Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

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Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

2016-10-28

Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients.

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Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

2017-08-01

The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.

Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production

International Nuclear Information System (INIS)

Stanley, E.R.

1979-01-01

Colony-stimulating factors (CSFs) stimulate the differentiation of immature precursor cells to mature granulocytes and macrophages. Purified 125 I-labeled murine L cell CSF has been used to develop a radioimmunoassay (RIA) that detects a subclass of CSFs that stimulates macrophage production. Murine CSF preparations that contain this subclass of CSF compete for all of the CSF binding sites on anti-L cell CSF antibody. With the exception of mouse serum, which can contain inhibitors of the bioassay, there is complete correspondence between activities determined by RIA and those determined by bioassay. The RIA is slightly more sensitive than the bioassay, detecting approximately 0.3 fmol of purified L cell CSF. It can also detect this subclass of CSF in chickens, rats, and humans. In the mouse, the subclass is distinguished from other CSFs by a murine cell bioassay dose-response curve in which 90% of the response occurs over a 10-fold (rather than a 100-fold) increase in concentration, by stimulating the formations of colonies contaning a high proportion of mononuclear (rather than granulocytic) cells, and by certain physical characteristics

Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival.

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Fan, Zhisong; Li, Yong; Zhao, Qun; Fan, Liqiao; Tan, Bibo; Zuo, Jing; Hua, Kelei; Ji, Qiang

2018-03-23

BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined. RESULTS The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.

The Effect of Electrical Stimulation in Improving Muscle Tone (Clinical)

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Azman, M. F.; Azman, A. W.

2017-11-01

Electrical stimulation (ES) and also known as neuromuscular electrical stimulation (NMES) and transcutaneous electrical stimulation (TES) involves the use of electrical current to stimulate the nerves or nerve endings that innervate muscle beneath the skin. Electrical stimulation may be applied superficially on the skin (transcutaneously) or directly into a muscle or muscles (intramuscularly) for the primary purpose of enhancing muscle function. The basic theoretical premise is that if the peripheral nerve can be stimulated, the resulting excitation impulse will be transmitted along the nerve to the motor endplates in the muscle, producing a muscle contraction. In this work, the effect of mere electrical stimulation to the muscle bulk and strength are tested. This paper explains how electrical stimulation can affect the muscle bulk, muscle size, muscle tone, muscle atrophy and muscle strength. The experiment and data collection are performed on 5 subjects and the results obtained are analyzed. This research aims to understand the full potential of electrical stimulation and identifying its possible benefits or disadvantages to the muscle properties. The results indicated that electrical stimulation alone able to improve muscle properties but with certain limits and precautions which might be useful in rehabilitation programme.

Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

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William Gemio Jacobsen Teixeira

2018-02-01

Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

Factors influencing parental decision making about stimulant treatment for attention-deficit/hyperactivity disorder.

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Ahmed, Rana; McCaffery, Kirsten J; Aslani, Parisa

2013-04-01

Attention-deficit/hyperactivity disorder (ADHD) is a pediatric psychological condition commonly treated with stimulant medications. Negative media reports and stigmatizing societal attitudes surrounding the use of these medications make it difficult for parents of affected children to accept stimulant treatment, despite it being first line therapy. The purpose of this study was to identify factors that influence parental decision making regarding stimulant treatment for ADHD. A systematic review of the literature was conducted to identify studies: 1) that employed qualitative methodology, 2) that highlighted treatment decision(s) about stimulant medication, 3) in which the decision(s) were made by the parent of a child with an official ADHD diagnosis, and 4) that examined the factors affecting the decision(s) made. Individual factors influencing parental treatment decision making, and the major themes encompassing these factors, were identified and followed by a thematic analysis. Eleven studies reporting on the experiences of 335 parents of children with ADHD were included. Four major themes encompassing influences on parents' decisions were derived from the thematic analysis performed: confronting the diagnosis, external influences, apprehension regarding therapy, and experience with the healthcare system. The findings of this systematic review reveal that there are multiple factors that influence parents' decisions about stimulant therapy. This information can assist clinicians in enhancing information delivery to parents of children with ADHD, and help reduce parental ambivalence surrounding stimulant medication use. Future work needs to address parental concerns about stimulants, and increase their involvement in shared decision making with clinicians to empower them to make the most appropriate treatment decision for their child.

Galvanic vestibular stimulation may improve anterior bending posture in Parkinson's disease.

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Okada, Yohei; Kita, Yorihiro; Nakamura, Junji; Kataoka, Hiroshi; Kiriyama, Takao; Ueno, Satoshi; Hiyamizu, Makoto; Morioka, Shu; Shomoto, Koji

2015-05-06

This study investigated the effects of binaural monopolar galvanic vestibular stimulation (GVS), which likely stimulates the bilateral vestibular system, on the anterior bending angle in patients with Parkinson's disease (PD) with anterior bending posture in a single-blind, randomized sham-controlled crossover trial. The seven PD patients completed two types of stimulation (binaural monopolar GVS and sham stimulation) applied in a random order 1 week apart. We measured each patient's anterior bending angles while he or she stood with eyes open and eyes closed before/after the stimulations. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS. The amount of change in the eyes-closed condition post-GVS was significantly larger than that by sham stimulation. The amount of change in anterior bending angles in the GVS condition was not significantly correlated with Unified Parkinson's Disease Rating Scale motor score, disease duration, the duration of the postural deformities, and the anterior bending angles before the GVS. Binaural monopolar GVS might improve anterior bending posture in PD patients, irrespective of the duration and the severity of disease and postural deformities. Binaural monopolar GVS might be a novel treatment strategy to improve anterior bending posture in PD.

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

International Nuclear Information System (INIS)

Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

2015-01-01

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Energy Technology Data Exchange (ETDEWEB)

Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

2015-03-27

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

Directory of Open Access Journals (Sweden)

El Husseiny Noha M

2011-03-01

Full Text Available Abstract Introduction Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. Case presentation We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutaneous vasculitic lesions following injection of a single dose of a granulocytic colony stimulating factor before a third cycle of chemotherapy to improve neutropenia. This is an unusual case and the pathogenesis is not fully understood. Our patient was not on any medical treatment except for bisoprolol for ischemic heart disease. Although aggressive management with steroids, anticoagulation and plasmapheresis had been carried out, the condition was aggressive and the patient's consciousness deteriorated. A magnetic resonance imaging scan of his brain revealed multiple ischemic foci that could be attributed to vasculitis of the brain. Conclusion The aim of this case report is to highlight the importance of monitoring patients on granulocytic colony-stimulating factor therapy, especially in the context of other conditions (such as a hematological malignancy that may lead to an adverse outcome.

Colony stimulating factors and their clinical implication

International Nuclear Information System (INIS)

Asano, Shigetaka

1989-01-01

Granulocytes and macrophage are dependent for their production and/or functional activation in vitro on the presence of a family of glycoproteins. They are generally called colony-stimulating factors (CSFs) because of their capacity to stimulate colony formation in semi-solid cultures, and are currently classified into four distinct subtypes, that is, Multi-CSF, GM-CSF, G-CSF and M-CSF, according to the cell type of colonies formed under their stimulation or their target cell specificity. All of the murine and human CSF subtypes and the genes for them have become available in a purified form and in a large scale, and now allow us to investigate their interactions, the mechanisms for their actions, the cell-cell interactions leading to their production and secretion, and their actions in vivo. Furthermore, the preclinical and/or clinical studies which were carried out using the purified CSFs strongly indicate that human CSFs will be effective strategies for preventing and treating opportunistic bacterial and fungal infection as a major cause of death in granulocytopenic patients. (author)

Audio-tactile stimulation: A tool to improve health and well-being?

NARCIS (Netherlands)

Dijk, E.O.; Nijholt, A.; Erp, J.B.F. van; Wolferen, G. van; Kuyper, E.

2013-01-01

Stimulation of the tactile sense or the hearing sense can be used to improve a person's health and well-being. For example, to make someone relax, feel better or sleep better. In this position paper, we present the concept of auditory-tactile stimulation for health and well-being. Through carefully

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

Science.gov (United States)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

Improving Sensorimotor Function Using Stochastic Vestibular Stimulation

Science.gov (United States)

Galvan, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Mulavara, A. P.; Oman, C. M.

2014-01-01

Astronauts experience sensorimotor changes during spaceflight, particularly during G-transition phases. Post flight sensorimotor changes may include postural and gait instability, spatial disorientation, and visual performance decrements, all of which can degrade operational capabilities of the astronauts and endanger the crew. Crewmember safety would be improved if these detrimental effects of spaceflight could be mitigated by a sensorimotor countermeasure and even further if adaptation to baseline could be facilitated. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor performance through stochastic resonance (SR). The SR phenomenon occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. Two studies have been initiated to investigate the beneficial effects and potential practical usage of SVS. In both studies, electrical vestibular stimulation is applied via electrodes on the mastoid processes using a constant current stimulator. The first study aims to determine the repeatability of the effect of vestibular stimulation on sensorimotor performance and perception in order to better understand the practical use of SVS. The beneficial effect of low levels of SVS on balance performance has been shown in the past. This research uses the same balance task repeated multiple times within a day and across days to study the repeatability of the stimulation effects. The balance test consists of 50 sec trials in which the subject stands with his or her feet together, arms crossed, and eyes closed on compliant foam. Varying levels of SVS, ranging from 0-700 micro A, are applied across different trials. The subject-specific optimal SVS level is that which results in the best balance performance as measured by inertial

Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

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Huston, Marshall W; Riegman, Adriaan R A; Yadak, Rana; van Helsdingen, Yvette; de Boer, Helen; van Til, Niek P; Wagemaker, Gerard

2014-10-01

Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning.

Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor

OpenAIRE

Hata, Yasuaki; Clermont, Allen Charles; Yamauchi, Teruaki; Pierce, Eric Adam; Suzuma, Izumi; Kagokawa, Hiroyuki; Yoshikawa, Hiroshi; Robinson, Gregory S.; Ishibashi, Tatsuro; Hashimoto, Toshihiko; Umeda, Fumio; Bursell, Sven E.; Aiello, Lloyd Paul

2000-01-01

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericy...

Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte-colony stimulating factor.

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Duffy, A; Dow, S; Ogilvie, G; Rao, S; Hackett, T

2010-08-01

Previously, dogs with canine parvovirus-induced neutropenia have not responded to treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF). However, recombinant canine G-CSF (rcG-CSF) has not been previously evaluated for treatment of parvovirus-induced neutropenia in dogs. We assessed the effectiveness of rcG-CSF in dogs with parvovirus-induced neutropenia with a prospective, open-label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG-CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG-CSF. We found that mean WBC and neutrophil counts were significantly higher (P parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

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Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving patient knowledge about sacral nerve stimulation using a patient based educational video.

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Jeppson, Peter Clegg; Clark, Melissa A; Hampton, Brittany Star; Raker, Christina A; Sung, Vivian W

2013-10-01

We developed a patient based educational video to address the information needs of women considering sacral nerve stimulation for overactive bladder. Five semistructured focus groups were used to identify patient knowledge gaps, information needs, patient acceptable terminology and video content preferences for a patient based sacral nerve stimulation educational video. Each session was transcribed, independently coded by 2 coders and examined using an iterative method. A 16-minute educational video was created to address previously identified knowledge gaps and information needs using patient footage, 3-dimensional animation and peer reviewed literature. We developed a questionnaire to evaluate participant sacral nerve stimulation knowledge and therapy attitudes. We then performed a randomized trial to assess the effect of the educational video vs the manufacturer video on patient knowledge and attitudes using our questionnaire. We identified 10 patient important domains, including 1) anatomy, 2) expectations, 3) sacral nerve stimulation device efficacy, 4) surgical procedure, 5) surgical/device complications, 6) post-procedure recovery, 7) sacral nerve stimulation side effects, 8) postoperative restrictions, 9) device maintenance and 10) general sacral nerve stimulation information. A total of 40 women with overactive bladder were randomized to watch the educational (20) or manufacturer (20) video. Knowledge scores improved in each group but the educational video group had a greater score improvement (76.6 vs 24.2 points, p <0.0001). Women who watched the educational video reported more favorable attitudes and expectations about sacral nerve stimulation therapy. Women with overactive bladder considering sacral nerve stimulation therapy have specific information needs. The video that we developed to address these needs was associated with improved short-term patient knowledge. Copyright © 2013 American Urological Association Education and Research, Inc

Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

Science.gov (United States)

Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

2018-04-01

See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving

Sensory-parietal cortical stimulation improves motor recovery in severe capsular infarct.

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Kim, Ra Gyung; Cho, Jongwook; Ree, Jinkyue; Kim, Hyung-Sun; Rosa-Neto, Pedro; Kim, Jin-Myung; Lee, Min-Cheol; Kim, Hyoung-Ihl

2016-12-01

The prevalence of subcortical white matter strokes in elderly patients is on the rise, but these patients show mixed responses to conventional rehabilitative interventions. To examine whether cortical electrical stimulation can promote motor recovery after white matter stroke, we delivered stimulation to a small or wide region of sensory-parietal cortex for two weeks in a rodent model of circumscribed subcortical capsular infarct. The sham-operated group (SOG) showed persistent and severe motor impairments together with decreased activation in bilateral sensorimotor cortices and striatum. In contrast, sensory-parietal cortex stimulation significantly improved motor recovery: final recovery levels were 72.9% of prelesion levels in the wide stimulation group (WSG) and 37% of prelesion levels in the small stimulation group (SSG). The microPET imaging showed reversal of cortical diaschisis in both groups: in both hemispheres for the WSG, and in the hemisphere ipsilateral to stimulation in the SSG. In addition, we observed activation of the corpus callosum and subcortical corticostriatal structures after stimulation. The results from the c-Fos mapping study were grossly consistent with the microPET imaging. Sensory-parietal cortex stimulation may therefore be a useful strategy for overcoming the limits of rehabilitative training in patients with severe forms of subcortical capsular infarct. © The Author(s) 2015.

Population health management guiding principles to stimulate collaboration and improve pharmaceutical care.

Science.gov (United States)

Steenkamer, Betty; Baan, Caroline; Putters, Kim; van Oers, Hans; Drewes, Hanneke

2018-04-09

Purpose A range of strategies to improve pharmaceutical care has been implemented by population health management (PHM) initiatives. However, which strategies generate the desired outcomes is largely unknown. The purpose of this paper is to identify guiding principles underlying collaborative strategies to improve pharmaceutical care and the contextual factors and mechanisms through which these principles operate. Design/methodology/approach The evaluation was informed by a realist methodology examining the links between PHM strategies, their outcomes and the contexts and mechanisms by which these strategies operate. Guiding principles were identified by grouping context-specific strategies with specific outcomes. Findings In total, ten guiding principles were identified: create agreement and commitment based on a long-term vision; foster cooperation and representation at the board level; use layered governance structures; create awareness at all levels; enable interpersonal links at all levels; create learning environments; organize shared responsibility; adjust financial strategies to market contexts; organize mutual gains; and align regional agreements with national policies and regulations. Contextual factors such as shared savings influenced the effectiveness of the guiding principles. Mechanisms by which these guiding principles operate were, for instance, fostering trust and creating a shared sense of the problem. Practical implications The guiding principles highlight how collaboration can be stimulated to improve pharmaceutical care while taking into account local constraints and possibilities. The interdependency of these principles necessitates effectuating them together in order to realize the best possible improvements and outcomes. Originality/value This is the first study using a realist approach to understand the guiding principles underlying collaboration to improve pharmaceutical care.

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

DEFF Research Database (Denmark)

Ripa, RS; Jorgensen, E; Wang, Y

2006-01-01

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group...

Improved reading measures in adults with dyslexia following transcranial direct current stimulation treatment.

Science.gov (United States)

Heth, Inbahl; Lavidor, Michal

2015-04-01

To better understand the contribution of the dorsal system to word reading, we explored transcranial direct current stimulation (tDCS) effects when adults with developmental dyslexia received active stimulation over the visual extrastriate area MT/V5, which is dominated by magnocellular input. Stimulation was administered in 5 sessions spread over two weeks, and reading speed and accuracy as well as reading fluency were assessed before, immediately after, and a week after the end of the treatment. A control group of adults with developmental dyslexia matched for age, gender, reading level, vocabulary and block-design WAIS-III sub-tests and reading level was exposed to the same protocol but with sham stimulation. The results revealed that active, but not sham stimulation, significantly improved reading speed and fluency. This finding suggests that the dorsal stream may play a role in efficient retrieval from the orthographic input lexicon in the lexical route. It also underscores the potential of tDCS as an intervention tool for improving reading speed, at least in adults with developmental dyslexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

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Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

2014-09-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. © The Author(s) 2014.

Improving the luteal phase after ovarian stimulation

DEFF Research Database (Denmark)

Andersen, Claus Yding; Vilbour Andersen, K

2014-01-01

The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final...... follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using...

Granulocyte colony-stimulating factor induces in vitro lymphangiogenesis

International Nuclear Information System (INIS)

Lee, Ae Sin; Kim, Dal; Wagle, Susbin Raj; Lee, Jung Eun; Jung, Yu Jin; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

2013-01-01

Highlights: •G-CSF induces tube formation, migration and proliferation of lymphatic cells. •G-CSF increases phosphorylation of MAPK and Akt in lymphatic endothelial cells. •MAPK and Akt pathways are linked to G-CSF-induced in vitro lymphangiogenesis. •G-CSF increases sprouting of a lymphatic ring. •G-CSF produces peritoneal lymphangiogenesis. -- Abstract: Granulocyte-colony stimulating factor (G-CSF) is reported to induce differentiation in cells of the monocyte lineage and angiogenesis in vascular endothelial cells, but its effects on lymphangiogenesis is uncertain. Here we examined the effects and the mechanisms of G-CSF-induced lymphangiogenesis using human lymphatic endothelial cells (hLECs). Our results showed that G-CSF induced capillary-like tube formation, migration and proliferation of hLECs in a dose- and time-dependent manner and enhanced sprouting of thoracic duct. G-CSF increased phosphorylation of Akt and ERK1/2 in hLECs. Supporting the observations, specific inhibitors of phosphatidylinositol 3′-kinase and MAPK suppressed the G-CSF-induced in vitro lymphangiogenesis and sprouting. Intraperitoneal administration of G-CSF to mice also stimulated peritoneal lymphangiogenesis. These findings suggest that G-CSF is a lymphangiogenic factor

A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

Directory of Open Access Journals (Sweden)

Deanna M Schmitt

Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

Explanation of application standards of hematopoietic stimulating factors in the treatment of acute radiation sickness

International Nuclear Information System (INIS)

Xing Zhiwei; Jiang Enhai; Wang Guilin; Luo Qingliang

2012-01-01

Occupational standard of the Ministry of health-Application Standards of Hematopoietic Stimulating Factors in the Treatment of Acute Radiation Sickness has been completed as a draft standard. Based on the wide study and analysis of related animal experimental literature about hematopoietic stimulating factor in the treatment of acute radiation sickness and domestic and foreign clinical reports about application of hematopoietic stimulating factor in radiation accidents in the past decade, the standard was enacted according to the suggestions of International Atomic Energy Agency and the United States Strategic National Stockpile Radiation Working Group and European countries about the application of hematopoietic stimulating factor. It is mainly used for nuclear accident emergency and the treatment of the bone marrow form of acute radiation sickness caused by radiation accidents. It also applies to other hematopoietic failure diseases. In order to implement this standard correctly, the relevant contents of the standard were interpreted in this article. (authors)

Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

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Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

2016-09-15

We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

Is transcranial direct current stimulation a potential method for improving response inhibition?

Science.gov (United States)

Kwon, Yong Hyun; Kwon, Jung Won

2013-04-15

Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area (pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase). Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer.

Science.gov (United States)

Huang, Yan-Shan; Wen, Xiao-Fang; Wu, Yi-Liang; Wang, Ye-Fei; Fan, Min; Yang, Zhi-Yu; Liu, Wei; Zhou, Lin-Fu

2010-03-01

The plasma half-life of therapeutic proteins is a critical factor in many clinical applications. Therefore, new strategies to prolong plasma half-life of long-acting peptides and protein drugs are in high demand. Here, we designed an artificial gelatin-like protein (GLK) and fused this hydrophilic GLK polymer to granulocyte-colony-stimulating factor (G-CSF) to generate a chimeric GLK/G-CSF fusion protein. The genetically engineered recombinant GLK/G-CSF (rGLK/G-CSF) fusion protein was purified from Pichia pastoris. In vitro studies demonstrated that rGLK/G-CSF possessed an enlarged hydrodynamic radius, improved thermal stability and retained full bioactivity compared to unfused G-CSF. Following a single subcutaneous administration to rats, the rGLK/G-CSF fusion protein displayed a slower plasma clearance rate and stimulated greater and longer lasting increases in circulating white blood cells than G-CSF. Our findings indicate that fusion with this artificial, hydrophilic, GLK polymer provides many advantages in the construction of a potent hematopoietic factor with extended plasma half-life. This approach could be easily applied to other therapeutic proteins and have important clinical applications. (c) 2009 Elsevier B.V. All rights reserved.

Culicoides antigen extract stimulates equine blood mononuclear (BMN) cell proliferation and the release of eosinophil adherence-inducing factor(s).

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Mckelvie, J; Foster, A P; Hamblin, A S; Cunningham, F M

2001-04-01

Intradermal injection of a Culicoides antigen extract (CAgX) induces T lymphocyte and eosinophil accumulation in the skin of horses with sweet itch. Blood mononuclear (BMN) cells from normal ponies proliferate when stimulated by mitogen (phytohaemagglutinin, PHA) or antigen (tetanus toxoid, TT) and, as shown here, release soluble factor(s) that induce eosinophil adherence. CAgX also caused concentration dependent proliferation of BMN cells from sweet itch and normal ponies [stimulation index: 29 (13) and 17 (7) for BMN cells from sweet itch and normal ponies, respectively during the active phase of disease; 4 microg protein ml(-1)CAgX; 168 h]. A heat labile factor(s) which caused eosinophil adherence was also released [sweet itch ponies: 6.0 (1.6) per cent adherence versus 1.3 (0.4) per cent; normal ponies: 6.6 (0.5) per cent adherence versus 0.9 (0.1) per cent for supernatants from CAgX (4 microg protein ml(-1); 48 hours) stimulated versus unstimulated BMN cells, respectively]. These results suggest that soluble proteins released from T lymphocytes could affect eosinophil function in the lesional skin of sweet itch horses. Copyright 2001 Harcourt Publishers Ltd.

Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

Science.gov (United States)

Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

2003-03-14

Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

Improving ideomotor limb apraxia by electrical stimulation of the left posterior parietal cortex.

Science.gov (United States)

Bolognini, Nadia; Convento, Silvia; Banco, Elisabetta; Mattioli, Flavia; Tesio, Luigi; Vallar, Giuseppe

2015-02-01

Limb apraxia, a deficit of planning voluntary gestures, is most frequently caused by damage to the left hemisphere, where, according to an influential neurofunctional model, gestures are planned, before being executed through the motor cortex of the hemisphere contralateral to the acting hand. We used anodal transcranial direct current stimulation delivered to the left posterior parietal cortex (PPC), the right motor cortex (M1), and a sham stimulation condition, to modulate the ability of six left-brain-damaged patients with ideomotor apraxia, and six healthy control subjects, to imitate hand gestures, and to perform skilled hand movements using the left hand. Transcranial direct current stimulation delivered to the left PPC reduced the time required to perform skilled movements, and planning, but not execution, times in imitating gestures, in both patients and controls. In patients, the amount of decrease of planning times brought about by left PPC transcranial direct current stimulation was influenced by the size of the parietal lobe damage, with a larger parietal damage being associated with a smaller improvement. Of interest from a clinical perspective, left PPC stimulation also ameliorated accuracy in imitating hand gestures in patients. Instead, transcranial direct current stimulation to the right M1 diminished execution, but not planning, times in both patients and healthy controls. In conclusion, by using a transcranial stimulation approach, we temporarily improved ideomotor apraxia in the left hand of left-brain-damaged patients, showing a role of the left PPC in planning gestures. This evidence opens up novel perspectives for the use of transcranial direct current stimulation in the rehabilitation of limb apraxia. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

Science.gov (United States)

Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

1999-05-01

Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

Electrical field stimulation promotes anastomotic healing in poorly perfused rat colon.

LENUS (Irish Health Repository)

Kennelly, Rory

2011-03-01

Hypoperfusion of the bowel is a risk factor for anastomotic failure. Electrical field stimulation has been shown to improve repair in ischemic tissue, but its influence in hypoperfused colon has not been investigated. The hypothesis of this experimental animal study was that electrical field stimulation improves anastomotic healing in ischemic bowel.

Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

Science.gov (United States)

Rom, Edith

2013-12-01

Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor

International Nuclear Information System (INIS)

Sherr, C.J.; Rettenmier, C.W.; Roussel, M.F.

