cylophosphamide and GM-CSF. The first 14 patients received GM-CSF by c.i, while subsequently 47 patients received it s.c. Comparison between the two groups showed that c.i. GM-CSF was more toxic in several respects. There was a higher need for erythrocyte and platelet transfusions and a significant deterioration in the performance status. This study indicates that subcutaneous GM-CSF is the preferred route of administration. Randomised trials are, however, needed to confirm these conclusions. PMID:8855987

  5. 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

  6. Obesity reduces left ventricular strains, torsion, and synchrony in mouse models: a cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance study

    PubMed Central

    2013-01-01

    Background Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV). Methods Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on the diet, mice were imaged with a 7 T ClinScan using a cine DENSE protocol. Three short-axis and two long-axis slices were acquired for quantification of strains, torsion and synchrony in the left ventricle. Results Left ventricular mass was increased by 15% (p = 0.032) with no change in volumes or ejection fraction. Subepicardial strain was lower in the obese mice with a 40% reduction in circumferential strain (p = 0.008) a 53% reduction in radial strain (p = 0.032) and a trend towards a 19% reduction in longitudinal strain (p = 0.056). By contrast, subendocardial strain was modestly reduced in the obese mice in the circumferential direction by 12% (p = 0.028), and no different in the radial (p = 0.690) or longitudinal (p = 0.602) directions. Peak torsion was reduced by 34% (p = 0.028). Synchrony of contraction was also reduced (p = 0.032) with a time delay in the septal-to-lateral direction. Conclusions Diet-induced obesity reduces left ventricular strains and torsion in mice. Reductions in cardiac strain are mostly limited to the subepicardium, with relative preservation of function in the subendocardium. Diet-induced obesity also leads to reduced synchrony of contraction and hypertrophy in mouse models. PMID:24380567

  7. Stimulation of adenosine A2A receptors reduces intracellular cholesterol accumulation and rescues mitochondrial abnormalities in human neural cell models of Niemann-Pick C1.

    PubMed

    Ferrante, A; De Nuccio, C; Pepponi, R; Visentin, S; Martire, A; Bernardo, A; Minghetti, L; Popoli, P

    2016-04-01

    Niemann Pick C 1 (NPC1) disease is an incurable, devastating lysosomal-lipid storage disorder characterized by hepatosplenomegaly, progressive neurological impairment and early death. Current treatments are very limited and the research of new therapeutic targets is thus mandatory. We recently showed that the stimulation of adenosine A2A receptors (A2ARs) rescues the abnormal phenotype of fibroblasts from NPC1 patients suggesting that A2AR agonists could represent a therapeutic option for this disease. However, since all NPC1 patients develop severe neurological symptoms which can be ascribed to the complex pathology occurring in both neurons and oligodendrocytes, in the present paper we tested the effects of the A2AR agonist CGS21680 in human neuronal and oligodendroglial NPC1 cell lines (i.e. neuroblastoma SH-SY5Y and oligodendroglial MO3.13 transiently transfected with NPC1 small interfering RNA). The down-regulation of the NPC1 protein effectively resulted in intracellular cholesterol accumulation and altered mitochondrial membrane potential. Both effects were significantly attenuated by CGS21680 (500 nM). The protective effects of CGS were prevented by the selective A2AR antagonist ZM241385 (500 nM). The involvement of calcium modulation was demonstrated by the ability of Bapta-AM (5-7 μM) in reverting the effect of CGS. The A2A-dependent activity was prevented by the PKA-inhibitor KT5720, thus showing the involvement of the cAMP/PKA signaling. These findings provide a clear in vitro proof of concept that A2AR agonists are promising potential drugs for NPC disease. PMID:26631535

  8. Reduced Mirror Neuron Activity in Schizophrenia and Its Association With Theory of Mind Deficits: Evidence From a Transcranial Magnetic Stimulation Study

    PubMed Central

    Mehta, Urvakhsh Meherwan; Thirthalli, Jagadisha; Basavaraju, Rakshathi; Gangadhar, Bangalore N.; Pascual-Leone, Alvaro

    2014-01-01

    Background: The “mirror-neuron system” has been proposed to be a neurophysiological substrate for social cognition (SC) ability. We used transcranial magnetic stimulation (TMS) paradigms to compare putative mirror neuron activity (MNA) in 3 groups: antipsychotic-naive, medicated schizophrenia patients, and healthy comparison subjects. We also explored the association between MNA and SC ability in patients. Methods: Fifty-four consenting right-handed schizophrenia patients (33 antipsychotic naive) and 45 matched healthy comparison subjects completed a TMS experiment to assess putative premotor MNA. We used 4 TMS paradigms of eliciting motor-evoked potentials (MEP) in the right first dorsal interosseous (FDI) muscle. These were applied while the subjects observed a goal-directed action involving the FDI (actual action and its video) and a static image. The difference in the amplitude of the MEP while they observed the static image and the action provided a measure of MNA. Subjects also underwent SC assessments (theory of mind [ToM], emotion processing, and social perception). Results: Two-way repeated measures ANOVA revealed significant group × occasion interaction effect in 3 TMS paradigms, indicating deficient motor facilitation during action observation relative to rest state in antipsychotic-naive schizophrenia patients as compared with the other two groups. Among patients, there were significant direct correlations between measures of MNA and ToM performance. Conclusions: Antipsychotic-naive schizophrenia patients have poorer MNA than medicated patients and healthy controls. Measures of putative MNA had significant and consistent associations with ToM abilities. These findings suggest a possibility of deficient mirror neuron system underlying SC deficits in schizophrenia. PMID:24214933

  9. 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". PMID:26006058

  10. 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

  11. 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.

  12. Diminished acyl-CoA synthetase isoform 4 activity in INS 832/13 cells reduces cellular epoxyeicosatrienoic acid levels and results in impaired glucose-stimulated insulin secretion.

    PubMed

    Klett, Eric L; Chen, Shufen; Edin, Matthew L; Li, Lei O; Ilkayeva, Olga; Zeldin, Darryl C; Newgard, Christopher B; Coleman, Rosalind A

    2013-07-26

    Glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells is potentiated by fatty acids (FA). The initial step in the metabolism of intracellular FA is the conversion to acyl-CoA by long chain acyl-CoA synthetases (Acsls). Because the predominantly expressed Acsl isoforms in INS 832/13 cells are Acsl4 and -5, we characterized the role of these Acsls in beta-cell function by using siRNA to knock down Acsl4 or Acsl5. Compared with control cells, an 80% suppression of Acsl4 decreased GSIS and FA-potentiated GSIS by 32 and 54%, respectively. Knockdown of Acsl5 did not alter GSIS. Acsl4 knockdown did not alter FA oxidation or long chain acyl-CoA levels. With Acsl4 knockdown, incubation with 17 mm glucose increased media epoxyeicosatrienoic acids (EETs) and reduced cell membrane levels of EETs. Further, exogenous EETs reduced GSIS in INS 832/13 cells, and in Acsl4 knockdown cells, an EET receptor antagonist partially rescued GSIS. These results strongly suggest that Acsl4 activates EETs to form EET-CoAs that are incorporated into glycerophospholipids, thereby sequestering EETs. Exposing INS 832/13 cells to arachidonate or linoleate reduced Acsl4 mRNA and protein expression and reduced GSIS. These data indicate that Acsl4 modulates GSIS by regulating the levels of unesterified EETs and that arachidonate controls the expression of its activator Acsl4. PMID:23766516

  13. Subcutaneous Injections of the Mannose-Sensitive Hemagglutination Pilus Strain of Pseudomonas aeruginosa Stimulate Host Immunity, Reduce Bladder Cancer Size and Improve Tumor Survival in Mice.

    PubMed

    Li, Tao; Yang, Li; Fu, Sheng-Jun; Xiao, Er-Long; Yuan, Xuan; Lu, Jian-Zhong; Ma, Bao-Liang; Shi, Ting-Kai; Wang, Zhi-Ping

    2015-09-01

    We wished to evaluate the effects of Pseudomonas aeruginosa (mannose-sensitive hemagglutination pilus strain, PA-MSHA) as an immunostimulating and anti-tumor agent for treatment of bladder cancer. Immunostimulating effects were assessed by the in vitro proliferation assay of murine splenic lymphocytes. Anti-tumor effects were studied in a subcutaneous tumor model established in female C57BL/6 mice using the MB49 bladder cell line. These mice received subcutaneous injections of normal saline (control group) or PA-MSHA (high, medium, or low dose, respectively, 1.6-2.0 × 10(9), 3.2- .0 × 10(8), 6.4-8.0 × 10(7) CFU/ml) twice a week for 3 weeks. Mice survival, tumor volume, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), serum levels of TNF-α and IFN-γ, and blood CD4(+) /CD8(+) counts were the study outcomes. We observed that PA-MSHA promoted the growth of splenic lymphocytes in vitro. In the murine tumor model, PA-MSHA prolonged mice survival and reduced tumor growth. Furthermore, VEGF and MVD were also diminished by PA-MSHA. Mice that received high and medium dose of PA-MSHA had significantly higher serum levels of IFN-γ and TNF-α (days 21 and 28), and higher levels of CD4(+) /CD8(+) cells (days 21 and 28). In conclusion, PA-MSHA exerts beneficial effects on increasing proliferation of murine splenic lymphocytes in vitro and inhibits the growth of bladder tumor in a murine model. Therefore, PA-MSHA may be useful an immunostimulating and anti-tumor agent for bladder cancer therapy. PMID:25724441

  14. Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase.

    PubMed

    Algire, Carolyn; Amrein, Lilian; Zakikhani, Mahvash; Panasci, Lawrence; Pollak, Michael

    2010-06-01

    The molecular mechanisms responsible for the association of obesity with adverse colon cancer outcomes are poorly understood. We investigated the effects of a high-energy diet on growth of an in vivo colon cancer model. Seventeen days following the injection of 5x10(5) MC38 colon carcinoma cells, tumors from mice on the high-energy diet were approximately twice the volume of those of mice on the control diet. These findings were correlated with the observation that the high-energy diet led to elevated insulin levels, phosphorylated AKT, and increased expression of fatty acid synthase (FASN) by the tumor cells. Metformin, an antidiabetic drug, leads to the activation of AMPK and is currently under investigation for its antineoplastic activity. We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN. Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage. Prior work showed that activating mutations of PI3K are associated with increased AKT activation and adverse outcome in colon cancer; our results demonstrate that the aggressive tumor behavior associated with a high-energy diet has similar effects on this signaling pathway. Furthermore, metformin is demonstrated to reverse the effects of the high-energy diet, thus suggesting a potential role for this agent in the management of a metabolically defined subset of colon cancers. PMID:20228137

  15. GLP-1 Receptor Stimulation Reduces Amyloid-β Peptide Accumulation and Cytotoxicity in Cellular and Animal Models of Alzheimer’s Disease

    PubMed Central

    Li, Yazhou; Duffy, Kara B.; Ottinger, Mary Ann; Ray, Balmiki; Bailey, Jason A.; Holloway, Harold W.; Tweedie, David; Perry, TracyAnn; Mattson, Mark P.; Kapogiannis, Dimitrios; Sambamurti, Kumar; Lahiri, Debomoy K.; Greiga, Nigel H.

    2010-01-01

    Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer’s disease (AD). Several pathological features are shared between diabetes and AD, including dysfunctional insulin signaling and a dysregulation of glucose metabolism. It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other. Hence, the present study characterized the effects of a clinically approved long-acting analogue, exendin-4 (Ex-4), of the endogenous insulin releasing incretin, glucagon-like peptide-1 (GLP-1), on stress-induced toxicity in neuronal cultures and on amyloid-β protein (Aβ) and tau levels in triple transgenic AD (3xTg-AD) mice with and without streptozocin (STZ)-induced diabetes. Ex-4 ameliorated the toxicity of Aβ and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. When 11 to 12.5 month old female 3xTg AD mice were challenged with STZ or saline, and thereafter treated with a continuous subcutaneous infusion of Ex-4 or vehicle, Ex-4 ameliorated the diabetic effects of STZ in 3xTg-AD mice, elevating plasma insulin and lowering both plasma glucose and hemoglobin A1c (HbA1c) levels. Furthermore, brain levels of Aβ protein precursor and Aβ, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice. Brain tau levels were unaffected following STZ challenge, but showed a trend toward elevation that was absent following Ex-4 treatment. Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance. PMID:20308787

  16. Infant Stimulation.

    ERIC Educational Resources Information Center

    International Children's Centre, Paris (France).

    This set of documents consists of English, French, and Spanish translations of four pamphlets on infant stimulation. The pamphlets provide information designed for lay persons, educators and primary care personnel, academics and professionals, and for health administrators and family-planning organizations. The contents cover infant needs; infant…

  17. Deep Brain Stimulation

    PubMed Central

    Perlmutter, Joel S.; Mink, Jonathan W.

    2015-01-01

    Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics. PMID:16776585

  18. 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.

  19. 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

  20. 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

  1. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.

    PubMed

    Conlon, M A; Tomas, F M; Owens, P C; Wallace, J C; Howarth, G S; Ballard, F J

    1995-08-01

    We have tested whether an animal with substantial amounts of both IGF-I and IGF-II in circulation, such as the guinea pig, would respond to chronic IGF infusion in the same manner as the adult rat, which has negligible amounts of IGF-II in blood. Female guinea pigs of 350 g body weight were continuously infused for 7 days with recombinant guinea pig IGF-I or -II (120 or 360 micrograms/day) or long R3 IGF-I (LR3IGF-I) (120 micrograms/day), an analogue which has much reduced affinities for IGF binding proteins. IGF-I or IGF-II infusion led to substantial increases in plasma IGF-I or IGF-II respectively in comparison with vehicle-infused animals. Nevertheless, body weight gain, feed intake, feed conversion efficiency and carcass composition were not significantly affected by any treatment (significance was deemed to be P < 0.05). Amongst the tissues examined only the fractional weight (g/kg body weight) of the adrenals was increased, and that only by the higher dose (360 micrograms/day) of IGF-I. However, the fractional weight of adrenals, gut, kidneys and spleen were significantly increased by LR3IGF-I, but again overall growth was not stimulated. A possible explanation for the lack of IGF-I effects is that total circulating IGF concentrations were not increased by these treatments. IGF-II significantly raised total IGF concentrations at the higher dose only. Plasma IGF-I was reduced by IGF-II infusion, as was plasma IGF-II by IGF-I infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7561636

  2. AICAR reduces the collagen-stimulated secretion of PDGF-AB and release of soluble CD40 ligand from human platelets: Suppression of HSP27 phosphorylation via p44/p42 MAP kinase

    PubMed Central

    Tsujimoto, Masanori; Tokuda, Haruhiko; Kuroyanagi, Gen; Yamamoto, Naohiro; Kainuma, Shingo; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Iida, Yuko; Kojima, Akiko; Sawada, Shigenobu; Doi, Tomoaki; Enomoto, Yukiko; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Kozawa, Osamu; Iwama, Toru

    2016-01-01

    We have previously reported that collagen-induced phosphorylation of heat shock protein (HSP) 27 via p44/p42 mitogen-activated protein (MAP) kinase in human platelets is sufficient to induce the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble cluster of differentiation 40 ligand (sCD40L). Adenosine monophosphate-activated protein kinase (AMPK), which is known to regulate energy homeostasis, has a crucial role as an energy sensor in various eukaryotic cells. The present study investigated the effects of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (AICAR), which is an activator of AMPK, on the collagen-induced activation of human platelets. It was demonstrated that AICAR dose-dependently reduced collagen-stimulated platelet aggregation up to 1.0 µM. Analysis of the size of platelet aggregates demonstrated that AICAR decreased the ratio of large aggregates (50–70 µm), whereas the ratio of small aggregates (9–25 µm) was increased by AICAR administration. AICAR markedly attenuated the phosphorylation levels of p44/p42 MAP kinase and HSP27, which are induced by collagen. Furthermore, AICAR significantly decreased the secretion of PDGF-AB and the collagen-induced release of sCD40L. These results indicated that AICAR-activated AMPK may reduce the secretion of PDGF-AB and the collagen-induced release of sCD40L by inhibiting HSP27 phosphorylation via p44/p42 MAP kinase in human platelets.

  3. Replacement of Lys Linker with Arg Linker Resulting in Improved Melanoma Uptake and Reduced Renal Uptake of Tc-99m-Labeled Arg-Gly-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Hybrid Peptide

    PubMed Central

    Yang, Jianquan; Guo, Haixun; Padilla, R. Steve; Berwick, Marianne; Miao, Yubin

    2010-01-01

    The purpose of this study was to reduce the non-specific renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide through structural modification or L-lysine co-injection. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3-13 {(Arg11)CCMSH} through the Arg linker (substituting the Lys linker) to generate a novel RGD-Arg-(Arg11)CCMSH hybrid peptide. The melanoma targeting and pharmacokinetic properties of 99mTc-RGD-Arg-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The effect of L-lysine co-injection on the renal uptake was determined through the co-injection of L-lysine with 99mTc-RGD-Arg-(Arg11)CCMSH or 99mTc-RGD-Lys-(Arg11)CCMSH. Replacement of the Lys linker with an Arg linker exhibited a profound effect in reducing the non-specific renal uptake of 99mTc-RGD-Arg-(Arg11)CCMSH, as well as increasing the tumor uptake of 99mTc-RGD-Arg-(Arg11)CCMSH compared to 99mTc-RGD-Lys-(Arg11)CCMSH. 99mTc-RGD-Arg-(Arg11)CCMSH exhibited high tumor uptake (21.41 ± 3.74% ID/g at 2 h post-injection) and prolonged tumor retention (6.81 ± 3.71% ID/g at 24 h post-injection) in B16/F1 melanoma-bearing mice. The renal uptake values of 99mTc-RGD-Arg-(Arg11)CCMSH were 40.14-64.08% of those of 99mTc-RGD-Lys-(Arg11)CCMSH (p<0.05) at 0.5, 2, 4 and 24 h post-injection. Co-injection of L-lysine was effective in decreasing the renal uptakes of 99mTc-RGD-Arg-(Arg11)CCMSH by 27.7% and 99mTc-RGD-Lys-(Arg11)CCMSH by 52.1% at 2 h post-injection. Substitution of the Lys linker with an Arg linker dramatically improved the melanoma uptake and reduced the renal uptake of 99mTc-RGD-Arg-(Arg11)CCMSH, warranting the further evaluation of 188Re-labeled RGD-Arg-(Arg11)CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future. PMID:20728365

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Ovarian stimulation in cancer patients.

    PubMed

    Cakmak, Hakan; Rosen, Mitchell P

    2013-05-01

    The patients referred for fertility preservation owing to a malignant disease do not represent the typical population of subfertile patients treated in IVF units. Cancer may affect multiple tissues throughout the body and can result in a variety of complications during controlled ovarian stimulation. Determination of the controlled ovarian stimulation protocol and gonadotropin dose for oocyte/embryo cryopreservation requires an individualized assessment. This review highlights the new protocols that are emerging to reduce time constraints and emphasizes management considerations to decrease complications. PMID:23635348

  9. 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

  10. Therapeutic stimulation versus ablation.

    PubMed

    Hariz, Marwan I; Hariz, Gun-Marie

    2013-01-01

    The renaissance of functional stereotactic neurosurgery was pioneered in the mid 1980s by Laitinen's introduction of Leksell's posteroventral pallidotomy for Parkinson´s disease (PD). This ablative procedure experienced a worldwide spread in the 1990s, owing to its excellent effect on dyskinesias and other symptoms of post-l-dopa PD. Modern deep brain stimulation (DBS), pioneered by Benabid and Pollak in 1987 for the treatment of tremor, first became popular when it was applied to the subthalamic nucleus (STN) in the mid 1990s, where it demonstrated a striking effect on all cardinal symptoms of advanced PD, and permitted reduced dosages of medication. DBS, as a nondestructive, adaptable, and reversible procedure that is proving safe in bilateral surgery on basal ganglia, has great appeal to clinicians and patients alike, despite the fact that it is expensive, laborious, and relies on very strict patient selection criteria, especially for STN DBS. Psychiatric surgery has experienced the same phenomenon, with DBS supplanting completely stereotactic ablative procedures. This chapter discusses the pros and cons of ablation versus stimulation and investigates the reasons why DBS has overshadowed proven efficient ablative procedures such as pallidotomy for PD, and capsulotomy and cingulotomy for obsessive-compulsive disorder and depression. PMID:24112885

  11. Noninvasive transcranial brain stimulation and pain.

    PubMed

    Rosen, Allyson C; Ramkumar, Mukund; Nguyen, Tam; Hoeft, Fumiko

    2009-02-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study. PMID:19126365

  12. 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

  13. ACTH (cosyntropin) stimulation test

    MedlinePlus

    ... The ACTH stimulation test measures how well the adrenal glands respond to adrenocorticotropic hormone ( ACTH ). ACTH is a ... produced in the pituitary gland that stimulates the adrenal glands to release a hormone called cortisol. How the ...

  14. 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. PMID:24906937

  15. Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats.

    PubMed

    Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A; McBride, William J

    2016-10-01

    Repeated local administration of ethanol (EtOH) sensitized the posterior ventral tegmental area (pVTA) to the local dopamine (DA)-stimulating effects of EtOH. Chronic alcohol drinking increased nucleus accumbens (NAC) DA transmission and pVTA glutamate transmission in alcohol-preferring (P) rats. The objectives of the present study were to determine the effects of chronic alcohol drinking by P rats on the (a) sensitivity and response of the pVTA DA neurons to the DA-stimulating actions of EtOH, and (b) negative feedback control of DA (via D2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D2/3 receptor antagonist sulpiride (100 or 200 μM) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR2/3 antagonist LY341495 (1 or 10 μM) was perfused through the pVTA via reverse microdialysis and local extracellular glutamate and DA levels were measured. EtOH produced a more robust increase of NACsh DA in the 'EtOH' than 'Water' groups (e.g., 150 mg% EtOH: to ∼ 210 vs 150% of baseline). In contrast, sulpiride increased DA release in the NACsh more in the 'Water' than 'EtOH' groups (e.g., 200 μM sulpiride: to ∼ 190-240 vs 150-160% of baseline). LY341495 (at 10 μM) increased extracellular glutamate and DA levels in the 'Water' (to ∼ 150-180% and 180-230% of baseline, respectively) but not the 'EtOH' groups. These results indicate that alcohol drinking enhanced the DA-stimulating effects of EtOH, and attenuated the functional activities of D2 auto-receptors and group II mGluRs within the pVTA. PMID:27260326

  16. 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

  17. Microscopic magnetic stimulation of neural tissue

    PubMed Central

    Bonmassar, Giorgio; Lee, Seung Woo; Freeman, Daniel K.; Polasek, Miloslav; Fried, Shelley I.; Gale, John T.

    2012-01-01

    Electrical stimulation is currently used to treat a wide range of cardiovascular, sensory and neurological diseases. Despite its success, there are significant limitations to its application, including incompatibility with magnetic resonance imaging, limited control of electric fields and decreased performance associated with tissue inflammation. Magnetic stimulation overcomes these limitations but existing devices (that is, transcranial magnetic stimulation) are large, reducing their translation to chronic applications. In addition, existing devices are not effective for deeper, sub-cortical targets. Here we demonstrate that sub-millimeter coils can activate neuronal tissue. Interestingly, the results of both modelling and physiological experiments suggest that different spatial orientations of the coils relative to the neuronal tissue can be used to generate specific neural responses. These results raise the possibility that micro-magnetic stimulation coils, small enough to be implanted within the brain parenchyma, may prove to be an effective alternative to existing stimulation devices. PMID:22735449

  18. 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

  19. 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

  20. 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

  1. Selectivity of optical stimulation in the auditory system

    NASA Astrophysics Data System (ADS)

    Izzo, Agnella D.; Pathria, Jyoti; Suh, Eul; Walsh, Joseph T., Jr.; Whitlon, Donna S.; Jansen, E. D.; Richter, Claus-Peter

    2006-02-01

    It is known that electrical current injected from cochlear implant contacts spreads within the cochlea, causing overlapping stimulation fields and possibly limiting the performance of cochlear implant users. We have investigated an alternative mechanism to stimulate auditory neurons in the gerbil cochlea using a laser, rather than electrical current. With the laser, it is possible to direct the light to a selected, known volume of tissue that is smaller than the electrically stimulated population of cells. In the present experiments, a transiently expressed transcription factor, c-FOS, was used to stain activated nerve cells. Immunohistochemical staining for c-FOS in the cochlea shows a small area of optical stimulation, which occurs directly opposite to the optical fiber. Additionally, masking data indicate that the laser can stimulate a small population of cells similar to an acoustic toneburst. Smaller populations of stimulated cells could reduce the amount of overlap in stimulation fields and allow more stimulation contacts in a neuroprothesis.

  2. The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage.

    PubMed

    Cejkova, Jitka; Olmiere, Celine; Cejka, Cestmir; Trosan, Peter; Holan, Vladimir

    2014-04-01

    The efficacy of a chemically modified dextran - heparan sulfate mimicking regenerating agent (RGTA) on the healing of the rabbit cornea injured with alkali was examined. The eyes were injured with 0.15 N NaOH applied on the cornea or with 1.0 N NaOH using a 8 mm diameter filter paper disk. Then RGTA or placebo was applied on the cornea. In the last group of rabbits, corneas injured with the high alkali concentration were left without any treatment for four weeks; subsequently, the corneas were treated with RGTA or placebo. The central corneal thickness was measured using a pachymeter. The corneas were examined morphologically, immunohistochemically and for real time-PCR. Compared to control (unaffected) corneas, following the application of low alkali concentration the expression of urokinase-type plasminogen activator, metalloproteinase 9, nitric oxide synthase and xanthine oxidase was increased in the injured corneal epithelium of placebo-treated eyes, whereas the expression of antioxidant enzymes was reduced. Nitrotyrosine and malondialdehyde stainings appeared in the corneal epithelium. RGTA application suppressed the antioxidant/prooxidant imbalance and reduced the expression of the above-mentioned immunohistochemical markers. The corneal thickness increased after alkali injury, decreased during corneal healing after RGTA treatment faster than after placebo application. Following the injury with the high alkali concentration, corneal inflammation and neovascularization were highly pronounced in placebo-treated corneas, whereas in RGTA-treated corneas they were significantly supressed. When RGTA or placebo application was started later after alkali injury and corneas were ulcerated, subsequent RGTA treatment healed the majority of them. In conclusion, RGTA facilitates the healing of injured corneas via a reduction of proteolytic, oxidative and nitrosative damage. PMID:24105332

  3. Music acupuncture stimulation method.

    PubMed

    Brătilă, F; Moldovan, C

    2007-01-01

    Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role. PMID:18767418

  4. 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.

  5. 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.

  6. Stimulating Children to Write.

    ERIC Educational Resources Information Center

    Edwards, Roy

    1985-01-01

    Special education students can be stimulated to write through a variety of activities, including representation, publicity and display tasks, activities featuring photographs, use of music and poetry, and projects in which students finish stories and describe novel materials. (CL)

  7. 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 ...

  8. Spinal cord stimulation

    MedlinePlus

    Spinal cord stimulation is a treatment for pain that uses a mild electric current to block nerve impulses ... stretched into the space on top of your spinal cord. These wires will be connected to a small ...

  9. Growth hormone stimulation test

    MedlinePlus

    The growth hormone (GH) stimulation test measures the ability of the body to produce GH. ... killing medicine (antiseptic). The first sample is drawn early in the morning. Medicine is given through the ...

  10. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  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. PMID:21401669

  12. Evaluation of Intradural Stimulation Efficiency and Selectivity in a Computational Model of Spinal Cord Stimulation

    PubMed Central

    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

  13. Effects of Color Stimulation on Performance and Activity of Hyperactive and Nonhyperactive Children.

    ERIC Educational Resources Information Center

    Zentall, Sydney S.

    1986-01-01

    A theoretically based investigation of color stimulation effects on hyperactivity was conducted. Findings were that stimulation added early or late to a sustained attention task can normalize the performance of hyperactive children and reduce their activity. (Author/LMO)

  14. 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.

  15. 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.

  16. 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.

  17. Neural stimulation with optical radiation

    PubMed Central

    Richter, Claus-Peter; Matic, Agnella Izzo; Wells, Jonathon D.; Jansen, E. Duco; Walsh, Joseph T.

    2012-01-01

    This paper reviews the existing research on infrared neural stimulation, a means of artificially stimulating neurons that has been proposed as an alternative to electrical stimulation. Infrared neural stimulation (INS) is defined as the direct induction of an evoked potential in response to a transient targeted deposition of optical energy. The foremost advantage of using optical radiation for neural stimulation is its spatial resolution. Exogenously applied or trans-genetically synthesized fluorophores are not used to achieve stimulation. Here, current work on INS is presented for motor nerves, sensory nerves, central nervous system, and in vitro preparations. A discussion follows addressing the mechanism of INS and its potential use in neuroprostheses. A brief review of neural depolarization involving other optical methods is also presented. Topics covered include optical stimulation concurrent with electrical stimulation, optical stimulation using exogenous fluorophores, and optical stimulation by transgenic induction of light-gated ion channels. PMID:23082105

  18. Neural stimulation with optical radiation.

    PubMed

    Richter, Claus-Peter; Matic, Agnella Izzo; Wells, Jonathon D; Jansen, E Duco; Walsh, Joseph T

    2011-01-01

    This paper reviews the existing research on infrared neural stimulation, a means of artificially stimulating neurons that has been proposed as an alternative to electrical stimulation. Infrared neural stimulation (INS) is defined as the direct induction of an evoked potential in response to a transient targeted deposition of optical energy. The foremost advantage of using optical radiation for neural stimulation is its spatial resolution. Exogenously applied or trans-genetically synthesized fluorophores are not used to achieve stimulation. Here, current work on INS is presented for motor nerves, sensory nerves, central nervous system, and in vitro preparations. A discussion follows addressing the mechanism of INS and its potential use in neuroprostheses. A brief review of neural depolarization involving other optical methods is also presented. Topics covered include optical stimulation concurrent with electrical stimulation, optical stimulation using exogenous fluorophores, and optical stimulation by transgenic induction of light-gated ion channels. PMID:23082105

  19. Brain stimulation in posttraumatic stress disorder

    PubMed Central

    Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  20. Vagal nerve stimulator: Evolving trends

    PubMed Central

    Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

    2013-01-01

    Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

  1. Copeptin under glucagon stimulation.

    PubMed

    Lewandowski, Krzysztof C; Lewiński, Andrzej; Skowrońska-Jóźwiak, Elżbieta; Stasiak, Magdalena; Horzelski, Wojciech; Brabant, Georg

    2016-05-01

    Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p < 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the time-dependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis. PMID:26578365

  2. Brain stimulation in migraine.

    PubMed

    Brighina, Filippo; Cosentino, Giuseppe; Fierro, Brigida

    2013-01-01

    Migraine is a very prevalent disease with great individual disability and socioeconomic burden. Despite intensive research effort in recent years, the etiopathogenesis of the disease remains to be elucidated. Recently, much importance has been given to mechanisms underlying the cortical excitability that has been suggested to be dysfunctional in migraine. In recent years, noninvasive brain stimulation techniques based on magnetic fields (transcranial magnetic stimulation, TMS) and on direct electrical currents (transcranial direct current stimulation, tDCS) have been shown to be safe and effective tools to explore the issue of cortical excitability, activation, and plasticity in migraine. Moreover, TMS, repetitive TMS (rTMS), and tDCS, thanks to their ability to interfere with and/or modulate cortical activity inducing plastic, persistent effects, have been also explored as potential therapeutic approaches, opening an interesting perspective for noninvasive neurostimulation for both symptomatic and preventive treatment of migraine and other types of headache. In this chapter we critically review evidence regarding the role of noninvasive brain stimulation in the pathophysiology and treatment of migraine, delineating the advantages and limits of these techniques together with potential development and future application. PMID:24112926

  3. Heliostat Stimulator operator's manual

    SciTech Connect

    Not Available

    1980-11-01

    The Heliostat Stimulator is a portable test tool, housed in a suitcase, which can be used to perform the following functions: (1) acceptance testing of newly manufactured Heliostat Controllers (HC) and Heliostat Field Controllers (HFC); (2) aid in the installation and alignment of Heliostats; and (3) provide diagnostic troubleshooting capability in the event of Heliostat failure in the field.

  4. 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.

  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. 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

  7. 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.

  8. Occipital nerve stimulation.

    PubMed

    Mammis, Antonios; Agarwal, Nitin; Mogilner, Alon Y

    2015-01-01

    Occipital nerve stimulation (ONS) is a form of neuromodulation therapy aimed at treating intractable headache and craniofacial pain. The therapy utilizes neurostimulating electrodes placed subcutaneously in the occipital region and connected to a permanently implanted programmable pulse generator identical to those used for dorsal column/spinal cord stimulation. The presumed mechanisms of action involve modulation of the trigeminocervical complex, as well as closure of the physiologic pain gate. ONS is a reversible, nondestructive therapy, which can be tailored to a patient's individual needs. Typically, candidates for successful ONS include those patients with migraines, Chiari malformation, or occipital neuralgia. However, recent MRSA infections, unrealistic expectations, and psychiatric comorbidities are generally contraindications. As with any invasive procedure, complications may occur including lead migration, infection, wound erosion, device failure, muscle spasms, and pain. The success of this therapy is dependent on careful patient selection, a preimplantation trial, meticulous implantation technique, programming strategies, and complication avoidance. PMID:25411143

  9. 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

  10. 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.

  11. Effectiveness of sensory stimulation on tactile extinction.

    PubMed

    Nico, D

    1999-07-01

    Eleven brain-damaged patients with extinction were asked to report double tactile stimuli before, during, and after optokinetic stimulation and transcutaneous electrical stimulation of the posterior neck region. The goal of the study was to test whether tactile extinction is sensitive to these experimental manipulations in order to better understand the nature of the disorder. Both of these sensory stimulations are known to be effective in modulating only higher-order (cognitive) disorders of spatial coding, such as visual hemineglect, deficit of position sense, hemianesthesia, etc. When applied to the side contralateral to the cerebral lesion, both optokinetic and transcutaneous electrical stimulation significantly affected patients' performances, increasing the amount of detections of contralesional double stimuli. A tendency towards worse performance was observed when sensory stimulation was applied to the ipsilesional side. The reported effectiveness in reducing tactile extinction suggests that the deficit can not be fully ascribed to a peripheral sensory disorder and that it reflects damage to a higher-order cognitive function involved in contralesional space representation or in the deployment of attention to that side of space. The nature of the close relationship between extinction and hemineglect is also discussed from the point of view of extinction as a deficit of space coding. PMID:10424416

  12. 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.

  13. Non-invasive neuromuscular electrical stimulation in patients with central nervous system lesions: an educational review.

    PubMed

    Schuhfried, Othmar; Crevenna, Richard; Fialka-Moser, Veronika; Paternostro-Sluga, Tatjana

    2012-02-01

    The aim of this educational review is to provide an overview of the clinical application of transcutaneous electrical stimulation of the extremities in patients with upper motor neurone lesions. In general two methods of electrical stimulation can be distinguished: (i) therapeutic electrical stimulation, and (ii) functional electrical stimulation. Therapeutic electrical stimulation improves neuromuscular functional condition by strengthening muscles, increasing motor control, reducing spasticity, decreasing pain and increasing range of motion. Transcutaneous electrical stimulation may be used for neuromuscular electrical stimulation inducing repetitive muscle contraction, electromyography-triggered neuromuscular electrical stimulation, position-triggered electrical stimulation and subsensory or sensory transcutaneous electric stimulation. Functional electrical stimulation provokes muscle contraction and thereby produces a functionally useful movement during stimulation. In patients with spinal cord injuries or stroke, electrical upper limb neuroprostheses are applied to enhance upper limb and hand function, and electrical lower limb neuroprostheses are applied for restoration of standing and walking. For example, a dropped foot stimulator is used to trigger ankle dorsiflexion to restore gait function. A review of the literature and clinical experience of the use of therapeutic electrical stimulation as well as of functional electrical stimulation in combination with botulinum toxin, exercise therapy and/or splinting are presented. Although the evidence is limited we conclude that neuromuscular electrical stimulation in patients with central nervous system lesions can be an effective modality to improve function, and that combination with other treatments has an additive therapeutic effect. PMID:22334346

  14. 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…

  15. Broadband stimulated Raman backscattering

    NASA Astrophysics Data System (ADS)

    Landgraf, B.; Aurand, B.; Lehmann, G.; Gangolf, T.; Schnell, M.; Kühl, T.; Spielmann, C.

    2016-07-01

    Broadband amplification employing stimulated Raman backscattering is demonstrated. Using seed pulses with a bandwidth of about 200 nm, we study the amplification in a wide spectral range in a single laser shot. With chirped pump pulses and a Ne gas jet, we observed under optimized conditions, amplification in a range of about 80 nm, which is sufficient to support the amplification of sub-20 fs pulses. This broad amplification range is also in excellent agreement with PIC simulations. The conversion efficiency is at certain wavelengths as high as 1.2% and was measured to be better than 6 × 10‑3 on average.

  16. Geothermal well stimulation

    SciTech Connect

    Sinclair, A.R.; Pittard, F.J.; Hanold, R.J.

    1980-01-01

    All available data on proppants and fluids were examined to determine areas in technology that need development for 300 to 500/sup 0/F (150/sup 0/ to 265/sup 0/C) hydrothermal wells. While fluid properties have been examined well into the 450/sup 0/F range, proppants have not been previously tested at elevated temperatures except in a few instances. The latest test data at geothermal temperatures is presented and some possible proppants and fluid systems that can be used are shown. Also discussed are alternative stimulation techniques for geothermal wells.

  17. ``Bloch wave'' modification of stimulated Raman by stimulated Brillouin scattering

    NASA Astrophysics Data System (ADS)

    Dodd, E. S.; Vu, H. X.; DuBois, D. F.; Bezzerides, B.