1988-01-01

The macrophage colony-stimulating factor, CSF-1, or M-CSF, is one of a family of hematopoietic growth factors that stimulates the proliferation of monocytes, macrophages, and their committed bone marrow progenitors. Unlike pluripotent hemopoietins such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3 or multi-CSF), which affect the growth of myeloid cells of several different hematopoietic lineages, CSF-1 acts only on cells of the mononuclear phagocyte series to stimulate their growth and enhance their survival. Retroviral transduction of the feline c-fms gene in the Susan McDonough and Hardy Zuckerman-5 (HZ-5) strains of feline sarcoma virus (FeSV) led to genetic alterations that endowed the recombined viral oncogene (v-fms) with the ability to transform cells in culture morphologically and to induce firbrosarcomas and hematopoietic neoplasms in susceptible animals. The v-fms oncogene product differs from the normal CSF-1 receptor in certain of its cardinal biochemical properties, most notably in exhibiting constitutively high basal levels of tyrosine kinase activity in the absence of its ligand. Comparative studies of the c-fms and v-fms genes coupled with analyses of engineered mutants and receptor chimeras have begun to pinpoint pertinent genetic alterations in the normal receptor gene that unmask its latent oncogenic potential. In addition, the availability of biologically active c-fms, v-fms, and CSF-1 cDNAs has allowed these genes to be mobilized and expressed in naive cells, thereby facilitating assays for receptor coupling with downstream components of the mitogenic pathway in diverse cell types

Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.

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El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun

2018-01-17

Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.

Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

Science.gov (United States)

Temple, D. R.; De Dios, Y. E.; Layne, C. S.; Bloomberg, J. J.; Mulavara, A. P.

2016-01-01

Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task.

Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

International Nuclear Information System (INIS)

Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

1990-01-01

A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

International Nuclear Information System (INIS)

Ahren, B.

1987-01-01

It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

Directory of Open Access Journals (Sweden)

Nahyun Choi

2018-02-01

Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

Science.gov (United States)

Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

2018-01-01

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.

Science.gov (United States)

Kageyama, R; Merlino, G T; Pastan, I

1989-09-15

Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

Science.gov (United States)

Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

2016-01-01

Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

Repetitive magnetic stimulation improves retinal function in a rat model of retinal dystrophy

Science.gov (United States)

Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael

2014-02-01

Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.

Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation

International Nuclear Information System (INIS)

Blanc-Brude, Olivier P.; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

2005-01-01

Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR 1 ). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR 1 -deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR 1 -specific agonists and inhibitors were used to demonstrate that PAR 1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR 1 and not PAR 2 . These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis

Quadruple Cone Coil with improved focality than Figure-8 coil in Transcranial Magnetic Stimulation

Science.gov (United States)

Rastogi, Priyam; Lee, Erik G.; Hadimani, Ravi L.; Jiles, David C.

Transcranial Magnetic Stimulation (TMS) is a non-invasive therapy which uses a time varying magnetic field to induce an electric field in the brain and to cause neuron depolarization. Magnetic coils play an important role in the TMS therapy since their coil geometry determines the focality and penetration's depth of the induced electric field in the brain. Quadruple Cone Coil (QCC) is a novel coil with an improved focality when compared to commercial Figure-8 coil. The results of this newly designed QCC coil are compared with the Figure-8 coil at two different positions of the head - vertex and dorsolateral prefrontal cortex, over the 50 anatomically realistic MRI derived head models. Parameters such as volume of stimulation, maximum electric, area of stimulation and location of maximum electric field are determined with the help of computer modelling of both coils. There is a decrease in volume of brain stimulated by 11.6 % and a modest improvement of 8 % in the location of maximum electric field due to QCC in comparison to the Figure-8 coil. The Carver Charitable Trust and The Galloway Foundation.

Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.

Science.gov (United States)

Elzinga, Kate; Tyreman, Neil; Ladak, Adil; Savaryn, Bohdan; Olson, Jaret; Gordon, Tessa

2015-07-01

Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Combining physical training with transcranial direct current stimulation to improve gait in Parkinson's disease: a pilot randomized controlled study.

Science.gov (United States)

Kaski, D; Dominguez, R O; Allum, J H; Islam, A F; Bronstein, A M

2014-11-01

To improve gait and balance in patients with Parkinson's disease by combining anodal transcranial direct current stimulation with physical training. In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real). Hospital Srio Libanes, Buenos Aires, Argentina. Sixteen community-dwelling patients with Parkinson's disease. Transcranial direct current stimulation with and without concomitant physical training. Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome). Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p stimulation-related improvements were seen in patients with more advanced disease. Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson's disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial. © The Author(s) 2014.

From amusic to musical?--Improving pitch memory in congenital amusia with transcranial alternating current stimulation.

Science.gov (United States)

Schaal, Nora K; Pfeifer, Jasmin; Krause, Vanessa; Pollok, Bettina

2015-11-01

Brain imaging studies highlighted structural differences in congenital amusia, a life-long perceptual disorder that is associated with pitch perception and pitch memory deficits. A functional anomaly characterized by decreased low gamma oscillations (30-40 Hz range) in the right dorsolateral prefrontal cortex (DLPFC) during pitch memory has been revealed recently. Thus, the present study investigates whether applying transcranial alternating current stimulation (tACS) at 35 Hz to the right DLPFC would improve pitch memory. Nine amusics took part in two tACS sessions (either 35 Hz or 90 Hz) and completed a pitch and visual memory task before and during stimulation. 35 Hz stimulation facilitated pitch memory significantly. No modulation effects were found with 90 Hz stimulation or on the visual task. While amusics showed a selective impairment of pitch memory before stimulation, the performance during 35 Hz stimulation was not significantly different to healthy controls anymore. Taken together, the study shows that modulating the right DLPFC with 35 Hz tACS in congenital amusia selectively improves pitch memory performance supporting the hypothesis that decreased gamma oscillations within the DLPFC are causally involved in disturbed pitch memory and highlight the potential use of tACS to interact with cognitive processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors.

Science.gov (United States)

Mies, Anna; Platzbecker, Uwe

2017-07-01

Patients with lower-risk myelodysplastic syndromes (MDS) are mainly affected by chronic anemia and fatigue. Treatment strategies aim to improve anemia and quality of life, as well as iron overload due to red blood cell transfusion support. To promote proliferation and differentiation of erythropoiesis, erythropoiesis-stimulating agents (ESAs) such as erythropoietin (EPO) and mimetics are applied as first-line therapy in a large fraction of lower-risk MDS patients. In general, ESAs yield favorable responses in about half of the patients, although responses are often short-lived. In fact, many ESA-refractory patients harbor defects in late-stage erythropoiesis downstream of EPO action. Novel transforming growth factor (TGF)-β superfamily inhibitors sotatercept and luspatercept represent a promising approach to alleviate anemia by stimulating erythroid differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved Pain Relief With Burst Spinal Cord Stimulation for Two Weeks in Patients Using Tonic Stimulation: Results From a Small Clinical Study.

Science.gov (United States)

Courtney, Peter; Espinet, Anthony; Mitchell, Bruce; Russo, Marc; Muir, Andrew; Verrills, Paul; Davis, Kristina

2015-07-01

Conventional spinal cord stimulation (SCS) delivers a tonic waveform with consistent stream of pulses; burst delivers groups of pulses separated by short pulse-free periods. The current study compared the short-term safety and efficacy of burst with tonic stimulation in subjects already receiving SCS. At 4 IRB-approved sites, 22 subjects previously implanted with an SCS device for intractable, chronic pain gave informed consent and received burst stimulation for 14 days. Subjects reported average daily Visual Analog Scale (VAS) for overall, trunk, and limb pain using tonic stimulation and after 7 and 14 days of burst stimulation. Thoughts about pain were assessed using the Pain Catastrophizing Scale. Areas of paresthesia were assessed during tonic and burst stimulation using body maps. Assessment of patient satisfaction and preferred stimulation occurred after 14 days of burst. Average daily overall VAS reduced 46% from a mean of 53.5 (±20.2) mm during tonic SCS to 28.5 (±18.1) mm during burst (p pain relief was the most common reason cited for preference. A majority of subjects reported improved pain relief using burst compared with tonic stimulation. Most subjects experienced less paresthesia during burst and preferred burst citing better pain relief. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

Science.gov (United States)

Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

2003-08-01

Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.

Science.gov (United States)

Price, B D; Morris, J D; Hall, A

1989-01-01

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase. PMID:2690829

Neurologic Complications of Psychomotor Stimulant Abuse.

Science.gov (United States)

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. © 2015 Elsevier Inc. All rights reserved.

Which factors obstruct or stimulate teacher educators to use ICT innovatively?

NARCIS (Netherlands)

Drent, Marjolein; Meelissen, Martina R.M.

2007-01-01

This article discusses the factors which stimulate or limit the innovative use of ICT by teacher educators in the Netherlands. Innovative use of ICT is defined as the use of ICT applications that support the educational objectives based on the needs of the current knowledge society. Explorative path

Transcranial infrared laser stimulation improves rule-based, but not information-integration, category learning in humans.

Science.gov (United States)

Blanco, Nathaniel J; Saucedo, Celeste L; Gonzalez-Lima, F

2017-03-01

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation on category learning tasks. Transcranial infrared laser stimulation is a new non-invasive form of brain stimulation that shows promise for wide-ranging experimental and neuropsychological applications. It involves using infrared laser to enhance cerebral oxygenation and energy metabolism through upregulation of the respiratory enzyme cytochrome oxidase, the primary infrared photon acceptor in cells. Previous research found that transcranial infrared laser stimulation aimed at the prefrontal cortex can improve sustained attention, short-term memory, and executive function. In this study, we directly investigated the influence of transcranial infrared laser stimulation on two neurobiologically dissociable systems of category learning: a prefrontal cortex mediated reflective system that learns categories using explicit rules, and a striatally mediated reflexive learning system that forms gradual stimulus-response associations. Participants (n=118) received either active infrared laser to the lateral prefrontal cortex or sham (placebo) stimulation, and then learned one of two category structures-a rule-based structure optimally learned by the reflective system, or an information-integration structure optimally learned by the reflexive system. We found that prefrontal rule-based learning was substantially improved following transcranial infrared laser stimulation as compared to placebo (treatment X block interaction: F(1, 298)=5.117, p=0.024), while information-integration learning did not show significant group differences (treatment X block interaction: F(1, 288)=1.633, p=0.202). These results highlight the exciting potential of transcranial infrared laser stimulation for cognitive enhancement and provide insight into the neurobiological underpinnings of category learning. Copyright © 2017 Elsevier Inc. All rights reserved.

STIMULATION OF DEFENSE FACTORS FOR OYSTERS DEPLOYED TO CONTAMINATED SITES IN PENSACOLA BAY, FLORIDA

Science.gov (United States)

A positive association between chemical contaminants and defense factors has been established for eastern oysters (Crassostrea virginica) from Florida, but it is unknown whether such factors can be stimulated through short-term exposure to contaminants in the field. Hatchery oyst...

Improved proper name recall in aging after electrical stimulation of the anterior temporal lobes

Directory of Open Access Journals (Sweden)

Lars A Ross

2011-10-01

Full Text Available Evidence from neuroimaging and neuropsychology suggests that portions of the anterior temporal lobes play a critical role in proper name retrieval. We previously found that anodal transcranial direct current stimulation (tDCS to the anterior temporal lobes improved retrieval of proper names in young adult. Here we extend that finding to older adults who tend to experience greater proper-naming deficits than young adults. The task was to look at pictures of famous faces or landmarks and verbally recall the associated proper name. Our results show a numerical improvement in face naming after left or right anterior temporal lobe stimulation, but a statistically significant effect only after left-lateralized stimulation. The magnitude of the enhancing effect was similar in older and younger adults but the lateralization of the effect differed depending on age. These results provide evidence that tDCS may be a useful tool for the neurorehabilitation of cognitive function in healthy and pathological cognitive decline.

Seven-star needle stimulation improves language and social interaction of children with autistic spectrum disorders.

Science.gov (United States)

Chan, Agnes S; Cheung, Mei-Chun; Sze, Sophia L; Leung, Winnie W

2009-01-01

This is a randomized controlled trial that aimed to evaluate the effect of the Seven-star Needle Stimulation treatment on children with Autistic Spectrum Disorders (ASD). Thirty-two children with ASD were assigned randomly into the treatment and control groups. Children in the treatment group underwent 30 sessions of stimulation over 6 weeks, while children in the control group were on a waiting list and did not receive treatment during this period of time. Intervention consisted of a treatment regime comprising of 30 sessions of Seven-star Needle Stimulation, delivered over 6 weeks. Each session lasted 5 to 10 min, children in the treatment group were stimulated at the front and back sides of their body and the head by using Seven-star Needles. The change in the children's behavior was evaluated using parents' report and neurophysiological changes were measured by quantitative EEG (qEEG). Results showed that the treatment group demonstrated significant improvement in language and social interaction, but not in stereotyped behavior or motor function, compared to the control group. qEEG spectral amplitudes in the treatment, but not in the control group, were also reduced significantly. The results suggested that Seven-star Needle Stimulation might be an effective intervention to improve language and social functioning of children with ASD.

Can stimulating massage improve joint repositioning error in patients with knee osteoarthritis?

DEFF Research Database (Denmark)

Lund, Hans; Henriksen, Marius; Bartels, Else M

2009-01-01

PURPOSE: The purpose of this study was to investigate the effect of massage applied to the thigh muscles on joint repositioning error (JRE) in patients suffering from osteoarthritis (OA).We hypothesized that stimulating massage of the muscles around an osteoarthritic knee joint, could improve the...

Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

Science.gov (United States)

Manenti, Rosa; Brambilla, Michela; Benussi, Alberto; Rosini, Sandra; Cobelli, Chiara; Ferrari, Clarissa; Petesi, Michela; Orizio, Italo; Padovani, Alessandro; Borroni, Barbara; Cotelli, Maria

2016-05-01

Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity

Science.gov (United States)

Ekelem, Andrew; Goldfarb, Michael

2018-01-01

Spasticity is a common comorbidity associated with spinal cord injury (SCI). Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated) to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four) walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236%) and peak knee flexion by 14.4° (56%). Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15%) at the hip motors and 734 mA (38%) at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the common

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity.

Science.gov (United States)

Ekelem, Andrew; Goldfarb, Michael

2018-01-01

Spasticity is a common comorbidity associated with spinal cord injury (SCI). Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated) to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four) walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236%) and peak knee flexion by 14.4° (56%). Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15%) at the hip motors and 734 mA (38%) at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the common

Supplemental Stimulation Improves Swing Phase Kinematics During Exoskeleton Assisted Gait of SCI Subjects With Severe Muscle Spasticity

Directory of Open Access Journals (Sweden)

Andrew Ekelem

2018-06-01

Full Text Available Spasticity is a common comorbidity associated with spinal cord injury (SCI. Robotic exoskeletons have recently emerged to facilitate legged mobility in people with motor complete SCI. Involuntary muscle activity attributed to spasticity, however, can prevent such individuals from using an exoskeleton. Specifically, although most exoskeleton technologies can accommodate low to moderate spasticity, the presence of moderate to severe spasticity can significantly impair gait kinematics when using an exoskeleton. In an effort to potentially enable individuals with moderate to severe spasticity to use exoskeletons more effectively, this study investigates the use of common peroneal stimulation in conjunction with exoskeleton gait assistance. The electrical stimulation is timed with the exoskeleton swing phase, and is intended to acutely suppress extensor spasticity through recruitment of the flexion withdrawal reflex (i.e., while the stimulation is activated to enable improved exoskeletal walking. In order to examine the potential efficacy of this approach, two SCI subjects with severe extensor spasticity (i.e., modified Ashworth ratings of three to four walked in an exoskeleton with and without supplemental stimulation while knee and hip motion was measured during swing phase. Stimulation was alternated on and off every ten steps to eliminate transient therapeutic effects, enabling the acute effects of stimulation to be isolated. These experiments indicated that common peroneal stimulation on average increased peak hip flexion during the swing phase of walking by 21.1° (236% and peak knee flexion by 14.4° (56%. Additionally, use of the stimulation decreased the swing phase RMS motor current by 228 mA (15% at the hip motors and 734 mA (38% at the knee motors, indicating improved kinematics were achieved with reduced effort from the exoskeleton. Walking with the exoskeleton did not have a significant effect on modified Ashworth scores, indicating the

Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

International Nuclear Information System (INIS)

Ellsworth, J.L.; Brown, C.; Cooper, A.D.

1988-01-01

The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

Production of humoral factors that stimulate spleen colony-forming units in mice irradiated with moderate doses of X rays

International Nuclear Information System (INIS)

Grande, T.; Gonzalez, J.; Tejero, C.; Maganto, G.; Bueren, J.A.

1990-01-01

The production of humoral factors that stimulate spleen colony-forming units (CFU-S) has been studied in irradiated mice using an in vivo diffusion chamber assay. The experiments show that a significant release of factors that stimulate CFU-S takes place in the first few days after irradiation with moderate doses of 1.5 or 5 Gy. In contrast, the release of significant amounts of these humoral factors was not seen in animals irradiated with either low (0.75 Gy) or high (10 Gy) doses of X rays. The correlation observed between the production of factors that stimulate the CFU-S and the hemopoietic regeneration kinetics of the irradiated mice suggests that these factors represent part of the physiological regulators controlling the proliferation of CFU-S

Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson's disease.

Science.gov (United States)

Su, Xin-Ling; Luo, Xiao-Guang; Lv, Hong; Wang, Jun; Ren, Yan; He, Zhi-Yi

2017-01-01

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies, however there were different conclusions about that through long- and short-term follow-ups. We aimed to investigate the factors which influence the predictive value of levodopa responsiveness, and discover more predictive factors of surgical outcomes. Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up. Clinical evaluations were performed 1 week before and 3 months after surgery. STN-DBS significantly improved motor function of PD patients after 3 months; preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function; gender, disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement; the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement. The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients, patients with shorter disease duration or shorter motor fluctuations; PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms, especially in their later disease stage.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

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Kimberly B. Hoang

2017-10-01

Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

Curcumin attenuates lipolysis stimulated by tumor necrosis factor-α or isoproterenol in 3T3-L1 adipocytes.

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Xie, Xiao-yun; Kong, Po-Ren; Wu, Jin-feng; Li, Ying; Li, Yan-xiang

2012-12-15

Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05). This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity. Copyright © 2012 Elsevier GmbH. All rights reserved.

Granulocyte-Macrophage Colony-Stimulating Factor Amplification of Interleukin-1β and Tumor Necrosis Factor Alpha Production in THP-1 Human Monocytic Cells Stimulated with Lipopolysaccharide of Oral Microorganisms

OpenAIRE

Baqui, A. A. M. A.; Meiller, Timothy F.; Chon, Jennifer J.; Turng, Been-Foo; Falkler, William A.

1998-01-01

Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1β and TNF-α production following GM-CSF suppl...

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

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Michal Hofer

2014-04-01

Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Komůrková, Denisa; Hoferová, Zuzana

2014-01-01

Roč. 19, č. 4 (2014), s. 4770-4778 ISSN 1420-3049 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : granulocyte colony-stimulating factor * radiation accident s * acute radiation syndrome Subject RIV: BO - Biophysics Impact factor: 2.416, year: 2014

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

DEFF Research Database (Denmark)

Ripa, Rasmus Sejersten; Jørgensen, Erik; Wang, Yongzhong

2006-01-01

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy...... hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core...

Tactile-STAR: A Novel Tactile STimulator And Recorder System for Evaluating and Improving Tactile Perception.

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Ballardini, Giulia; Carlini, Giorgio; Giannoni, Psiche; Scheidt, Robert A; Nisky, Ilana; Casadio, Maura

2018-01-01

Many neurological diseases impair the motor and somatosensory systems. While several different technologies are used in clinical practice to assess and improve motor functions, somatosensation is evaluated subjectively with qualitative clinical scales. Treatment of somatosensory deficits has received limited attention. To bridge the gap between the assessment and training of motor vs. somatosensory abilities, we designed, developed, and tested a novel, low-cost, two-component (bimanual) mechatronic system targeting tactile somatosensation: the Tactile-STAR -a tactile stimulator and recorder. The stimulator is an actuated pantograph structure driven by two servomotors, with an end-effector covered by a rubber material that can apply two different types of skin stimulation: brush and stretch. The stimulator has a modular design, and can be used to test the tactile perception in different parts of the body such as the hand, arm, leg, big toe, etc. The recorder is a passive pantograph that can measure hand motion using two potentiometers. The recorder can serve multiple purposes: participants can move its handle to match the direction and amplitude of the tactile stimulator, or they can use it as a master manipulator to control the tactile stimulator as a slave. Our ultimate goal is to assess and affect tactile acuity and somatosensory deficits. To demonstrate the feasibility of our novel system, we tested the Tactile-STAR with 16 healthy individuals and with three stroke survivors using the skin-brush stimulation. We verified that the system enables the mapping of tactile perception on the hand in both populations. We also tested the extent to which 30 min of training in healthy individuals led to an improvement of tactile perception. The results provide a first demonstration of the ability of this new system to characterize tactile perception in healthy individuals, as well as a quantification of the magnitude and pattern of tactile impairment in a small cohort of

Sensory stimulation programme to improve recovery in comatose patients.

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Oh, Hyunsoo; Seo, Whasook

2003-05-01

The purpose of this study was to examine whether positive changes in consciousness level after applying a sensory stimulation programme exceed natural recovery. A single experimental group interrupted time series design was used. Subjects were brain-injured patients who were hospitalized at a university hospital in South Korea. The sensory stimulation programme was composed of auditory, visual, olfactory, gustatory, tactile and physical stimulation. Levels of consciousness were evaluated using the Glasgow Coma Scale. The intervention was carried out twice, first for 4 weeks, then a recession period was allowed for 4 weeks, and immediately after this the second intervention was implemented for 4 weeks. Results showed significant alterations in consciousness levels 2 weeks after starting intervention 1. This effect increased gradually and was maintained for 3-4 weeks. However, consciousness levels began to decrease 2 weeks after terminating intervention 1 and this decrement continued until starting intervention 2. The pattern of improvement of intervention 1 could be represented as a gradual onset and temporary duration model. At the beginning of intervention 2, consciousness levels were maintained at a low level. However, they began to increase again after 2 weeks and this increment continued even after terminating intervention 2. Therefore, the effect of intervention 2 could be represented as a gradual onset and permanent duration model. These results suggest that an intervention programme should be applied for more than 1 month to achieve a permanent effect on consciousness levels and that at least 2 weeks are required for any significant effect.

Transcranial Direct Current Stimulation Does Not Improve Language Outcome in Subacute Poststroke Aphasia.

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Spielmann, Kerstin; van de Sandt-Koenderman, W Mieke E; Heijenbrok-Kal, Majanka H; Ribbers, Gerard M

2018-04-01

The aim of the present study is to investigate the effect of transcranial direct current stimulation on word-finding treatment outcome in subacute poststroke aphasia. In this multi-center, double-blind, randomized controlled trial with 6-month follow-up, we included 58 patients with subacute aphasia (transcranial direct current stimulation (1 mA, 20 minutes; experimental group) or sham transcranial direct current stimulation (control group) over the left inferior frontal gyrus. The primary outcome measure was the Boston Naming Test. Secondary outcome measures included naming performance for trained/untrained picture items and verbal communication. Both the experimental (n=26) and the control group (n=32) improved on the Boston Naming Test over the intervention period and 6-month follow-up; however, there were no significant differences between groups. Also for the secondary outcome measures, no significant differences were found. The results of the present study do not support an effect of transcranial direct current stimulation as an adjuvant treatment in subacute poststroke aphasia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp. Unique identifier: NTR4364. © 2018 American Heart Association, Inc.

[Aural Stimulation with Capsaicin Ointment Improved the Swallowing Function in Patients with Dysphagia: Evaluation by the SMRC Scale].

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Kondo, Eiji; Jinnouchi, Osamu; Ohnishi, Hiroki; Kawata, Ikuji; Takeda, Noriaki

2015-11-01

Cough and swallowing reflexes are important airway-protective mechanisms against aspiration. Angiotensin-converting enzyme (ACE) inhibitors, one of the side effects of which is cough, have been reported to reduce the incidence of aspiration pneumonia in hypertensive patients with stroke. ACE inhibitors have also been reported to improve the swallowing function in post-stroke patients. On the other hand, stimulation of the Arnold nerve, the auricular branch of the vagus, triggers the cough reflex (Arnold's ear-cough reflex). Capsaicin, an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), has been shown to activate the peripheral sensory C-fibers. Stimulation of the sensory branches of the vagus in the laryngotracheal mucosa with capsaicin induces the cough reflex and has been reported to improve the swallowing function in patients with dysphagia. In our previous study, we showed that aural stimulation of the Arnold nerve with 0.025% capsaicin ointment improved the swallowing function, as evaluated by the endoscopic swallowing score, in 26 patients with dysphagia. In the present study, the video images of swallowing recorded in the previous study were re-evaluated using the SMRC scale by an independent otolaryngologist who was blinded to the information about the patients and the endoscopic swallowing score. The SMRC scale is used to evaluate four aspects of the swallowing function: 1) Sensory: the initiation of the swallowing reflex as assessed by the white-out timing; 2) Motion: the ability to hold blue-dyed water in the oral cavity and induce laryngeal elevation; 3) Reflex: glottal closure and the cough reflex induced by touching the epiglottis or arytenoid with the endoscope; 4) Clearance: pharyngeal clearance of the blue-dyed water after swallowing. Accordingly, we demonstrated that a single application of capsaicin ointment to the external auditory canal of patients with dysphagia significantly improved the R, but not the S, M or C scores, and this

Can Transcranial Direct Current Stimulation Improve Cognitive Functioning in Adults with Schizophrenia?

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Schretlen, David J; van Steenburgh, Joseph J; Varvaris, Mark; Vannorsdall, Tracy D; Andrejczuk, Megan A; Gordon, Barry

Cognitive impairment is nearly ubiquitous in schizophrenia. First-degree relatives of persons with schizophrenia often show similar but milder deficits. Current methods for the treatment of schizophrenia are often ineffective in cognitive remediation. Since transcranial direct current stimulation (tDCS) can enhance cognitive functioning in healthy adults, it might provide a viable option to enhance cognition in schizophrenia. We sought to explore whether tDCS can be tolerated by persons with schizophrenia and potentially improve their cognitive functioning. We examined the effects of anodal versus cathodal tDCS on working memory and other cognitive tasks in five outpatients with schizophrenia and six first-degree relatives of persons with schizophrenia. Each participant completed tasks thought to be mediated by the prefrontal cortex during two 30-minute sessions of tDCS to the left and right dorsolateral prefrontal cortex (DLPFC). Anodal stimulation over the left DLPFC improved performance relative to cathodal stimulation on measures of working memory and aspects of verbal fluency relevant to word retrieval. The patient group showed differential changes in novel design production without alteration of overall productivity, suggesting that tDCS might be capable of altering self-monitoring and executive control. All participants tolerated tDCS well. None withdrew from the study or experienced any adverse reaction. We conclude that adults with schizophrenia can tolerate tDCS while engaging in cognitive tasks and that tDCS can alter their performance.

Mechanical stimulation improves tissue-engineered human skeletal muscle

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Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

2002-01-01

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity

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Stephanie eWallner

2015-08-01

Full Text Available Granulocyte-colony stimulating factor (G-CSF is a growth factor that has originally been identified several decades ago as a hematopoietic factor required mainly for the generation of neutrophilic granulocytes, and is in clinical use for that. More recently, it has been discovered that G-CSF also plays a role in the brain as a growth factor for neurons and neural stem cells, and as a factor involved in the plasticity of the vasculature. We review and discuss these dual properties in view of the neuroregenerative potential of this growth factor.

Prefronto-Cerebellar Transcranial Direct Current Stimulation Improves Sleep Quality in Euthymic Bipolar Patients: A Brief Report

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Amedeo Minichino

2014-01-01

Full Text Available Introduction. Sleep problems are common in bipolar disorder (BD and may persist during the euthymic phase of the disease. The aim of the study was to improve sleep quality of euthymic BD patients through the administration of prefronto-cerebellar transcranial direct current stimulation (tDCS. Methods. 25 euthymic outpatients with a diagnosis of BD Type I or II have been enrolled in the study. tDCS montage was as follows: cathode on the right cerebellar cortex and anode over the left dorsolateral prefrontal cortex (DLPFC; the intensity of stimulation was set at 2 mA and delivered for 20 min/die for 3 consecutive weeks. The Pittsburgh Sleep Quality Index (PSQI was used to assess sleep quality at baseline and after the tDCS treatment. Results. PSQI total score and all PSQI subdomains, with the exception of “sleep medication,” significantly improved after treatment. Discussion. This is the first study where a positive effect of tDCS on the quality of sleep in euthymic BD patients has been reported. As both prefrontal cortex and cerebellum may play a role in regulating sleep processes, concomitant cathodal (inhibitory stimulation of cerebellum and anodal (excitatory stimulation of DLPFC may have the potential to modulate prefrontal-thalamic-cerebellar circuits leading to improvements of sleep quality.

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation.

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Vuksanović, Jasmina; Jelić, Milan B; Milanović, Sladjan D; Kačar, Katarina; Konstantinović, Ljubica; Filipović, Saša R

2015-01-01

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca's area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area's inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass

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Lara Maris Nápolis

2011-01-01

Full Text Available BACKGROUND: High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients. However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. OBJECTIVE: To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study. METHODS: Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim were assessed. RESULTS: Thirteen (46.4% patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation. Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6% non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01. Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05. CONCLUSIONS: We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD.

Granulocyte colony-stimulating factor and leukemogenesis

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Lorena Lobo de Figueiredo

2004-01-01

Full Text Available THE granulocyte colony-stimulating factor (G-CSF plays an important role in normal granulopoiesis. Its functions are mediated by specific receptors on the surface of responsive cells and, upon ligand binding, several cytoplasmic tyrosine kinases are activated. The cytoplasmic region proximal to the membrane of the G-CSF receptor (G-CSF-R transduces proliferative and survival signals, whereas the distal carboxy-terminal region transduces maturation signals and suppresses the receptor's proliferative signals. Mutations in the G-CSF-R gene resulting in truncation of the carboxy-terminal region have been detected in a subset of patients with severe congenital neutropenia who developed acute myelogenous leukemia (AML. In addition, the AML1-ETO fusion protein, expressed in leukemic cells harboring the t(8;21, disrupt the physiological function of transcription factors such as C/EBPα and C/EBPε, which in turn deregulate G-CSF-R expression. The resulting high levels of G-CSF-R and G-CSF-dependent cell proliferation may be associated with pathogenesis of AML with t(8;21. Moreover, in vitro and in vivo studies demonstrated that G-CSF may act as a co-stimulus augmenting the response of PML-RARα acute promyelocytic leukemia cells to all-trans-retinoic acid treatment. Finally, in the PLZF-RARα acute promyelocytic leukemia transgenic model, G-CSF deficiency suppressed leukemia development. Altogether, these data suggest that the G-CSF signaling pathway may play a role in leukemogenesis.

Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis: A Randomized Trial.

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Knutson, Jayme S; Gunzler, Douglas D; Wilson, Richard D; Chae, John

2016-10-01

It is unknown whether one method of neuromuscular electrical stimulation for poststroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) with cyclic neuromuscular electrical stimulation (cNMES). Stroke patients with chronic (>6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the laboratory for 12 weeks. The task practice for the CCFES group was stimulation assisted. The primary outcome was change in Box and Block Test (BBT) score at 6 months post treatment. Upper extremity Fugl-Meyer and Arm Motor Abilities Test were also measured. At 6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% confidence interval [CI], 2.2-7.0), than the cNMES group, 1.8 (95% CI, 0.6-3.0), between-group difference of 2.8 (95% CI, 0.1-5.5), P=0.045. No significant between-group difference was found for the upper extremity Fugl-Meyer (P=0.888) or Arm Motor Abilities Test (P=0.096). Participants who had the largest improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI, 5.6-13.6), were greater than those of the cNMES group, 4.1 (95% CI, 1.7-6.5), between-group difference of 5.5 (95% CI, 0.8-10.2), P=0.023. CCFES improved hand dexterity more than cNMES in chronic stroke survivors. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00891319. © 2016 American Heart Association, Inc.

Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.

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Boggio, Paulo S; Nunes, Alice; Rigonatti, Sergio P; Nitsche, Michael A; Pascual-Leone, Alvaro; Fregni, Felipe

2007-01-01

Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (pmotor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient.

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Kilgard, Michael P; Rennaker, Robert L; Alexander, Jen; Dawson, Jesse

2018-01-01

Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitation can enhance neural plasticity in the primary sensory and motor cortices, improve forelimb function after stroke in animal models and improve motor function in patients with arm weakness after stroke. To gain "first-in-man" experience of VNS paired with tactile training in a patient with severe sensory impairment after stroke. During the long-term follow-up phase of a clinical trial of VNS paired with motor rehabilitation, a 71-year-old man who had made good motor recovery had ongoing severe sensory loss in his left hand and arm. He received VNS paired with tactile therapy in an attempt to improve his sensory function. During twenty 2-hour sessions, each passive and active tactile event was paired with a 0.5 second burst of 0.8 mA VNS. Sensory function was measured before, halfway through, and after this therapy. The patient did not report any side effects during or following VNS+Tactile therapy. Quantitative measures revealed lasting and clinically meaningful improvements in tactile threshold, proprioception, and stereognosis. After VNS+Tactile therapy, the patient was able to detect tactile stimulation to his affected hand that was eight times less intense, identify the joint position of his fingers in the affected hand three times more often, and identify everyday objects using his affected hand seven times more often, compared to baseline. Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials.

FACTORS THAT STIMULATE THE ECOSYSTEM ROMANIAN ENTREPRENEURIAL

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ENEA CONSTANŢA

2017-12-01

Full Text Available Entrepreneurship has begun to grapple with the global economic and financial crisis, and entrepreneurs have become "heroes" capable of delivering impetus to fragile economies. Small and innovative companies account for 99% of all Europe's active companies and offer 66% of available jobs. In the context of a worrying unemployment rate that persists in many countries of the world, entrepreneurship has become a viable solution to economic problems. Entrepreneurship can not be defined precisely, and the multidimensionality and homogeneity of the concept makes it very difficult to generalize the conclusions of studies for regions other than those for which they were originally developed. The objective of the present study is to carry out a comprehensive analysis of the Romanian entrepreneurial ecosystem and the factors that have the power to stimulate it, thus allowing the design of efficient policies for the development of Romanian entrepreneurship.

Transport medicine, osteochondrosis, diagnostic, preventions of complications, physiotherapy, impulse magnetic stimulation

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V. V. Loboiko

2017-01-01

  Summary Offered us medical and rehabilitation complex using pulsed magnetic stimulation for the prevention and treatment of complications of destructive-degenerative disorders of the spine in patients with low back pain lumbar zone greatly increases the effectiveness sanogenetic mechanisms to improve trophic processes in the spinal segments, both in the area of formation of pathological disorders and in areas distal lower extremities. The positive dynamics of functioning structures spinal nerve under the influence of pulsed magnetic stimulation provides improved hemodynamic performance throughout the vascular bed in the lower extremities. It was established that the basis sanogenetic improve the mechanisms of blood vessels, are processes that define their tone, elasticity and adequacy of response to treatment and rehabilitation influence factors. High efficiency pulsed magnetic stimulation achieved by potentiating its effect on biological effects, which are formed in the body using standard treatments for osteoarthritis. Key words. Transport medicine, osteochondrosis, diagnostic, preventions of complications, physiotherapy, impulse magnetic stimulation.

Transcranial direct current stimulation (tDCS) facilitates overall visual search response times but does not interact with visual search task factors.

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Sung, Kyongje; Gordon, Barry

2018-01-01

Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.

Improving Balance Function Using Low Levels of Electrical Stimulation of the Balance Organs

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Bloomberg, Jacob; Reschke, Millard; Mulavara, Ajitkumar; Wood, Scott; Serrador, Jorge; Fiedler, Matthew; Kofman, Igor; Peters, Brian T.; Cohen, Helen

2012-01-01

Crewmembers returning from long-duration space flight face significant challenges due to the microgravity-induced inappropriate adaptations in balance/ sensorimotor function. The Neuroscience Laboratory at JSC is developing a method based on stochastic resonance to enhance the brain s ability to detect signals from the balance organs of the inner ear and use them for rapid improvement in balance skill, especially when combined with balance training exercises. This method involves a stimulus delivery system that is wearable/portable providing imperceptible electrical stimulation to the balance organs of the human body. Stochastic resonance (SR) is a phenomenon whereby the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. This phenomenon of SR is based on the concept of maximizing the flow of information through a system by a non-zero level of noise. Application of imperceptible SR noise coupled with sensory input in humans has been shown to improve motor, cardiovascular, visual, hearing, and balance functions. SR increases contrast sensitivity and luminance detection; lowers the absolute threshold for tone detection in normal hearing individuals; improves homeostatic function in the human blood pressure regulatory system; improves noise-enhanced muscle spindle function; and improves detection of weak tactile stimuli using mechanical or electrical stimulation. SR noise has been shown to improve postural control when applied as mechanical noise to the soles of the feet, or when applied as electrical noise at the knee and to the back muscles.

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

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Marcus eMeinzer

2014-09-01

Full Text Available Language facilitation by transcranial direct current stimulation (tDCS in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia. However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI, which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1 can enhance language functions.This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal and bihemispheric (dual tDCS in eighteen healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects.Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions.Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. fMRI revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

Science.gov (United States)

Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M; Nachtigall, Laura; Ulm, Lena; Flöel, Agnes

2014-01-01

Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in

Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

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Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

2015-09-01

Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells

International Nuclear Information System (INIS)

Kasai, K.; Hiraiwa, M.; Emoto, T.; Akimoto, K.; Takaoka, T.; Shimoda, S.I.

1987-01-01

Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E 2 production by cultured porcine thyroid cells were examined. Both phorbol 12-myristate 13-acetate (PMA) and EGF stimulated prostaglandin E 2 production by the cells in dose related fashion. PMA stimulated prostaglandin E 2 production over fifty-fold with the dose of 10 -7 M compared with control. EGF (10 -7 M) also stimulated it about ten-fold. The ED 50 values of PMA and EGF were respectively around 1 x 10 -9 M and 5 x 10 -10 M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E 2 production from 1 to 24-h incubation. The release of radioactivity from [ 3 H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E 2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells. 36 references, 2 figures, 1 table

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

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Stone, Austin V.; Loeser, Richard F.; Vanderman, Kadie S.; Long, David L.; Clark, Stephanie C.; Ferguson, Cristin M.

2014-01-01

Objective Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. Design Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. Results Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. Conclusions Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes. PMID:24315792

Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

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Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

2014-08-20

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

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Taub, Mary, E-mail: biochtau@buffalo.edu

2016-03-11

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

International Nuclear Information System (INIS)

Taub, Mary

2016-01-01

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Improved Selectivity From a Wavelength Addressable Device for Wireless Stimulation of Neural Tissue

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Elif Ç. Seymour

2014-02-01

Full Text Available Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume. Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other.

Increasing Goat Productivity Through the Improvement of Endogenous Secretion of Pregnant Hormones Using Follicle Stimulating Hormone

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Andriyanto Andriyanto

2011-05-01

Full Text Available Abstract. Previous studies reported that the improvement of endogenous estrogen and progesterone secretions during gestation improved fetal prenatal growth, birth weight, mammary gland growth and development, milk production, litter size, pre- and post-weaning growths. An experiment was conducted to apply the improvement of endogenous secretion of pregnant hormones during pregnancy to increase goat productivity. Thirty-six female ettawah-cross does were divided into 2 groups. Group 1 (control: 18 does included does without improvement of endogenous secretion of pregnant hormones and Group 2 (treatment: 18 does included does with improvement of endogenous secretion of pregnant hormones using follicle stimulating hormones to stimulate super ovulation. The application of this technology increased total offspring born (control: 25 offspring; treatment: 42 offspring, average litter size (control: 1.88; treatment: 2.33, offspring birth weight (control: 2.85±0.50 kg; treatment: 3.82±0.40 kg, and does milk production (control: 1.36±0.34 L/does/day; treatment: 2.10±0.21 L/does/day. Offspring born to does with improved endogenous secretion of pregnant hormones had better weaning weight (control: 11.17±1.99 kg/offspring; treatment: 14.5±1.11 kg/offspring. At weaning period, does with improved endogenous secretion of pregnant hormones produced offspring with total weaning weight twice as heavy as control does (control: 189.9 kg; treatment: 403.6 kg. By a simple calculation of economic analysis, this technology application could increase gross revenue per does until weaning by Rp. 432.888,89. It was concluded that this technology is economically feasible to be applied in small-scale farm. Key Words: follicle stimulating hormone, pregnant hormones, endogenous secretion, super ovulation, ettawah-cross does

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

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Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

2014-06-01

In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling.

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Sharmin, Farzana; McDermott, Casey; Lieberman, Jay; Sanjay, Archana; Khan, Yusuf

2017-05-01

Autografts have been shown to stimulate osteogenesis, osteoclastogenesis, and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics. In this study, we have demonstrated largely sequential delivery of bone morphogenetic protein-2 and vascular endothelial growth factor from the same coated allograft. Release data showed that loading both growth factors onto a polymeric coating with two different techniques resulted in short-term (95% release within 2 weeks) and long-term (95% release within 5 weeks) delivery kinetics. We have also demonstrated how released VEGF, traditionally associated with angiogenesis, can also provide a stimulus for allograft remodeling via resorption. Bone marrow derived mononuclear cells were co-cultured with VEGF released from the coated allograft and showed a statistically significant (p exposed to VEGF released from the allografts over controls (p < 0.05). These results indicate that by using different loading protocols temporal control can be achieved when delivering multiple growth factors from a polymer-coated allograft. Further, released VEGF can also stimulate osteoclastogenesis that may enhance allograft incorporation, and thus mitigate long-term clinical complications. © 2017 Orthopedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1086-1095, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

DEFF Research Database (Denmark)

Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

2015-01-01

INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

Non-invasive brain stimulation for fine motor improvement after stroke: a meta-analysis.

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O'Brien, A T; Bertolucci, F; Torrealba-Acosta, G; Huerta, R; Fregni, F; Thibaut, A

2018-05-09

The aim of this study was to determine whether non-invasive brain stimulation (NIBS) techniques improve fine motor performance in stroke. We searched PubMed, EMBASE, Web of Science, SciELO and OpenGrey for randomized clinical trials on NIBS for fine motor performance in stroke patients and healthy participants. We computed Hedges' g for active and sham groups, pooled data as random-effects models and performed sensitivity analysis on chronicity, montage, frequency of stimulation and risk of bias. Twenty-nine studies (351 patients and 152 healthy subjects) were reviewed. Effect sizes in stroke populations for transcranial direct current stimulation and repeated transcranial magnetic stimulation were 0.31 [95% confidence interval (CI), 0.08-0.55; P = 0.010; Tau 2 , 0.09; I 2 , 34%; Q, 18.23; P = 0.110] and 0.46 (95% CI, 0.00-0.92; P = 0.05; Tau 2 , 0.38; I 2 , 67%; Q, 30.45; P = 0.007). The effect size of non-dominant healthy hemisphere transcranial direct current stimulation on non-dominant hand function was 1.25 (95% CI, 0.09-2.41; P = 0.04; Tau 2 , 1.26; I 2 , 93%; Q, 40.27; P < 0.001). Our results show that NIBS is associated with gains in fine motor performance in chronic stroke patients and healthy subjects. This supports the effects of NIBS on motor learning and encourages investigation to optimize their effects in clinical and research settings. © 2018 EAN.

Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

International Nuclear Information System (INIS)

Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T.

1991-01-01

Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes

Electrical stimulation of transplanted motoneurons improves motor unit formation

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Liu, Yang; Grumbles, Robert M.

2014-01-01

Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

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Sandra Geschka

Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

Exploring bikeability in a metropolitan setting: stimulating and hindering factors in commuting route environments

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Wahlgren Lina

2012-03-01

Full Text Available Abstract Background Route environments may influence people's active commuting positively and thereby contribute to public health. Assessments of route environments are, however, needed in order to better understand the possible relationship between active commuting and the route environment. The aim of this study was, therefore, to assess the potential associations between perceptions of whether the route environment on the whole hinders or stimulates bicycle commuting and perceptions of environmental factors. Methods The Active Commuting Route Environment Scale (ACRES was used for the assessment of bicycle commuters' perceptions of their route environments in the inner urban parts of Greater Stockholm, Sweden. Bicycle commuters (n = 827 were recruited by advertisements in newspapers. Simultaneous multiple regression analyses were used to assess the relation between predictor variables (such as levels of exhaust fumes, noise, traffic speed, traffic congestion and greenery and the outcome variable (hindering - stimulating route environments. Two models were run, (Model 1 without and (Model 2 with the item traffic: unsafe or safe included as a predictor. Results Overall, about 40% of the variance of hindering - stimulating route environments was explained by the environmental predictors in our models (Model 1, R2 = 0.415, and Model 2, R 2= 0.435. The regression equation for Model 1 was: y = 8.53 + 0.33 ugly or beautiful + 0.14 greenery + (-0.14 course of the route + (-0.13 exhaust fumes + (-0.09 congestion: all types of vehicles (p ≤ 0.019. The regression equation for Model 2 was y = 6.55 + 0.31 ugly or beautiful + 0.16 traffic: unsafe or safe + (-0.13 exhaust fumes + 0.12 greenery + (-0.12 course of the route (p ≤ 0.001. Conclusions The main results indicate that beautiful, green and safe route environments seem to be, independently of each other, stimulating factors for bicycle commuting in inner urban areas. On the other hand, exhaust

Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

Science.gov (United States)

Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

2010-09-01

We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

Granulocyte-macrophage colony-stimulating factor amplification of interleukin-1beta and tumor necrosis factor alpha production in THP-1 human monocytic cells stimulated with lipopolysaccharide of oral microorganisms.

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Baqui, A A; Meiller, T F; Chon, J J; Turng, B F; Falkler, W A

1998-05-01

Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1beta and TNF-alpha production following GM-CSF supplementation with lipopolysaccharide (LPS) from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. LPS of P. gingivalis or F. nucleatum was prepared by a phenol-water extraction method and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determination of total protein and endotoxin contents. Resting THP-1 cells were treated with LPS of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) by using different concentrations for various time periods. Production of IL-1beta and TNF-alpha in THP-1 cells was measured by solid-phase enzyme-linked immunosorbent assay. Reverse transcription (RT)-PCR was used to evaluate the gene expression of resting and treated THP-1 cells. IL-1beta was not detected in untreated THP-1 cells. IL-1beta production was, however, stimulated sharply at 4 h. GM-CSF amplified IL-1beta production in THP-1 cells treated with LPS from both oral anaerobes. No IL-1beta-specific mRNA transcript was detected in untreated THP-1 cells. However, IL-1beta mRNA was detected by RT-PCR 2 h after stimulation of THP-1 cells with LPS from both organisms. GM-CSF did not shorten the IL-1beta transcriptional activation time. GM-CSF plus F. nucleatum or P. gingivalis LPS activated THP-1 cells to produce a 1.6-fold increase in TNF-alpha production at 4 h over LPS stimulation alone. These investigations with the in vitro THP-1 model indicate that there may be an increase in the cellular immune response to oral

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

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Weifeng Lu

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05. rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05. RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05. Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

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Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

2014-01-01

The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

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Du, Zhiyong; Bondarenko, Olexandr; Wang, Dingkun; Rouabhia, Mahmoud; Zhang, Ze

2016-06-01

Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities. © 2015 Wiley Periodicals, Inc.

Small subchondral drill holes improve marrow stimulation of articular cartilage defects.

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Eldracher, Mona; Orth, Patrick; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2014-11-01

Subchondral drilling is an established marrow stimulation technique. Osteochondral repair is improved when the subchondral bone is perforated with small drill holes, reflecting the physiological subchondral trabecular distance. Controlled laboratory study. A rectangular full-thickness chondral defect was created in the trochlea of adult sheep (n = 13) and treated with 6 subchondral drillings of either 1.0 mm (reflective of the trabecular distance) or 1.8 mm in diameter. Osteochondral repair was assessed after 6 months in vivo by macroscopic, histological, and immunohistochemical analyses and by micro-computed tomography. The application of 1.0-mm subchondral drill holes led to significantly improved histological matrix staining, cellular morphological characteristics, subchondral bone reconstitution, and average total histological score as well as significantly higher immunoreactivity to type II collagen and reduced immunoreactivity to type I collagen in the repair tissue compared with 1.8-mm drill holes. Analysis of osteoarthritic changes in the cartilage adjacent to the defects revealed no significant differences between treatment groups. Restoration of the microstructure of the subchondral bone plate below the chondral defects was significantly improved after 1.0-mm compared to 1.8-mm drilling, as shown by higher bone volume and reduced thickening of the subchondral bone plate. Likewise, the microarchitecture of the drilled subarticular spongiosa was better restored after 1.0-mm drilling, indicated by significantly higher bone volume and more and thinner trabeculae. Moreover, the bone mineral density of the subchondral bone in 1.0-mm drill holes was similar to the adjacent subchondral bone, whereas it was significantly reduced in 1.8-mm drill holes. No significant correlations existed between cartilage and subchondral bone repair. Small subchondral drill holes that reflect the physiological trabecular distance improve osteochondral repair in a translational

Rhizobial Nodulation Factors Stimulate Mycorrhizal Colonization of Nodulating and Nonnodulating Soybeans.

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Xie, Z. P.; Staehelin, C.; Vierheilig, H.; Wiemken, A.; Jabbouri, S.; Broughton, W. J.; Vogeli-Lange, R.; Boller, T.

1995-08-01

Legumes form tripartite symbiotic associations with noduleinducing rhizobia and vesicular-arbuscular mycorrhizal fungi. Co-inoculation of soybean (Glycine max [L.] Merr.) roots with Bradyrhizobium japonicum 61-A-101 considerably enhanced colonization by the mycorrhizal fungus Glomus mosseae. A similar stimulatory effect on mycorrhizal colonization was also observed in nonnodulating soybean mutants when inoculated with Bradyrhizobium japonicum and in wild-type soybean plants when inoculated with ineffective rhizobial strains, indicating that a functional rhizobial symbiosis is not necessary for enhanced mycorrhiza formation. Inoculation with the mutant Rhizobium sp. NGR[delta]nodABC, unable to produce nodulation (Nod) factors, did not show any effect on mycorrhiza. Highly purified Nod factors also increased the degree of mycorrhizal colonization. Nod factors from Rhizobium sp. NGR234 differed in their potential to promote fungal colonization. The acetylated factor NodNGR-V (MeFuc, Ac), added at concentrations as low as 10-9 M, was active, whereas the sulfated factor, NodNGR-V (MeFuc, S), was inactive. Several soybean flavonoids known to accumulate in response to the acetylated Nod factor showed a similar promoting effect on mycorrhiza. These results suggest that plant flavonoids mediate the Nod factor-induced stimulation of mycorrhizal colonization in soybean roots.

Granulocyte colony-stimulating factor protects mice during respiratory virus infections.