    2013-03-01

    Using the reduced-description particle-in-cell (RPIC) method, we study the coupling of backward stimulated Raman scattering (BSRS) and backward stimulated Brillouin scattering (BSBS) in regimes where the reflectivity involves the nonlinear behavior of particles trapped in the daughter plasma waves. The temporal envelope of a Langmuir wave (LW) obeys a Schrödinger equation where the potential is the periodic electron density fluctuation resulting from an ion-acoustic wave (IAW). The BSRS-driven LWs in this case have a Bloch wave structure and a modified dispersion due to the BSBS-driven spatially periodic IAW, which includes frequency band gaps at kLW˜kIAW/2˜k0 (kLW, kIAW, and k0 are the wave number of the LW, IAW, and incident pump electromagnetic wave, respectively). This band structure and the associated Bloch wave harmonic components are distinctly observed in RPIC calculations of the electron density fluctuation spectra and this structure may be observable in Thomson scatter. Bloch wave components grow up in the LW spectrum, and are not the result of isolated BSRS. Self-Thomson scattered light from these Bloch wave components can have forward scattering components. The distortion of the LW dispersion curve implies that the usual relationship connecting the frequency shift of the BSRS-scattered light and the density of origin of this light may become inaccurate. The modified LW frequency results in a time-dependent frequency shift that increases as the IAW grows, detunes the BSRS frequency matching condition, and reduces BSRS growth. A dependence of the BSRS reflectivity on the IAW Landau damping results because this damping determines the levels of IAWs. The time-dependent reflectivity in our simulations is characterized by bursts of sub-picosecond pulses of BSRS alternating with multi-ps pulses of BSBS, and BSRS is observed to decline precipitously as soon as SBS begins to grow from low levels. In strong BSBS regimes, the Bloch wave effects in BSRS are

  18. 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

  19. BIOPHYSICAL STIMULATION FOR NONUNIONS.

    PubMed

    Della Bella, E; Tschon, M; Stagni, C; Dallari, D; Fini, M

    2015-01-01

    Nonunions account for 5-10% on the total number of fractures. Biophysical stimulation is a non-surgical, conservative, frequently used therapy in nonunions and a greater efficacy has been demonstrated for pulsed electromagnetic fields (PEMF). The mechanisms of action of PEMF at cellular and molecular levels are still under debate and no dose-response study is available. Moreover, the vast majority of in vitro studies were conducted on healthy cells. The primary aim of the research was to investigate the capacity of PEMF with different exposure times to stimulate the osteogenic process in cells from the callus of a nonunion patient. Another important objective was the characterization of nonunion cells in terms of clonogenicity, cluster of differentiation expression and the tri-lineage differentiation capacity. Overall, the results indicated the presence of osteochondroprogenitor cells in the callus of a nonunion, with an impairment in the osteogenic differentiation process. PEMF may enhance cell viability, the formation of osteoid matrix and accelerate the process of osteogenic differentiation. BMP-4 production, TIMP1 and TIMP2 expression were influenced, as well as VEGFA, whose early upregulation may account for a possible improvement in both the osteogenic and vasculogenic processes. In conclusion, even with some discussed limitations, these preliminary data showed the presence of a multipotent progenitor population and suggested some hints of the effect of PEMF on nonunion cells. PMID:26652488

  20. 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. PMID:25846152

  1. 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

  2. Central nervous system stimulants and sport practice

    PubMed Central

    Avois, L; Robinson, N; Saudan, C; Baume, N; Mangin, P; Saugy, M

    2006-01-01

    Background and objectives Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. Results CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti‐doping laboratories statistics and the media, and their potentially serious adverse effects. Conclusions Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced. PMID:16799095

  3. Microwave-stimulated superconductivity due to presence of vortices

    NASA Astrophysics Data System (ADS)

    Lara, Antonio; Aliev, Farkhad G.; Silhanek, Alejandro V.; Moshchalkov, Victor V.

    2015-03-01

    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.

  4. 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

  5. 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.

  6. 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

  7. Femtosecond Stimulated Raman Spectroscopy.

    PubMed

    Dietze, Daniel R; Mathies, Richard A

    2016-05-01

    Femtosecond stimulated Raman spectroscopy (FSRS) is an ultrafast nonlinear optical technique that provides vibrational structural information with high temporal (sub-50 fs) precision and high spectral (10 cm(-1) ) resolution. Since the first full demonstration of its capabilities ≈15 years ago, FSRS has evolved into a mature technique, giving deep insights into chemical and biochemical reaction dynamics that would be inaccessible with any other technique. It is now being routinely applied to virtually all possible photochemical reactions and systems spanning from single molecules in solution to thin films, bulk crystals and macromolecular proteins. This review starts with an historic overview and discusses the theoretical and experimental concepts behind this technology. Emphasis is put on the current state-of-the-art experimental realization and several variations of FSRS that have been developed. The unique capabilities of FSRS are illustrated through a comprehensive presentation of experiments to date followed by prospects. PMID:26919612

  8. 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

  9. Stimulated coherent transition radiation

    SciTech Connect

    Hung-chi Lihn

    1996-03-01

    Coherent radiation emitted from a relativistic electron bunch consists of wavelengths longer than or comparable to the bunch length. The intensity of this radiation out-numbers that of its incoherent counterpart, which extends to wavelengths shorter than the bunch length, by a factor equal to the number of electrons in the bunch. In typical accelerators, this factor is about 8 to 11 orders of magnitude. The spectrum of the coherent radiation is determined by the Fourier transform of the electron bunch distribution and, therefore, contains information of the bunch distribution. Coherent transition radiation emitted from subpicosecond electron bunches at the Stanford SUNSHINE facility is observed in the far-infrared regime through a room-temperature pyroelectric bolometer and characterized through the electron bunch-length study. To measure the bunch length, a new frequency-resolved subpicosecond bunch-length measuring system is developed. This system uses a far-infrared Michelson interferometer to measure the spectrum of coherent transition radiation through optical autocorrelation with resolution far better than existing time-resolved methods. Hence, the radiation spectrum and the bunch length are deduced from the autocorrelation measurement. To study the stimulation of coherent transition radiation, a special cavity named BRAICER is invented. Far-infrared light pulses of coherent transition radiation emitted from electron bunches are delayed and circulated in the cavity to coincide with subsequent incoming electron bunches. This coincidence of light pulses with electron bunches enables the light to do work on electrons, and thus stimulates more radiated energy. The possibilities of extending the bunch-length measuring system to measure the three-dimensional bunch distribution and making the BRAICER cavity a broadband, high-intensity, coherent, far-infrared light source are also discussed.

  10. Usage possibilities of laser stimulation in ophthalmology

    NASA Astrophysics Data System (ADS)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz

    1996-03-01

    The laser stimulation is used in ophthalmology as a supplement toother way of therapy. Nowadays, the following types of procedures are being performed: eyeball anterior segment stimulation, lacrimal gland stimulation, eyeball posterior pole stimulation, trigeminal nerve opening stimulation. Laser stimulation can be used as an independent procedure or together with pharmacological treatment.

  11. New stimulation pattern design to improve P300-based matrix speller performance at high flash rate

    NASA Astrophysics Data System (ADS)

    Polprasert, Chantri; Kukieattikool, Pratana; Demeechai, Tanee; Ritcey, James A.; Siwamogsatham, Siwaruk

    2013-06-01

    Objective. We propose a new stimulation pattern design for the P300-based matrix speller aimed at increasing the minimum target-to-target interval (TTI). Approach. Inspired by the simplicity and strong performance of the conventional row-column (RC) stimulation, the proposed stimulation is obtained by modifying the RC stimulation through alternating row and column flashes which are selected based on the proposed design rules. The second flash of the double-flash components is then delayed for a number of flashing instants to increase the minimum TTI. The trade-off inherited in this approach is the reduced randomness within the stimulation pattern. Main results. We test the proposed stimulation pattern and compare its performance in terms of selection accuracy, raw and practical bit rates with the conventional RC flashing paradigm over several flash rates. By increasing the minimum TTI within the stimulation sequence, the proposed stimulation has more event-related potentials that can be identified compared to that of the conventional RC stimulations, as the flash rate increases. This leads to significant performance improvement in terms of the letter selection accuracy, the raw and practical bit rates over the conventional RC stimulation. Significance. These studies demonstrate that significant performance improvement over the RC stimulation is obtained without additional testing or training samples to compensate for low P300 amplitude at high flash rate. We show that our proposed stimulation is more robust to reduced signal strength due to the increased flash rate than the RC stimulation.

  12. Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

    PubMed Central

    Sun, Ya-jie; Chen, Ying; Pang, Chong; Wu, Ning; Li, Jin

    2014-01-01

    Aim: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. Methods: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. Results: AZA (50–200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50–200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50–200 mg/kg, ip) and diazepam (0.25–1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. Conclusion: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism. PMID:24335844

  13. 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.

  14. 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. PMID:11067581

  15. 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

  16. Transcranial electrical stimulator producing high amplitude pulses and pulse trains.

    PubMed

    Suihko, V; Eskola, H

    1998-01-01

    Transcranial electrical stimulation can be used for clinical investigations of the central nervous system and for monitoring of motor nerve tracts during surgical operations. We wished to reduce the pain involved with the transcranial electrical stimulation and to improve the usefulness of the method for monitoring during surgical operations. A dedicated transcranial electrical stimulator was designed having special features to reduce the pain sensation and the nerve blocking effect of anaesthetics. It provides constant current and constant voltage stimulation pulses with very short duration and high amplitude. The pulse length is adjustable in the range of 15 to 125 microseconds, while the maximum amplitude is 100 V and 1 A for voltage and current stimulation modes, respectively. Special features included high-repetition-rate pulse trains (50-2000 pulses s-1) and a three-electrode stimulation configuration. We suggest that the electrical transcranial stimulation has the potential to be a relatively painless method for routine clinical investigations and a reliable method for monitoring during surgery. PMID:9807743

  17. [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

  18. Peripheral nerve/field stimulation for neuropathic pain.

    PubMed

    Deogaonkar, Milind; Slavin, Konstantin V

    2014-01-01

    Peripheral nerve stimulation and peripheral nerve field stimulation are emerging as a viable neuromodulatory therapy in the treatment of refractory pain. Although the technology of percutaneous stimulation has been available for decades, recent advancements have broadened the number of indications. Success of treatment revolves around identifying the correct patient population, and the selection and placement of the appropriate electrodes and implantable pulse generators. Most results to date have come from case reports and retrospective studies. However, given the promising outcomes in reducing otherwise medically refractory pain, future randomized controlled studies are needed to assess this emerging technology. PMID:24262894

  19. 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%.

  20. 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…

  1. 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…

  2. Early Identification and Infant Stimulation

    ERIC Educational Resources Information Center

    Lintz, Brenda

    1976-01-01

    This article describes the Zucker Center's program in Toledo, Ohio which identifies children with developmental delays and enrolls them in a demonstration infant stimulation program. The center provides educational programs in neonatal care, nutrition, general stimulation, and parenting techniques. Available from: PS 504 969. (JMB)

  3. Dichotic Stimulation and Mental Retardation.

    ERIC Educational Resources Information Center

    Mosley, James L.; Virbancic, Mirna I.

    1990-01-01

    This paper reviews literature on the use of dichotic stimulation in individuals with mental retardation, and examines how noninvasive dichotic stimulation relates to hemisphere lateralization. Common findings are discussed concerning direction and magnitude of ear asymmetries, patterns of intrusion errors, and speech lateralization of Down…

  4. 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

  5. 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. PMID:27013938

  6. 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

  7. Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation

    PubMed Central

    Berényi, Antal; Belluscio, Mariano; Mao, Dun; Buzsáki, György

    2016-01-01

    Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients. PMID:22879515

  8. 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.

  9. 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

  10. 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.

  11. Nanoparticle-enhanced infrared neural stimulation

    NASA Astrophysics Data System (ADS)

    Paviolo, Chiara; Thompson, Alexander C.; Yong, Jiawey; Brown, William G. A.; Stoddart, Paul R.

    2014-12-01

    Objective. Recent research has demonstrated that nerves can be stimulated by transient heating associated with the absorption of infrared light by water in the tissue. There is a great deal of interest in using this technique in neural prostheses, due to the potential for increased localization of the stimulus and minimization of contact with the tissue. However, thermal modelling suggests that the full benefits of increased localization may be reduced by cumulative heating effects when multiple stimulus sites and/or high repetition rates are used. Approach. Here we review recent in vitro and in vivo results suggesting that the transient heating associated with plasmon absorption in gold nanorods can also be used to stimulate nerves. Main results. Patch clamp experiments on cultured spiral ganglion neurons exhibited action potentials when exposed to 780 nm light at the plasmon absorption peak, while the amplitude of compound action potentials in the rat sciatic nerve were increased by laser irradiation of gold nanorods in the vicinity of the plasma membrane. Similarly, calcium imaging studies of NG108-15 neuronal cells incubated with Au nanorods revealed an increased level of intracellular calcium activity synchronized with laser exposure. Significance. Given that the plasmon absorption peak of gold nanorods can be matched with the transparency window of biological tissues, these results demonstrate that nanorod absorbers hold great promise to enhance the process of infrared neural stimulation for future applications in neural prostheses and fundamental studies in neuroscience.

  12. Bilateral subthalamic nucleus stimulation improves balance control in Parkinson's disease

    PubMed Central

    Colnat-Coulbois, S; Gauchard, G; Maillard, L; Barroche, G; Vespignani, H; Auque, J; Perrin, P.

    2005-01-01

    Background: Parkinson's disease (PD), the most common basal ganglia degenerative disease, affects balance control, especially when patients change balance strategy during postural tasks. Bilateral chronic stimulation of the subthalamic nucleus (STN) is therapeutically useful in advanced PD, and reduces the motor signs of patients. Nevertheless, the effects of STN stimulation on postural control are still debatable. Aims: To assess the impact of bilateral STN stimulation on balance control in PD and to determine how basal ganglia related sensorimotor modifications act on neurosensorial organisation of balance and motor postural programming. Methods: Twelve subjects aged 45–70 years underwent unified Parkinson's disease rating scale motor (part III) clinical tests, static and dynamic posturography, including sensory organisation and adaptation tests, shortly before and six months after bilateral implantation of electrodes into the STN. Results: The postoperative static test showed an improvement in postural control precision both in eyes open and eyes closed conditions. The dynamic test highlighted the decreased number of falls and the ability of the patients to develop more appropriate sensorimotor strategies when stimulated. The sensory organisation test showed an improvement of equilibrium score and, thus, a better resolution of sensorial conflicts. Conclusions: STN stimulation allowed a reduction in rigidity and therefore an improvement in the ability to use muscular proprioception as reliable information, resulting in vestibulo-proprioceptive conflict suppression. STN stimulation has a synergistic effect with levodopa for postural control. Accordingly, non-dopaminergic pathways could be involved in postural regulation and STN stimulation may influence the functioning of these pathways. PMID:15897498

  13. 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

  14. [Deep brain stimulation for movement disorders: indications, results and complications].

    PubMed

    Fleury, Vanessa; Vingerhoets, François; Horvath, Judit; Pollak, Pierre; Burkhard, Pierre

    2015-04-29

    Movement disorders such as Parkinson's disease (PD), essential tremor (ET) and dystonia can benefit from deep brain stimulation (DBS). DBS is considered when symptoms are disabling despite optimal medical therapy. Contraindications include dementia, uncontrolled psychiatric disease and/or comorbid conditions with potential for evolution. Targets are the subthalamic nucleus for PD, the ventral intermediate nucleus for ET and the globus pallidus internus for dystonia. The beneficial effet of DBS has been well documented for symptom control. Optimal target localization of the electrodes reduces the occurrence of side-effects. Stimulation-induced adverse effects can usually be abolished by turning the stimulation off, changing the active contact or other stimulation parameters. PMID:26062221

  15. A precision mechanical nerve stimulator

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    An electromechanical device, used to apply and monitor stimulating pulses to a mammalian motor nerve, has been successfully developed at NASA Langley Research Center. Two existing force transducers, a flight skin friction balance and a miniature skin friction balance which were designed for making aerodynamic drag measurements, were modified and incorporated to form this precision instrument. The nerve stimulator is a type one servomechanism capable of applying and monitoring stimulating pulses of 0 to 10 grams with a precision of better than +/- 0.05 grams. Additionally, the device can be independently used to apply stimulating pulses by displacing the nerve from 0 to 0.25 mm with a precision of better than +/- 0.001 mm while measuring the level of the load applied.

  16. 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.

  17. Neural stimulation and recording electrodes.

    PubMed

    Cogan, Stuart F

    2008-01-01

    Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes. PMID:18429704

  18. Magnetically stimulated fluid flow patterns

    ScienceCinema

    Martin, Jim; Solis, Kyle

    2014-08-06

    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.

  19. 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.

  20. 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)

  1. 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

  2. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    PubMed

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  3. Facilitatory effect of paired-pulse stimulation by transcranial magnetic stimulation with biphasic wave-form.

    PubMed

    Julkunen, Petro; Järnefelt, Gustaf; Savolainen, Petri; Laine, Jarmo; Karhu, Jari

    2016-08-01

    Transcranial magnetic stimulation (TMS) is used to probe corticospinal excitability by stimulating the motor cortex. Our aim was to enhance the effects of biphasic TMS by coupling a suprathreshold test pulse and a following subthreshold priming pulse to induce short-interval intracortical facilitation (SICF), which is conventionally produced with monophasic TMS. Biphasic TMS could potentially induce the SICF effect with better energy-efficiency and with lower stimulus intensities. This would make the biphasic paired-pulses better applicable in patients with reduced cortical excitability. A prototype stimulator was built to produce biphasic paired-pulses. Resting motor thresholds (rMTs) from the right and left hand abductor pollicis brevis muscles, and the right tibialis anterior muscle of eight healthy volunteers were determined using single-pulse paradigm with neuronavigated TMS. The rMTs and MEPs were measured using single-pulses and three paired-pulse setups (interstimulus interval, ISI of 3, 7 or 15ms). The rMTs were lower and MEPs were higher with biphasic paired-pulses compared to single-pulses. The SICF effect was greatest at 3ms ISI. This suggests that the application of biphasic paired-pulses to enhance stimulation effects is possible. PMID:27215172

  4. 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

  5. Emerging Neural Stimulation Technologies for Bladder Dysfunctions

    PubMed Central

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

    2015-01-01

    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. PMID:25833475

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve.

    PubMed

    Yoo, Paul B; Hincapie, Juan G; Hamann, Jason J; Ruble, Stephen B; Wolf, Patrick D; Grill, Warren M

    2011-01-01

    Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy. PMID:22254997

  15. 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

  16. Towards a closed-loop system for stimulation and recording: an in vitro approach with embryonic cardiomyocytes.

    PubMed

    Nguyen, Thoa; Braeken, Dries; Musa, Silke; Krylychkina, Olga; Bartic, Carmen; Gielen, Georges; Eberle, Wolfgang

    2010-01-01

    Closed loop systems, in which stimulation parameters are adjusted according to recorded signals would reduce the occurrence of side effects of stimulation and broaden current therapeutic options. As a step towards a closed-loop clinical system, we developed a single electrode stimulation / recording system for an in vitro microelectrode array. The system was used in vitro to simultaneously stimulate and record cardiac cells. Results indicated that stimulation artifacts depend on the distance between recording electrode and stimulating electrode and on the voltage amplitude. No artifact reduction algorithm was required for detecting cardiac action potentials 2ms after stimulation if the stimulation pulses were less than or equal to ± 1.5 V, and the distance from stimulation site was more than 200 µm. Cardiac signal propagation was also investigated with this system. PMID:21096211

  17. Adaptive fuzzy logic restriction rules for error correction and safe stimulation patterns during functional electrical stimulation.

    PubMed

    Hansen, M; Haugland, M K

    2001-01-01

    Adaptive restriction rules based on fuzzy logic have been developed to eliminate errors and to increase stimulation safety in the foot-drop correction application, specifically when using adaptive logic networks to provide a stimulation control signal based on neural activity recorded from peripheral sensory nerve branches. The fuzzy rules were designed to increase flexibility and offer easier customization, compared to earlier versions of restriction rules. The rules developed quantified the duration of swing and stance phases into states of accepting or rejecting new transitions, based on the cyclic nature of gait and statistics on the current gait patterns. The rules were easy to custom design for a specific application, using linguistic terms to model the actions of the rules. The rules were tested using pre-recorded gait data processed through a gait event detector and proved to reduce detection delay and the number of errors, compared to conventional rules. PMID:11601442

  18. PKCβ Inhibitors Attenuate Amphetamine-Stimulated Dopamine Efflux.

    PubMed

    Zestos, Alexander G; Mikelman, Sarah R; Kennedy, Robert T; Gnegy, Margaret E

    2016-06-15

    Amphetamine abuse afflicts over 13 million people, and there is currently no universally accepted treatment for amphetamine addiction. Amphetamine serves as a substrate for the dopamine transporter and reverses the transporter to cause an increase in extracellular dopamine. Activation of the beta subunit of protein kinase C (PKCβ) enhances extracellular dopamine in the presence of amphetamine by facilitating the reverse transport of dopamine and internalizing the D2 autoreceptor. We previously demonstrated that PKCβ inhibitors block amphetamine-stimulated dopamine efflux in synaptosomes from rat striatum in vitro. In this study, we utilized in vivo microdialysis in live, behaving rats to assess the effect of the PKCβ inhibitors, enzastaurin and ruboxistaurin, on amphetamine-stimulated locomotion and increases in monoamines and their metabolites. A 30 min perfusion of the nucleus accumbens core with 1 μM enzastaurin or 1 μM ruboxistaurin reduced efflux of dopamine and its metabolite 3-methoxytyramine induced by amphetamine by approximately 50%. The inhibitors also significantly reduced amphetamine-stimulated extracellular levels of norepinephrine. The stimulation of locomotor behavior by amphetamine, measured simultaneously with the analytes, was comparably reduced by the PKCβ inhibitors. Using a stable isotope label retrodialysis procedure, we determined that ruboxistaurin had no effect on basal levels of dopamine, norepinephrine, glutamate, or GABA. In addition, normal uptake function through the dopamine transporter was unaltered by the PKCβ inhibitors, as measured in rat synaptosomes. Our results support the utility of using PKCβ inhibitors to reduce the effects of amphetamine. PMID:26996926

  19. 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

  20. 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

  1. 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.

  2. Electromagnetic Induction Heat Generation of Nano-ferrofluid and Other Stimulants for Heavy Oil Recovery

    NASA Astrophysics Data System (ADS)

    Pramana, A. A.; Abdassah, D.; Rachmat, S.; Mikrajuddin, A.

    2010-10-01

    Nano-ferrofluid and graphite-fluid are proposed to be used as stimulants for heavy oil recovery processes using electromagnetic induction. The heat generation in the stimulants will be used for reducing the viscosity of heavy oil. The temperature increase of the stimulants are observed with the presence of electromagnetic induction. These increments are better compared to those of the varying concentration of salt water (brine) usually exist in the oil reservoir.

  3. ["Dual Guidance"?- Parallel combination of ultrasound-guidance and nerve stimulation - Pro].

    PubMed

    Neuburger, Michael

    2015-07-01

    Combination of ultrasound and nerve stimulation technique could be useful under several conditions. Nerve stimulation canvarify the position of the nerve in case of bad preconditions during ultrasound. The knowledge of the importance of low and critical threshold currents could help to identify the needle tip. Thus the combination of ultrasound and nerve stimulation could lead to reduced unintentional intraneural injections and may result in a higher safety standard in peripheral regional anesthesia. PMID:26230888

  4. Electrical Stimulation of Visual Cortex Can Immediately Improve Spatial Vision.

    PubMed

    Reinhart, Robert M G; Xiao, Wenxi; McClenahan, Laura J; Woodman, Geoffrey F

    2016-07-25

    We can improve human vision by correcting the optics of our lenses [1-3]. However, after the eye transduces the light, visual cortex has its own limitations that are challenging to correct [4]. Overcoming these limitations has typically involved innovative training regimes that improve vision across many days [5, 6]. In the present study, we wanted to determine whether it is possible to immediately improve the precision of spatial vision with noninvasive direct-current stimulation. Previous work suggested that visual processing could be modulated with such stimulation [7-9]. However, the short duration and variability of such effects made it seem unlikely that spatial vision could be improved for more than several minutes [7, 10]. Here we show that visual acuity in the parafoveal belt can be immediately improved by delivering noninvasive direct current to visual cortex. Twenty minutes of anodal stimulation improved subjects' vernier acuity by approximately 15% and increased the amplitude of the earliest visually evoked potentials in lockstep with the behavioral effects. When we reversed the orientation of the electric field, we impaired resolution and reduced the amplitude of visually evoked potentials. Next, we found that anodal stimulation improved acuity enough to be measurable with the relatively coarse Snellen test and that subjects with the poorest acuity benefited the most from stimulation. Finally, we found that stimulation-induced acuity improvements were accompanied by changes in contrast sensitivity at high spatial frequencies. PMID:27374337

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Action research through stimulated recall

    NASA Astrophysics Data System (ADS)

    O'Brien, John

    1993-12-01

    The emphasis in classroom learning research has moved from process-product models to the mediating process paradigm. The stimulated-recall interview and thik aloud techniques are the two main processes that have been used in attempts to find out what goes on inside students' heads while they are learning. For example, this researcher has used the stimulated-recall interview technique to identify the workplace thinking of a marine science researcher, and the in-class thinking of a year eleven biology student. Such studies as these have produced findings with important implications for the classroom teacher in the role of action researcher. This paper describes how to conduct stimulated-recall interviews and discusses some classroom implications from the two studies.

  10. 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

  11. Comparing the Induced Muscle Fatigue Between Asynchronous and Synchronous Electrical Stimulation in Able-Bodied and Spinal Cord Injured Populations.

    PubMed

    Downey, Ryan J; Bellman, Matthew J; Kawai, Hiroyuki; Gregory, Chris M; Dixon, Warren E

    2015-11-01

    Neuromuscular electrical stimulation (NMES) has been shown to impart a number of health benefits and can be used to produce functional outcomes. However, one limitation of NMES is the onset of NMES-induced fatigue. Multi-channel asynchronous stimulation has been shown to reduce NMES-induced fatigue compared to conventional single-channel stimulation. However, in previous studies in man, the effect of stimulation frequency on the NMES-induced fatigue has not been examined for asynchronous stimulation. Low stimulation frequencies are known to reduce fatigue during conventional stimulation. Therefore, the aim of this study was to examine the fatigue characteristics of high- and low-frequency asynchronous stimulation as well as high- and low-frequency conventional stimulation. Experiments were performed in both able-bodied and spinal cord injured populations. Low frequency asynchronous stimulation is found to have significant fatigue benefits over high frequency asynchronous stimulation as well as high- and low-frequency conventional stimulation, motivating its use for rehabilitation and functional electrical stimulation (FES). PMID:25350934

  12. 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.

  13. 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

  14. An Evaluation of Stimulant Medication on the Reinforcing Effects of Play

    ERIC Educational Resources Information Center

    LaRue, Robert H.; Northup, John, Jr.; Baumeister, Alan A.; Hawkins, Mike F.; Seale, Lauren; Williams, Tara; Ridgway, Andrea

    2008-01-01

    Although a vast literature has indicated that stimulant medications are effective for reducing inappropriate behavior in children with attention deficit hyperactivity disorder (ADHD), the effects of stimulant medication on ancillary behaviors (e.g., play) have yet to be investigated with the same rigor. We used a reinforcer assessment procedure to…

  15. Antisera against electrophoretically purified tubulin stimulate colchicine-binding activity.

    PubMed

    Aubin, J E; Subrahmanyan, L; Kalnins, V I; Ling, V

    1976-04-01

    Several rabbit antisera have been prepared against reduced and alkylated, electrophoretically purified tubulin isolated from chick brain. These antisera give a single precipitin line in Ouchterlony double diffusion plates when tested against partially purified tubulin, and label specifically microtubule- and tubulin-containing structures, such as mitotic spindles, cilia, and vinblastine-induced crystals, in a variety of cells. The same antisera also display the unique ability to stimulate the colchicine-binding activity of tubulin preparations from chick brain and Chinese hamster ovary tissue culture cells. This specific stimulation of colchicine binding activity is also obtained with the gamma globulin fractions purified by ammonium sulfate precipitation of these antisera. PMID:57619

  16. Improvement of sleep architecture in PD with subthalamic nucleus stimulation.

    PubMed

    Arnulf, I; Bejjani, B P; Garma, L; Bonnet, A M; Houeto, J L; Damier, P; Derenne, J P; Agid, Y

    2000-12-12

    High-frequency stimulation of the subthalamic nucleus (STN) was used to investigate the relationship of sleep disorders with motor handicap in PD. In 10 insomniac patients with PD, stimulation reduced nighttime akinesia by 60% and completely suppressed axial and early morning dystonia, but did not alleviate periodic leg movements (n = 3) or REM sleep behavior disorders (n = 5). Total sleep time increased by 47%; wakefulness after sleep onset decreased by 51 minutes. Insomnia in patients with PD may predominantly result from nighttime motor disability. PMID:11113233

  17. 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.

  18. ELECTROSTATIC STIMULATION OF FABRIC FILTRATION

    EPA Science Inventory

    The paper gives results of an investigation of the concept of electrostatic stimulation of fabric filtration (ESFF) at pilot scale. The pilot unit consisted of a conventional baghouse in parallel with an ESFF baghouse, allowing direct comparison. Reported results are for pulse-cl...

  19. 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…

  20. [Energy resonance through cutaneous stimulation].

    PubMed

    Fouchier, Patrick

    2014-12-01

    Energy resonance through cutaneous stimulation is a method basedon "listening" through the fingers to the body's vibrations at various points on the skin corresponding to the meridians used in Chinese medicine. It helps to relieve the patient by balancing the body's energies. It can be carried out by any caregiver after specific training. PMID:25630081

  1. 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.

  2. 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. PMID:26269552

  3. 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. PMID:24112897

  4. 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

  5. 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.

  6. Clinical applications of electrical stimulation after spinal cord injury.

    PubMed

    Creasey, Graham H; Ho, Chester H; Triolo, Ronald J; Gater, David R; DiMarco, Anthony F; Bogie, Kath M; Keith, Michael W

    2004-01-01

    During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development. PMID:15484667

  7. Complications of deep brain stimulation surgery.

    PubMed

    Beric, A; Kelly, P J; Rezai, A; Sterio, D; Mogilner, A; Zonenshayn, M; Kopell, B

    2001-01-01

    Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson's disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications. PMID:12378060

  8. Electrostatic stimulation of fabric filtration - an update

    SciTech Connect

    Furlong, D.A.; Greiner, G.P.; Van Osdell, D.W.; Hovis, L.S.

    1985-10-01

    The paper gives results of an investigation of the concept of electrostatic stimulation of fabric filtration (ESFF) on a slipstream of a pulverized-coal-fired boiler using reverse-air-cleaned woven fiberglass filter bags. Operation was demonstrated using ESFF at a glass-to-cloth ratio (G/C) of 6. An un-electrified control house was operated simultaneously at a G/C of 3. Under these conditions, the ESFF house maintained a pressure drop equal to or less than that of the control baghouse. In addition to reducing the filter cake pressure drop, ESFF was observed to apparently have long-term benefits in preventing irremovable dust buildup in the fabric.

  9. 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

  10. 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

  11. 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. PMID:26443701

  12. Network mechanisms of responsiveness to continuous theta-burst stimulation.

    PubMed

    Rizk, Sviatlana; Ptak, Radek; Nyffeler, Thomas; Schnider, Armin; Guggisberg, Adrian G

    2013-10-01

    Continuous theta-burst stimulation (cTBS) can modify behavior, but effects are inconsistent and their mechanisms insufficiently understood. As coherence in resting-state networks influences human behavior, we hypothesized that cTBS may act via modulation of neural oscillation coherence. This study used electroencephalography (EEG) to investigate whether behavioral effects of cTBS on visuospatial attention are associated with coherence changes in the attention network. In healthy human subjects, cTBS of the right posterior parietal cortex (PPC) and the right frontal eye field was compared with sham stimulation. Effects on visuospatial attention were quantified with a visual exploration task, and network effects were assessed from surface EEG with inverse solutions and source coherence analyses. Before stimulation, left visual exploration was linearly correlated with alpha-band coherence between the right temporo-parietal cortex and the rest of the brain. Posterior parietal cortex stimulation induced neglect-like visual exploration behavior in the majority, but not all, subjects. It reduced alpha-band coherence between the stimulation site and the rest of the brain but also enhanced it between the contralateral left parietal cortex and the rest of the brain. The contralateral increase correlated with the induced reduction in left visual attention. The behavioral response of individual participants to cTBS could be predicted by coherence in the right temporo-parietal junction before stimulation. Behavioral effects of cTBS therefore depend on network states before stimulation and are linearly associated with changes in network interactions. In particular, cTBS modulates an interhemispheric competition in alpha-band coherence. EEG network imaging might help to optimize therapeutic cTBS in the future. PMID:23941616

  13. Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation

    PubMed Central

    Fortuna, Michal G; Stornetta, Ruth L; West, Gavin H; Guyenet, Patrice G

    2009-01-01

    The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN neurons) that provide a pH-regulated excitatory drive to the central respiratory pattern generator. Here we test whether ccRTN neurons respond to stimulation of the perifornical hypothalamus (PeF), a region that regulates breathing during sleep, stress and exercise. PeF stimulation with gabazine increased blood pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in isoflurane-anaesthetized rats. Gabazine produced an approximately parallel upward shift of the steady-state relationship between ccRTN neuron firing rate and end-tidal CO2, and a similar shift of the relationship between PND and end-tidal CO2. The central respiratory modulation of ccRTN neurons persisted after gabazine without a change in pattern. Morphine administration typically abolished PND and reduced the discharge rate of most ccRTN neurons (by 25% on average). After morphine administration, PeF stimulation activated the ccRTN neurons normally but PND activation and the central respiratory modulation of the ccRTN neurons were severely attenuated. In the same rat preparation, most (58%) ccRTN neurons expressed c-Fos after exposure to hypercapnic hyperoxia (6–7% end-tidal CO2; 3.5 h; no hypothalamic stimulation) and 62% expressed c-Fos under hypocapnia (∼3% end-tidal CO2) after PeF stimulation. Under baseline conditions (∼3% end-tidal CO2, hyperoxia, no PeF stimulation) few (11%) ccRTN neurons expressed c-Fos. In summary, most ccRTN neurons are excited by posterior hypothalamic stimulation while retaining their normal response to CNS acidification. ccRTN neurons probably contribute both to the chemical drive of breathing and to the feed-forward control of breathing associated with emotions and or locomotion. PMID:19752119

  14. The Effects of Stimulation Strategy on Joint Movement Elicited by Intraspinal Microstimulation.

    PubMed

    Roshani, Amir; Erfanian, Abbas

    2016-07-01

    The goal of this study was to characterize the effects of stimulation parameters and multielectrode stimulation on selectivity, range of motion, recruitment characteristics, and fatigue during intraspinal microstimulation (ISMS). A custom-made multielectrode array was implanted into the activation pool of the rat dorsiflexor muscle where the stimulation produced the highest movement range on the ankle joint and the least effect on the other joints. The results show that the selectivity could be significantly enhanced using multielectrode stimulation strategy. Moreover, the fatigue was significantly reduced using multielectrode synchronous stimulation with respect to single-electrode stimulation. For a given charge, stimulation with higher current amplitude and shorter pulse duration produced greater range of motion than that with lower amplitude and longer pulse duration. However, the stimulation with shorter duration caused greater fatigue than that with longer. In addition, there was a significant difference in time constant of spinal response obtained with different pulse amplitudes during pulse width (PW) modulation. The time constant decreased with increasing pulse amplitude. However, there was no significant effect of pulse duration on time constant during pulse amplitude (PA) modulation. The results suggest that the motor neurons (MNs) within the spinal cord can be recruited according to size principle by appropriate selection of stimulation parameters. Based on these results an efficient stimulation strategy can be designed for control of movement performance (i.e., speed of movement, fatigue, range of motion, and selectivity) during ISMS. PMID:26685256

  15. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    PubMed

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. PMID:27163199

  16. 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

  17. 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

  18. Magnetic-motor-root stimulation: review.

    PubMed

    Matsumoto, Hideyuki; Hanajima, Ritsuko; Terao, Yasuo; Ugawa, Yoshikazu

    2013-06-01

    Magnetic stimulation can activate the human central and peripheral nervous systems non-invasively and virtually painlessly. Magnetic stimulation over the spinal enlargements can activate spinal nerves at the neuroforamina (magnetic-neuroforamina stimulation). This stimulation method provides us with information related to the latency of compound-muscle action potential (CMAP), which is usually interpreted as peripheral motor-conduction time (PMCT). However, this stimulation method has faced several problems in clinical applications. One is that supramaximal CMAPs were unobtainable. Another is that magnetic stimulation did not usually activate the spinal nerves in the spinal canal, i.e., the cauda equina, which prevented an evaluation of its conduction. For these reasons, magnetic-neuroforamina stimulation was rarely used to evaluate the conduction of peripheral nerves. It was mainly used to evaluate the conduction of the corticospinal tract using the parameter of central motor-conduction time (CMCT), which was calculated by subtracting PMCT from the latency of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex. Recently, supramaximal stimulation has been achieved in magnetic-neuroforamina stimulation, and this has contributed to the measurement of both CMAP size and latency. The achievement of supramaximal stimulation is ascribed to the increase in magnetic-stimulator output and a novel coil, the magnetic augmented translumbosacral stimulation (MATS) coil. The most proximal part of the cauda equina can be reliably activated using the MATS coil (magnetic-conus stimulation), thus contributing to the measurement of cauda equina conduction time (CECT) and cortico-conus motor-conduction time (CCCT). These recent developments in magnetic-motor-root stimulation enable us to more precisely evaluate the conduction of the proximal part of peripheral nerves and that of the corticospinal tract for lower-limb muscles

  19. 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

  20. 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

  1. 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

  2. Comparison of motility stimulants for cryopreserved human semen.

    PubMed

    Hammitt, D G; Bedia, E; Rogers, P R; Syrop, C H; Donovan, J F; Williamson, R A

    1989-09-01

    Caffeine, pentoxifylline, 2-deoxyadenosine, cyclic adenosine monophosphate (cAMP), relaxin, adenosine, kallikrein, and calcium were compared for their ability to stimulate motility of cryopreserved sperm. Caffeine, pentoxifylline, and 2-deoxyadenosine significantly increased the percentage of motile sperm at 15, 30, 45, and 60 minutes after administration. Sperm velocity was significantly increased by caffeine at 0, 15, 30, and 45 minutes, and by pentoxifylline at 0, 45, and 60 minutes. Consistent stimulation was not observed for other chemicals. Caffeine, pentoxifylline, and 2-deoxyadenosine were then examined for their ability to provide motility stimulation after removal with washing. With the exception of caffeine, percent motility and velocity for stimulated and untreated sperm were similar after washing. A significant reduction in motility was observed at 48 hours after washing for caffeine. The percentage of hamster oocytes penetrated at 24 hours after washing was significantly reduced for caffeine, 2-deoxyadenosine, and pentoxifylline combined with 2-deoxyadenosine. Pentoxifylline-treated sperm showed no reduction in fertilizing capacity. These results indicate that, of the chemicals examined, pentoxifylline is superior for motility stimulation of cryopreserved sperm. PMID:2550282

  3. 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

  4. Deep brain stimulation: new directions.

    PubMed

    Ostergard, T; Miller, J P

    2014-12-01

    The role of deep brain stimulation (DBS) in the treatment of movement disorders is well established, but there has recently been a proliferation of additional indications that have been shown to be amenable to this technology. The combination of innovative approaches to neural interface technology with novel target identification based on previously discovered clinical effects of lesioning procedures has led to a fundamental paradigm for new directions in the application of DBS. The historical use of neurosurgical lesioning procedures in the treatment of psychiatric diseases such as obsessive compulsive disorder provided an initial opportunity to expand the use of DBS. The list is rapidly expanding and now includes major depressive disorder, Tourette's syndrome, addiction disorders, and eating disorders. Keen observations by neurosurgeons using these devices have lead to the incidental discovery of treatments for diseases without previous neurosurgical treatments. These discoveries are breaking new ground in the treatment of disorders of cognition, headache syndromes, disorders of consciousness, and epilepsy. Two features of DBS make it well-suited for treatment of disorders of nervous system function. First, the reversible, non-lesional nature of DBS allows for investigation of new targets without the morbidity of permanent side effects. Second, the programmable nature of DBS allows practitioners to alter stimulation patterns to minimize side effects and potentially improve efficacy through reprogramming. More importantly, proper scientific evaluation of new targets is aided by the ability to turn stimulation on and off with evaluators blinded to the stimulation status. Knowledge of these emerging therapies is important for practitioners, as there are many situations where a single target can effectively treat the symptoms of more than one disease. The intersection of advances in neuromodulation, neurophysiology, neuroimaging, and functional neuroanatomy has

  5. 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.