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Tamar Hermesh

Full Text Available A burst in the production of pro-inflammatory molecules characterizes the beginning of the host response to infection. Cytokines, chemokines, and growth factors work in concert to control pathogen replication and activate innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF mobilizes and activates hematopoietic cells from the bone marrow, and it has been shown to mediate the generation of effective immunity against bacterial and fungal infections. G-CSF is produced at high levels in the lungs during infection with influenza and parainfluenza viruses, but its role during these infections is unknown. Here we show that during infection of mice with a non-lethal dose of influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+ granulocytes that control the extent of the lung pro-inflammatory response. Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain mouse survival.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition.

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Obeso, Ignacio; Wilkinson, Leonora; Teo, James T; Talelli, Penelope; Rothwell, John C; Jahanshahi, Marjan

Stopping an ongoing motor response or resolving conflict induced by conflicting stimuli are associated with activation of a right-lateralized network of inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA) and subthalamic nucleus (STN). However, the roles of the right IFG and pre-SMA in stopping a movement and in conflict resolution remain unclear. We used continuous theta burst stimulation (cTBS) to examine the involvement of the right IFG and pre-SMA in inhibition and conflict resolution using the conditional stop signal task. We measured stop signal reaction time (SSRT, measure of reactive inhibition), response delay effect (RDE, measure of proactive action restraint) and conflict induced slowing (CIS, measure of conflict resolution). Stimulation over the pre-SMA resulted in significantly shorter SSRTs (improved inhibition) compared to sham cTBS. This effect was not observed for CIS, RDE, or any other measures. cTBS over the right IFG had no effect on SSRT, CIS, RDE or on any other measure. The improvement of SSRT with cTBS over the pre-SMA suggests its critical contribution to stopping ongoing movements. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcranial alternating current stimulation with sawtooth waves: simultaneous stimulation and EEG recording

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James eDowsett

2016-03-01

Full Text Available Transcranial alternating current stimulation (tACS has until now mostly been administered as an alternating sinusoidal wave. Despite modern tACS stimulators being able to deliver alternating current with any arbitrary shape there has been no systematic exploration into the relative benefits of different waveforms. As tACS is a relatively new technique there is a huge parameter space of unexplored possibilities which may prove superior or complimentary to the traditional sinusoidal waveform. Here we begin to address this with an investigation into the effects of sawtooth wave tACS on individual alpha power. Evidence from animal models suggests that the gradient and direction of an electric current should be important factors for the subsequent neural firing rate; we compared positive and negative ramp sawtooth waves to test this. An additional advantage of sawtooth waves is that the resulting artefact in the electroencephalogram (EEG recording is significantly simpler to remove than a sine wave; accordingly we were able to observe alpha oscillations both during and after stimulation.We found that positive ramp sawtooth, but not negative ramp sawtooth, significantly enhanced alpha power during stimulation relative to sham (p<0.01. In addition we tested for an after-effect of both sawtooth and sinusoidal stimulation on alpha power but in this case did not find any significant effect. This preliminary study paves the way for further investigations into the effect of the gradient and direction of the current in tACS which could significantly improve the usefulness of this technique.

Electrical stimulation of the dorsolateral prefrontal cortex improves memory monitoring.

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Chua, Elizabeth F; Ahmed, Rifat

2016-05-01

The ability to accurately monitor one's own memory is an important feature of normal memory function. Converging evidence from neuroimaging and lesion studies have implicated the dorsolateral prefrontal cortex (DLPFC) in memory monitoring. Here we used high definition transcranial direct stimulation (HD-tDCS), a non-invasive form of brain stimulation, to test whether the DLPFC has a causal role in memory monitoring, and the nature of that role. We used a metamemory monitoring task, in which participants first attempted to recall the answer to a general knowledge question, then gave a feeling-of-knowing (FOK) judgment, followed by a forced choice recognition task. When participants received DLPFC stimulation, their feeling-of-knowing judgments were better predictors of memory performance, i.e., they had better memory monitoring accuracy, compared to stimulation of a control site, the anterior temporal lobe (ATL). Effects of DLPFC stimulation were specific to monitoring accuracy, as there was no significant increase in memory performance, and if anything, there was poorer memory performance with DLPFC stimulation. Thus we have demonstrated a causal role for the DLPFC in memory monitoring, and showed that electrically stimulating the left DLPFC led people to more accurately monitor and judge their own memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improved multivariate polynomial factoring algorithm

International Nuclear Information System (INIS)

Wang, P.S.

1978-01-01

A new algorithm for factoring multivariate polynomials over the integers based on an algorithm by Wang and Rothschild is described. The new algorithm has improved strategies for dealing with the known problems of the original algorithm, namely, the leading coefficient problem, the bad-zero problem and the occurrence of extraneous factors. It has an algorithm for correctly predetermining leading coefficients of the factors. A new and efficient p-adic algorithm named EEZ is described. Bascially it is a linearly convergent variable-by-variable parallel construction. The improved algorithm is generally faster and requires less store then the original algorithm. Machine examples with comparative timing are included

Enhanced Motor Skill Acquisition in the Non-dominant Upper Extremity using Intermittent Theta Burst Stimulation and Transcranial Direct Current Stimulation

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Ray eButts

2014-06-01

Full Text Available Individuals suffering from motor impairments often require physical therapy (PT to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS and bihemispheric transcranial direct current stimulation may increase the speed and extent of motor learning/relearning and that this increase may be related to brain derived neurotrophic factor (BDNF. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-hours, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15 or control group (n = 12. iTBS (20 trains of 10 pulse triplets each delivered at 80% AMT / 50Hz over 191.84 seconds and bihemispheric tDCS (1.0 ma for 20 minutes were used as a primer to, and in conjunction with, 20 minutes of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function Test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-hours post training (p = 0.055, and were significant at 7-days post training (p < 0.05. These results suggest that the combined iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

Predictive potential of pre-operative functional neuroimaging in patients treated with subthalamic stimulation

International Nuclear Information System (INIS)

Sestini, Stelvio; Castagnoli, Antonio; Pupi, Alberto; Sciagra, Roberto; Ammannati, Franco; Ramat, Silvia; Sorbi, Sandro; Mansi, Luigi

2010-01-01

The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Ten patients underwent rCBF SPECT and motor Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease. (orig.)

Predictive potential of pre-operative functional neuroimaging in patients treated with subthalamic stimulation

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Sestini, Stelvio; Castagnoli, Antonio [Ospedale Misericordia e Dolce, Department of Diagnostic Imaging, Nuclear Medicine Unit, Prato (Italy); Pupi, Alberto; Sciagra, Roberto [University of Florence, Department of Clinical Physiopathology, Nuclear Medicine Unit, Florence (Italy); Ammannati, Franco; Ramat, Silvia; Sorbi, Sandro [University of Florence, Department of Neurological and Psychiatric Sciences, Florence (Italy); Mansi, Luigi [University II Naples, Department of Diagnostic Imaging, Nuclear Medicine Unit, Naples (Italy)

2010-01-15

The aim of this study was to investigate the predictive potential of pre-operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area (pre-SMA) and clinical factors in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) stimulation. Ten patients underwent rCBF SPECT and motor Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post-operatively during stimulation at 5 and 42 months. Statistical parametric mapping (SPM) was used to extract rCBF values in the pre-SMA because it is related with motor improvement. Post-operative outcomes included motor response to stimulation and percent improvement in UPDRS. Pre-operative predictors were explored by correlation test, linear regression and multivariate analyses. Higher pre-operative rCBF in the pre-SMA and younger age were associated with favourable outcomes at 5 and 42 months. Pre-operative rCBF results were significantly associated with baseline clinical factors. This study shows that PD patients with younger age have higher rCBF values in the pre-SMA and better outcome, thus giving the rationale to the hypothesis that STN stimulation could be considered early in the course of disease. (orig.)

Corrosion of conductive polypyrrole: Effects of environmental factors, electrochemical stimulation, and doping anions

International Nuclear Information System (INIS)

Qi Kai; Qiu Yubing; Chen Zhenyu; Guo Xingpeng

2012-01-01

Highlights: ► Corrosive galvanic cells form on PPy film with the electrochemical reduction of O 2. ► Suitable electrochemical stimulation can inhibit the PPy’s corrosion. ► PPy film doped with larger sized anions has better corrosion resistance performance. - Abstract: The effects of environmental factors, electrochemical stimulation, and doping anions on the corrosion behaviour of conductive polypyrrole (PPy) films in alkaline aqueous media were studied with cyclic voltammetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. High concentrations of electrolyte, low dissolved oxygen and low temperatures enhance the stability of PPy. Polarising PPy at a negative potential inhibits its corrosion obviously. PPy doped with large counter anions shows better corrosion resistance than PPy doped with small counter ions. The possible mechanism involved in PPy corrosion process is discussed.

Granulocyte Macrophage Colony Stimulating Factor Supplementation in Culture Media for Subfertile Women Undergoing Assisted Reproduction Technologies: A Systematic Review

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Siristatidis, Charalampos; Vogiatzi, Paraskevi; Salamalekis, George; Creatsa, Maria; Vrachnis, Nikos; Glujovsky, Demián; Iliodromiti, Zoe; Chrelias, Charalampos

2013-01-01

Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure. PMID:23509457

Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

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Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

2016-03-01

Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for fibroblast growth factor-2 as a mediator of amphetamine-enhanced motor improvement following stroke.

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William A Wolf

Full Text Available Previously we have shown that addition of amphetamine to physical therapy results in enhanced motor improvement following stroke in rats, which was associated with the formation of new motor pathways from cortical projection neurons of the contralesional cortex. It is unclear what mechanisms are involved, but amphetamine is known to induce the neuronal release of catecholamines as well as upregulate fibroblast growth factor-2 (FGF-2 expression in the brain. Since FGF-2 has been widely documented to stimulate neurite outgrowth, the present studies were undertaken to provide evidence for FGF-2 as a neurobiological mechanism underlying amphetamine-induced neuroplasticity. In the present study rats that received amphetamine plus physical therapy following permanent middle cerebral artery occlusion exhibited significantly greater motor improvement over animals receiving physical therapy alone. Amphetamine plus physical therapy also significantly increased the number of FGF-2 expressing pyramidal neurons of the contralesional cortex at 2 weeks post-stroke and resulted in significant axonal outgrowth from these neurons at 8 weeks post-stroke. Since amphetamine is a known releaser of norepinephrine, in vitro analyses focused on whether noradrenergic stimulation could lead to neurite outgrowth in a manner requiring FGF-2 activity. Primary cortical neurons did not respond to direct stimulation by norepinephrine or amphetamine with increased neurite outgrowth. However, conditioned media from astrocytes exposed to norepinephrine or isoproterenol (a beta adrenergic agonist significantly increased neurite outgrowth when applied to neuronal cultures. Adrenergic agonists also upregulated FGF-2 expression in astrocytes. Pharmacological analysis indicated that beta receptors and alpha1, but not alpha2, receptors were involved in both effects. Antibody neutralization studies demonstrated that FGF-2 was a critical contributor to neurite outgrowth induced by

Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats.

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Bendella, H; Pavlov, S P; Grosheva, M; Irintchev, A; Angelova, S K; Merkel, D; Sinis, N; Kaidoglou, K; Skouras, E; Dunlop, S A; Angelov, Doychin N

2011-07-01

We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.

Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1.

Science.gov (United States)

Sugiyama, A; Uehara, A; Iki, K; Matsushita, K; Nakamura, R; Ogawa, T; Sugawara, S; Takada, H

2002-01-01

Black-pigmented anaerobic bacteria, such as Porphyromonas gingivalis and Prevotella intermedia, are amongst the predominant bacteria in periodontal pockets and have been implicated in periodontal diseases. To elucidate the roles of gingival keratinocytes, which are the first cells encountered by oral bacteria in periodontal diseases, human gingival keratinocytes in primary culture were stimulated with cell-surface components of P gingivalis and Pr. intermedia. A glycoprotein fraction from Pr. intermedia (PGP) clearly augmented the release of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, as determined by enzyme-linked immunosorbent assay. This PGP also induced expression of intercellular adhesion molecule-1 (ICAM-1), as determined by flow cytometry. The augmentation of mRNA expression for these molecules was also confirmed by reverse transcription PCR. In contrast, lipopolysaccharide (LPS) from Pr. intermedia and Escherichia coli was completely inactive in these assays. LPS fraction and purified fimbriae from P gingivalis exhibited weak activities. Cytokine production and ICAM-1 expression by gingival keratinocytes might cause accumulation and activation of neutrophils in the epithelium and, therefore, may be involved in the initiation and development of inflammation in periodontal tissues.

Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction

Science.gov (United States)

Kobayashi, Kanichiro; Takahashi, Naoyuki; Jimi, Eijiro; Udagawa, Nobuyuki; Takami, Masamichi; Kotake, Shigeru; Nakagawa, Nobuaki; Kinosaki, Masahiko; Yamaguchi, Kyoji; Shima, Nobuyuki; Yasuda, Hisataka; Morinaga, Tomonori; Higashio, Kanji; Martin, T. John; Suda, Tatsuo

2000-01-01

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF–dependent bone marrow macrophages (M-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for 3 d with mouse tumor necrosis factor α (TNF-α) in the presence of M-CSF. Osteoclast formation induced by TNF-α was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti–RANK (ODF/RANKL receptor) antibody. Experiments using M-BMMφ prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-α. Osteoclasts induced by TNF-α formed resorption pits on dentine slices only in the presence of IL-1α. These results demonstrate that TNF-α stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL–RANK system. TNF-α together with IL-1α may play an important role in bone resorption of inflammatory bone diseases. PMID:10637272

A Randomized Case-Controlled Study of Recombinant Human Granulocyte Colony Stimulating Factor for the Treatment of Sepsis in Preterm Neutropenic Infants

OpenAIRE

Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

2015-01-01

To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Methods: Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were ...

Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Marlieke Scholten

2017-10-01

Full Text Available Conventional subthalamic deep brain stimulation for Parkinson’s disease (PD presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG. Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i Off stimulation, (ii STN stimulation (alone, and (iii SNr stimulation (alone. SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry. Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.

A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization

DEFF Research Database (Denmark)

Ziebe, Søren; Loft, Anne; Povlsen, Betina B

2013-01-01

To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).......To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR)....

Transcranial brain stimulation: closing the loop between brain and stimulation

DEFF Research Database (Denmark)

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

2016-01-01

-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......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...

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Moroni, Maria, E-mail: maria.moroni@usuhs.edu [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Ngudiankama, Barbara F. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (United States); Christensen, Christine [Division of Comparative Pathology, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Olsen, Cara H. [Biostatistics Consulting Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Owens, Rossitsa [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Lombardini, Eric D. [Veterinary Medicine Department, Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand); Holt, Rebecca K. [Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Whitnall, Mark H. [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)

2013-08-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation.

Science.gov (United States)

Moroni, Maria; Ngudiankama, Barbara F; Christensen, Christine; Olsen, Cara H; Owens, Rossitsa; Lombardini, Eric D; Holt, Rebecca K; Whitnall, Mark H

2013-08-01

We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. Published by Elsevier Inc.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

International Nuclear Information System (INIS)

Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

2013-01-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes

Cerebellar transcranial direct current stimulation improves adaptive postural control.

Science.gov (United States)

Poortvliet, Peter; Hsieh, Billie; Cresswell, Andrew; Au, Jacky; Meinzer, Marcus

2018-01-01

Rehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration. Twenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP). Baseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery. We demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals. Future studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects.

Science.gov (United States)

Fiori, Valentina; Coccia, Michela; Marinelli, Chiara V; Vecchi, Veronica; Bonifazi, Silvia; Ceravolo, M Gabriella; Provinciali, Leandro; Tomaiuolo, Francesco; Marangolo, Paola

2011-09-01

A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis.

Science.gov (United States)

Goodwill, Alicia M; Lum, Jarrad A G; Hendy, Ashlee M; Muthalib, Makii; Johnson, Liam; Albein-Urios, Natalia; Teo, Wei-Peng

2017-11-01

Parkinson's disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106-0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188-1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research.

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

Science.gov (United States)

Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

2015-06-01

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

Science.gov (United States)

Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

2017-05-01

Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

Science.gov (United States)

Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

2012-01-01

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

Science.gov (United States)

Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

2013-12-01

Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The effect of aroma stimulation during isotonic exercise on the rating of perceived exertion and blood fatigue factors of athletes with patellofemoral pain syndrome.

Science.gov (United States)

Kim, Sangsoo; Choo, JongHoo; Ju, Sungbum

2018-02-01

[Purpose] The purpose of this study is to examine the effect of aroma stimulation during isotonic exercise on the rating of perceived exertion (RPE) and the blood fatigue factors of athletes who have patellofemoral pain syndrome (PFPS). [Subjects and Methods] The research subjects were seven athletes in their twenties who suffer from PFPS. They were divided into a control group and an aroma stimulation group and performed isotonic exercises repeatedly. After exercising, the RPE and blood fatigue factors, including creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and ammonia, were measured through blood sampling. [Results] The aroma stimulus group showed significantly lower RPE than the control group immediately after exercising, which included leg presses, leg curls, bicep curls, and leg extensions. Among the blood fatigue factors, the change in LDH indicated the effect of aroma stimulation. [Conclusion] We confirmed that aroma stimulation during isotonic exercise has the positive effect of reducing the RPE and blood fatigue factors, such as blood LDH, of the athletes with PFPS.

A New Visual Stimulation Program for Improving Visual Acuity in Children with Visual Impairment: A Pilot Study

Science.gov (United States)

Tsai, Li-Ting; Hsu, Jung-Lung; Wu, Chien-Te; Chen, Chia-Ching; Su, Yu-Chin

2016-01-01

The purpose of this study was to investigate the effectiveness of visual rehabilitation of a computer-based visual stimulation (VS) program combining checkerboard pattern reversal (passive stimulation) with oddball stimuli (attentional modulation) for improving the visual acuity (VA) of visually impaired (VI) children and children with amblyopia and additional developmental problems. Six children (three females, three males; mean age = 3.9 ± 2.3 years) with impaired VA caused by deficits along the anterior and/or posterior visual pathways were recruited. Participants received eight rounds of VS training (two rounds per week) of at least eight sessions per round. Each session consisted of stimulation with 200 or 300 pattern reversals. Assessments of VA (assessed with the Lea symbol VA test or Teller VA cards), visual evoked potential (VEP), and functional vision (assessed with the Chinese-version Functional Vision Questionnaire, FVQ) were carried out before and after the VS program. Significant gains in VA were found after the VS training [VA = 1.05 logMAR ± 0.80 to 0.61 logMAR ± 0.53, Z = –2.20, asymptotic significance (2-tailed) = 0.028]. No significant changes were observed in the FVQ assessment [92.8 ± 12.6 to 100.8 ±SD = 15.4, Z = –1.46, asymptotic significance (2-tailed) = 0.144]. VEP measurement showed improvement in P100 latency and amplitude or integration of the waveform in two participants. Our results indicate that a computer-based VS program with passive checkerboard stimulation, oddball stimulus design, and interesting auditory feedback could be considered as a potential intervention option to improve the VA of a wide age range of VI children and children with impaired VA combined with other neurological disorders. PMID:27148014

A New Visual Stimulation Program for Improving Visual Acuity in Children with Visual Impairment: A Pilot Study.

Science.gov (United States)

Tsai, Li-Ting; Hsu, Jung-Lung; Wu, Chien-Te; Chen, Chia-Ching; Su, Yu-Chin

2016-01-01

The purpose of this study was to investigate the effectiveness of visual rehabilitation of a computer-based visual stimulation (VS) program combining checkerboard pattern reversal (passive stimulation) with oddball stimuli (attentional modulation) for improving the visual acuity (VA) of visually impaired (VI) children and children with amblyopia and additional developmental problems. Six children (three females, three males; mean age = 3.9 ± 2.3 years) with impaired VA caused by deficits along the anterior and/or posterior visual pathways were recruited. Participants received eight rounds of VS training (two rounds per week) of at least eight sessions per round. Each session consisted of stimulation with 200 or 300 pattern reversals. Assessments of VA (assessed with the Lea symbol VA test or Teller VA cards), visual evoked potential (VEP), and functional vision (assessed with the Chinese-version Functional Vision Questionnaire, FVQ) were carried out before and after the VS program. Significant gains in VA were found after the VS training [VA = 1.05 logMAR ± 0.80 to 0.61 logMAR ± 0.53, Z = -2.20, asymptotic significance (2-tailed) = 0.028]. No significant changes were observed in the FVQ assessment [92.8 ± 12.6 to 100.8 ±SD = 15.4, Z = -1.46, asymptotic significance (2-tailed) = 0.144]. VEP measurement showed improvement in P100 latency and amplitude or integration of the waveform in two participants. Our results indicate that a computer-based VS program with passive checkerboard stimulation, oddball stimulus design, and interesting auditory feedback could be considered as a potential intervention option to improve the VA of a wide age range of VI children and children with impaired VA combined with other neurological disorders.

A new visual stimulation program for improving visual acuity in children with visual impairment: a pilot study

Directory of Open Access Journals (Sweden)

Li-Ting eTsai

2016-04-01

Full Text Available The purpose of this study was to investigate the effectiveness of visual rehabilitation of a computer-based visual stimulation (VS program combining checkerboard pattern reversal (passive stimulation with oddball stimuli (attentional modulation for improving the visual acuity (VA of visually impaired (VI children and children with amblyopia and additional developmental problems. Six children (3 females, 3 males; mean age = 3.9 ± 2.3 years with impaired VA caused by deficits along the anterior and/or posterior visual pathways were recruited. Participants received eight rounds of VS training (two rounds per week of at least 8 sessions per round. Each session consisted of stimulation with 200 or 300 pattern reversals. Assessments of VA (assessed with the Lea symbol VA test or Teller VA cards, visual evoked potential (VEP, and functional vision (assessed with the Chinese-version Functional Vision Questionnaire, FVQ were carried out before and after the VS program. Significant gains in VA were found after the VS training (VA=1.05 logMAR ± 0.80 to 0.61 logMAR ± 0.53, Z=-2.20, asymptotic significance (2-tailed =0.028. No significant changes were observed in the FVQ assessment (92.8 ± 12.6 to 100.8 ± SD=15.4, Z=-1.46, asymptotic significance (2-tailed = 0.144. VEP measurement showed improvement in P100 latency and amplitude or integration of the waveform in two participants. Our results indicate that a computer-based VS program with passive checkerboard stimulation, oddball stimulus design, and interesting auditory feedback could be considered as a potential intervention option to improve the VA of a wide age range of VI children and children with impaired VA combined with other neurological disorders.

Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

Directory of Open Access Journals (Sweden)

Junghwan Suh

2013-12-01

Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

Science.gov (United States)

Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

2014-10-01

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals

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Francisco V. Santos

2013-06-01

Full Text Available BACKGROUND: Interferential electrical stimulation (IES, which may be linked to greater penetration of deep tissue, may restore blood flow by sympathetic nervous modulation; however, studies have found no association between the frequency and duration of the application and blood flow. We hypothesized that 30 min of IES applied to the ganglion stellate region might improve blood flow redistribution. OBJECTIVES: The purpose of this study was to determine the effect of IES on metaboreflex activation in healthy individuals. METHOD: Interferential electrical stimulation or a placebo stimulus (same protocol without electrical output was applied to the stellate ganglion region in eleven healthy subjects (age 25±1.3 years prior to exercise. Mean blood pressure (MBP, heart rate (HR, calf blood flow (CBF and calf vascular resistance (CVR were measured throughout exercise protocols (submaximal static handgrip exercise and with recovery periods with or without postexercise circulatory occlusion (PECO+ and PECO -, respectively. Muscle metaboreflex control of calf vascular resistance was estimated by subtracting the area under the curve when circulation was occluded from the area under the curve from the AUC without circulatory occlusion. RESULTS: At peak exercise, increases in mean blood pressure were attenuated by IES (p<0.05, and the effect persisted under both the PECO+ and PECO- treatments. IES promoted higher CBF and lower CVR during exercise and recovery. Likewise, IES induced a reduction in the estimated muscle metaboreflex control (placebo, 21±5 units vs. IES, 6±3, p<0.01. CONCLUSION: Acute application of IES prior to exercise attenuates the increase in blood pressure and vasoconstriction during exercise and metaboreflex activation in healthy subjects.

[Continuous improvement of portable domestic pelvic floor neuromuscular electrical stimulation on the pelvic floor function of patients with urinary incontinence].

Science.gov (United States)

Sun, Zhijing; Zhu, Lan; Lang, Jinghe; Wang, Wei; Shi, Honghui; Pang, Hongxia; Shi, Xinwen

2015-12-01

To evaluate continuous improvement of portable domestic pelvic floor neuromuscular electrical stimulation on the pelvic floor function of patients with stress urinary incontinence after short-term pelvic floor electrophysiological treatment in hospital. Totally 60 women with stress urinary incontinence were recruited for this randomized controlled trial. The control group including a total of 30 patients, only received 4 weeks pelvic floor electrophysiological treatment in the hospital. Family consolidation treatment group (experimental group) including 30 patients, after 4-week treatment in hospital, received 12-week of pelvic floor neuromuscular electrical stimulation using portable electrical stimulator at home under the guidance of doctors. In post-treatment 6 months and 9 months, 1-hour pad test was measured for urine leakage, pelvic floor electrical physiological parameters were assessed, and subjective improvement of symptoms of urinary incontinence were evaluated. All these data were analysed to compare the effect of the two groups. In 9 months after treatment, average change of urine leakage, the control group and experiment group were (75±24)% versus (99±3)%, the difference was statistically significant (Pcontinuous improvement of pelvic floor function.