  6. Multimedia stimulation for psychophysiological investigation.

    PubMed

    McCullagh, P J; Gent, G P; McAllister, H G

    1999-01-01

    This paper describes a multimedia approach to sensory stimulation in psychophysiological studies. High resolution colour images are presented to a subject by a Delphi stimulus program, controlled by a data acquisition system which concurrently records cognitive Event Related Potentials from the subject. The acquisition PC is linked to the stimulus PC using serial communications and requests slide material using a character based protocol. The sound card in the data acquisition system can present concurrent complex auditory stimuli for multimedia experiments. PMID:10724966

  7. 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

  8. Interleukin-6 Stimulates Defective Angiogenesis.

    PubMed

    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

    2015-08-01

    The cytokine IL6 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 IL6 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, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 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-IL6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies, there was an association between levels of IL6 mRNA, Jagged1, and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease, and stroke. PMID:26081809

  9. Phosphate stimulates CFTR Cl- channels.

    PubMed Central

    Carson, M R; Travis, S M; Winter, M C; Sheppard, D N; Welsh, M J

    1994-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels appear to be regulated by hydrolysis of ATP and are inhibited by a product of hydrolysis, ADP. We assessed the effect of the other product of hydrolysis, inorganic phosphate (P(i)), on CFTR Cl- channel activity using the excised inside-out configuration of the patch-clamp technique. Millimolar concentrations of P(i) caused a dose-dependent stimulation of CFTR Cl- channel activity. Single-channel analysis demonstrated that the increase in macroscopic current was due to an increase in single-channel open-state probability (po) and not single-channel conductance. Kinetic modeling of the effect of P(i) using a linear three-state model indicated that the effect on po was predominantly the result of an increase in the rate at which the channel passed from the long closed state to the bursting state. P(i) also potentiated activity of channels studied in the presence of 10 mM ATP and stimulated Cl- currents in CFTR mutants lacking much of the R domain. Binding studies with a photoactivatable ATP analog indicated that Pi decreased the amount of bound nucleotide. These results suggest that P(i) increased CFTR Cl- channel activity by stimulating a rate-limiting step in channel opening that may occur by an interaction of P(i) at one or both nucleotide-binding domains. Images FIGURE 8 PMID:7532021

  10. 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 ...

  11. 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

  12. Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine.

    PubMed

    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

  13. Effects of intermittent theta burst stimulation on spasticity after stroke.

    PubMed

    Kim, Dae Hyun; Shin, Ji Cheol; Jung, Seungsoo; Jung, Tae-Min; Kim, Deog Young

    2015-07-01

    Spasticity is a common cause of long-term disability in poststroke hemiplegic patients. We investigated whether intermittent theta burst stimulation (iTBS) could reduce upper-limb spasticity after a stroke. Fifteen hemiplegic stroke patients were recruited for a double-blind sham-controlled cross-over design study. A single session of iTBS or sham stimulation was delivered on the motor hotspot of the affected flexor carpi radialis muscle in a random and counterbalanced order with a 1-week interval. Modified Ashworth scale (MAS), modified Tardieu scale (MTS), H-wave/M-wave amplitude ratio, peak torque (PT), peak torque angle (PTA), work of affected wrist flexor, and rectified integrated electromyographic activity of the flexor carpi radialis muscle were measured before, immediately after, 30 min after, and 1 week after iTBS or sham stimulation. Repeated-measures analysis of variance showed a significant interaction between time and intervention for the MAS, MTS, PT, PTA, and rectified integrated electromyographic activity (P<0.05), indicating that these parameters were significantly improved by iTBS compared with sham stimulation. However, the H-wave/M-wave amplitude ratio and work were not affected. MAS and MTS significantly improved for at least 30 min after iTBS, but the other parameters only improved immediately after iTBS (P<0.05). In conclusion, iTBS on the affected hemisphere may help to reduce poststroke spasticity transiently. PMID:26011507

  14. 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.

  15. 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.

  16. 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.

  17. 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)

  18. Effects of sympathetic stimulation and applied catecholamines on mechanical and electrical responses to stimulation of the vagus nerve in guinea-pig isolated trachea.

    PubMed Central

    McCaig, D. J.

    1987-01-01

    Mechanical and electrical responses to stimulation of the vagus nerve were studied in the isolated, innervated trachea of the guinea-pig. In approximately half the preparations tested, the amplitudes of mechanical constrictor responses to stimulation of the vagus were reduced substantially during a period of sympathetic stimulation. Vagal responses were unaltered in the remainder. In single trachealis cells, stimulation of the vagus nerve or sympathetic stellate ganglion elicited depolarization and hyperpolarization, respectively. Vagally-mediated depolarization was decreased, unchanged or increased in amplitude after a period of sympathetic stimulation. Isoprenaline almost abolished mechanical responses induced by stimulation of the vagus, and this effect was blocked by propranolol. Noradrenaline attenuated markedly vagal mechanical responses also, and this effect was blocked by a combination of propranolol and phentolamine. Both noradrenaline and isoprenaline hyperpolarized single trachealis cells and greatly reduced the amplitude of vagally-mediated depolarization. Neither sympathetic stimulation nor applied catecholamines altered mechanical responses to applied acetylcholine, strongly suggesting that their effects on vagal responses are predominantly presynaptic. PMID:3607363

  19. Transcutaneous functional electrical stimulator "Compex Motion".

    PubMed

    Keller, Thierry; Popovic, Milos R; Pappas, Ion P I; Müller, Pierre-Yves

    2002-03-01

    Research groups in the field of functional electrical stimulation (FES) are often confronted with the fact that existing and commercially available FES stimulators do not provide sufficient flexibility and cannot be used to perform different FES tasks. The lack of flexibility of the commercial systems until now forced various FES research teams to develop their own stimulators. This paper presents a newly developed firmware and graphical programming software for the commercial Compex 2 stimulator which enhances the versatility and capabilities of the stimulator from a medical and therapeutic device to a neuroprosthesis and research tool. The new stimulator, called Compex Motion, can now be used to develop various custom-made neuroprostheses, neurological assessment devices, muscle exercise systems, and experimental setups for physiological studies. It can be programmed to generate any arbitrary stimulation sequence that can be controlled or regulated by various external sensors, sensory systems, or laboratory equipment. By interconnecting two or more Compex Motion stimulators, the number of stimulation channels can be increased to multiples of four channels, 8, 12, 16, 20, and so forth. The stimulation sequences and the control strategies are programmed and stored on exchangeable credit card-sized memory chip cards. The stimulator has four biphasic current-regulated stimulation channels and two general purpose analog input channels that can be configured to measure the output voltage of a variety of sensors such as goniometers, inclinometers, gyroscopes, or electromyographic (EMG) sensors. For real-time EMG control of the stimulation patterns, an EMG processing algorithm with software stimulation artifact blanking was implemented. The Compex Motion stimulator is manufactured by the Swiss company Compex SA and is currently undergoing clinical trials. PMID:11940017

  20. Hypothalamic thermal stimulation modulates vasopressin release in hyperosmotically stimulated rabbits.

    PubMed

    Keil, R; Gerstberger, R; Simon, E

    1994-10-01

    Under thermoneutral conditions conscious rabbits received systemic infusions of NaCl as hypertonic solution (90 mueq.min-1.kg body wt-1), which raised their plasma osmolality from 283 to 312 mosmol/kgH2O. Rabbits receiving isotonic saline served as controls. Hypertonic stimulation induced a 60% reduction of both respiratory frequency and evaporative water loss. Rectal temperature rose by 0.4 degrees C despite enhanced peripheral vasodilation as indicated by increased ear skin temperature. Plasma vasopressin (AVP), aldosterone (ALDO), and corticosterone (COR) were significantly elevated from 6 to 16 pg/ml, 90 to 180 pg/ml, and 17 to 40 ng/ml, respectively. To elucidate the importance of central temperature for AVP and adrenal corticosteroid release, hypothalamic thermal stimulations (20 min) were superimposed during established iso- and hyperosmotic steady-state conditions. Different from isosmotic controls, hyperosmotic animals responded to hypothalamic cooling (37 degrees C) with a significant decrease in plasma AVP from 16 to 13 pg/ml and to hypothalamic warming (41 degrees C) with a significant rise from 16 to 19 pg/ml. A weak temperature effect on COR release was also disclosed, especially of hypothalamic cooling, which significantly lowered plasma COR from 42 to 34 ng/ml. These results provide evidence for positive local temperature coefficients of hypothalamic control of AVP release and suggest a similar property also for the control of COR release by the hypothalamo-adenohypophysial axis. PMID:7943420

  1. 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

  2. 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

  3. 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

  4. 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

  5. Multichannel magnetic stimulation system design considering mutual couplings among the stimulation coils.

    PubMed

    Han, Byung H; Chun, In K; Lee, Sang C; Lee, Soo Y

    2004-05-01

    We introduce some simulation and experiment results of the multichannel magnetic stimulator development that has been carried out as an initial attempt to realize a multichannel functional magnetic stimulator. For efficient functional magnetic stimulations, precise spatial localization of stimulation sites without any movements of the stimulation coils is very important. We have found that the mutual coupling effect among the adjacent stimulation coils in the coil array has to be considered in the determination of the charge voltages in some coil array configurations. Experimental results obtained with a 4-channel magnetic stimulator are presented. PMID:15132507

  6. 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.

  7. 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. PMID:26691398

  8. 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

  9. 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. PMID:26061152

  10. Opiate withdrawal behavior after focal brain stimulation.

    PubMed

    Williams, D A; Thorn, B E

    1984-11-01

    Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal. PMID:6542676

  11. Suprachoroidal electrical stimulation: effects of stimulus pulse parameters on visual cortical responses

    NASA Astrophysics Data System (ADS)

    John, Sam E.; Shivdasani, Mohit N.; Williams, Chris E.; Morley, John W.; Shepherd, Robert K.; Rathbone, Graeme D.; Fallon, James B.

    2013-10-01

    Objective. Neural responses to biphasic constant current pulses depend on stimulus pulse parameters such as polarity, duration, amplitude and interphase gap. The objective of this study was to systematically evaluate and optimize stimulus pulse parameters for a suprachoroidal retinal prosthesis. Approach. Normally sighted cats were acutely implanted with platinum electrode arrays in the suprachoroidal space. Monopolar stimulation comprised of monophasic and biphasic constant current pulses with varying polarity, pulse duration and interphase gap. Multiunit responses to electrical stimulation were recorded in the visual cortex. Main results. Anodal stimulation elicited cortical responses with shorter latencies and required lower charge per phase than cathodal stimulation. Clinically relevant retinal stimulation required relatively larger charge per phase compared with other neural prostheses. Increasing the interphase gap of biphasic pulses reduced the threshold of activation; however, the benefits of using an interphase gap need to be considered in light of the pulse duration and polarity used and other stimulation constraints. Based on our results, anodal first biphasic pulses between 300-1200 µs are recommended for suprachoroidal retinal stimulation. Significance. These results provide insights into the efficacy of different pulse parameters for suprachoroidal retinal stimulation and have implications for the design of safe and clinically relevant stimulators for retinal prostheses.

  12. Fascicular selectivity in transverse stimulation with a nerve cuff electrode: a theoretical approach.

    PubMed

    Deurloo, Kirsten E I; Holsheimer, Jan; Bergveld, Piet

    2003-10-01

    The performance of cathode-anode configurations in a cuff electrode to stimulate a single fascicle in a nerve trunk has been investigated theoretically. A three-dimensional volume conductor model of a nerve trunk with four fascicles in a cuff electrode and a model of myelinated nerve fiber stimulation were used to calculate the recruitment of 15 m fibers in each fascicle. The effect of a monopole, a transverse bipole (anode opposite the cathode), and a narrow transverse tripole (guarded cathode) in selectively stimulating 15 m fibers in each fascicle has been quantified and presented as recruitment curves. It is predicted that selective fascicle stimulation is advanced most by stimulation with a bipole in a plane perpendicular to the axis of the nerve trunk. Monopoles and conventional longitudinal tripoles perform less well, as does a longitudinal tripole with an additional "steering" anode. Apart from transverse bipolar stimulation an additional anode may be used to maximally fit the area of excitation to the topography of the fascicle to be recruited. As compared to monopolar and longitudinal tripolar stimulation, the slope of the recruitment curves in transverse bipolar stimulation is reduced considerably, thus allowing improved fine tuning of nerve (and thus force) recruitment. Another advantage of this method is a minimal number of cable connections to the cuff electrode. The cost of the improved selectivity is an increased stimulation current. PMID:22151073

  13. 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.

  14. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.

    PubMed

    Thomas, Karen E; Sapone, Anna; Fasano, Alessio; Vogel, Stefanie N

    2006-02-15

    Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD. PMID:16456012

  15. Intraphagosomal oxygen in stimulated macrophages.

    PubMed

    James, P E; Grinberg, O Y; Michaels, G; Swartz, H M

    1995-05-01

    A new electron paramagnetic resonance (EPR)-based method was developed to obtain selective information on pO2 in a specific intracellular compartment (phagosomes). This method did not require the use of a broadening agent thereby eliminating one of the potential sources of experimental error with EPR oximetry. An oxygen-sensitive probe (4-(Trimethylammonium) 2,2,6,6-tetramethylpiperidine-d17-1-oxyl iodide (d-Cat1)) which has a net positive charge, was incorporated selectively into the phagosomes of macrophages stimulated with zymosan. Extracellular oxygen was measured by addition of a neutral nitroxide (4-oxo-2,2,6,6-tetramethylpiperidine-d16-1-oxyl (15N PDT)) to this same sample. Measurements based on EPR linewidths showed the average intraphagosomal oxygen concentration to be 11.2 +/- 3.4 microM lower than that measured from the extracellular compartment when the sample was perfused with air, and this was increased on stimulation of mitochondrial consumption or by increasing the oxygen concentration in the extracellular compartment. These experiments provide what we believe to be the first reported measurements of the oxygen concentration in a specific intracellular location (intraphagosomal) and its comparison with the oxygen concentration in the extracellular space. The observed gradient cannot be explained in terms of known coefficients of diffusion, and these results are consistent with previous reports that a gradient in oxygen concentration can occur between the average intracellular and extracellular concentration of oxygen. PMID:7706368

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. Adenosine metabolism in phytohemagglutinin-stimulated human lymphocytes.

    PubMed Central

    Snyder, F F; Mendelsohn, J; Seegmiller, J E

    1976-01-01

    The association of a human genetic deficiency of adenosine deaminase activity with combined immunodeficiency prompted a study of the effects of adenosine and of inhibition of adenosine deaminase activity on human lymphocyte transformation and a detailed study of adenosine metabolism throughout phytohemagglutinin-induced blastogenesis. The adenosine deaminase inhibitor, coformycin, at a concentration that inhibited adenosine deaminase activity more than 95%, or 50 muM adenosine, did not prevent blastogenesis by criteria of morphology or thymidine incorporation into acid-precipitable material. The combination of coformycin and adenosine, however, substantially reduced both the viable cell count and the incorporation of thymidine into DNA in phytohemagglutinin-stimulated lymphocytes. Incubation of lymphocytes with phytohemagglutinin for 72 h produced a 12-fold increase in the rate of deamination and a 6-fold increase in phosphorylation of adenosine by intact lymphocytes. There was no change in the apparent affinity for adenosine with either deamination or phosphorylation. The increased rates of metabolism, apparent as early as 3 h after addition of mitogen, may be due to increased entry of the nucleoside into stimulated lymphocytes. Increased adenosine metabolism was not due to changes in total enzyme activity; after 72 h in culture, the ratios of specific activities in extracts of stimulated to unstimulated lymphocytes were essentially unchanged for adenosine kinase, 0.92, and decreased for adenosine deaminase, 0.44. As much as 38% of the initial lymphocyte adenosine deaminase activity accumulated extracellularly after a 72-h culture with phytohemagglutinin. In phytohemagglutinin-stimulated lymphocytes, the principal route of adenosine metabolism was phosphorylation at less than 5 muM adenosine, and deamination at concentrations greater than 5 muM. In unstimulated lymphocytes, deamination was the principal route of adenosine metabolism over the range of adenosine

  3. 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

  4. The Effect of Surface Electrical Stimulation on Vocal Fold Position

    PubMed Central

    Humbert, Ianessa A.; Poletto, Christopher J.; Saxon, Keith G.; Kearney, Pamela R.; Ludlow, Christy L.

    2008-01-01

    Objectives/Hypothesis Closure of the true and false vocal folds is a normal part of airway protection during swallowing. Individuals with reduced or delayed true vocal fold closure can be at risk for aspiration and benefit from intervention to ameliorate the problem. Surface electrical stimulation is currently used during therapy for dysphagia, despite limited knowledge of its physiological effects. Design Prospective single effects study. Methods The immediate physiological effect of surface stimulation on true vocal fold angle was examined at rest in 27 healthy adults using ten different electrode placements on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during passive inspiration were used to measure change in true vocal fold angle with stimulation. Results Vocal fold angles changed only to a small extent during two electrode placements (p ≤ 0.05). When two sets of electrodes were placed vertically on the neck the mean true vocal fold abduction was 2.4 degrees; while horizontal placements of electrodes in the submental region produced a mean adduction of 2.8 degrees (p=0.03). Conclusions Surface electrical stimulation to the submental and neck regions does not produce immediate true vocal fold adduction adequate for airway protection during swallowing and one position may produce a slight increase in true vocal fold opening. PMID:18043496

  5. Self-Triggered Functional Electrical Stimulation During Swallowing

    PubMed Central

    Burnett, Theresa A.; Mann, Eric A.; Stoklosa, Joseph B.; Ludlow, Christy L.

    2006-01-01

    Hyolaryngeal elevation is essential for airway protection during swallowing and is mainly a reflexive response to oropharyngeal sensory stimulation. Targeted intramuscular electrical stimulation can elevate the resting larynx and, if applied during swallowing, may improve airway protection in dysphagic patients with inadequate hyolaryngeal motion. To be beneficial, patients must synchronize functional electrical stimulation (FES) with their reflexive swallowing and not adapt to FES by reducing the amplitude or duration of their own muscle activity. We evaluated the ability of nine healthy adults to manually synchronize FES with hyolaryngeal muscle activity during discrete swallows, and tested for motor adaptation. Hooked-wire electrodes were placed into the mylo- and thyrohyoid muscles to record electromyographic activity from one side of the neck and deliver monopolar FES for hyolaryngeal elevation to the other side. After performing baseline swallows, volunteers were instructed to trigger FES with a thumb switch in synchrony with their swallows for a series of trials. An experimenter surreptitiously disabled the thumb switch during the final attempt, creating a foil. From the outset, volunteers synchronized FES with the onset of swallow-related thyrohyoid activity (~225 ms after mylohyoid activity onset), preserving the normal sequence of muscle activation. A comparison between average baseline and foil swallows failed to show significant adaptive changes in the amplitude, duration, or relative timing of activity for either muscle, indicating that the central pattern generator for hyolaryngeal elevation is immutable with short term stimulation that augments laryngeal elevation during the reflexive, pharyngeal phase of swallowing. PMID:16107520

  6. 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.

  7. Analysis and Optimization of Pulse Dynamics for Magnetic Stimulation

    PubMed Central

    Goetz, Stefan M.; Truong, Cong Nam; Gerhofer, Manuel G.; Peterchev, Angel V.; Herzog, Hans-Georg; Weyh, Thomas

    2013-01-01

    Magnetic stimulation is a standard tool in brain research and has found important clinical applications in neurology, psychiatry, and rehabilitation. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received less attention. Typically, the magnetic field waveform is determined by available device circuit topologies rather than by consideration of what is optimal for neural stimulation. This paper analyzes and optimizes the waveform dynamics using a nonlinear model of a mammalian axon. The optimization objective was to minimize the pulse energy loss. The energy loss drives power consumption and heating, which are the dominating limitations of magnetic stimulation. The optimization approach is based on a hybrid global-local method. Different coordinate systems for describing the continuous waveforms in a limited parameter space are defined for numerical stability. The optimization results suggest that there are waveforms with substantially higher efficiency than that of traditional pulse shapes. One class of optimal pulses is analyzed further. Although the coil voltage profile of these waveforms is almost rectangular, the corresponding current shape presents distinctive characteristics, such as a slow low-amplitude first phase which precedes the main pulse and reduces the losses. Representatives of this class of waveforms corresponding to different maximum voltages are linked by a nonlinear transformation. The main phase, however, scales with time only. As with conventional magnetic stimulation pulses, briefer pulses result in lower energy loss but require higher coil voltage than longer pulses. PMID:23469168

  8. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.

    PubMed

    Berger, Allan L; Randak, Christoph O; Ostedgaard, Lynda S; Karp, Philip H; Vermeer, Daniel W; Welsh, Michael J

    2005-02-18

    Compounds that enhance either the function or biosynthetic processing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel may be of value in developing new treatments for cystic fibrosis (CF). Previous studies suggested that the herbal extract curcumin might affect the processing of a common CF mutant, CFTR-DeltaF508. Here, we tested the hypothesis that curcumin influences channel function. Curcumin increased CFTR channel activity in excised, inside-out membrane patches by reducing channel closed time and prolonging the time channels remained open. Stimulation was dose-dependent, reversible, and greater than that observed with genistein, another compound that stimulates CFTR. Curcumin-dependent stimulation required phosphorylated channels and the presence of ATP. We found that curcumin increased the activity of both wild-type and DeltaF508 channels. Adding curcumin also increased Cl(-) transport in differentiated non-CF airway epithelia but not in CF epithelia. These results suggest that curcumin may directly stimulate CFTR Cl(-) channels. PMID:15582996

  9. PP2 prevents isoproterenol stimulation of cardiac pacemaker activity.

    PubMed

    Huang, Jianying; Lin, Yen-Chang; Hileman, Stan; Martin, Karen H; Hull, Robert; Yu, Han-Gang

    2015-02-01

    Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) using tyrosine kinase inhibitors for cancer therapy. We report here that a widely used selective inhibitor of Src tyrosine kinases, PP2, can inhibit and prevent isoproterenol stimulation of cardiac pacemaker activity. In dissected rat sinus node, PP2 inhibited and prevented isoproterenol stimulation of spontaneous beating rate. In isolated sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (If) by negatively shifting the activation curve and decelerating activation kinetics, associated with decreased cell surface expression and reduced tyrosine phosphorylation of hyperpolarization-activated cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. In human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed isoproterenol stimulation of HCN4 and inhibited HCN4-573x, a cAMP-insensitive human HCN4 mutant. Isoprotenrenol had little effects on HCN4-573x. These results demonstrated that inhibition of presumably tyrosine Src kinase activity in heart by PP2 decreased and prevented the potential β-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the key channel protein that controls the heart rate. PMID:25658311

  10. Turning off the central contribution to contractions evoked by neuromuscular electrical stimulation.

    PubMed

    Dean, J C; Yates, L M; Collins, D F

    2008-08-01

    Neuromuscular electrical stimulation can generate contractions through both peripheral and central mechanisms. The peripheral mechanism involves the direct activation of motor axons, while the central mechanism involves the activation of sensory axons that recruit spinal neurons through a reflex pathway. For use in functional electrical stimulation. One must have control over turning the central mechanism on and off. We investigated whether inhibition developed through antagonist muscle (tibialis anterior, TA) contractions elicited by electrical stimulation or by volition can turn off the central mechanism in triceps surae. Both electrical stimulation and voluntary contractions of TA reduced or eliminated plantar flexion torque produced by the central mechanism, indicating that inhibition induced via these contractions can effectively turn off the central contribution to force. These findings suggest that patterns of electrical stimulation may be able to generate periodic muscle contractions by turning the central contribution to muscular contractions on and off. PMID:18537146

  11. 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. PMID:26208917

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Axonal model for temperature stimulation.

    PubMed

    Fribance, Sarah; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-10-01

    Recent studies indicate that a rapid increase in local temperature plays an important role in nerve stimulation by laser. To analyze the temperature effect, our study modified the classical HH axonal model by incorporating a membrane capacitance-temperature relationship. The modified model successfully simulated the generation and propagation of action potentials induced by a rapid increase in local temperature when the Curie temperature of membrane capacitance is below 40 °C, while the classical model failed to simulate the axonal excitation by temperature stimulation. The new model predicts that a rapid increase in local temperature produces a rapid increase in membrane capacitance, which causes an inward membrane current across the membrane capacitor strong enough to depolarize the membrane and generate an action potential. If the Curie temperature of membrane capacitance is 31 °C, a temperature increase of 6.6-11.2 °C within 0.1-2.6 ms is required for axonal excitation and the required increase is smaller for a faster increase. The model also predicts that: (1) the temperature increase could be smaller if the global axon temperature is higher; (2) axons of small diameter require a smaller temperature increase than axons of large diameter. Our study indicates that the axonal membrane capacitance-temperature relationship plays a critical role in inducing the transient membrane depolarization by a rapidly increasing temperature, while the effects of temperature on ion channel kinetics cannot induce depolarization. The axonal model developed in this study will be very useful for analyzing the axonal response to local heating induced by pulsed infrared laser. PMID:27342462

  18. NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

    PubMed Central

    Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Bernabeu, Montserrat; Tormos, Jose M.; Pascual-Leone, Alvaro

    2012-01-01

    Brain stimulation techniques have evolved in the last few decades with more novel methods capable of painless, noninvasive brain stimulation. While the number of clinical trials employing noninvasive brain stimulation continues to increase in a variety of medication-resistant neurological and psychiatric diseases, studies evaluating their diagnostic and therapeutic potential in traumatic brain injury (TBI) are largely lacking. This review introduces different techniques of noninvasive brain stimulation, which may find potential use in TBI. We cover transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), low-level laser therapy (LLLT) and transcranial doppler sonography (TCD) techniques. We provide a brief overview of studies to date, discuss possible mechanisms of action, and raise a number of considerations when thinking about translating these methods to clinical use. PMID:21691215

  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. 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.

  1. 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

  2. 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)

  3. Optical stimulation of peripheral nerves in vivo

    NASA Astrophysics Data System (ADS)

    Wells, Jonathon D.

    This dissertation documents the emergence and validation of a new clinical tool that bridges the fields of biomedical optics and neuroscience. The research herein describes an innovative method for direct neurostimulation with pulsed infrared laser light. Safety and effectiveness of this technique are first demonstrated through functional stimulation of the rat sciatic nerve in vivo. The Holmium:YAG laser (lambda = 2.12 mum) is shown to operate at an optimal wavelength for peripheral nerve stimulation with advantages over standard electrical neural stimulation; including contact-free stimulation, high spatial selectivity, and lack of a stimulation artifact. The underlying biophysical mechanism responsible for transient optical nerve stimulation appears to be a small, absorption driven thermal gradient sustained at the axonal layer of nerve. Results explicitly prove that low frequency optical stimulation can reliably stimulate without resulting in tissue thermal damage. Based on the positive results from animal studies, these optimal laser parameters were utilized to move this research into the clinic with a combined safety and efficacy study in human subjects undergoing selective dorsal rhizotomy. The clinical Holmium:YAG laser was used to effectively stimulate human dorsal spinal roots and elicit functional muscle responses recorded during surgery without evidence of nerve damage. Overall these results predict that this technology can be a valuable clinical tool in various neurosurgical applications.

  4. Vestibular Stimulation for Stress Management in Students

    PubMed Central

    Kumar, Sai Sailesh; Rajagopalan, Archana

    2016-01-01

    Introduction Although several methods are developed to alleviate stress among college students, logistic limitations in adopting them have limited their utility. Aim Hence, we aimed to test a very practical approach to alleviate stress among college students by achieving vestibular stimulation using swings. Materials and Methods In this study 60 male and female participants were randomly assigned into vestibular stimulation or control groups. Depression, anxiety, stress scores, sleep quality, heart rate, blood pressure, Autonomic functions, respiratory, haematological, cognitive function, Quality of life were recorded before and after 1st, 7th, 14th, 21st, 28th days of vestibular stimulation. Results STAI S and STAI T scores were significantly improved on day 28th following vestibular stimulation. Diastolic and mean arterial blood pressure were significantly decreased and remained within normal limits in vestibular group on day 28th following vestibular stimulation. Postural fall in blood pressure was significantly improved on day 14 onwards, following vestibular stimulation. Respiratory rate was significantly improved on day 7 onwards, following vestibular stimulation. PSQI sleep disturbance, PSQI sleep latency, PSQI total score and bleeding time was significantly improved following vestibular stimulation. Conclusion Our study supports the adoption of vestibular stimulation for stress management. Hence, placement of swings in college campuses must be considered, which may be a simple approach to alleviate stress among college students. PMID:27042457

  5. Unilateral magnetic stimulation of the phrenic nerve.

    PubMed Central

    Mills, G. H.; Kyroussis, D.; Hamnegard, C. H.; Wragg, S.; Moxham, J.; Green, M.

    1995-01-01

    BACKGROUND--Electrical stimulation of the phrenic nerve is a useful non-volitional method of assessing diaphragm contractility. During the assessment of hemidiaphragm contractility with electrical stimulation, low twitch transdiaphragmatic pressures may result from difficulty in locating and stimulating the phrenic nerve. Cervical magnetic stimulation overcomes some of these problems, but this technique may not be absolutely specific and does not allow the contractility of one hemidiaphragm to be assessed. This study assesses both the best means of producing supramaximal unilateral magnetic phrenic stimulation and its reproducibility. This technique is then applied to patients. METHODS--The ability of four different magnetic coils to produce unilateral phrenic stimulation in five normal subjects was assessed from twitch transdiaphragmatic pressure (TwPDI) measurements and diaphragmatic electromyogram (EMG) recordings. The results from magnetic stimulation were compared with those from electrical stimulation. To determine whether the magnetic field affects the contralateral phrenic nerve as well as the intended phrenic nerve, EMG recordings from each hemidiaphragm were compared during stimulation on the same side and the opposite side relative to the recording electrodes. The EMG recordings were made from skin surface electrodes in five normal subjects and from needle electrodes placed in the diaphragm during cardiac surgery in six patients. Similarly, the direction of hemidiaphragm movement was evaluated by ultrasonography. To determine the usefulness of the technique in patients the 43 mm mean diameter double coil was used in 54 patients referred for assessment of possible respiratory muscle weakness. These results were compared with unilateral electrical phrenic stimulation, maximum sniff PDI, and TwPDI during cervical magnetic stimulation. RESULTS--In the five normal subjects supramaximal stimulation was established for eight out of 10 phrenic nerves with the 43

  6. Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study...

  7. 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

  8. Distractibility Among Advantaged and Disadvantaged Preschool Children: Effects of Cubicles vs. High Levels of Stimulation on Task Performance

    ERIC Educational Resources Information Center

    Somervill, John W.; And Others

    1978-01-01

    Compared the task performance of children under high levels of variable auditory and visual distraction, reduced stimulation as achieved by cubicles, and normal environmental conditions where no effort was made to raise or lower the level of external stimulation. (Author/AM)

  9. Prefrontal transcranial direct current stimulation facilitates affective flexibility.

    PubMed

    Aboulafia-Brakha, Tatiana; Manuel, Aurelie L; Ptak, Radek

    2016-06-01

    Performance on paradigms involving switching between emotional and non-emotional task-sets (affective flexibility) predicts emotion regulation abilities and is impaired in patients with different emotional disorders. A better understanding of how neurostimulation techniques such as transcranial direct current stimulation (tDCS) influence affective switching may provide support for the improvement of rehabilitation programs. In the current study healthy volunteers received anodal tDCS over the right dorsolateral prefrontal cortex (DLPFC), the left DLPFC or sham stimulation while performing an affective-switching task. Participants had to repeat or switch between facial judgments of emotional expressions (emotional task-set) or gender (non-emotional task-set). Right tDCS resulted in faster responses in the gender task only when it followed a judgment of emotion. These effects were not observed following left tDCS. Further, switching away from emotion was easier for the right compared to left tDCS group (reduced switch costs for gender), while switching away from gender toward emotion was easier for the left compared to the right group (reduced switch-costs for emotion). In sum, tDCS over the DLPFC may modulate affective flexibility and right stimulation may be particularly helpful to facilitate disengagement from emotional task-sets. The usefulness of tDCS-trained affective switching may be further investigated on larger therapeutic protocols targeting emotional disorders. PMID:27039163

  10. 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

  11. Electrical Stimulation Counteracts Muscle Decline in Seniors

    PubMed Central

    Kern, Helmut; Barberi, Laura; Löfler, Stefan; Sbardella, Simona; Burggraf, Samantha; Fruhmann, Hannah; Carraro, Ugo; Mosole, Simone; Sarabon, Nejc; Vogelauer, Michael; Mayr, Winfried; Krenn, Matthias; Cvecka, Jan; Romanello, Vanina; Pietrangelo, Laura; Protasi, Feliciano; Sandri, Marco; Zampieri, Sandra; Musaro, Antonio

    2014-01-01

    The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise. We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function. We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity. ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF-1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis. Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging. PMID:25104935

  12. [Addiction to cocaine and other stimulants].

    PubMed

    Lacoste, Jérôme; Delavenne-Garcia, Héloïse; Charles-Nicolas, Aimé; Duarte Garcia, Frederico; Jehel, Louis

    2012-12-01

    Due to many available forms (powder, pasta base, freebase and crack…) and because of multiple routes of administration (intranasal, intravenous, or smoked), cocaine has become in 30 years one of the most consumed illegal drugs worldwide, after cannabis. While the frequency of consumption decreases in North America, it continues to rise in Europe, and in some countries in South America, including Brazil, despite a growing knowledge of its specific effects, physical complications and psychiatric consequences. Elsewhere (notably in Asia and Indian Ocean), amphetamine and other stimulants (including methamphetamine), whose properties and patterns of use are very similar to those of cocaine, tend to replace it. Another amphetamine derivative, MDMA or ecstasy, is also consumed by many young people of less than 25 years, in Europe and North America, in a festive setting, with specific consequences and special procedures of care. Although there is currently no consensus for a specific medication, the most appropriate therapeutic approach seems to involve a psychosocial treatment associated with an anticraving medication, which will reduce compulsive desire to consume, in order to facilitate the psychotherapeutic and social care. However, pharmacological research remains very active, and many options are explored (GABAergic or dopaminergic agonists, amphetamine derivatives with long half-life, vaccine…), whether to treat addiction to cocaine or to methamphetamine. PMID:23021656

  13. Amphetamine stimulates movement through thalamocortical glutamate release

    PubMed Central

    Mabrouk, Omar S; Semaan, Daniel Z; Mikelman, Sarah; Gnegy, Margaret E; Kennedy, Robert T

    2014-01-01

    The ventrolateral thalamus (VL) is a primary relay point between the basal ganglia and the primary motor cortex (M1). Using dual probe microdialysis and locomotor behavior monitoring, we investigated the contribution of VL input into M1 during amphetamine (AMPH)-stimulated monoamine release and hyperlocomotion in rats. Tetrodotoxin (TTX) (10 uM) perfusion into the VL significantly lowered hyperactivity induced by AMPH (1 mg/kg i.p.). This behavioral response corresponded to reduced cortical glutamate and monoamine release. To determine which glutamate receptors the thalamocortical projections acted upon, we perfused either the AMPA/kainate receptor antagonist NBQX (10 μM) or the NMDA receptor antagonist (MK-801) intracortically followed by systemic AMPH. The results show that AMPA/kainate, and to a lesser extent NMDA receptors, mediated the observed effects. Since glutamate-monoamine interactions could possibly occur through local or circuit-based mechanisms, we isolated and perfused M1 tissue ex vivo to determine the extent of local glutamate-dopamine interactions. Taken together, these results demonstrate that AMPH generates hyperlocomotive states via thalamocortical signaling and that cortical AMPA receptors are an important mediator of these effects. PMID:23889359

  14. Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing.

    PubMed

    Lam, Mai T; Nauta, Allison; Meyer, Nathaniel P; Wu, Joseph C; Longaker, Michael T

    2013-03-01

    Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds. PMID:23072446

  15. 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

  16. 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

  17. 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

  18. 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

  19. Spinal Cord Stimulation for Neuropathic Pain

    PubMed Central

    2005-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology. Clinical Need SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage. The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada. Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain. Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS. The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable

  20. 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

  1. Coil Design Considerations for Deep Transcranial Magnetic Stimulation

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2014-01-01

    Objectives To explore the field characteristics and design tradeoffs of coils for deep transcranial magnetic stimulation (dTMS). Methods We simulated parametrically two dTMS coil designs on a spherical head model using the finite element method, and compare them with five commercial TMS coils, including two that are FDA approved for the treatment of depression (ferromagnetic-core figure-8 and H1 coil). Results Smaller coils have a focality advantage over larger coils; however, this advantage diminishes with increasing target depth. Smaller coils have the disadvantage of producing stronger field in the superficial cortex and requiring more energy. When the coil dimensions are large relative to the head size, the electric field decay in depth becomes linear, indicating that, at best, the electric field attenuation is directly proportional to the depth of the target. Ferromagnetic cores improve electrical efficiency for targeting superficial brain areas; however magnetic saturation reduces the effectiveness of the core for deeper targets, especially for highly focal coils. Distancing winding segments from the head, as in the H1 coil, increases the required stimulation energy. Conclusions Among standard commercial coils, the double cone coil offers high energy efficiency and balance between stimulated volume and superficial field strength. Direct TMS of targets at depths of ~ 4 cm or more results in superficial stimulation strength that exceeds the upper limit in current rTMS safety guidelines. Approaching depths of ~ 6 cm is almost certainly unsafe considering the excessive superficial stimulation strength and activated brain volume. Significance Coil design limitations and tradeoffs are important for rational and safe exploration of dTMS. PMID:24411523

  2. Modeling the effects of hydraulic stimulation on geothermal reservoirs

    NASA Astrophysics Data System (ADS)

    De Simone, Silvia; Vilarrasa, Victor; Carrera, Jesús; Alcolea, Andrés; Meier, Peter

    2013-04-01

    Geothermal energy represents a huge power source that can provide clean energy in potentially unlimited supply. When designing geothermal energy production from deep hot rocks, permeability is considered to control the economic efficiency of the heat extraction operations. In fact, a high permeability heat exchanger is required to achieve a cost-competitive power generation. The typical procedure entails intercepting naturally fractured rocks and enhancing their permeability by means of stimulation. Hydraulic stimulation is the most widely used method. It involves the massive injection of a large volume of water at high flow rates to increase the downhole pore pressure. This overpressure reduces the effective stresses, which tends to induce shearing along the fracture planes. In this way permeability is enhanced due to dilatancy, especially in the direction perpendicular to shear. These processes usually trigger microseismic events, which are sometimes of sufficient magnitude to be felt by the local population. This causes a negative impact on the local population and may compromise the continuation of the project. Hence, understanding the mechanisms triggering these induced micro-earthquakes is important to properly design and manage geothermal stimulation and operations so as to prevent them. We analyzed the thermo-hydro-mechanical response of a fractured deep rock mass subjected to hydraulic stimulation. Considering that seismicity is triggered when failure condition are reached, we studied the variation of the stress regime due to the hydraulic and thermal perturbations during fluid injection. Starting with a simplified model with constant permeability fault zones, more sophisticated schemes are considered to simulate the behavior of the discontinuity zones, including permeability variation associated to temperature, pressure and stress regime changes. Numerical simulations are performed using the finite element numerical code CODE_BRIGHT, which allows to solve

  3. Ovarian stimulation in patients with breast cancer

    PubMed Central

    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

  4. 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.