Physical activity stimulation program for children with cerebral palsy did not improve physical activity: a randomised trial

NARCIS (Netherlands)

van Wely, L.; Balemans, A.C.J.; Becher, J.G.; Dallmeijer, A.J.

2014-01-01

Question: In children with cerebral palsy, does a 6-month physical activity stimulation program improve physical activity, mobility capacity, fitness, fatigue and attitude towards sports more than usual paediatric physiotherapy? Design: Multicentre randomised controlled trial with concealed

Timing of granulocyte-colony stimulating factor treatment after acute myocardial infarction and recovery of left ventricular function: results from the STEMMI trial

DEFF Research Database (Denmark)

Overgaard, Mikkel; Ripa, Rasmus Sejersten; Wang, Yongzhong

2010-01-01

Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial.......Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial....

Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis

DEFF Research Database (Denmark)

Nielsen, H

1993-01-01

After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease...

Motor cortex stimulation does not improve dystonia secondary to a focal basal ganglia lesion.

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Rieu, Isabelle; Aya Kombo, Magaly; Thobois, Stéphane; Derost, Philippe; Pollak, Pierre; Xie, Jing; Pereira, Bruno; Vidailhet, Marie; Burbaud, Pierre; Lefaucheur, Jean Pascal; Lemaire, Jean Jacques; Mertens, Patrick; Chabardes, Stephan; Broussolle, Emmanuel; Durif, Franck

2014-01-14

To assess the efficacy of epidural motor cortex stimulation (MCS) on dystonia, spasticity, pain, and quality of life in patients with dystonia secondary to a focal basal ganglia (BG) lesion. In this double-blind, crossover, multicenter study, 5 patients with dystonia secondary to a focal BG lesion were included. Two quadripolar leads were implanted epidurally over the primary motor (M1) and premotor cortices, contralateral to the most dystonic side. The leads were placed parallel to the central sulcus. Only the posterior lead over M1 was activated in this study. The most lateral or medial contact of the lead (depending on whether the dystonia predominated in the upper or lower limb) was selected as the anode, and the other 3 as cathodes. One month postoperatively, patients were randomly assigned to on- or off-stimulation for 3 months each, with a 1-month washout between the 2 conditions. Voltage, frequency, and pulse width were fixed at 3.8 V, 40 Hz, and 60 μs, respectively. Evaluations of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain intensity (visual analog scale), and quality of life (36-Item Short Form Health Survey) were performed before surgery and after each period of stimulation. Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS. Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion. This study provides Class I evidence that bipolar epidural MCS with the anode placed over the motor representation of the most affected limb failed to improve any clinical feature in dystonia secondary to a focal BG lesion.

Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA).

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Trebbastoni, Alessandro; Raccah, Ruggero; de Lena, Carlo; Zangen, Abraham; Inghilleri, Maurizio

2013-07-01

To date, no therapies are available for the logopenic variant of primary progressive aphasia (LPPA). Even though deep repetitive transcranial magnetic stimulation (rTMS) may improve cognitive functions in some neurodegenerative disorders, no previous studies investigated its effects in patients with LPPA. Our aim was to investigate the effects on cognitive function of high frequency rTMS (hf-rTMS) delivered over the left dorso-lateral prefrontal cortex (DLPFC) through a coil designed for deep rTMS, compared to a SHAM stimulation, in a right-handed patient with LPPA. The patient presented a progressive language impairment (phonological errors in speech and naming, impaired single word retrieval and sentences repetition) and predominant left perisylvian atrophy and hypoperfusion. He received four stimulation cycles (two REAL and two SHAM) each of whom lasted 20 min for 5 consecutive days. Patient's performances in frontal, visuo-spatial and linguistic tasks were evaluated before and after each stimulation session. Test scores after REAL were compared with those obtained at baseline and after SHAM. We found a temporary and highly significant improvement in the linguistic skills (both oral and written tasks) but not in the other cognitive domains tested, after REAL, but not SHAM stimulations. Hf-rTMS delivered over the DLPFC could improve language in LPPA by enhancing long-term potentiation and synaptic plasticity within the stimulated and interconnected areas involved in language network. Our findings might prompt future researches into the feasibility and efficacy of deep hf-rTMS as a therapeutic tool in progressive aphasia syndromes and other neurodegenerative disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Design of Recombinant Stem Cell Factor macrophage Colony Stimulating Factor Fusion Proteins and their Biological Activity In Vitro

Science.gov (United States)

Chen, Tao; Yang, Jie; Wang, Yuelang; Zhan, Chenyang; Zang, Yuhui; Qin, Junchuan

2005-05-01

Stem cell factor (SCF) and macrophage colony stimulating factor (M-CSF) can act in synergistic way to promote the growth of mononuclear phagocytes. SCF-M-CSF fusion proteins were designed on the computer using the Homology and Biopolymer modules of the software packages InsightII. Several existing crystal structures were used as templates to generate models of the complexes of receptor with fusion protein. The structure rationality of the fusion protein incorporated a series of flexible linker peptide was analyzed on InsightII system. Then, a suitable peptide GGGGSGGGGSGG was chosen for the fusion protein. Two recombinant SCF-M-CSF fusion proteins were generated by construction of a plasmid in which the coding regions of human SCF (1-165aa) and M-CSF (1-149aa) cDNA were connected by this linker peptide coding sequence followed by subsequent expression in insect cell. The results of Western blot and activity analysis showed that these two recombinant fusion proteins existed as a dimer with a molecular weight of 84 KD under non-reducing conditions and a monomer of 42 KD at reducing condition. The results of cell proliferation assays showed that each fusion protein induced a dose-dependent proliferative response. At equimolar concentration, SCF/M-CSF was about 20 times more potent than the standard monomeric SCF in stimulating TF-1 cell line growth, while M-CSF/SCF was 10 times of monomeric SCF. No activity difference of M-CSF/SCF or SCF/M-CSF to M-CSF (at same molar) was found in stimulating the HL-60 cell linear growth. The synergistic effect of SCF and M-CSF moieties in the fusion proteins was demonstrated by the result of clonogenic assay performed with human bone mononuclear, in which both SCF/M-CSF and M-CSF/SCF induced much higher number of CFU-M than equimolar amount of SCF or M-CSF or that of two cytokines mixture.

Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia.

Science.gov (United States)

Inobe, Jun-ichi; Kato, Takashi

2013-01-01

Electric stimulation (ES) has been recognized as an effective method to improve motor function to paralysed patients with stroke. It is important for ES to synchronize with voluntary movement. To enhance this co-ordination, the finger-equipped electrode (FEE) was developed. The purpose of this study was to evaluate FEE in improving motor function of upper extremities (UEs) in patients with chronic stroke. The study participants included four patients with chronic stroke who received FEE electronic stimulation (FEE-ES) plus passive and active training and three control patients who underwent training without FEE-ES. The patients were treated five times weekly for 4 weeks. UE motor function was evaluated before and after treatment using Fugl-Meyer Assessment (FMA) and Brunnstrom recovery staging. The mean age of patients in each group was 60-years and there was a mean of 49 months since the onset of symptoms. All patients had severe UE weakness. The patients receiving FEE-ES had greater improvement in UE function than control patients (total, proximal and distal FMA, p FEE-ES may be an effective treatment for patients with chronic stroke.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

Science.gov (United States)

Mhaskar, Rahul; Clark, Otavio Augusto Camara; Lyman, Gary; Engel Ayer Botrel, Tobias; Morganti Paladini, Luciano; Djulbegovic, Benjamin

2014-10-30

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

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Zhan-chi Zhang

2015-01-01

Full Text Available In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Improving visual functions in adult amblyopia with combined perceptual training and transcranial random noise stimulation (tRNS

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Gianluca eCampana

2014-12-01

Full Text Available Amblyopia is a visual disorder due to an abnormal pattern of functional connectivity of the visual cortex and characterized by several visual deficits of spatial vision including impairments of visual acuity (VA and of the contrast sensitivity function (CSF. Despite being a developmental disorder caused by reduced visual stimulation during early life (critical period, several studies have shown that extensive visual perceptual training can improve VA and CSF in people with amblyopia even in adulthood. With the present study we assessed whether a much shorter perceptual training regime, in association with high-frequency transcranial electrical stimulation (hf-tRNS, was able to improve visual functions in a group of adult participants with amblyopia. Results show that, in comparison with previous studies where a large number sessions with a similar training regime were used (Polat, Ma-Naim, Belkin & Sagi, 2004, here just eight sessions of training in contrast detection under lateral masking conditions combined with hf-tRNS, were able to substantially improve VA and CSF in adults with amblyopia.

Repetitive Transcranial Magnetic Stimulation Improves Handwriting in Parkinson’s Disease

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Bubblepreet K. Randhawa

2013-01-01

Full Text Available Background. Parkinson disease (PD is characterized by hypometric movements resulting from loss of dopaminergic neurons in the substantia nigra. PD leads to decreased activation of the supplementary motor area (SMA; the net result of these changes is a poverty of movement. The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation (rTMS over the SMA on a fine motor movement, handwriting (writing cursive “l”s, and on cortical excitability, in individuals with PD. Methods. In a cross-over design, ten individuals with PD were randomized to receive either 5 Hz or control stimulation over the SMA. Immediately following brain stimulation right handed writing was assessed. Results. 5 Hz stimulation increased vertical size of handwriting and diminished axial pressure. In addition, 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex. Conclusions. These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance, perhaps by altering cortical excitability across a network of brain regions. Further, these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD.

Effects of transcranial direct current stimulation on language improvement and cortical activation in nonfluent variant primary progressive aphasia.

Science.gov (United States)

Wang, Jie; Wu, Dongyu; Chen, Yan; Yuan, Ying; Zhang, Meikui

2013-08-09

We investigate the effects of transcranial direct current stimulation (tDCS) on language improvement and cortical activation in nonfluent variant primary progressive aphasia (nfvPPA). A 67-year-old woman diagnosed as nfvPPA received sham-tDCS for 5 days over the left posterior perisylvian region (PPR) in the morning and over left Broca's area in the afternoon in Phases A1 and A2, and tDCS for 5 days with an anodal electrode over the left PPR in the morning and over left Broca's area in the afternoon in Phases B1 and B2. Auditory word comprehension, picture naming, oral word reading and word repetition subtests of the Psycholinguistic Assessment in Chinese Aphasia (PACA) were administered before and after each phase. The EEG nonlinear index of approximate entropy (ApEn) was calculated before Phase A1, and after Phases B1 and B2. Our findings revealed that the patient improved greatly in the four subtests after A-tDCS and ApEn indices increased in stimulated areas and non-stimulated areas. We demonstrated that anodal tDCS over the left PPR and Broca's area can improve language performance of nfvPPA. tDCS may be used as an alternative therapeutic tool for PPA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

Science.gov (United States)

Ruszczak, Z; Ciborska, L; Kaszuba, A

1988-12-01

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

Directory of Open Access Journals (Sweden)

Jing Luo

2017-02-01

Full Text Available Repetitive transcranial magnetic stimulation (rTMS has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF/tropomyosin-related kinase B (TrkB pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO, following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX, NeuN and glial fibrillary acidic protein (GFAP, and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

SP-transcription factors are involved in basal MVP promoter activity and its stimulation by HDAC inhibitors.

Science.gov (United States)

Steiner, Elisabeth; Holzmann, Klaus; Pirker, Christine; Elbling, Leonilla; Micksche, Michael; Berger, Walter

2004-04-23

The major vault protein (MVP) has been implicated in multidrug resistance, cellular transport, and malignant transformation. In this study we aimed to identify crucial MVP promoter elements that regulate MVP expression. By mutation as well as deletion analysis a conserved proximal GC-box element was demonstrated to be essential for basal human MVP promoter transactivation. Binding of Sp-family transcription factors but not AP2 to this element in vitro and in vivo was shown by EMSA and ChIP assays, respectively. Inhibition of GC-box binding by a dominant-negative Sp1-variant and by mithramycin A distinctly attenuated MVP promoter activity. In Sp-null Drosophila cells, the silent human MVP promoter was transactivated by several human Sp-family members. In human cells the MVP promoter was potently stimulated by the histone deacetylase (HDAC) inhibitors butyrate (NaB) and trichostatin A (TSA), resulting in enhanced MVP expression. This stimulation was substantially decreased by mutation of the single GC-box and by application of mithramycin A. Treatment with HDAC inhibitors led to a distinct decrease of Sp1 but increase of Sp3 binding in vivo to the respective promoter sequence as demonstrated by ChIP assays. Summarising, this study identifies variations in Sp-transcription factor binding to a single proximal GC-box element as critical for basal MVP promoter activation and its stimulation by HDAC inhibitors.

Noninvasive brain stimulation of the parietal lobe for improving neurologic, neuropsychologic, and neuropsychiatric deficits.

Science.gov (United States)

Bolognini, Nadia; Miniussi, Carlo

2018-01-01

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are noninvasive brain stimulation (NIBS) tools that are now widely used in neuroscientific research in humans. The fact that both TMS and tES are able to modulate brain plasticity and, in turn, affect behavior is opening up new horizons in the treatment of brain circuit and plasticity disorders. In the present chapter, we will first provide the reader with a brief background on the basic principles of NIBS, describing the electromagnetic and physical foundations of TMS and tES, as well as the current knowledge of the neurophysiologic basis of their effects on brain activity and plasticity. In the main part, we will outline studies aimed at improving persistent symptoms and deficits in patients suffering from neurologic and neuropsychiatric disorders featured by dysfunction of the parietal lobe. The emerging view is that NIBS of parietal areas holds the promise to overcome various sensory, motor, and cognitive disorders that are often refractory to standard medical or behavioral therapies. The chapter closes with an outlook on further developments in this realm, discussing novel therapeutic approaches that could lead to more effective rehabilitation procedures, better suited for the specific parietal lobe dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

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Patrick Biggar

2017-09-01

Full Text Available Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

OpenAIRE

England, Timothy J.; Sprigg, Nikola; Alasheev, Andrey M.; Belkin, Andrey A.; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M.

2016-01-01

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and typ...

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

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Hui Wang

2016-01-01

Full Text Available Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS. Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01–5.27, p=0.001, and without sleep disturbance (OR: 2.51, 95%CI: 1.56–4.1, p=0.005 adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48–5.19, p=0.002 compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance.

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus

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Li, Bei; Wang, Meiye; Li, Ming; Yin, Shankai

2016-01-01

Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS). Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS) was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs) were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01–5.27, p = 0.001), and without sleep disturbance (OR: 2.51, 95%CI: 1.56–4.1, p = 0.005) adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48–5.19, p = 0.002) compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance. PMID:27847647

How do aggregated patient-reported outcome measures data stimulate health care improvement? A realist synthesis

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Dalkin, Sonia; Gibbons, Elizabeth; Wright, Judy; Valderas, Jose Maria; Meads, David; Black, Nick

2017-01-01

Objectives Internationally, there has been considerable debate about the role of data in supporting quality improvement in health care. Our objective was to understand how, why and in what circumstances the feedback of aggregated patient-reported outcome measures data improved patient care. Methods We conducted a realist synthesis. We identified three main programme theories underlying the use of patient-reported outcome measures as a quality improvement strategy and expressed them as nine ‘if then’ propositions. We identified international evidence to test these propositions through searches of electronic databases and citation tracking, and supplemented our synthesis with evidence from similar forms of performance data. We synthesized this evidence through comparing the mechanisms and impact of patient-reported outcome measures and other performance data on quality improvement in different contexts. Results Three programme theories were identified: supporting patient choice, improving accountability and enabling providers to compare their performance with others. Relevant contextual factors were extent of public disclosure, use of financial incentives, perceived credibility of the data and the practicality of the results. Available evidence suggests that patients or their agents rarely use any published performance data when selecting a provider. The perceived motivation behind public reporting is an important determinant of how providers respond. When clinicians perceived that performance indicators were not credible but were incentivized to collect them, gaming or manipulation of data occurred. Outcome data do not provide information on the cause of poor care: providers needed to integrate and interpret patient-reported outcome measures and other outcome data in the context of other data. Lack of timeliness of performance data constrains their impact. Conclusions Although there is only limited research evidence to support some widely held theories of how

Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

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S Montagnani

2009-12-01

Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

A single trial of transcutaneous electrical nerve stimulation (TENS) improves spasticity and balance in patients with chronic stroke.

Science.gov (United States)

Cho, Hwi-young; In, Tae Sung; Cho, Ki Hun; Song, Chang Ho

2013-03-01

Spasticity management is pivotal for achieving functional recovery of stroke patients. The purpose of this study was to investigate the effects of a single trial of transcutaneous electrical nerve stimulation (TENS) on spasticity and balance in chronic stroke patients. Forty-two chronic stroke patients were randomly allocated into the TENS (n = 22) or the placebo-TENS (n = 20) group. TENS stimulation was applied to the gastrocnemius for 60 min at 100 Hz, 200 µs with 2 to 3 times the sensory threshold (the minimal threshold in detecting electrical stimulation for subjects) after received physical therapy for 30 min. In the placebo-TENS group, electrodes were placed but no electrical stimulation was administered. For measuring spasticity, the resistance encountered during passive muscle stretching of ankle joint was assessed using the Modified Ashworth Scale, and the Hand held dynamometer was used to assess the resistive force caused by spasticity. Balance ability was measured using a force platform that measures postural sway generated by postural imbalance. The TENS group showed a significantly greater reduction in spasticity of the gastrocnemius, compared to the placebo-TENS group (p TENS resulted in greater balance ability improvements, especially during the eyes closed condition (p TENS provides an immediately effective means of reducing spasticity and of improving balance in chronic stroke patients. The present data may be useful to establish the standard parameters for TENS application in the clinical setting of stroke.

Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

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Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

2013-12-01

Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. © 2013.

The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

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Chao-Huei Yang

2016-01-01

Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

Stimulating thought: a functional MRI study of transcranial direct current stimulation in schizophrenia.

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Orlov, Natasza D; O'Daly, Owen; Tracy, Derek K; Daniju, Yusuf; Hodsoll, John; Valdearenas, Lorena; Rothwell, John; Shergill, Sukhi S

2017-09-01

Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia. © The Author (2017). Published by Oxford

Using Low Levels of Stochastic Vestibular Stimulation to Improve Balance Function.

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Rahul Goel

Full Text Available Low-level stochastic vestibular stimulation (SVS has been associated with improved postural responses in the medio-lateral (ML direction, but its effect in improving balance function in both the ML and anterior-posterior (AP directions has not been studied. In this series of studies, the efficacy of applying low amplitude SVS in 0-30 Hz range between the mastoids in the ML direction on improving cross-planar balance function was investigated. Forty-five (45 subjects stood on a compliant surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in ML, AP and combined APML directions. Results show that binaural bipolar SVS given in the ML direction significantly improved balance performance with the peak of optimal stimulus amplitude predominantly in the range of 100-500 μA for all the three directions, exhibiting stochastic resonance (SR phenomenon. Objective perceptual and body motion thresholds as estimates of internal noise while subjects sat on a chair with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical stimuli were also measured. In general, there was no significant difference between estimates of perceptual and body motion thresholds. The average optimal SVS amplitude that improved balance performance (peak SVS amplitude normalized to perceptual threshold was estimated to be 46% in ML, 53% in AP, and 50% in APML directions. A miniature patch-type SVS device may be useful to improve balance function in people with disabilities due to aging, Parkinson's disease or in astronauts returning from long-duration space flight.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

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Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

2015-08-01

In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

International Nuclear Information System (INIS)

Chan, C.P.; Bowen-Pope, D.F.; Ross, R.; Krebs, E.G.

1986-01-01

Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125 I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

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Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

2015-04-01

Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth.

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Koppes, Abigail N; Nordberg, Andrea L; Paolillo, Gina M; Goodsell, Nicole M; Darwish, Haley A; Zhang, Linxia; Thompson, Deanna M

2014-02-01

Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8 h stimulation over a range of DC fields (0-200 mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50 mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72 h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in

The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

DEFF Research Database (Denmark)

Nielsen, S D; Sørensen, T U; Aladdin, H

2000-01-01

This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was ...

Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation

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James K. Hoffman

2015-01-01

Full Text Available Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.

Effectiveness of Sensory Stimulation to Improve Arousal and Alertness of People in a Coma or Persistent Vegetative State After Traumatic Brain Injury: A Systematic Review.

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Padilla, René; Domina, Anna

2016-01-01

This systematic review evaluates the effectiveness of sensory stimulation to improve arousal and alertness of people in a coma or persistent vegetative state after traumatic brain injury (TBI). Databases searched included Medline, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews. The search was limited to outcomes studies published in English in peer-reviewed journals between 2008 and 2013. Included studies provide strong evidence that multimodal sensory stimulation improves arousal and enhances clinical outcomes for people in a coma or persistent vegetative state after TBI. Moderate evidence was also provided for auditory stimulation, limited evidence was provided for complex stimuli, and insufficient evidence was provided for median nerve stimulation. Interventions should be tailored to client tolerance and premorbid preferences. Bimodal or multimodal stimulation should begin early, be frequent, and be sustained until more complex activity is possible. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

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Mendonça, Marcelo D; Barbosa, Raquel; Seromenho-Santos, Alexandra; Reizinho, Carla; Bugalho, Paulo

2018-04-01

Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors.

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Devandir Antonio de Souza Junior

Full Text Available Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7 in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.

Stimulating and Developing High School Students’Motivation in Their English Learning

Institute of Scientific and Technical Information of China (English)

笈文婷

2014-01-01

Stimulating learning motivation refers to transforming potential learning motivation to learning behavior.Motivation is the core of learning process,keeping right and long-lasting power is the premise of English learning.As for present English teaching,teachers often face students lacking learning interests and learning motivation,so how to stimulate and develop these students’learning motivation is a universal prob-lem for many teachers,of course it is a difficult problem.The essay aims at analyzing the classifications of English learning motivation,the influen-tial factors of learning motivation and how to improve English learning motivation from many ways.

Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

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Yao-xian Xiang

2015-01-01

Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

Inhibition of colony-stimulating factor 1 receptor early in disease ameliorates motor deficits in SCA1 mice.

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Qu, Wenhui; Johnson, Andrea; Kim, Joo Hyun; Lukowicz, Abigail; Svedberg, Daniel; Cvetanovic, Marija

2017-05-25

Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1. Transgenic mouse model of SCA1, ATXN1[82Q] mice, and wild-type littermate controls were treated with PLX from 3 weeks of age. The effects of PLX on microglial density, astrogliosis, motor behavior, atrophy, and gene expression of Purkinje neurons were examined at 3 months of age. PLX treatment resulted in the elimination of 70-80% of microglia from the cerebellum of both wild-type and ATXN1[82Q] mice. Importantly, PLX ameliorated motor deficits in SCA1 mice. While we have not observed significant improvement in the atrophy or disease-associated gene expression changes in Purkinje neurons upon PLX treatment, we have detected reduced expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and increase in the protein levels of wild-type ataxin-1 and post-synaptic density protein 95 (PSD95) that may help improve PN function. A decrease in the number of microglia during an early stage of disease resulted in the amelioration of motor deficits in SCA1 mice.

Growth Factor Supplementation Improves Native and Engineered Meniscus Repair in Vitro

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Ionescu, Lara C.; Lee, Gregory C.; Huang, Kevin L.; Mauck, Robert L.

2012-01-01

Few therapeutic options exist for meniscus repair after injury. Local delivery of growth factors may stimulate repair and create a favorable environment for engineered replacement materials. In this study, we assessed the effect of basic fibroblast growth factor (bFGF) (a pro-mitotic agent) and transforming growth factor beta 3 (TGF-β3) (a pro-matrix formation agent) on meniscus repair and the integration/maturation of electrospun poly(ε-caprolactone) (PCL) scaffolds for meniscus tissue engineering. Circular meniscus repair constructs were formed and refilled with either native tissue or scaffolds. Repair constructs were cultured in serum-containing media for 4 and 8 weeks with various growth factor formulations, and assessed for mechanical strength, biochemical content, and histological appearance. Results showed that either short-term delivery of bFGF or sustained delivery of TGF-β3 increased integration strength for both juvenile and adult bovine tissue, with similar findings for engineered materials. While TGF-β3 increased proteoglycan content in the explants, bFGF did not increase DNA content after 8 weeks. This work suggests that in vivo delivery of bFGF or TGF-β3 may stimulate meniscus repair, but that the time course of delivery will strongly influence success. Further, this study demonstrates that electrospun scaffolds are a promising material for meniscus tissue engineering, achieving comparable or superior integration compared to native tissue. PMID:22698946

Stimulants improve theory of mind in children with attention deficit/hyperactivity disorder.