  5. Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions.

    PubMed

    Gonzalez, Omar Garcia; Assfalg, Robin; Koch, Sylvia; Schelling, Adrian; Meena, Jitendra K; Kraus, Johann; Lechel, Andre; Katz, Sarah-Fee; Benes, Vladimir; Scharffetter-Kochanek, Karin; Kestler, Hans A; Günes, Cagatay; Iben, Sebastian

    2014-01-01

    In addition to performing its canonical function, Telomerase Reverse Transcriptase (TERT) has been shown to participate in cellular processes independent of telomerase activity. Furthermore, although TERT mainly localizes to Cajal bodies, it is also present within the nucleolus. Because the nucleolus is the site of rDNA transcription, we investigated the possible role of telomerase in regulating RNA polymerase I (Pol I). Here we show that TERT binds to rDNA and stimulates transcription by Pol I during liver regeneration and Ras-induced hyperproliferation. Moreover, the inhibition of telomerase activity by TERT- or TERC-specific RNA interference, the overexpression of dominant-negative-TERT, and the application of the telomerase inhibitor imetelstat reduce Pol I transcription and the growth of tumour cells. In vitro, telomerase can stimulate the formation of the transcription initiation complex. Our results demonstrate how non-canonical features of telomerase may direct Pol I transcription in oncogenic and regenerative hyperproliferation. PMID:25118183

  6. Stimulation of Photophosphorylation and Cytochrome c Photooxidation by Pteridines 1

    PubMed Central

    Maclean, F. I.; Fujita, Y.; Forrest, H. S.; Myers, J.

    1966-01-01

    A number of pteridines were examined for activity in promoting photophosphorylation in broken spinach chloroplasts and in stimulating cytochrome c photooxidation in sonicated chloroplasts. Correlation was found between activities for the 2 reactions. Photophosphorylation promoted by pteridines was inhibited by DCMU and by anaerobic conditions. It is concluded that pteridines may stimulate photophosphorylation by linking photosystem 1 with molecular oxygen and thereby allowing noncyclic electron flow. Aromatic pteridines in both the 2,4-dihidroxy- and 2-amino-4-hydroxy-series were active; substitution at the 6 (or 7) position was a necessary but not sufficient condition for activity in both reactions. Reducing agents increased photophosphorylation activity of aromatic pteridines and an oxidant increased activity of a tetrahydropteridine. It is postulated that pteridines are most active in their semiquinone or unstable dihydro forms. PMID:5938184

  7. Actin Polymerization is Stimulated by Actin Crosslinking Protein Palladin

    PubMed Central

    Gurung, Ritu; Yadav, Rahul; Brungardt, Joseph G.; Orlova, Albina; Egelman, Edward H.; Beck, Moriah R.

    2016-01-01

    The actin scaffold protein palladin regulates both normal cell migration and invasive cell motility, processes that require the coordinated regulation of actin dynamics. However, the potential effect of palladin on actin dynamics has remained elusive. Here we show that the actin binding immunoglobulin-like domain of palladin, which is directly responsible for both actin binding and bundling, also stimulates actin polymerization in vitro. Palladin eliminated the lag phase that is characteristic of the slow nucleation step of actin polymerization. Furthermore, palladin dramatically reduced depolymerization, slightly enhanced the elongation rate, and did not alter the critical concentration. Microscopy and in vitro crosslinking assays reveal differences in actin bundle architecture when palladin is incubated with actin before or after polymerization. These results suggest a model whereby palladin stimulates a polymerization-competent form of G-actin, akin to metal ions, either through charge neutralization or conformational changes. PMID:26607837

  8. Reduce HIV Risk

    MedlinePlus

    ... incidence could be reduced if people changed their sexual behaviors. Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Spring 2008 ...

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Sphenopalatine Ganglion Stimulation in Neurovascular Headaches.

    PubMed

    Schoenen, Jean

    2015-01-01

    The interest for the sphenopalatine ganglion (SPG) in neurovascular headaches dates back to 1908 when Sluder presented his work on the role of the SPG in 'nasal headaches', which are now part of the trigeminal autonomic cephalalgias and cluster headache (ICHD-III-beta). Since then various interventions with blocking or lesional properties have targeted the SPG (transnasal injection of lidocaine and other agents, alcohol or steroid injections, radiofrequency lesions, or even ganglionectomy); success rates vary, but benefit is usually transient. Here we briefly review some anatomophysiological characteristics of the SPG and hypotheses about its pathophysiological role in neurovascular headaches before describing recent therapeutic results obtained with electrical stimulation of the SPG. Based on results of a prospective randomized controlled study, SPG stimulation appears to be an effective treatment option for patients with chronic cluster headaches; efficacy data indicate that acute electrical stimulation of the SPG provides significant attack pain relief and in many cases pain freedom compared to sham stimulation. Moreover, in some patients SPG stimulation has been associated with a significant and clinically meaningful reduction in cluster headache attack frequency; this preventive effect of SPG stimulation warrants further investigation. For migraine attacks, the outcome of a proof-of-concept study using a temporary electrode implanted in the pterygopalatine fossa was less encouraging; however, an ongoing multicenter trial is evaluating the efficacy of long-term SPG stimulation against sham stimulation for acute and preventive treatment in patients with frequent migraine. PMID:26394372

  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. PMID:24195387

  16. 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)[

  17. Brain Stimulation May Help People with Anorexia

    MedlinePlus

    ... html Brain Stimulation May Help People With Anorexia Depression treatment cut urge to restrict food, study says To ... after they underwent repetitive transcranial stimulation (rTMS), a treatment approved for depression. "With rTMS we targeted ... an area of the ...

  18. Are Prescription Stimulants “Smart Pills”?

    PubMed Central

    Smith, M. Elizabeth; Farah, Martha J.

    2013-01-01

    Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. PMID:21859174

  19. 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

  20. Ovarian stimulation and granulosa-cell tumour.

    PubMed

    Willemsen, W; Kruitwagen, R; Bastiaans, B; Hanselaar, T; Rolland, R

    1993-04-17

    Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation--ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present. PMID:8096944

  1. Wirelessly powering miniature implants for optogenetic stimulation

    NASA Astrophysics Data System (ADS)

    Yeh, Alexander J.; Ho, John S.; Tanabe, Yuji; Neofytou, Evgenios; Beygui, Ramin E.; Poon, Ada S. Y.

    2013-10-01

    Conventional methods for in vivo optogenetic stimulation require optical fibers or mounted prosthesis. We present an approach for wirelessly powering implantable stimulators using electromagnetic midfield. By exploiting the properties of the midfield, we demonstrate the ability to generate high intensity light pulses in a freely moving animal.

  2. Evidence of plasma fluctuations and their effect on the growth of stimulated Brillouin and stimulated Raman scattering in laser plasmas

    SciTech Connect

    Montgomery, D.S.; Fernandez, J.C.; Cobble, J.A.

    1997-11-01

    The reflectivity levels of stimulated Brillouin scattering (SBS) in recent large scale length laser plasma experiments is much lower than expected for conditions where the convective gain exponent is expected to be large. Long wavelength velocity fluctuations caused during the plasma formation process, or by parametric instabilities themselves, have been proposed as a mechanism to detune SBS in these experiments and reduce its gain. Evidence of large velocity fluctuation levels is found in the time-resolved SBS spectra from these experiments, and correlates with observed changes in the reflectivity of both SBS and stimulated Raman scattering (SRS). The authors present evidence of fluctuations which increase as the plasma density systematically increases, and discuss their effect on the growth of parametric instabilities.

  3. 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

  4. 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

  5. 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.

  6. Spatially selective photoconductive stimulation of live neurons

    PubMed Central

    Campbell, Jacob; Singh, Dipika; Hollett, Geoffrey; Dravid, Shashank M.; Sailor, Michael J.; Arikkath, Jyothi

    2014-01-01

    Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology. PMID:24904287

  7. Adaptive deep brain stimulation in Parkinson's disease.

    PubMed

    Beudel, M; Brown, P

    2016-01-01

    Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application. PMID:26411502

  8. Development of VCSELs for optical nerve stimulation

    NASA Astrophysics Data System (ADS)

    Dummer, Matthew; Johnson, Klein; Hibbs-Brenner, Mary; Keller, Matthew; Gong, Tim; Wells, Jonathon; Bendett, Mark

    2011-03-01

    Neural stimulation using infrared optical pulses has numerous potential advantages over traditional electrical stimulation, including improved spatial precision and no stimulation artifact. However, realization of optical stimulation in neural prostheses will require a compact and efficient optical source. One attractive candidate is the vertical cavity surface emitting laser. This paper presents the first report of VCSELs developed specifically for neurostimulation applications. The target emission wavelength is 1860 nm, a favorable wavelength for stimulating neural tissues. Continuous wave operation is achieved at room temperature, with maximum output power of 2.9 mW. The maximum lasing temperature observed is 60° C. Further development is underway to achieve power levels necessary to trigger activation thresholds.

  9. Fabrication and initial testing of the μDBS: a novel Deep Brain Stimulation electrode with thousands of individually controllable contacts.

    PubMed

    Willsie, Andrew; Dorval, Alan

    2015-01-01

    High frequency electrical stimulation of deep brain structures such as the subthalamic nucleus in Parkinson's disease or thalamus for essential tremor is used clinically to reduce symptom severity. Deep brain stimulation activates neurons in specific brain structures and connection pathways, overriding aberrant neural activity associated with symptoms. While optimal deep brain stimulation might activate a particular neural structure precisely, existing deep brain stimulation can only generate roughly-spherical regions of activation that do not overlap with any target anatomy. Additionally, side effects linked to stimulation may be the result of limited control over placement of stimulation and its subsequent spread out of optimal target boundaries. We propose a novel lead with thousands of individually controllable contacts capable of asymmetric stimulation profiles. Here we outline the design motivation, manufacturing process, and initial testing of this new electrode design, placing it on track for further directional stimulation studies. PMID:25981752

  10. Endothelin-1 stimulates resistin gene expression.

    PubMed

    Tang, Ya-Chu; Liu, Chi-Wei; Chang, Hsin-Huei; Juan, Chi-Chang; Kuo, Yow-Chii; Kao, Chung-Cheng; Huang, Yao-Ming; Kao, Yung-Hsi

    2014-03-01

    Resistin and endothelin (ET)-1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET-1 to act on resistin gene expression is still unknown. Using 3T3-L1 adipocytes, we investigated the signaling pathways involved in ET-1-stimulated resistin gene expression. The up-regulation of resistin mRNA expression by ET-1 depends on concentration and timing. The concentration of ET-1 that increased resistin mRNA levels by 100%-250% was approximately 100 nM for a range of 0.25-12 hours of treatment. Treatment with actinomycin D blocked ET-1-increased resistin mRNA levels, suggesting that the effect of ET-1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type-A receptor, such as N-[1-Formyl-N-[N-[(hexahydro-1H-azepin-1-yl)carbonyl]-L-leucyl]-D-tryptophyl]-D-tryptophan (BQ610), but not with the ET type-B receptor antagonist N-[(cis-2,6-Dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D-norleucine (BQ788), blocked ET-1, increased the levels of resistin mRNA, and phosphorylated levels of downstream signaling molecules, such as ERK1/2, c-Jun N-terminal kinases (JNKs), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3). Moreover, pretreatment of specific inhibitors of either ERK1/2 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene [U0126] and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one [PD98059], two inhibitors of MEK1), JNKs (SP600125), phosphatidylinositol 3-kinase/AKT (LY294002 and Wortmannin), or Janus kinase 2 (JAK2)/STAT3 ((E)-2-Cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide, AG490) prevented ET-1-increased levels of resistin mRNA and reduced the ET-1-stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist 4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl

  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. Callus stimulation in distraction osteogenesis.

    PubMed

    Mofid, Mehrdad M; Inoue, Nozomu; Atabey, Atay; Marti, Guy; Chao, Edmund Y S; Manson, Paul N; Vander Kolk, Craig A

    2002-04-15

    Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared. Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the

  13. Bacterial porins stimulate bone resorption.

    PubMed Central

    Meghji, S; Henderson, B; Nair, S P; Tufano, M A

    1997-01-01

    Porins are abundant outer membrane proteins of gram-negative bacteria involved in transport of low-molecular-mass molecules. During the past decade, porins from a number of bacteria have also been shown to have proinflammatory activities including inducing the synthesis of proinflammatory mediators (cytokines, platelet-activating factor, and nitric oxide) in cultured cells and inducing inflammation in vivo. With this range of actions, it was possible that porins could also interact with bone cells to cause aberrant bone remodeling and that this could contribute to the bone destruction seen in gram-negative bone infections. By using purified preparations of Salmonella typhimurium and Pseudomonas aeruginosa porins, in the presence of polymyxin B, it was possible to induce concentration-dependent loss of calcium from cultured murine calvaria at porin concentrations in the range of 1 to 10 nM. The mechanism of action of the porins was determined by the inclusion of inhibitors of cyclooxygenase or inflammatory cytokines in the culture media. The bone-resorbing activity of both porins was not inhibited by the cyclooxygenase inhibitor indomethacin or by neutralizing the activity of tumor necrosis factor. Indeed, relatively high concentrations of these agents produced an unexpected increase in the bone resorption induced by the porins. In contrast, porin-induced bone resorption could be inhibited by relatively high concentrations of the natural inhibitor of interleukin-1 (IL-1 receptor antagonist). It appears that these porins stimulate bone resorption by a mechanism distinct from that of lipopolysaccharide, and the possibility therefore exists that porins play a role in bone destruction in gram-negative bacterial infections of bone. PMID:9119467

  14. Effects of electrical stimulation in C2C12 muscle constructs

    PubMed Central

    Park, Hyoungshin; Bhalla, Rajat; Saigal, Rajiv; Radisic, Milica; Watson, Nicki; Langer, Robert; Vunjak-Novakovic, Gordana

    2009-01-01

    Electrical stimulation affects the deposition of extracellular matrices and cellular differentiation. Type I collagen is one of the most abundant extracellular matrix proteins; however, not much is known about the effects of electrical stimulation on collagen type I deposition in C2C12 cells. Thus, we studied the effects of electrical voltage and stimulation frequency in 3D cultured C2C12 muscle cells in terms of metabolic activity, type I collagen deposition and cell morphology. Electrically excitable C2C12 muscle cells were seeded in collagen scaffolds and stimulated with rectangular signals of voltage (2, 5, 7 V) and frequency (1, 2 Hz), using parallel carbon electrodes spaced 1 cm apart. Metabolic activity was quantified by the glucose: lactate concentration ratio in the medium. Apoptotic activity was assessed by TUNEL staining and changes in collagen deposition were identified by immunohistology. The ultrastructure of the tissue was examined by TEM. Glucose and lactate analysis indicated that all groups had similar metabolic activity. TUNEL stain showed no significant difference in apoptotic damage induced by electrical stimulation compared to the control. Samples stimulated at 2 Hz exhibited reduced collagen deposition compared to the control and 1 Hz stimulated samples. Muscle-protein marker desmin was highly expressed in constructs stimulated with 1 Hz/5 V sample. TEM revealed that the stimulated samples developed highly organized sarcomeres, which coincided with improved contractile properties in the 1 Hz/5 V- and 2 Hz/5 V-stimulated groups. Our data implicate that a specific electrical frequency may modulate type I collagen accumulation and a specific voltage may affect the differentiation of muscle sarcomeres in excitable cells. PMID:18512267

  15. 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

  16. 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

  17. 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

    2015-01-01

    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

  18. Enhancement of Analgesic Effect by Combination of Non-Noxious Stimulation and Noxious Stimulation in Humans.

    PubMed

    Fujii-Abe, Keiko; Umino, Masahiro; Fukayama, Haruhisa; Kawahara, Hiroshi

    2016-02-01

    The aim of the this study was to investigate the combined effects of heterosegmental non-noxious and noxious stimulation on electrically induced tooth pain. The late component of somatosensory-evoked potentials (SEP), induced by electrical tooth stimulation and pain intensity, were examined under electrical stimulation to forearms. Noxious, non-noxious, and combined non-noxious and noxious electrical stimulation were applied to median nerves on the forearms. Four experimental sessions (ie, control session, combined non-noxious and noxious stimulation session, non-noxious stimulation session, and noxious stimulation session were performed for each subject at each 10-minute interval for 30 minutes. The amplitudes of the SEP and VAS scores in the combined stimulation session decreased significantly compared with those in the control session and the reduction rates were 51.1% (13.4 μV) and 41.0% (23.5 mm), respectively. These results show that the combined stimulation has a more potent analgesic effect than that of either the non-noxious or the noxious stimulation. It is suggested that a potent analgesia was produced by an activated central mechanism, including endogenous opioid and descending pain inhibitory systems due to combined non-noxious and noxious stimulation. PMID:25490991

  19. 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

  20. 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.

  1. [Model based study of myocardial stimulation mechanisms].

    PubMed

    Weiss, I; Urbaszek, A; Schaldach, M

    1997-01-01

    The present study investigated the mechanisms of electrical stimulation of a myocardial fibre with the aim of developing improved minimally invasive stimulation methods. Using a dynamic myocyte model, the ionic currents crossing the voltage-dependent channels of the membrane are computed. To trigger an action potential, the membrane must first be depolarized to the threshold potential, when further depolarization continues spontaneously through the avalanche-like opening of the sodium channels. For the development of an action potential, not merely the amount of charge injected into the cell during the stimulus is of importance, but an above-threshold magnitude of the stimulation current is also required. The smallest energy required is achieved when the stimulus duration is chosen to be equal to the chronaxie. A second aspect of the study concerned the far-field stimulation of a muscle fibre, achieved by generating a potential gradient along the fibre. First, using a continuous fibre model, the fibre activating function is computed. In a more detailed study, the discrete segmental structure of the fibre determined by the gap junctions is taken into account, and the impact of these junctions on the activating function analysed. By optimizing the electrode configuration, an appropriate activating function results which guarantees successful stimulation when its maximum is above than threshold potential. The most important finding is that the myocardium can be stimulated by floating electrodes, thus opening up new possibilities for a less invasive electro-stimulation of the heart. PMID:9172726

  2. 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

  3. 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.