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Maoz, Hagai; Tsviban, Lior; Gvirts, Hila Z; Shamay-Tsoory, Simone G; Levkovitz, Yechiel; Watemberg, Nathan; Bloch, Yuval

2014-03-01

Impairments in 'theory of mind' (ToM) were linked to social cognition and reciprocal relationships deficits in children with attention deficit/hyperactivity disorder (ADHD). Twenty-four children with ADHD (13 with inattentive type and 11 with combined type, mean age 10.2 years) completed the Interpersonal Reactivity Index (IRI), a self-reported empathy questionnaire. All children performed the 'faux pas' task and a computerized ToM task in two different sessions either with or without administration of methylphenidate (MPH). Administration of MPH was associated with an improvement in cognitive and affective ToM. Children with ADHD-combined type had significantly lower scores in total IRI and the fantasy scale compared to children with ADHD-inattentive type. We conclude that deficits in empathy and ToM may play an important role in the impairments in social cognition and peer relationship in children with ADHD, especially children a hyperactive component. Stimulants may improve ToM and empathic functions. Future studies including larger samples and additional cognitive tasks are warranted in order to generalize these results and to identify possible underlying mechanisms for improvement in ToM following the administration of MPH.

Human Granulocyte Colony-Stimulating Factor (hG-CSF) Expression in Plastids of Lactuca sativa

OpenAIRE

Sharifi Tabar, Mehdi; Habashi, Ali Akbar; Rajabi Memari, Hamid

2013-01-01

Background: Human granulocyte colony-stimulating factor (hG-CSF) can serve as valuable biopharmaceutical for research and treatment of the human blood cancer. Transplastomic plants have been emerged as a new and high potential candidate for production of recombinant biopharmaceutical proteins in comparison with transgenic plants due to extremely high level expression, biosafety and many other advantages. Methods: hG-CSF gene was cloned into pCL vector between prrn16S promoter and TpsbA ter...

Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line

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Y Kobayashi

2009-06-01

Full Text Available Low-intensity pulsed ultrasound (LIPUS stimulation has been shown to effect differentiation and activation of human chondrocytes. A study involving stimulation of rabbit disc cells with LIPUS revealed upregulation of cell proliferation and proteoglycan (PG synthesis. However, the effect of LIPUS on human nucleus pulposus cells has not been investigated. In the present study, therefore, we investigated whether LIPUS stimulation of a human nucleus pulposus cell line (HNPSV-1 exerted a positive effect on cellular activity. HNPSV-1 cells were encapsulated in 1.2% sodium alginate solution at 1x105 cells/ml and cultured at 10 beads/well in 6-well plates. The cells were stimulated for 20 min each day using a LIPUS generator, and the effects of LIPUS were evaluated by measuring DNA and PG synthesis. Furthermore, mRNA expression was analyzed by cDNA microarray using total RNA extracted from the cultured cells. Our study revealed no significant difference in cell proliferation between the control and the ultrasound treated groups. However, PG production was significantly upregulated in HNPSV cells stimulated at intensities of 15, 30, 60, and 120 mW/cm2 compared with the control. The results of cDNA array showed that LIPUS significantly stimulated the gene expression of growth factors and their receptors (BMP2, FGF7, TGFbetaR1 EGFRF1, VEGF. These findings suggest that LIPUS stimulation upregulates PG production in human nucleus pulposus cells by the enhancement of several matrix-related genes including growth factor-related genes. Safe and non-invasive stimulation using LIPUS may be a useful treatment for delaying the progression of disc degeneration.

Visual training paired with electrical stimulation of the basal forebrain improves orientation-selective visual acuity in the rat.

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Kang, Jun Il; Groleau, Marianne; Dotigny, Florence; Giguère, Hugo; Vaucher, Elvire

2014-07-01

The cholinergic afferents from the basal forebrain to the primary visual cortex play a key role in visual attention and cortical plasticity. These afferent fibers modulate acute and long-term responses of visual neurons to specific stimuli. The present study evaluates whether this cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repeatedly for 2 weeks to an orientation-specific grating with or without coupling this visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after the exposure to the orientation-specific grating, was increased in the group of trained rats with simultaneous basal forebrain/visual stimulation. The increase in visual acuity was not observed when visual training or basal forebrain stimulation was performed separately or when cholinergic fibers were selectively lesioned prior to the visual stimulation. The visual evoked potentials show a long-lasting increase in cortical reactivity of the primary visual cortex after coupled visual/cholinergic stimulation, as well as c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. This study opens the possibility of establishing efficient rehabilitation strategies for facilitating visual capacity.

Artificial Walking Technologies to Improve Gait in Cerebral Palsy: Multichannel Neuromuscular Stimulation.

Science.gov (United States)

Rose, Jessica; Cahill-Rowley, Katelyn; Butler, Erin E

2017-11-01

Cerebral palsy (CP) is the most common childhood motor disability and often results in debilitating walking abnormalities, such as flexed-knee and stiff-knee gait. Current medical and surgical treatments are only partially effective in improving gait abnormalities and may cause significant muscle weakness. However, emerging artificial walking technologies, such as step-initiated, multichannel neuromuscular electrical stimulation (NMES), can substantially improve gait patterns and promote muscle strength in children with spastic CP. NMES may also be applied to specific lumbar-sacral sensory roots to reduce spasticity. Development of tablet computer-based multichannel NMES can leverage lightweight, wearable wireless stimulators, advanced control design, and surface electrodes to activate lower-limb muscles. Musculoskeletal models have been used to characterize muscle contributions to unimpaired gait and identify high muscle demands, which can help guide multichannel NMES-assisted gait protocols. In addition, patient-specific NMES-assisted gait protocols based on 3D gait analysis can facilitate the appropriate activation of lower-limb muscles to achieve a more functional gait: stance-phase hip and knee extension and swing-phase sequence of hip and knee flexion followed by rapid knee extension. NMES-assisted gait treatment can be conducted as either clinic-based or home-based programs. Rigorous testing of multichannel NMES-assisted gait training protocols will determine optimal treatment dosage for future clinical trials. Evidence-based outcome evaluation using 3D kinematics or temporal-spatial gait parameters will help determine immediate neuroprosthetic effects and longer term neurotherapeutic effects of step-initiated, multichannel NMES-assisted gait in children with spastic CP. Multichannel NMES is a promising assistive technology to help children with spastic CP achieve a more upright, functional gait. © 2017 International Center for Artificial Organs and

Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer's disease: a pilot study.

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Eliasova, Ilona; Anderkova, Lubomira; Marecek, Radek; Rektorova, Irena

2014-11-15

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool for modulating cortical activity. In this pilot study, we evaluated the effects of high frequency rTMS applied over the right inferior frontal gyrus (IFG) on cognitive functions in patients with amnestic mild cognitive impairment (MCI) or incipient dementia due to Alzheimer's disease (AD). Ten patients (6 men; 4 women, mean age of 72 ± 8 years; MMSE 23 ± 3.56) were enrolled in a randomized, placebo-controlled study with a crossover design. All participants received 2 sessions of 10 Hz rTMS over the non-dominant right hemisphere in random order: IFG (active stimulation site) and vertex (control stimulation site). Intensities were adjusted to 90% of resting motor threshold. A total of 2250 pulses were applied in a session. The Trail Making Test (TMT), the Stroop test, and the complex visual scene encoding task (CVSET) were administered before and immediately after each session. The Wilcoxon paired test was used for data analysis. Stimulation applied over the IFG induced improvement in the TMT parts A (p = 0.037) and B (p = 0.049). No significant changes were found in the Stroop test or the CVSET after the IFG stimulation. We observed no significant cognitive aftereffects of rTMS applied over the vertex. High frequency rTMS of the right IFG induced significant improvement of attention and psychomotor speed in patients with MCI/mild dementia due to AD. This pilot study is part of a more complex protocol and ongoing research. Copyright © 2014 Elsevier B.V. All rights reserved.

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia.

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Bradnam, Lynley V; Graetz, Lynton J; McDonnell, Michelle N; Ridding, Michael C

2015-01-01

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer's dystonia, 3 musician's dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer's Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

International Nuclear Information System (INIS)

Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

1986-01-01

The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

Myeloprotective Action of Combined Application of Ukrainian Recombinant Granulocyte Colony Stimulating Factor (r-GCSF and Enterosorbent С2 in Rats with Malignant Guerin Carcinoma

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Todor, I.M.

2015-03-01

Full Text Available The aim of the study is to analyze myeloprotective effect of novel enterosorbents alone and in combination with two recombinant granulocyte colony stimulating factors: Neupogen (Switzerland and r- GCSF (Ukraine. It is proven that Ukrainian version of recombinant granulocyte colony stimulating factor r-GCSF does not concede officinal drug Neupogen (Switzerland by its experimental therapeutic action and combined use with enterosorbent C2 significantly increases myeloprotective effect of both GCSF versions.

A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

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Cihun-Siyong Alex Gong

2015-05-01

Full Text Available Deep brain stimulation (DBS is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design.

Effect of granulocyte colony stimulating factor (G-CSF on IVF outcomes in infertile women: An RCT

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Maryam Eftekhar

2016-05-01

Full Text Available Background: Despite major advances in assisted reproductive techniques, the implantation rates remain relatively low. Some studies have demonstrated that intrauterine infusion of granulocyte colony stimulating factor (G-CSF improves implantation in infertile women. Objective: To assess the G-CSF effects on IVF outcomes in women with normal endometrial thickness. Materials and methods: In this randomized controlled clinical trial, 100 infertile women with normal endometrial thickness who were candidate for IVF were evaluated in two groups. Exclusion criteria were positive history of repeated implantation failure (RIF, endocrine disorders, severe endometriosis, congenital or acquired uterine anomaly and contraindication for G-CSF (renal disease, sickle cell disease, or malignancy. In G-CSF group (n=50, 300 μg trans cervical intrauterine of G-CSF was administered at the oocyte retrieval day. Controls (n=50 were treated with standard protocol. Chemical, clinical and ongoing pregnancy rates, implantation rate, and miscarriage rate were compared between groups. Results: Number of total and mature oocytes (MII, two pronuclei (2PN, total embryos, transferred embryos, quality of transferred embryos, and fertilization rate did not differ significantly between two groups. So there were no significant differences between groups in chemical, clinical and ongoing pregnancy rate, implantation rate, and miscarriage rate Conclusion: our result showed in normal IVF patients with normal endometrial thickness, the intrauterine infusion of G-CSF did not improve pregnancy outcomes.

Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

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Sixel-Döring, Friederike; Trenkwalder, Claudia; Kappus, Christoph; Hellwig, Dieter

2010-02-01

Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

Improvement of Isolated Myoclonus Phenotype in Myoclonus Dystonia after Pallidal Deep Brain Stimulation

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Ritesh Ramdhani

2016-03-01

Full Text Available Background: Myoclonus–dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE. In medically refractory cases, deep brain stimulation (DBS has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus–dystonia (one SGCE positive and the other SGCE negative who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi. Methods: We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. Results: Both patients demonstrated complete amelioration of all aspects of myoclonus within 6–12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz with amplitudes greater than 2.5 V provided therapeutic benefit. Discussion: This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus–dystonia, regardless of the presence of SGCE mutation.

Combined Stimulation with the Tumor Necrosis Factor α and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices

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Francis Finot

2012-01-01

Full Text Available The culture liver slices are mainly used to investigate drug metabolism and xenobiotic-mediated liver injuries while apoptosis and proliferation remain unexplored in this culture model. Here, we show a transient increase in LDH release and caspase activities indicating an ischemic injury during the slicing procedure. Then, caspase activities decrease and remain low in cultured slices demonstrating a low level of apoptosis. The slicing procedure is also associated with the G0/G1 transition of hepatocytes demonstrated by the activation of stress and proliferation signalling pathways including the ERK1/2 and JNK1/2/3 MAPKinases and the transient upregulation of c-fos. The cells further progress up to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA levels after the slicing procedure and at 24 h of culture, respectively. The stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but fails to activate expression of late G1 and S phase markers such as cyclin D1 and Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle. However, we found that combined stimulation by the proinflammatory cytokine tumor necrosis factor α and the epidermal growth factor promotes the commitment to DNA replication as observed in vivo during the liver regeneration.

Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures

International Nuclear Information System (INIS)

Morales, T.I.

1991-01-01

Previous work showed that transforming growth factor-beta 1 (TGF-beta 1), added alone to bovine cartilage organ cultures, stimulated [35S]sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-beta 1 stimulation: (1) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (2) link-stable proteoglycan aggregates are assembled, (3) the hybrid chondroitin sulfate/keratan sulfate monomeric species is synthesized, and (4) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-beta 1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-beta 1 to basal samples respectively, the monomers were larger (Kav on Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by approximately 3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from approximately 4% (basal) to approximately 6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function

Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

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Kondo, Eiji; Jinnouchi, Osamu; Nakano, Seiichi; Ohnishi, Hiroki; Kawata, Ikuji; Okamoto, Hidehiko; Takeda, Noriaki

2017-01-01

The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. A randomized, placebo-controlled, double-blind, comparative study. Secondary hospital. Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

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Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C. (Univ. of California, San Francisco (USA))

1990-06-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

International Nuclear Information System (INIS)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C.

1990-01-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection

Vagal stimulation in heart failure.

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De Ferrari, Gaetano M

2014-04-01

Heart failure (HF) is accompanied by an autonomic imbalance that is almost always characterized by both increased sympathetic activity and withdrawal of vagal activity. Experimentally, vagal stimulation has been shown to exert profound antiarrhythmic activity and to improve cardiac function and survival in HF models. A open-label pilot clinical study in 32 patients with chronic HF has shown safety and tolerability of chronic vagal stimulation associated with subjective (improved quality of life and 6-min walk test) and objective improvements (reduced left ventricular systolic volumes and improved left ventricular ejection fraction). Three larger clinical studies, including a phase III trial are currently ongoing and will evaluate the clinical role of this new approach.

Glucose Stimulation of Transforming Growth Factor-β Bioactivity in Mesangial Cells Is Mediated by Thrombospondin-1

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Poczatek, Maria H.; Hugo, Christian; Darley-Usmar, Victor; Murphy-Ullrich, Joanne E.

2000-01-01

Glucose is a key factor in the development of diabetic complications, including diabetic nephropathy. The development of diabetic glomerulosclerosis is dependent on the fibrogenic growth factor, transforming growth factor-β (TGF-β). Previously we showed that thrombospondin-1 (TSP-1) activates latent TGF-β both in vitro and in vivo. Activation occurs as the result of specific interactions of latent TGF-β with TSP-1, which potentially alter the conformation of latent TGF-β. As glucose also up-regulates TSP-1 expression, we hypothesized that the increased TGF-β bioactivity observed in rat and human mesangial cells cultured with high glucose concentrations is the result of latent TGF-β activation by autocrine TSP-1. Glucose-induced bioactivity of TGF-β in mesangial cell cultures was reduced to basal levels by peptides from two different sequences that antagonize activation of latent TGF-β by TSP, but not by the plasmin inhibitor, aprotinin. Furthermore, glucose-dependent stimulation of matrix protein synthesis was inhibited by these antagonist peptides. These studies demonstrate that glucose stimulation of TGF-β activity and the resultant matrix protein synthesis are dependent on the action of autocrine TSP-1 to convert latent TGF-β to its biologically active form. These data suggest that antagonists of TSP-dependent TGF-β activation may be the basis of novel therapeutic approaches for ameliorating diabetic renal fibrosis. PMID:11021838

Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis

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Dai, Chenkai; Fridman, Gene Y.; Chiang, Bryce; Davidovics, Natan; Melvin, Thuy-Anh; Cullen, Kathleen E.; Della Santina, Charles C.

2012-01-01

By sensing three-dimensional (3D) head rotation and electrically stimulating the three ampullary branches of a vestibular nerve to encode head angular velocity, a multichannel vestibular prosthesis (MVP) can restore vestibular sensation to individuals disabled by loss of vestibular hair cell function. However, current spread to afferent fibers innervating non-targeted canals and otolith endorgans can distort the vestibular nerve activation pattern, causing misalignment between the perceived and actual axis of head rotation. We hypothesized that over time, central neural mechanisms can adapt to correct this misalignment. To test this, we rendered five chinchillas vestibular-deficient via bilateral gentamicin treatment and unilaterally implanted them with a head mounted MVP. Comparison of 3D angular vestibulo-ocular reflex (aVOR) responses during 2 Hz, 50°/s peak horizontal sinusoidal head rotations in darkness on the first, third and seventh days of continual MVP use revealed that eye responses about the intended axis remained stable (at about 70% of the normal gain) while misalignment improved significantly by the end of one week of prosthetic stimulation. A comparable time course of improvement was also observed for head rotations about the other two semicircular canal axes and at every stimulus frequency examined (0.2–5 Hz). In addition, the extent of disconjugacy between the two eyes progressively improved during the same time window. These results indicate that the central nervous system rapidly adapts to multichannel prosthetic vestibular stimulation to markedly improve 3D aVOR alignment within the first week after activation. Similar adaptive improvements are likely to occur in other species, including humans. PMID:21374081

Transcutaneous electrical nerve stimulation (TENS) improves the diabetic cytopathy (DCP) via up-regulation of CGRP and cAMP.

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Ding, Liucheng; Song, Tao; Yi, Chaoran; Huang, Yi; Yu, Wen; Ling, Lin; Dai, Yutian; Wei, Zhongqing

2013-01-01

The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n=15), DM group (n=15) and control group (n=15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

Evaluation of the effectiveness of transcranial direct current stimulation (tDCS) and psychosensory stimulation through DOCS scale in a minimally conscious subject.

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Dimitri, Danilo; De Filippis, Daniela; Galetto, Valentina; Zettin, Marina

2017-04-01

The aim of our study was to assess the effectiveness of transcranial direct current stimulation (tDCS) on alertness improvement in a patient in a minimally conscious state (MCS) by means of disorders of consciousness scale combined with psycho-sensory stimulation. The effects of tDCS on muscle hypertonia through the Ashworth scale were also examined. tDCS was performed through a two-channel intra-cephalic stimulator. After stimulation, the patient followed a psychosensory stimulation training. Results pointed out an increase in DOCunit score, as well as an increase in alertness maintenance and an improvement in muscle hypertonia, although a MCS state persisted.

Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease.

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Antoniades, Chrystalina A; Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z; Green, Alexander L; FitzGerald, James J

2015-09-23

from one circuit within the brain to another, as a result of overactivity of certain nerve cells. By demonstrating that stimulation of an area called the globus pallidus interna partially reverses deficits in voluntary control of eye movements, this study shows that stimulation can improve information flow between circuits, probably by calming down the overactive cells. Copyright © 2015 the authors 0270-6474/15/3513043-10$15.00/0.

Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease.

NARCIS (Netherlands)

Helmich, R.C.G.; Siebner, H.R.; Bakker, M.; Munchau, A.; Bloem, B.R.

2006-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions

Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

International Nuclear Information System (INIS)

Carter, M.G.; Shukla, S.D.

1987-01-01

Human platelet concentrate from the American Red Cross Blood Center was stored at 24 degree C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying 32 P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 x 10 -7 M PAF at 37 degree C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for 32 P-phosphoinositides. The percent stimulation of 32 P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage

Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.

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Yates, A P; Rustamov, O; Roberts, S A; Lim, H Y N; Pemberton, P W; Smith, A; Nardo, L G

2011-09-01

Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation. Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols. Embryo transfer rates increased significantly (79-87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9-27.7%, P= 0.002 and 15.9-23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9-2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups. Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

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Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Gonchar, Ilya V., E-mail: ample@mail.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kharchenko, Marianna V., E-mail: mariannakharchenko@gmail.com [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kornilova, Elena S., E-mail: lenkor@mail.cytspb.rssi.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya, St.Petersburg, 195251 (Russian Federation)

2016-04-22

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

International Nuclear Information System (INIS)

Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

2016-01-01

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Plasma rich in growth factors (PRGF-Endoret) reduces neuropathologic hallmarks and improves cognitive functions in an Alzheimer's disease mouse model.

Science.gov (United States)

Anitua, Eduardo; Pascual, Consuelo; Antequera, Desiree; Bolos, Marta; Padilla, Sabino; Orive, Gorka; Carro, Eva

2014-07-01

Impaired growth factor function is thought to drive many of the alterations observed in Alzheimer's disease (AD) patients. Endogenous regenerative technology, PRGF (plasma rich in growth factor)-Endoret, is designed for the delivery of a complex pool of patient's own active morphogens that may stimulate tissue regeneration. We obtained and characterized PRGF-Endoret preparations from human blood. We used, as experimental approach in vivo, APP/PS1 mice, characterized by age-dependent brain amyloid-β (Aβ) accumulation. Intranasal administration of PRGF-Endoret to APP/PS1 mice resulted in an important decrease in brain Aβ deposition and tau phosphorylation. PRGF-Endoret-treated APP/PS1 mice also showed decreased astrocyte reactivity, and prevented protein synaptic loss. In vitro approaches demonstrated that PRGF-Endoret treatment modulated astrocyte activation, reducing inflammatory responses, and promoted Aβ degradation. Furthermore, PRGF-Endoret stimulated global improvements in anxiety, learning, and memory behaviors. Our findings show that PRGF-Endoret exerts multifunctional and complementary effects that result in the reversal of the broad range of cognitive deficits in AD, suggesting that PRGF-Endoret may hold promise as an innovative therapy in AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.

Science.gov (United States)

Harada, Naoaki; Zhao, Juan; Kurihara, Hiroki; Nakagata, Naomi; Okajima, Kenji

2011-08-01

The stimulation of sensory neurons in the gastrointestinal (GI) tract improves cognitive function by increasing the hippocampal production of insulin-like growth factor-I (IGF-I) in mice. In the current study, we examined whether oral administration of desalted deep-sea water (DSW) increases the hippocampal production of IGF-I by stimulating sensory neurons in the GI tract, thereby improving cognitive function in mice. Desalted DSW increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT) mice by activating transient receptor potential vanilloid 1. The plasma levels of IGF-I and tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus were increased by oral administration of desalted DSW in WT mice. In these animals, nociceptive information originating from the GI tract was transmitted to the hippocampus via the spinothalamic pathway. Improvement of spatial learning was observed in WT mice after administration of desalted DSW. Distilled DSW showed results similar to those of desalted DSW in vitro and in vivo. None of the effects of desalted DSW in WT mice were observed after the administration of desalted DSW in CGRP-knockout (CGRP-/-) mice. No volatile compounds were detected in distilled DSW on GC-MS analysis. These observations suggest that desalted DSW may increase the hippocampal IGF-I production via sensory neuron stimulation in the Gl tract, thereby improving cognitive function in mice. Such effects of desalted DSW might not be dependent on the minerals but are dependent on the function of the water molecule itself. Copyright © 2011 Mosby, Inc. All rights reserved.

Pedagogical Factors Stimulating the Self-Development of Students' Multi-Dimensional Thinking in Terms of Subject-Oriented Teaching

Science.gov (United States)

Andreev, Valentin I.

2014-01-01

The main aim of this research is to disclose the essence of students' multi-dimensional thinking, also to reveal the rating of factors which stimulate the raising of effectiveness of self-development of students' multi-dimensional thinking in terms of subject-oriented teaching. Subject-oriented learning is characterized as a type of learning where…

Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

DEFF Research Database (Denmark)

Zohlnhofer, D.; Dibra, A.; Koppara, T.

2008-01-01

OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

Bicycling to school improves the cardiometabolic risk factor profile

DEFF Research Database (Denmark)

Ostergaard, Lars; Børrestad, Line A B; Tarp, Jakob

2012-01-01

To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children.......To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children....

Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

OpenAIRE

Gunduz, Aysegul; Kumru, Hatice; Pascual-Leone, Alvaro

2014-01-01

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving ...

EGF–FGF2 stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs)

International Nuclear Information System (INIS)

Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves; Bittencourt, Denise Avani; Visoni, Silvia; Jeremias, Talita Silva; Costa, Ana Paula; Leal, Rodrigo Bainy; Trentin, Andrea Gonçalves

2014-01-01

Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF 2 ) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF 2 , however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF 2 in neuronal differentiation protocols. - Highlights: • EPI-NCSCs express

Influence of in vitro irradiation upon LIF production by ConA stimulated mononuclear cells

International Nuclear Information System (INIS)

Sandru, G.; Veraguth, P.

1981-01-01

Leukocyte migration inhibitory factor (LIF) activity of culture supernatants of in vitro irradiated Concanavalin A (ConA) stimulated lymphocytes was tested by measuring granulocyte migration from clotted plasma droplets placed in flat bottom microplates. The specificity of inhibition was assured by pretreating the assay supernatants with anti-LIF antibodies which abrogated granulocyte migration inhibition but did not impair guinea pig Peritoneal Exudate Cells (PEC) migration inhibition. In vitro irradiation (150-1200 rads) of MNC cultures either before or after ConA stimulation did not impair lymphokine production and sometimes significantly improved the supernatants' LIF activity as compared with that of unirradiated cultures. The existence of radiosensitive suppressor cells regulating LIF production by ConA stimulated mononuclear cells is suggested

Drivers and Risk Factors of Unplanned 30-Day Readmission Following Spinal Cord Stimulator Implantation.

Science.gov (United States)

Elsamadicy, Aladine A; Sergesketter, Amanda; Ren, Xinru; Mohammed Qasim Hussaini, Syed; Laarakker, Avra; Rahimpour, Shervin; Ejikeme, Tiffany; Yang, Siyun; Pagadala, Promila; Parente, Beth; Xie, Jichun; Lad, Shivanand P

2018-01-01

Unplanned 30-day readmission rates contribute significantly to growing national healthcare expenditures. Drivers of unplanned 30-day readmission after spinal cord stimulator (SCS) implantation are relatively unknown. The aim of this study was to determine drivers of 30-day unplanned readmission following SCS implantation. The National Readmission Database was queried to identify all patients who underwent SCS implantation for the 2013 calendar year. Patients were grouped by readmission status, "No Readmission" and "Unplanned 30-day Readmission." Patient demographics and comorbidities were collected for each patient. The primary outcome of interest was the rate of unplanned 30-day readmissions and associated driving factors. A multivariate analysis was used to determine independent predictors of unplanned 30-day readmission after SCS implantation. We identified 1521 patients who underwent SCS implantation, with 113 (7.4%) experiencing an unplanned readmission within 30 days. Baseline patient demographics, comorbidities, and hospital characteristics were similar between both cohorts. The three main drivers for 30-day readmission after SCS implantation include: 1) infection (not related to SCS device), 2) infection due to device (limited to only hardware infection), and 3) mechanical complication of SCS device. Furthermore, obesity was found to be an independent predictor of 30-day readmission (OR: 1.86, p = 0.008). Our study suggests that infectious and mechanical complications are the primary drivers of unplanned 30-day readmission after SCS implantation, with obesity as an independent predictor of unplanned readmission. Given the technological advancements in SCS, repeated studies are necessary to identify factors associated with unplanned 30-day readmission rates after SCS implantation to improve patient outcomes and reduce associated costs. © 2017 International Neuromodulation Society.

Improvements in fitness are not obligatory for exercise training-induced improvements in CV risk factors.

Science.gov (United States)

Hartman, Yvonne A W; Hopman, Maria T E; Schreuder, Tim H; Verheggen, Rebecca J H M; Scholten, Ralph R; Oudegeest-Sander, Madelijn H; Poelkens, Fleur; Maiorana, Andrew J; Naylor, Louise H; Willems, Peter H; Tack, Cees J; Thijssen, Dick H J; Green, Daniel J

2018-02-01

The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8-52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P > 0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34

Science.gov (United States)

Gow, Deborah J.; Garceau, Valerie; Kapetanovic, Ronan; Sester, David P.; Fici, Greg J.; Shelly, John A.; Wilson, Thomas L.; Hume, David A.

2012-01-01

Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models for evaluating potential therapeutic applications of CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor-dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF-1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active on mouse, human, cat and dog cells. IL-34 was previously shown to be species-specific, with mouse and human proteins demonstrating limited cross-species activity. The pig CSF-1R was equally responsive to both mouse and human IL-34. Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R complexes, we discuss the molecular basis for the species specificity. PMID:22974529

Improving Sensorimotor Function and Adaptation using Stochastic Vestibular Stimulation

Science.gov (United States)

Galvan, R. C.; Bloomberg, J. J.; Mulavara, A. P.; Clark, T. K.; Merfeld, D. M.; Oman, C. M.

2014-01-01

Astronauts experience sensorimotor changes during adaption to G-transitions that occur when entering and exiting microgravity. Post space flight, these sensorimotor disturbances can include postural and gait instability, visual performance changes, manual control disruptions, spatial disorientation, and motion sickness, all of which can hinder the operational capabilities of the astronauts. Crewmember safety would be significantly increased if sensorimotor changes brought on by gravitational changes could be mitigated and adaptation could be facilitated. The goal of this research is to investigate and develop the use of electrical stochastic vestibular stimulation (SVS) as a countermeasure to augment sensorimotor function and facilitate adaptation. For this project, SVS will be applied via electrodes on the mastoid processes at imperceptible amplitude levels. We hypothesize that SVS will improve sensorimotor performance through the phenomena of stochastic resonance, which occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. In line with the theory of stochastic resonance, a specific optimal level of SVS will be found and tested for each subject [1]. Three experiments are planned to investigate the use of SVS in sensory-dependent tasks and performance. The first experiment will aim to demonstrate stochastic resonance in the vestibular system through perception based motion recognition thresholds obtained using a 6-degree of freedom Stewart platform in the Jenks Vestibular Laboratory at Massachusetts Eye and Ear Infirmary. A range of SVS amplitudes will be applied to each subject and the subjectspecific optimal SVS level will be identified as that which results in the lowest motion recognition threshold, through previously established, well developed methods [2,3,4]. The second experiment will investigate the use of optimal SVS in facilitating sensorimotor adaptation to system

Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer

NARCIS (Netherlands)

deGraaf, H; Willemse, PHB; Bong, SB; Piersma, H; Tjabbes, T; vanVeelen, H; Coenen, JLLM; deVries, EGE

1996-01-01

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

Science.gov (United States)

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

2017-04-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

Peripheral tactile sensory perception of older adults improved using subsensory electrical noise stimulation.

Science.gov (United States)

Breen, Paul P; Serrador, Jorge M; O'Tuathail, Claire; Quinlan, Leo R; McIntosh, Caroline; ÓLaighin, Gearóid

2016-08-01

Loss of tactile sensory function is common with aging and can lead to numbness and difficulty with balance and gait. In previous work we found that subsensory electrical noise stimulation (SENS) applied to the tibial nerve improved tactile perception in the soles of the feet of healthy adults. In this work we aimed to determine if SENS remained effective in an older adult population with significant levels of sensory loss. Older adult subjects (N=8, female = 4, aged 65-80) had SENS applied via surface electrodes placed proximally to the medial and lateral malleoli. Vibration perception thresholds (VPTs) were assessed in six conditions, two control conditions (no SENS) and four SENS conditions (zero mean ±15µA, 30µA, 45µA and 60µA SD). VPT was assessed at three sites on the plantar aspect of the foot. Vibration perception was significantly improved in the presence of ±30µA SENS and by 16.2±2.4% (mean ± s.e.m.) when optimised for each subject. The improvement in perception was similar across all VPT test sites. Copyright © 2016 IPEM. All rights reserved.

Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

DEFF Research Database (Denmark)

Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

2013-01-01

Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

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

Science.gov (United States)

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

Science.gov (United States)

Massin, Nathalie

2017-03-01

The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However

Electrical stimulation and motor recovery.

Science.gov (United States)

Young, Wise

2015-01-01

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

Development of a Field Management Standard for Improving Human Factors

International Nuclear Information System (INIS)

Yun, Young Su; Son, Il Moon; Son, Byung Chang; Kwak, Hyo Yean

2009-07-01

This project is to develop a management guideline for improving human performances as a part of the Human Factors Management System of Kori unit 1 which is managing all of human factors items such as man-machine system interfaces, work procedures, work environments, and human reliabilities in nuclear power plants. Human factors engineering includes an human factors suitability analysis and improvement of human works, an analysis of accidents by human error, an improvement of work environment, an establishment of human factors management rules and a development of human resources to manage and perform those things consistently. For assisting these human factors engineering tasks, we developed human factors management guidelines, checklists and work procedures to be used in staffing, qualification, training, and human information requirements and workload. We also provided a software tool for managing the above items. Additionally, contents and an item pool for a human factors qualifying examination and training programs were developed. A procedures improvement and a human factors V and V on the Kori unit 1 have been completed as a part of this project, too

Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Suellen M. Andrade

2017-01-01

Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson's disease.

Science.gov (United States)

Gulberti, A; Hamel, W; Buhmann, C; Boelmans, K; Zittel, S; Gerloff, C; Westphal, M; Engel, A K; Schneider, T R; Moll, C K E

2015-03-01

While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury.

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Jae-Yol Lim

Full Text Available OBJECTIVES: Vocal fold (VF scarring remains a therapeutic challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF facilitates epithelial wound healing, and recently, growth factor therapy has been applied to promote tissue repair. This study was undertaken to investigate the effect of GM-CSF on VF wound healing in vivo and in vitro. METHODS: VF scarring was induced in New Zealand white rabbits by direct injury. Immediately thereafter, either GM-CSF or PBS was injected into the VFs of rabbits. Endoscopic, histopathological, immunohistochemical, and biomechanical evaluations of VFs were performed at 3 months post-injury. Human vocal fold fibroblasts (hVFFs were cultured with GM-CSF. Production of type I and III collagen was examined immunocytochemically, and the synthesis of elastin and hyaluronic acids was evaluated by ELISA. The mRNA levels of genes related to ECM components and ECM production-related growth factors, such as HGF and TGF-ß1, were examined by real time RT-PCR. RESULTS: The GM-CSF-treated VFs showed reduced collagen deposition in comparison to the PBS-injected controls (P<0.05. Immunohistochemical staining revealed lower amounts of type I collagen and fibronectin in the GM-CSF-treated VFs (P<0.05 and P<0.01, respectively. Viscous and elastic shear moduli of VF samples were significantly lower in the GM-CSF group than in the PBS-injected group (P<0.001 and P<0.01, respectively. Mucosal waves in the GM-CSF group showed significant improvement when compared to the PBS group (P = 0.0446. GM-CSF inhibited TGF-β1-induced collagen synthesis by hVFFs (P<0.05 and the production of hyaluronic acids increased at 72 hours post-treatment (P<0.05. The expressions of HAS-2, tropoelastin, MMP-1, HGF, and c-Met mRNA were significantly increased by GM-CSF, although at different time points (P<0.05. CONCLUSION: The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF

Electrical stimulation in exercise training

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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

Symptomatic relief precedes improvement of myocardial blood flow in patients under spinal cord stimulation

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Koulousakis Athanassios

2005-05-01

Full Text Available Abstract Background Spinal cord electrical stimulation (SCS has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion. Methods A prospective study to investigate the short- and long-term effect of spinal cord stimulation (SCS on myocardial ischemia in patients with refractory angina pectoris and coronary multivessel disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy 3 months and 12 months after the beginning of neurostimulation. To further examine the relation between cardiac perfusion and functional status of the patients we measured exercise capacity (bicycle ergometry and 6-minute walk test, symptoms and quality of life (Seattle Angina Questionnaire [SAQ], as well. Results 31 patients (65 ± 11 SEM years; 25 male, 6 female were included into the study. The average consumption of short acting nitrates (SAN decreased rapidly from 12 ± 1.6 times to 3 ± 1 times per week. The walking distance and the maximum workload increased from 143 ± 22 to 225 ± 24 meters and 68 ± 7 to 96 ± 12 watt after 3 months. Quality of life increased (SAQ significantly after 3 month compared to baseline, as well. No further improvement was observed after one year of treament. Despite the symptomatic relief and the improvement in maximal workload computer based analysis (Emory Cardiac Toolbox of the MIBI-SPECT studies after 3 months of treatment did not show significant alterations of myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6 with decrease of ischemia, 2 patients dropped out during initial test phase

Adaptive deep brain stimulation in advanced Parkinson disease.

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Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

2013-09-01

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

Science.gov (United States)

Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

2017-12-29

To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Transcranial Alternating Current Stimulation Attenuates Neuronal Adaptation.

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Kar, Kohitij; Duijnhouwer, Jacob; Krekelberg, Bart

2017-03-01

We previously showed that brief application of 2 mA (peak-to-peak) transcranial currents alternating at 10 Hz significantly reduces motion adaptation in humans. This is but one of many behavioral studies showing that weak currents applied to the scalp modulate neural processing. Transcranial stimulation has been shown to improve perception, learning, and a range of clinical symptoms. Few studies, however, have measured the neural consequences of transcranial current stimulation. We capitalized on the strong link between motion perception and neural activity in the middle temporal (MT) area of the macaque monkey to study the neural mechanisms that underlie the behavioral consequences of transcranial alternating current stimulation. First, we observed that 2 mA currents generated substantial intracranial fields, which were much stronger in the stimulated hemisphere (0.12 V/m) than on the opposite side of the brain (0.03 V/m). Second, we found that brief application of transcranial alternating current stimulation at 10 Hz reduced spike-frequency adaptation of MT neurons and led to a broadband increase in the power spectrum of local field potentials. Together, these findings provide a direct demonstration that weak electric fields applied to the scalp significantly affect neural processing in the primate brain and that this includes a hitherto unknown mechanism that attenuates sensory adaptation. SIGNIFICANCE STATEMENT Transcranial stimulation has been claimed to improve perception, learning, and a range of clinical symptoms. Little is known, however, how transcranial current stimulation generates such effects, and the search for better stimulation protocols proceeds largely by trial and error. We investigated, for the first time, the neural consequences of stimulation in the monkey brain. We found that even brief application of alternating current stimulation reduced the effects of adaptation on single-neuron firing rates and local field potentials; this mechanistic

Increased macrophage colony-stimulating factor levels in patients with Graves' disease.

Science.gov (United States)

Morishita, Eriko; Sekiya, Akiko; Hayashi, Tomoe; Kadohira, Yasuko; Maekawa, Mio; Yamazaki, Masahide; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2008-10-01

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P production of M-CSF in patients with GD.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

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Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

EGF–FGF{sub 2} stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs)

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Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves; Bittencourt, Denise Avani; Visoni, Silvia; Jeremias, Talita Silva [Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil); Costa, Ana Paula; Leal, Rodrigo Bainy [Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil); Trentin, Andrea Gonçalves, E-mail: andrea.trentin@ufsc.br [Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil)

2014-09-10

Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF{sub 2}) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF{sub 2}, however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF{sub 2} in neuronal differentiation protocols. - Highlights: • EPI

Paresthesia-Independence: An Assessment of Technical Factors Related to 10 kHz Paresthesia-Free Spinal Cord Stimulation.

Science.gov (United States)

De Carolis, Giuliano; Paroli, Mery; Tollapi, Lara; Doust, Matthew W; Burgher, Abram H; Yu, Cong; Yang, Thomas; Morgan, Donna M; Amirdelfan, Kasra; Kapural, Leonardo; Sitzman, B Todd; Bundschu, Richard; Vallejo, Ricardo; Benyamin, Ramsin M; Yearwood, Thomas L; Gliner, Bradford E; Powell, Ashley A; Bradley, Kerry

2017-05-01

Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming. To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy. Prospective, multicenter, non-randomized, non-controlled interventional study. Outpatient pain clinic at 10 centers across the US and Italy. Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a

Stimulation of phagocytosis by sulforaphane

International Nuclear Information System (INIS)

Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

2011-01-01

Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → 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-μm 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 -/- 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.

Stimulation of phagocytosis by sulforaphane

Energy Technology Data Exchange (ETDEWEB)

Suganuma, Hiroyuki, E-mail: hsuganu1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Fahey, Jed W., E-mail: jfahey@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Bryan, Kelley E., E-mail: kbryanm1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Healy, Zachary R., E-mail: zhealy1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Talalay, Paul, E-mail: ptalalay@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States)

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.

Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors

International Nuclear Information System (INIS)

Talmadge, J.E.; Tribble, H.; Pennington, R.; Bowersox, O.; Schneider, M.A.; Castelli, P.; Black, P.L.; Abe, F.

1989-01-01

Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation

Transcranial alternating current stimulation (tACS

Directory of Open Access Journals (Sweden)

Andrea eAntal

2013-06-01

Full Text Available Transcranial alternating current stimulation (tACS seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency or desynchronize (e.g. by the application of several frequencies cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the ripple range induces intensity dependent inhibition or excitation in the motor cortex most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

Science.gov (United States)

Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

2016-01-01

Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions: influence of stimulated indigenous microbiota

NARCIS (Netherlands)

Marty, F.; Gueuné, H.; Malard, E.; Sánchez-Amaya, J.M.; Sjögren, L.; Abbas, B.; Quillet, L.; van Loosdrecht, M.C.M.; Muyzer, G.

2014-01-01

Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion

Comparison of dopamine kinetics in the larval Drosophila ventral nerve cord and protocerebrum with improved optogenetic stimulation.

Science.gov (United States)

Privman, Eve; Venton, B Jill

2015-11-01

Dopamine release and uptake have been studied in the Drosophila larval ventral nerve cord (VNC) using optogenetics to stimulate endogenous release. However, other areas of the central nervous system remain uncharacterized. Here, we compare dopamine release in the VNC and protocerebrum of larval Drosophila. Stimulations were performed with CsChrimson, a new, improved, red light-activated channelrhodopsin. In both regions, dopamine release was observed after only a single, 4 ms duration light pulse. Michaelis-Menten modeling was used to understand release and uptake parameters for dopamine. The amount of dopamine released ([DA]p ) on the first stimulation pulse is higher than the average [DA]p released from subsequent pulses. The initial and average amount of dopamine released per stimulation pulse is smaller in the protocerebrum than in the VNC. The average Vmax of 0.08 μM/s in the protocerebrum was significantly higher than the Vmax of 0.05 μM/s in the VNC. The average Km of 0.11 μM in the protocerebrum was not significantly different from the Km of 0.10 μM in the VNC. When the competitive dopamine transporter (DAT) inhibitor nisoxetine was applied, the Km increased significantly in both regions while Vmax stayed the same. This work demonstrates regional differences in dopamine release and uptake kinetics, indicating important variation in the amount of dopamine available for neurotransmission and neuromodulation. We use a new optogenetic tool, red light activated CsChrimson, to stimulate the release of dopamine in the ventral nerve cord and medial protocerebrum of the larval Drosophila central nervous system. We monitored extracellular dopamine by fast scan cyclic voltammetry and used Michaelis-Menten modeling to probe the regulation of extracellular dopamine, discovering important similarities and differences in these two regions. © 2015 International Society for Neurochemistry.

Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

Science.gov (United States)

Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

2015-01-01

Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

Macrophage colony-stimulating factor induces prolactin expression in rat pituitary gland.

Science.gov (United States)

Hoshino, Satoya; Kurotani, Reiko; Miyano, Yuki; Sakahara, Satoshi; Koike, Kanako; Maruyama, Minoru; Ishikawa, Fumio; Sakatai, Ichiro; Abe, Hiroyuki; Sakai, Takafumi

2014-06-01

We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

DEFF Research Database (Denmark)

Jinquan, T; Quan, S; Jacobi, H H

2000-01-01

-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m......Ab blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

The application of online transcranial random noise stimulation and perceptual learning in the improvement of visual functions in mild myopia.

Science.gov (United States)

Camilleri, Rebecca; Pavan, Andrea; Campana, Gianluca

2016-08-01

It has recently been demonstrated how perceptual learning, that is an improvement in a sensory/perceptual task upon practice, can be boosted by concurrent high-frequency transcranial random noise stimulation (tRNS). It has also been shown that perceptual learning can generalize and produce an improvement of visual functions in participants with mild refractive defects. By using three different groups of participants (single-blind study), we tested the efficacy of a short training (8 sessions) using a single Gabor contrast-detection task with concurrent hf-tRNS in comparison with the same training with sham stimulation or hf-tRNS with no concurrent training, in improving visual acuity (VA) and contrast sensitivity (CS) of individuals with uncorrected mild myopia. A short training with a contrast detection task is able to improve VA and CS only if coupled with hf-tRNS, whereas no effect on VA and marginal effects on CS are seen with the sole administration of hf-tRNS. Our results support the idea that, by boosting the rate of perceptual learning via the modulation of neuronal plasticity, hf-tRNS can be successfully used to reduce the duration of the perceptual training and/or to increase its efficacy in producing perceptual learning and generalization to improved VA and CS in individuals with uncorrected mild myopia. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Frequency Repetitive Sensory Stimulation as Intervention to Improve Sensory Loss in Patients with Complex Regional Pain Syndrome I.

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David, Marianne; Dinse, Hubert R; Mainka, Tina; Tegenthoff, Martin; Maier, Christoph

2015-01-01

Achieving perceptual gains in healthy individuals or facilitating rehabilitation in patients is generally considered to require intense training to engage neuronal plasticity mechanisms. Recent work, however, suggested that beneficial outcome similar to training can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation (rSS). For example, high-frequency repetitive sensory stimulation (HF-rSS) enhances tactile performance and induces cortical reorganization in healthy subjects and patients after stroke. Patients with complex regional pain syndrome (CRPS) show impaired tactile performance associated with shrinkage of cortical maps. We here investigated the feasibility and efficacy of HF-rSS, and low-frequency rSS (LF-rSS) to enhance tactile performance and reduce pain intensity in 20 patients with CRPS type I. Intermittent high- or low-frequency electrical stimuli were applied for 45 min/day to all fingertips of the affected hand for 5 days. Main outcome measures were spatial two-point-discrimination thresholds and mechanical detection thresholds measured on the tip of the index finger bilaterally. Secondary endpoint was current pain intensity. All measures were assessed before and on day 5 after the last stimulation session. HF-rSS applied in 16 patients improved tactile discrimination on the affected hand significantly without changes contralaterally. Current pain intensity remained unchanged on average, but decreased in four patients by ≥30%. This limited pain relief might be due to the short stimulation period of 5 days only. In contrast, after LF-rSS, tactile discrimination was impaired in all four patients, while detection thresholds and pain were not affected. Our data suggest that HF-rSS could be used as a novel approach in CRPS treatment to improve sensory loss. Longer treatment periods might be required to induce consistent pain relief.

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

Science.gov (United States)

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.

Science.gov (United States)

Welch, William P; Sitwat, Bilal; Sogawa, Yoshimi

2018-06-01

To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

Prefronto–cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder

Directory of Open Access Journals (Sweden)

Minichino A

2015-08-01

Full Text Available Amedeo Minichino, Francesco Saverio Bersani, Laura Bernabei, Francesco Spagnoli, Lucilla Vergnani, Alessandra Corrado, Ines Taddei, Massimo Biondi, Roberto Delle Chiaie Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Objective: The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD using transcranial direct current stimulation (tDCS applied to cerebellar and prefrontal cortices.Methods: Twenty-five BD outpatients underwent prefrontal (anodal and cerebellar (cathodal tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS.Results: After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved.Conclusion: Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto–thalamic–cerebellar circuit activity pattern, which can be disrupted in BD. Keywords: cerebellum, dorsolateral prefrontal cortex, neuropsychology, cognition 

Isolation, nucleotide sequence and expression of a cDNA encoding feline granulocyte colony-stimulating factor.

Science.gov (United States)

Dunham, S P; Onions, D E

2001-06-21

A cDNA encoding feline granulocyte colony stimulating factor (fG-CSF) was cloned from alveolar macrophages using the reverse transcriptase-polymerase chain reaction. The cDNA is 949 bp in length and encodes a predicted mature protein of 174 amino acids. Recombinant fG-CSF was expressed as a glutathione S-transferase fusion and purified by affinity chromatography. Biological activity of the recombinant protein was demonstrated using the murine myeloblastic cell line GNFS-60, which showed an ED50 for fG-CSF of approximately 2 ng/ml. Copyright 2001 Academic Press.

Proliferation-stimulating effect of colony stimulating factor 2 on porcine trophectoderm cells is mediated by activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase.

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Wooyoung Jeong

Full Text Available Colony-stimulating factor 2 (CSF2, also known as granulocyte macrophage colony-stimulating factor, facilitates mammalian embryonic development and implantation. However, biological functions and regulatory mechanisms of action of porcine endometrial CSF2 in peri-implantation events have not been elucidated. The aim of present study was to determine changes in cellular activities induced by CSFs and to access CSF2-induced intracellular signaling in porcine primary trophectoderm (pTr cells. Differences in expression of CSF2 mRNA in endometrium from cyclic and pregnant gilts were evaluated. Endometrial CSF2 mRNA expression increases during the peri-implantation period, Days 10 to 14 of pregnancy, as compared to the estrous cycle. pTr cells obtained in Day 12 of pregnancy were cultured in the presence or absence of CSF2 (20 ng/ml and LY294002 (20 µM, U0126 (20 µM, rapamycin (20 nM, and SB203580 (20 µM. CSF2 in pTr cell culture medium at 20 ng/ml significantly induced phosphorylation of AKT1, ERK1/2, MTOR, p70RSK and RPS6 protein, but not STAT3 protein. Also, the PI3K specific inhibitor (LY294002 abolished CSF2-induced increases in p-ERK1/2 and p-MTOR proteins, as well as CSF2-induced phosphorylation of AKT1. Changes in proliferation and migration of pTr cells in response to CSF2 were examined in dose- and time-response experiments. CSF2 significantly stimulated pTr cell proliferation and, U0126, rapamycin and LY294002 blocked this CSF2-induced proliferation of pTr cells. Collectively, during the peri-implantation phase of pregnancy in pigs, endometrial CSF2 stimulates proliferation of trophectoderm cells by activation of the PI3K-and ERK1/2 MAPK-dependent MTOR signal transduction cascades.

Improvement of posture stability by vibratory stimulation following anterior cruciate ligament reconstruction.

Science.gov (United States)

Brunetti, O; Filippi, G M; Lorenzini, M; Liti, A; Panichi, R; Roscini, M; Pettorossi, V E; Cerulli, G

2006-11-01

Surgical reconstruction of the anterior cruciate ligament (ACL) may reduce, but it does not always eliminate, knee and body instability because of a persisting proprioceptive deficit. In order to enhance body stability, a new protocol of treatment has been proposed consisting of mechanical vibration (100 Hz frequency and < 20 microm amplitude) of the quadriceps muscle in the leg that has undergone ACL reconstruction. In our trials, stimulation was performed when the quadriceps muscle was kept isometrically contracted. Treatment was started one month after surgery. Vibration was applied for short periods over three consecutive days. Nine months after treatment, postural stability was re-evaluated with the subjects standing on one leg with open and with closed eyes. The postural stability of the subjects having undergone vibration treatment, standing on the operated leg was significantly improved one day after treatment when evaluated as mean of speed and elliptic area of the center of pressure. The improvement persisted and increased during the following weeks. Peak torques of the operated leg extensor muscles also increased and reached values close to that of the leg, which had not been operated. Conversely, the balance of the untreated subjects standing on the operated leg did not improve and the restoration of the extensor muscle peak torque was poor. It is concluded that short lasting proprioceptive activation by vibration may lead to a faster and more complete equilibrium recovery probably by permanently changing the network controlling knee posture.