  4. Genistein stimulates electrogenic Cl- secretion via phosphodiesterase modulation in the mouse jejunum.

    PubMed

    Chao, Pin-Chun; Hamilton, Kirk L

    2009-09-01

    Previously, we demonstrated that genistein stimulated Cl(-) secretion in the mouse jejunum (Baker MJ and Hamilton KL, Am J Physiol Cell Physiol 287: C1636-C1645, 2004); however, the mode of action of genistein still remains unclear. Here, we examined the activation of Cl(-) secretion by the modulation of phosphodiesterases (PDEs) by genistein (75 microM) in the mouse jejunum with the Ussing short-circuit current (I(sc)) technique. Drugs tested included theophylline (10 mM), a nonspecific PDE inhibitor; 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MM-IBMX; 100 microM), erythro-9-(2-hydroxyl-3-nonyl)-adenine (EHNA; 40 microM), milrinone (100 microM), and rolipram (40 and 100 microM), which are specific inhibitors of PDE1-PDE4, respectively. Theophylline stimulated a bumetanide-sensitive I(sc), indicative of Cl(-) secretion, and abolished genistein's stimulatory action on I(sc). Neither 8-MM-IBMX nor EHNA altered the basal I(sc) nor did these PDE inhibitors affect the stimulatory action of genistein on the I(sc) of the mouse jejunum. Rolipram had no effect on basal I(sc), but it reduced the genistein-stimulated I(sc) compared with time-matched control tissues. Milrinone stimulated a concentration-dependent increase in I(sc). Bumetanide (10 microM) inhibited 60 +/- 4% of milrinone-induced I(sc). Pretreating tissues with milrinone prevented genistein from stimulating I(sc), and pretreatment with genistein reduced the effect of milrinone on I(sc). H89 (50 microM), a PKA inhibitor, reduced the milrinone-stimulated I(sc). Likewise, H89 reduced the genistein-stimulated I(sc). Here, we demonstrate, for the first time, that genistein activates Cl(-) secretion of the mouse jejunum via inhibition of a PDE3-dependent pathway. PMID:19535515

  5. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function.

    PubMed

    Lee, Robert J; Workman, Alan D; Carey, Ryan M; Chen, Bei; Rosen, Phillip L; Doghramji, Laurel; Adappa, Nithin D; Palmer, James N; Kennedy, David W; Cohen, Noam A

    2016-01-01

    Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6-12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases. PMID:27623953

  6. Heating rate controller for thermally stimulated conductivity and thermoluminescence measurements.

    NASA Technical Reports Server (NTRS)

    Manning, E. G.; Littlejohn, M. A.; Oakley, E. M.; Hutchby , J. A.

    1972-01-01

    A temperature controller is described which enables the temperature of a sample mounted on a cold finger to be varied linearly with time. Heating rates between 0.5 and 10 K/min can be achieved for temperatures between 90 and 300 K. Provision for terminating the sample heating at any temperature between these extremes is available. The temperature can be held at the terminating temperature or be reduced to the starting temperature in a matter of minutes. The controller has been used for thermally stimulated conductivity measurements and should be useful for thermoluminescence measurements as well.

  7. Stimulation Technologies for Deep Well Completions

    SciTech Connect

    Stephen Wolhart

    2005-06-30

    The Department of Energy (DOE) is sponsoring the Deep Trek Program targeted at improving the economics of drilling and completing deep gas wells. Under the DOE program, Pinnacle Technologies conducted a study to evaluate the stimulation of deep wells. The objective of the project was to review U.S. deep well drilling and stimulation activity, review rock mechanics and fracture growth in deep, high-pressure/temperature wells and evaluate stimulation technology in several key deep plays. This report documents results from this project.

  8. Electrical Cerebral Stimulation Modifies Inhibitory Systems

    NASA Astrophysics Data System (ADS)

    Cuéllar-Herrera, M.; Rocha, L.

    2003-09-01

    Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

  9. Crack detection by stimulated infrared thermography

    NASA Astrophysics Data System (ADS)

    Bodnar, Jean-Luc

    2014-03-01

    In this paper, the potential of stimulated infrared thermography is studied for the detection of cracks located in metallic materials. To start with, the feasibility of the method is shown with the use of numerical simulations. Stimulated infrared thermography allows detecting emerging cracks in samples whether reflective or not as well as non-emerging cracks. In addition, crack detection is due to the radiative effects and/or the thermal effects induced by the defects. Then, the experimental device implemented for the study is detailed. Finally, experiments confirm that stimulated infrared thermography enables to detect microscopic cracks, whether emerging or non-emerging, in metal samples.

  10. Tumor necrosis factor induced stimulation of granulopoiesis and radioprotection.

    PubMed

    Urbaschek, R; Männel, D N; Urbaschek, B

    1987-01-01

    Human recombinant tumor necrosis factor, TNF, was used to assess its ability to stimulate granulopoiesis and to protect mice against lethal irradiation, effects known to be inducable with TNF-rich postendotoxin serum from BCG infected mice (BCG/ET serum). Although the endotoxin contamination of this TNF preparation is extremely low its effects were compared in endotoxin low responder C3H/HeJ mice and susceptible NMRI mice. TNF is a potent inducer of serum colony stimulating activity, CSA, in both mouse strains. In peripheral blood a marked granulocytosis with a concomitant decrease in lymphocytes and monocytopenia occurs at 2 hours after injection of TNF. Moreover, TNF induces an increase in the number of splenic myelopoietic committed stem cells (GM-CFC, granulocyte-macrophage colony forming cells) determined five days after injection. The lethality rate, registered over 30 days after exposure to 660 cGy whole body X-irradiation is reduced to 40% in C3H/HeJ mice as compared to 75% in control animals. The reduction in lethality is observed both, when TNF was injected 24 hours before or after irradiation. In vitro, TNF significantly increases the number of colonies in the presence of CSA in bone marrow cultures. TNF per se does not effect colony growth. The studies reported here demonstrate that TNF is a myelopoiesis stimulating factor in mice which may be related to the reduction in lethality following whole body irradiation. PMID:3306175

  11. Phosphorylation-independent stimulation of DNA topoisomerase II alpha activity.

    PubMed

    Kimura, K; Saijo, M; Tanaka, M; Enomoto, T

    1996-05-01

    It has been suggested that casein kinase II phosphorylates DNA topoisomerase II alpha (topo II alpha) in mouse FM3A cells, by comparison of phosphopeptide maps of topo II alpha labeled in intact cells and of topo II alpha phosphorylated by various kinases in vitro. The phosphorylation of purified topo II alpha by casein kinase II, which attached a maximum of two phosphate groups per topo II alpha molecule, had no effect on the activity of topo II alpha. Dephosphorylation of purified topo II alpha by potato acid phosphatase, which almost completely dephosphorylated the topo II alpha, did not reduce the activity of topo II alpha. The incubation itself, regardless of phosphorylation or dephosphorylation status, stimulated the enzyme activity in both reactions. Topo II alpha activity was stimulated by incubation in a medium containing low concentrations of glycerol but not in that containing high concentrations of glycerol, such as the 50% in which purified topo II alpha is stored. The stimulation of topo II alpha activity by incubation was dependent on the concentration of topo II alpha, requiring a relatively high concentration of topo II alpha. PMID:8631919

  12. Epilepsia partialis continua responsive to neocortical electrical stimulation.

    PubMed

    Valentin, Antonio; Ughratdar, Ismail; Cheserem, Beverly; Morris, Robert; Selway, Richard; Alarcon, Gonzalo

    2015-08-01

    Epilepsia partialis continua (EPC), defined as a syndrome of continuous focal jerking, is a rare form of focal status epilepticus that usually affects a distal limb, and when prolonged, can produce long-lasting deficits in limb function. Substantial electrophysiologic evidence links the origin of EPC to the motor cortex; thus surgical resection carries the risk of significant handicap. We present two patients with focal, drug-resistant EPC, who were admitted for intracranial video-electroencephalography monitoring to elucidate the location of the epileptogenic focus and identification of eloquent motor cortex with functional mapping. In both cases, the focus resided at or near eloquent motor cortex and therefore precluded resective surgery. Chronic cortical stimulation delivered through subdural strips at the seizure focus (continuous stimulation at 60-130 Hz, 2-3 mA) resulted in >90% reduction in seizures and abolition of the EPC after a follow-up of 22 months in both patients. Following permanent implantation of cortical stimulators, no adverse effects were noted. EPC restarted when intensity was reduced or batteries depleted. Battery replacement restored previous improvement. This two-case report opens up avenues for the treatment of this debilitating condition. PMID:26174165

  13. Modulation of Untruthful Responses with Non-Invasive Brain Stimulation

    PubMed Central

    Fecteau, Shirley; Boggio, Paulo; Fregni, Felipe; Pascual-Leone, Alvaro

    2013-01-01

    Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts. PMID:23550273

  14. Stimulation of proteolytic digestion by intestinal goblet cell mucus.

    PubMed

    Shora, W; Forstner, G G; Forstner, J F

    1975-03-01

    Intestinal goblet cell mucus (GCM) was added to incubations of casein and trypsin (or chymotrypsin) to discover whether mucus could inhibit proteolysis. Contrary to expectation, GCM stimulated casein hydrolysis, reaching a maximum effect at a GCM to casein ratio (w/w) of 0.083. GCM did not contain proteolytic enzymes or proenzymes as contaminants, nor did GCM serve as a substrate for trypsin. Stimulation was not reduced by removing 85% of the sialic acid from GCM. Harsh physical treatment (boiling and freezing) of casein decreased (50%) the GCM effect, as did partial predigestion of casein by trypsin, and elevation of trypsin concentration beyond 3 mug per ml. Thus the undegraded structure of casein appeared to be important for the stimulation of proteolysis by GCM. GCM also enhanced the hydrolysis by trypsin of intestinal brush border membrane protein, but had no effect on the hydrolysis of hemoglobin, albumin, or benzoyl arginine ethyl ester. These results suggest that GCM reacts with specific substrates, in a fashion which promotes their digestion by trypsin or chymotrypsin. PMID:1112451

  15. Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs

    SciTech Connect

    Greeley, G.H. Jr.; Lluis, F.; Gomex, G.; Ishizuka, J.; Holland, B.; Thompson, J.C. )

    1988-04-01

    Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids that share structural homologies with pancreatic polypeptide (PP). PP is predominantly found in the endocrine pancreas. PYY is primarily found in mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY is found in both the peripheral and central nervous system. Previous studies indicate that these peptides can interact with the autonomic nervous system. The objective of the present experiments was to study the effect of PYY on neurally stimulated insulin release in conscious dogs. Intravenous administration of PYY (100, 200, and 400 pmol{center dot}kg{sup {minus}1} {center dot}h{sup {minus}1}) reduced 2-DG-stimulated insulin release in a dose-dependent manner (P <0.05) without affecting plasma glucose levels. Administration of NPY, but not PP, reduced 2-DG-stimulated release of insulin. The inhibitory action of PYY on 2-DG-stimulated insulin release persisted in the presence of atropine or phentolamine treatment; however, hexamethonium alone or phentolamine plus propranolol treatment blocked the inhibitory action of PYY. Release of insulin stimulated by the {beta}-agonist isoproterenol was also inhibited by PYY. These results indicate that PYY can inhibit autonomic neurotransmission by a mechanism that may involve ganglionic or postganglionic inhibition of {beta}-adrenergic stimulation. The findings suggest a role for PYY and NPY in the autonomic regulation of insulin release.

  16. Impaired stimulation of glucose transport in cardiac myocytes exposed to very low-density lipoproteins.

    PubMed

    Papageorgiou, I; Viglino, C; Brulhart-Meynet, M-C; James, R W; Lerch, R; Montessuit, C

    2016-07-01

    We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin. Exposure of cardiac myocytes to VLDL reduced both insulin-and oligomycin-stimulated glucose uptake. The reduction of glucose uptake was associated with a moderately reduced tyrosine phosphorylation of the insulin receptor. No reduction of the phosphorylation of the downstream effectors of insulin signaling Akt and AS160 was however observed. Similarly only a modest reduction of the activating phosphorylation of the AMP-activated kinase (AMPK) was observed in response to oligomycin. Similar to our previous observations with free fatty acids, inhibition of fatty acid oxidation restored oligomycin-stimulated glucose uptake. In conclusions, VLDL-derived fatty acids impair stimulated glucose transport in cardiac myocytes by a mechanism that seems to be mediated by a fatty acid oxidation intermediate. Thus, in the clinical context of the metabolic syndrome high VLDL may contribute to enhancement of ischemic injury by reduction of metabolic stress-stimulated glucose uptake. PMID:27052924

  17. Effect of stimulating the lumbar skin caudal to a complete spinal cord injury on hindlimb locomotion.

    PubMed

    Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Desaulniers, Corinne; Frigon, Alain

    2015-01-15

    Sensory feedback is a potent modulator of the locomotor pattern generated by spinal networks. The purpose of this study was to assess the effect of cutaneous inputs from the back on the spinal-generated locomotor pattern. The spinal cord of six adult cats was transected at low thoracic levels. Cats were then trained to recover hindlimb locomotion. During experiments, the skin overlying lumbar vertebrae L2 to L7 was mechanically stimulated by a small calibrated clip or by manual pinching. Trials without and with cutaneous stimulation were performed at a treadmill speed of 0.4 m/s. Although manually pinching the skin completely stopped hindlimb locomotion and abolished weight support, cutaneous stimulation with the calibrated clip produced smaller effects. Specifically, more focalized cutaneous stimulation with the clip reduced flexor and extensor muscle activity and led to a more caudal positioning of the paw at contact and liftoff. Moreover, cutaneous stimulation with the clip led to a greater number of steps with improper nonplantigrade paw placements at contact and paw drag at the stance-to-swing transition. The most consistent effects on the hindlimb locomotor pattern were observed with cutaneous stimulation at midlumbar levels, from L3 to L5. The results indicate that cutaneous stimulation of the skin modulates the excitability of spinal circuits involved in generating locomotion and weight support, particularly at spinal segments thought to be critical for rhythm generation. PMID:25339715

  18. Development of network-based multichannel neuromuscular electrical stimulation system for stroke rehabilitation.

    PubMed

    Qu, Hongen; Xie, Yongji; Liu, Xiaoxuan; He, Xin; Hao, Manzhao; Bao, Yong; Xie, Qing; Lan, Ning

    2016-01-01

    Neuromuscular electrical stimulation (NMES) is a promising assistive technology for stroke rehabilitation. Here we present the design and development of a multimuscle stimulation system as an emerging therapy for people with paretic stroke. A network-based multichannel NMES system was integrated based on dual bus architecture of communication and an H-bridge current regulator with a power booster. The structure of the system was a body area network embedded with multiple stimulators and a communication protocol of controlled area network to transmit muscle stimulation parameter information to individual stimulators. A graphical user interface was designed to allow clinicians to specify temporal patterns and muscle stimulation parameters. We completed and tested a prototype of the hardware and communication software modules of the multichannel NMES system. The prototype system was first verified in nondisabled subjects for safety, and then tested in subjects with stroke for feasibility with assisting multijoint movements. Results showed that synergistic stimulation of multiple muscles in subjects with stroke improved performance of multijoint movements with more natural velocity profiles at elbow and shoulder and reduced acromion excursion due to compensatory trunk rotation. The network-based NMES system may provide an innovative solution that allows more physiological activation of multiple muscles in multijoint task training for patients with stroke. PMID:27149687

  19. Analysis of High-Perimeter Planar Electrodes for Efficient Neural Stimulation

    PubMed Central

    Wei, Xuefeng F.; Grill, Warren M.

    2009-01-01

    Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to two, three or four times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input–output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries. PMID:19936312

  20. Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries.

    PubMed

    Chao, Hsiang-Tai; Lee, Shu-Yu; Lee, Horng-Mo; Liao, Tien-Ling; Wei, Yau-Huei; Kao, Shu-Huei

    2005-05-01

    Superovulation by injection of exogenous gonadotropin is the elementary method to produce in vivo-derived embryos for embryo transfer in women. Increased oocyte aneuploidy, embryo mortality, fetal growth retardation, and congenital abnormalities have been studied at higher-dose stimulations. Ovarian and oocyte biological aging possibly may have adverse implications for human oocyte competence with repeated hyperstimulation. In this study, we found that reduced competence for the human oocyte has been associated with degenerative embryo upsurge during embryo culture and failure to develop into the blastocyst stage in the three, four, five, and six stimulation cycles. On the other hand, the numbers of ovulated oocytes were decreased in the groups with more ovarian stimulation. More aggregated mitochondria were found in the cytoplasm of the repetitively stimulated embryos. Higher amounts of oxidative damage including 8-OH-dG, lipoperoxides, and carbonyl proteins were also revealed in the ovaries with more cycle numbers of ovarian stimulation. Higher proportions of mtDNA mutations were also found. The detected molecular size of the mutated band was approximately 675 bp. Increased amounts of carbonyl proteins were also revealed after repeated stimulation. An understanding of the relationship between oocyte competence and ovarian responses to stimulation in the mouse may provide insights into the origin of oocyte defects and the biology of ooplasmic aging that could be of clinical relevance in the diagnosis and treatment of human infertility. PMID:15965057

  1. Vanadium Nitrogenase Reduces CO*

    PubMed Central

    Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W.

    2011-01-01

    Vanadium nitrogenase not only reduces dinitrogen to ammonia but also reduces carbon monoxide to ethylene, ethane, and propane. The parallelism between the two reactions suggests a potential link in mechanism and evolution between the carbon and nitrogen cycles on Earth. PMID:20689010

  2. Vanadium nitrogenase reduces CO.

    PubMed

    Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W

    2010-08-01

    Vanadium nitrogenase not only reduces dinitrogen to ammonia but also reduces carbon monoxide to ethylene, ethane, and propane. The parallelism between the two reactions suggests a potential link in mechanism and evolution between the carbon and nitrogen cycles on Earth. PMID:20689010

  3. Reducible oxide based catalysts

    DOEpatents

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  4. Reducing Teacher Incompetence.

    ERIC Educational Resources Information Center

    Rich, John Martin

    1988-01-01

    Suggests how administrators may reduce teacher incompetence. Teacher incompetence can be reduced if administrators fully understand and undertake appropriate preventive and remedial measures. Two sections comprise this article. First, a taxonomy of teacher incompetence reveals the magnitude of the problem. Second, preventive and remedial measures…

  5. SULFATE-REDUCING BACTERIA IN THE SEAGRASS RHIZOSPHERE

    EPA Science Inventory

    Seagrasses are rooted in anoxic sediments that support high levels of microbial activity including utilization of sulfate as a terminal electron acceptor which is reduced to sulfide. Sulfate reduction in seagrass bed sediments is stimulated by input of organic carbon through the ...

  6. Reducing Aggressive Male Behavior in Elementary School: Promising Practices

    ERIC Educational Resources Information Center

    Holmes, Barbara; Gibson, Jamel; Morrison-Danner, Dietrich

    2014-01-01

    Student aggression and violent behavior, especially among males, is pervasive and problematic in the classroom. When incorporated in the lesson design, promising practices (music, movement, and visual stimulation) are evidence-based strategies that may reduce male aggression in the classroom.

  7. Development of a tactile stimulator with simultaneous visual and auditory stimulation using E-Prime software.

    PubMed

    Kim, Hyung-Sik; Yeon, Hong-Won; Choi, Mi-Hyun; Kim, Ji-Hye; Choi, Jin-Seung; Park, Jang-Yeon; Jun, Jae-Hoon; Yi, Jeong-Han; Tack, Gye-Rae; Chung, Soon-Cheol

    2013-01-01

    In this study, a tactile stimulator was developed, which can stimulate visual and auditory senses simultaneously by using the E-Prime software. This study tried to compensate for systematic stimulation control and other problems that occurred with previously developed tactile stimulators. The newly developed system consists of three units: a control unit, a drive unit and a vibrator. Since the developed system is a small, lightweight, simple structure with low electrical consumption, a maximum of 35 stimulation channels and various visual and auditory stimulation combinations without delay time, the previous systematic problem is corrected in this study. The system was designed to stimulate any part of the body including the fingers. Since the developed tactile stimulator used E-Prime software, which is widely used in the study of visual and auditory senses, the stimulator is expected to be highly practical due to a diverse combination of stimuli, such as tactile-visual, tactile-auditory, visual-auditory and tactile-visual-auditory stimulation. PMID:22149159

  8. Towards a Switched-Capacitor based Stimulator for efficient deep-brain