Well screening for matrix stimulation treatments

International Nuclear Information System (INIS)

Saavedra, N; Solano, R; Gidley, J; Reyes, C.A; Rodriguez; Kondo, F; Hernandez, J

1998-01-01

Matrix acidizing is a stimulation technique only applicable to wells with surrounding damage. It is therefore very important to differentiate the real formation damage from the damage caused by flow Ni dynamic effects. The mechanical damage corresponds to flow restrictions caused by partial penetration, poor perforation as well as to reduce diameters of the production tubing. The dynamic effects are generated by inertia caused by high flow rates and high-pressure differentials. A common practice in our oil fields is to use a general formulation as acid treatment, most of the times without previous lab studies that guarantee the applicability of the treatment in the formation. Additionally, stimulation is randomly applied even treating undamaged wells with negative results and in the best of the cases, loss of the treatment. The selection of the well for matrix stimulation is an essential factor for the success of the treatment. Selection is done through the evaluation of the skin factor (S) and of the economic benefits of reducing the skin in comparison to the cost of the work. The most appropriate tool for skin evaluation is a good pressure test where the radial flow period can be identified. Nevertheless, we normally find-outdated tests most of the times taken with inaccurate tools. The interpretation problem is worsened by completions in which there is simultaneous production from several sand packages and it is difficult to individually differentiate damage factors. This works states a procedure for the selection of wells appropriate for stimulation; it also proposes a method to evaluate the skin factor when there are no accurate interpretations of the pressure tests. A new and increasingly applied methodology to treat wells with high water cuts, which are usually discarded due to the risk of stimulating water zones, is also mentioned

Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF activity.

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Gözde Isik

Full Text Available HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs that target the envelope glycoprotein complex (Env. An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed Env(GM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized Env(GM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric Env(GM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins.

Chimeric HIV-1 Envelope Glycoproteins with Potent Intrinsic Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Activity*

Science.gov (United States)

Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

2013-01-01

HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed EnvGM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized EnvGM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric EnvGM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins. PMID:23565193

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

Science.gov (United States)

Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Improvements in Attention and Decision-Making Following Combined Behavioral Training and Brain Stimulation.

Science.gov (United States)

Filmer, Hannah L; Varghese, Elizabeth; Hawkins, Guy E; Mattingley, Jason B; Dux, Paul E

2017-07-01

In recent years there has been a significant commercial interest in 'brain training' - massed or spaced practice on a small set of tasks to boost cognitive performance. Recently, researchers have combined cognitive training regimes with brain stimulation to try and maximize training benefits, leading to task-specific cognitive enhancement. It remains unclear, however, whether the performance gains afforded by such regimes can transfer to untrained tasks, or how training and stimulation affect the brain's latent information processing dynamics. To examine these issues, we applied transcranial direct current stimulation (tDCS) over the prefrontal cortex while participants undertook decision-making training over several days. Anodal, relative to cathodal/sham tDCS, increased performance gains from training. Critically, these gains were reliable for both trained and untrained tasks. The benefit of anodal tDCS occurred for left, but not right, prefrontal stimulation, and was absent for stimulation delivered without concurrent training. Modeling revealed left anodal stimulation combined with training caused an increase in the brain's rate of evidence accumulation for both tasks. Thus tDCS applied during training has the potential to modulate training gains and give rise to transferable performance benefits for distinct cognitive operations through an increase in the rate at which the brain acquires information. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Exploration of contextual factors in a successful quality improvement collaborative in English ambulance services: cross‐sectional survey

Science.gov (United States)

Phung, Viet‐Hai; Essam, Nadya; Asghar, Zahid; Spaight, Anne

2015-01-01

Abstract Rationale, aims and objectives Clinical leadership and organizational culture are important contextual factors for quality improvement (QI) but the relationship between these and with organizational change is complex and poorly understood. We aimed to explore the relationship between clinical leadership, culture of innovation and clinical engagement in QI within a national ambulance QI Collaborative (QIC). Methods We used a self‐administered online questionnaire survey sent to front‐line clinicians in all 12 English ambulance services. We conducted a cross‐sectional analysis of quantitative data and qualitative analysis of free‐text responses. Results There were 2743 (12% of 22 117) responses from 11 of the 12 participating ambulance services. In the 3% of responders that were directly involved with the QIC, leadership behaviour was significantly higher than for those not directly involved. QIC involvement made no significant difference to responders' perceptions of the culture of innovation in their organization, which was generally considered poor. Although uptake of QI methods was low overall, QIC members were significantly more likely to use QI methods, which were also significantly associated with leadership behaviour. Conclusions Despite a limited organizational culture of innovation, clinical leadership and use of QI methods in ambulance services generally, the QIC achieved its aims to significantly improve pre‐hospital care for acute myocardial infarction and stroke. We postulate that this was mediated through an improvement subculture, linked to the QIC, which facilitated large‐scale improvement by stimulating leadership and QI methods. Further research is needed to understand success factors for QI in complex health care environments. PMID:26303398

Factors stimulating content marketing

Directory of Open Access Journals (Sweden)

Naser Azad

2016-02-01

Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

Stimulation Technologies for Deep Well Completions

Energy Technology Data Exchange (ETDEWEB)

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.

Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

Directory of Open Access Journals (Sweden)

Stéphanie eOlière

2013-09-01

Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

Science.gov (United States)

Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

2017-01-01

Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Impact of Soft Factors on Quality Improvement in Manufacturing Industry

Science.gov (United States)

Chan, Shiau Wei; Fauzi Ahmad, Md; Kong, Mei Wan

2017-08-01

Nowadays, soft factors have become the key factors of success in quality improvement of an organisation. Many organisations have neglected the importance of soft factors, this may influence the organisational performance. Hence, the purpose of this research is to examine the impact of soft factors on quality improvement in manufacturing industries. Six hypotheses were examined while considering six dimensions of soft factors including management commitment, customer focus, supplier relationship, employee involvement, training and education, and reward and recognition that have a positive impact on quality improvement. In this study, eighty one managers from the quality department were randomly selected in the manufacturing industry in Batu Pahat, Johor. The questionnaires were distributed to them. The researcher analysed the quantitatively collected data using descriptive analysis and correlation analysis. The findings of this study revealed that all soft factors are correlated to the quality improvement in an organisation with a high significant value but the regression analysis shows that the supplier relationship and employee involvement has more significant impact on quality improvement as compared to other soft factors which contributes of this study.

The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

Science.gov (United States)

Coon, C; Beagley, K W; Bao, S

2009-08-01

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.

Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work.

Science.gov (United States)

Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

2015-12-01

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects' characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contextual factors and effective school improvement

NARCIS (Netherlands)

Sun, Hechuan; Creemers, Bert P. M.; de Jong, Rob

This research provides policy-makers, researchers, and educators at all levels with a glimpse of the contextual influence on effective school improvement (ESI) in 8 European countries. What are the factors at the contextual level, particularly at the national level, which influence ESI? Are there

Mild ovarian stimulation for IVF: 10 years later

DEFF Research Database (Denmark)

Fauser, Bart C J M; Nargund, Geeta; Andersen, Anders Nyboe

2010-01-01

Ovarian stimulation to achieve multiple follicle development has been an integral part of IVF treatment. In the context of improved laboratory performance, the need for a large number of oocytes as an integral part of a successful IVF programme may be questioned. The aim of the current debate...... is to summarize the studies performed during the last decade to develop the concept of mild stimulation aiming to obtain fewer than eight oocytes. Here we examine the balance between IVF success and patient discomfort, and complications and cost, and how these might improve by simpler ovarian stimulation...

Improvement of macrophage dysfunction by administration of anti-transforming growth factor-beta antibody in EL4-bearing hosts.

Science.gov (United States)

Maeda, H; Tsuru, S; Shiraishi, A

1994-11-01

An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice. TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in that from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against Mv1Lu cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-beta activity was abrogated by administration of anti-TGF-beta antibody to EL4-bearing mice. While a large amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-beta antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-beta contributes to macrophage dysfunction and that the administration of specific antibody for TGF-beta reverses macrophage dysfunction in EL4-bearing hosts.

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

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Magda Paula Pereira do Nascimento

2011-09-01

Full Text Available Multinucleated giant cells (MGC are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF in association with other cytokines such as interferon-gamma (IFN-γ, tumour necrosis factor-alpha, interleukin (IL-10 or transforming growth factor beta (TGF-β1 on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg. The generation of MGC was determined by fusion index (FI and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18. The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

Science.gov (United States)

Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

2016-06-01

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

A Comparison Study of Growth Factor Expression following Treatment with Transcutaneous Electrical Nerve Stimulation, Saline Solution, Povidone-Iodine, and Lavender Oil in Wounds Healing

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Adalet Koca Kutlu

2013-01-01

Full Text Available This study compared the effects of transcutaneous electrical nerve stimulation (TENS, saline solution (SS, povidone-iodine (PI, and lavender oil (Lavandula angustifolia through expression of growth factors in a rat model of wound healing. Six experimental groups were established, each containing 8 rats: a healthy group with no incision wounds, an incision-control group, an incision and TENS group, an incision and SS group, an incision and PI group, and an incision and lavender oil group. Experiments continued for 5 days, after which the skin in the excision area was removed. Tissue concentrations of epidermal growth factor (EGF and platelet-derived growth factor (PDGF-A were measured using enzyme-linked immunosorbent assay (ELISA. Tissue expressions of EGF, PDGF-A, and fibroblast growth factor (FGF-2 were determined using immunohistochemistry. Wound closure progressed more rapidly in the TENS and lavender oil groups than in the control and other study groups. In particular, PDGF-A expressions in the dermis and EGF expression in the epidermis were significantly intense in the TENS group (P<0.05. In addition, ELISA levels of growth factors such as PDGF-A and EGF were significantly higher in TENS group compared to the control group (P<0.05. These immunohistochemical and ELISA results suggest that TENS may improve wound healing through increasing growth factors in the dermis and epidermis more than other topical applications.

Porcine granulocyte-colony stimulating factor (G-CSF) delivered via replication-defective adenovirus induces a sustained increase in circulating peripheral blood neutrophils

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The use of immunomodulators is a promising area for biotherapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease, particularly during periods of peak disease incidence. Cytokines, including granulocyte colony-stimulating factor (G-CSF), are one class of compounds that...

Stimulation of tendon repair by platelet concentrate, CDMP-2 and mechanical loading in animal models

OpenAIRE

Virchenko, Olena

2007-01-01

Growth factor delivery may be useful to accelerate the rate of tendon healing. We studied Platelet Concentrate, which in effect can be regarded as a cocktail of growth factors relevant for tendon healing. In a rat Achilles tendon transection model, one postoperative injection of Platelet Concentrate resulted in increased strength even 3 weeks later. Mechanical stimulation improves the repair of ruptured tendons. We studied the effects of platelets upon Achilles tendon regenerates in rats 3, 5...

Burst stimulation improves hemodynamics during resuscitation after prolonged ventricular fibrillation.

Science.gov (United States)

Walcott, Gregory; Melnick, Sharon; Killingsworth, Cheryl; Ideker, Raymond

2009-02-01

Although return of spontaneous circulation (ROSC) is frequently achieved during resuscitation for sudden cardiac arrest, systolic blood pressure can then decrease, requiring additional myocardial support. Previous studies have shown that a series of 1-ms electrical pulses delivered through the defibrillation patches during ventricular fibrillation (VF) can stimulate the autonomic nervous system to increase myocardial function following defibrillation. We hypothesized that a similar series of electrical pulses could increase myocardial function and blood pressure during the early post-resuscitation period. Six swine were studied that underwent 6-7 min. Each animal received 5, 10, 15, or 20 pulse packets consisting of 6 10 A, 1-ms pulses every 3-4 s in random order whenever systolic blood pressure became less than 50 mmHg. All four sets of pulse packets were delivered to each animal. Systolic blood pressure and cardiac function (left ventricular +dP/dt) were increased to pre-stimulation levels or above by all four sets of pulse packets. The increases were significantly greater for the longer than the shorter number of pulse packets. The mean+/-SD duration of the time that the systolic pressure remained above 50 mmHg following pulse delivery was 4.2+/-2.5 min. Electrical stimulation during regular rhythm following prolonged VF and resuscitation can increase blood pressure and cardiac function to above prestimulation levels.

Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells

Science.gov (United States)

Xia, Harry Hua-Xiang; Lam, Shiu Kum; Chan, Annie O.O.; Lin, Marie Chia Mi; Kung, Hsiang Fu; Ogura, Keiji; Berg, Douglas E.; Wong, Benjamin C. Y.

2005-01-01

AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type H pylori strain (TN2)and its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H

Studies for improved understanding of lipid distributions in human skin by combining stimulated and spontaneous Raman microscopy.

Science.gov (United States)

Klossek, A; Thierbach, S; Rancan, F; Vogt, A; Blume-Peytavi, U; Rühl, E

2017-07-01

Advanced Raman techniques, such as stimulated Raman spectroscopy (SRS), have become a valuable tool for investigations of distributions of substances in biological samples. However, these techniques lack spectral information and are therefore highly affected by cross-sensitivities, which are due to blended Raman bands. One typical example is the symmetric CH 2 stretching vibration of lipids, which is blended with the more intense Raman band of proteins. We report in this work an approach to reduce such cross-sensitivities by a factor of 8 in human skin samples. This is accomplished by careful spectral deconvolutions revealing the neat spectra of skin lipids. Extensive Raman studies combining the complementary advantages of fast mapping and scanning, i.e. SRS, as well as spectral information provided by spontaneous Raman spectroscopy, were performed on the same skin regions. In addition, an approach for correcting artifacts is reported, which are due to transmission and reflection geometries in Raman microscopy as well as scattering of radiation from rough and highly structured skin samples. As a result, these developments offer improved results obtained from label-free spectromicroscopy provided by Raman techniques. These yield substance specific information from spectral regimes in which blended bands dominate. This improvement is illustrated by studies on the asymmetric CH 2 stretching vibration of lipids, which was previously difficult to identify due to the strong background signal from proteins. The advantage of the correction procedures is demonstrated by higher spatial resolution permitting to perform more detailed investigations on lipids and their composition in skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus

Energy Technology Data Exchange (ETDEWEB)

Hattori, Naoya; Bengel, Frank M.; Nekolla, Stephan G.; Drzezga, Alexander E.; Schwaiger, Markus [Nuklearmedizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technischen Universitaet Muenchen (Germany); Schnell, Oliver; Rihl, Julian; Standl, Eberhard [Diabetes Research Center, Schwabing City Hospital, Munich (Germany)

2002-07-01

Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1{+-}17.5 vs 63.2{+-}14.9 mg 100 g{sup -1} min{sup -1}, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28{+-}0.35; controls, 1.55{+-}0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81{+-}17 ml 100 g{sup -1} min{sup -1}; saline, 75{+-}19 ml 100 g{sup -1} min{sup -1}, P=NS) or MVR (deferoxamine, 1.0{+-}0.5 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}; saline, 1.2{+-}0.6 mmHg ml{sup -1} 100 g{sup -1} min{sup -1}, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary

A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes without Growth Factor Stimulation

Science.gov (United States)

2011-01-01

A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes Without Growth Factor Stimulation...Ph.D.3 This work describes the differentiation of adipose-derived mesenchymal stem cells (ASC) in a composite hy- drogel for use as a vascularized...tissue from a single population of ASC. This work underscores the importance of the extracellular matrix in controlling stem cell phenotype. It is our

Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

DEFF Research Database (Denmark)

Frödin, M; Sekine, N; Roche, E

1995-01-01

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

Therapeutic riding followed by rhythmic auditory stimulation to improve balance and gait in a subject with orthopedic pathologies.

Science.gov (United States)

Ungermann, Cathryn M; Gras, Laura Z

2011-12-01

The study objectives were to investigate the effect of therapeutic riding with a subject who had an orthopedic diagnosis. This is a single-subject case report. The study was conducted at an equestrian facility with an indoor riding arena. The subject was a 59-year-old woman with grade I spondylolisthesis at L4/L5 and multilevel lumbar spinal stenosis in central and foraminal canals. The subject had an anterior cervical fusion of C3-C7. The subject has been ambulating with a straight cane due to her history of frequent falls. Gait, agility, strength, range of motion, and balance testing were performed. The subject had impairments of bilateral lower extremities with an ataxic gait pattern and was at risk for continued falls according to the balance measures. The intervention comprised therapeutic riding sessions 3 times a week for 20 minutes for 4 weeks. Each riding session was immediately followed by a 10-minute independent walking program with a metronome for rhythmic auditory stimulation. The outcome measures were as follows: Manual muscle testing and range of motion of the lower extremities, Gait Speed Test, Dynamic Gait Index, Four-Square Step Test, Chair Stand Test, Single Leg Stance. Improvements were seen in lower extremity strength and range of motion and balance. The subject improved on balance scores, placing her out of the risk for falls category. Therapeutic riding followed by rhythmic auditory stimulation improved lower extremity range of motion, strength, and balance with this subject.

Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia.

Science.gov (United States)

Spiegel, Daniel P; Byblow, Winston D; Hess, Robert F; Thompson, Benjamin

2013-10-01

Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

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Yuhei Nishimura

2016-07-01

Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

High frequency repetitive sensory stimulation as intervention to improve sensory loss in patients with complex regional pain syndrome (CRPS I

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Marianne eDavid

2015-11-01

Full Text Available Achieving perceptual gains in healthy individuals, or facilitating rehabilitation in patients is generally considered to require intense training to engage neuronal plasticity mechanisms. Recent work, however, suggested that beneficial outcome similar to training can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation (rSS. For example, high-frequency repetitive sensory stimulation (HF-rSS enhances tactile performance and induces cortical reorganization in healthy subjects and patients after stroke. Patients with complex regional pain syndrome (CRPS show impaired tactile performance associated with shrinkage of cortical maps. We here investigated the feasibility and efficacy of HF-rSS, and low-frequency rSS (LF-rSS to enhance tactile performance and reduce pain intensity in 20 patients with CRPS type I. Intermittent high or low frequency electrical stimuli were applied for 45min/day to all fingertips of the affected hand for 5 days. Main outcome measures were spatial 2-point-discrimination thresholds and mechanical detection thresholds measured on the tip of the index finger bilaterally. Secondary endpoint was current pain intensity. All measures were assessed before and on day 5 after the last stimulation session. HF-rSS applied in 16 patients improved tactile discrimination on the affected hand significantly without changes contralaterally. Current pain intensity remained unchanged on average, but decreased in 4 patients by 30%. This limited pain relief might be due to the short stimulation period of 5 days only. In contrast, after LF-rSS, tactile discrimination was impaired in all 4 patients, while detection thresholds and pain were not affected. Our data suggest that HF-rSS could be used as a novel approach in CRPS treatment to improve sensory loss. Longer treatment periods might be required to induce consistent pain relief.

Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

Science.gov (United States)

Roh, Hee-Tae; So, Wi-Young

2017-01-01

Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.

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Ghazaleh Samoudi

Full Text Available BACKGROUND: The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA hemilesion model of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the γ-amino buturic acid (GABA transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN, the striatum or the ventromedial thalamus (VM. Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN. CONCLUSIONS/SIGNIFICANCE: SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for

Predictive factors for pregnancy outcome following controlled ovarian stimulation and intrauterine insemination

International Nuclear Information System (INIS)

Yildrim, G.; Turkgeldi, L.S.; Koroglu, N.; Mervetalmac, A.

2017-01-01

To establish predictive factors for positive pregnancy outcome in cases of controlled ovarian stimulation and intrauterine insemination. Methods: The retrospective study was conducted at Kanuni Sultan Suleyman Training and Research Hospital and comprised subjects having undergone ovulation induction cycles and intrauterine insemination between June 2010 and June 2015. Data was analysed in terms of various parameters affecting clinical pregnancy rates. SPSS 23 was used for statistical analysis. Results: There were 475 patients having undergone a total of 923 cycles. Pregnancy was established in 133(28%) patients. Univariate analysis of biological/clinical variables revealed the presence of secondary infertility, high endometrial thickness, antral follicle number, post wash total motile sperm count and midluteal progesterone levels following intrauterine insemination to be associated with positive pregnancy outcomes (p<0.05 each). Multiple logistic regression analysis was performed to establish factors that affected the pregnancy rate. The aetiology and type of infertility and high midluteal progesterone levels following intrauterine insemination were found to be statistically significant predictors of pregnancy (p<0.05 each). Conclusion: The best chance of pregnancy was found in cases with anovulatory infertility, a history of prior pregnancy, and high midluteal progesterone levels following treatment with gonadotrophins and intrauterine insemination. (author)

Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2.

Science.gov (United States)

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

2015-06-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Tissue localization and fate in mice of injected multipotential colony-stimulating factor

International Nuclear Information System (INIS)

Metcalf, D.; Nicola, N.A.

1988-01-01

The hemopoietic regulator multipotential colony-stimulating factor [Multi-CSF (interleukin 3)] has proliferative effects on a wide range of hemopoietic cells in vitro and in vivo. Native or recombination Multi-CSF injected intravenoulsy into adult mice had an initial half-life of 3-5 min and a second phase of 50 min. Clear labeling of hemopoietic cells was observed in the bone marrow and spleen of mice injected intravenously with recombinant 125 I-labeled Multi-CSF showing that injected Multi-CSF can obtain access to such cells in situ. A high proportion of injected 125 I-labeled Multi-CSF of both types became localized in the liver and in the kidney (in cells of the Bowman's capsule and proximal renal tubules). The kidney appeared to be an active site of degradation of Multi-CSF with the early appearance of low molecular weight labeled material in the urine

Spinal Cord Stimulation Provides Pain Relief with Improved Psychosocial Function: Results from EMP3OWER.

Science.gov (United States)

Rosenberg, Jason; Fabi, Alain; Candido, Kenneth; Knezevic, Nick; Creamer, Michael; Carayannopoulos, Alexios; Ghodsi, Abdi; Nelson, Christopher; Bennett, Matthew

2016-12-01

The EMP 3 OWER™ study evaluated spinal cord stimulation (SCS) safety and efficacy and the associated changes in psychosocial and functional outcomes. Upon informed consent and IRB approval, 620 eligible subjects were enrolled prior to SCS trial evaluation and were assessed at baseline, 3, 6 and 12 months post-implant. Patient-reported pain relief (PRP), numerical rating scale (NRS), satisfaction, quality of life (QOL), and pain disability index (PDI) were assessed at all follow-up visits while the pain catastrophizing scale (PCS), short form-36 (SF-36), short form-McGill pain questionnaire version 2 (SF-MPQ-2), and the state-trait anxiety inventory (STAI) were assessed at the 6- and 12-month follow-up visits. Device and/or procedure-related adverse events were also recorded and reported. Subjects reporting a PRP ≥ 50% were considered responders. Repeated measures analysis of variance (RMANOVA) examined the changes across time for all continuous measures. A total of 401 (71%) subjects received a permanent implant. Mean (±SD) patient-reported pain relief was 59.3% (±26.2), 59.2% (±28.9), and 58.2% (±32.0) at 3, 6, and 12 months, respectively. A majority of enrolled subjects were responders at 3 (75.5%), 6 (74.7%), and 12 months (69.7%). RMANOVA revealed a statistically significant change for NRS, PCS, PDI, SF-36, SF-MPQ-2, and STAI scores. At 3 months, the majority of subjects (85.7%) were either very satisfied or satisfied with their device, with similar results at 6 and 12 months. At 3 months, the majority of subjects (73.3%) reported greatly improved or improved QOL with similar results at 6 and 12 months. Spinal cord stimulation provided pain relief and significant improvement of patient psychological and functional outcome measures. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

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Elsner, Bernhard; Kwakkel, Gert; Kugler, Joachim; Mehrholz, Jan

2017-09-13

Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. CRD42016042055. We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

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Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

Transcutaneous electrical nerve stimulation improves low back pain during pregnancy.

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Keskin, E A; Onur, O; Keskin, H L; Gumus, I I; Kafali, H; Turhan, N

2012-01-01

To compare the efficiency of transcutaneous electrical nerve stimulation (TENS) with those of exercise and acetaminophen for the treatment of pregnancy-related low back pain (LBP) during the third trimester of pregnancy. This prospective study included 79 subjects (≥32 gestational weeks) with visual analog scale (VAS) pain scores ≥5. Participants were divided randomly into a control group (n = 21) and three treatment groups [exercise (n = 19); acetaminophen (n = 19); TENS (n = 20)]. The VAS and the Roland-Morris disability questionnaire (RMDQ) were completed before and 3 weeks after treatment to assess the impact of pain on daily activities. During the study period, pain intensity increased in 57% of participants in the control group, whereas pain decreased in 95% of participants in the exercise group and in all participants in the acetaminophen and TENS groups. Post-treatment VAS and RMDQ values were significantly lower in the treatment groups (p pain relief in the TENS group than in the exercise and acetaminophen groups (p TENS application on pregnant women was observed during the study. TENS is an effective and safe treatment modality for LBP during pregnancy. TENS improved LBP more effectively than did exercise and acetaminophen. Copyright © 2012 S. Karger AG, Basel.

Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

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Vonberg, Isabelle; Ehlen, Felicitas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

2016-01-01

Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

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Isabelle Vonberg

Full Text Available Reduced verbal fluency (VF has been reported in patients with Parkinson's disease (PD, especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS. To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS.Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields. The results were compared to those of eleven healthy control subjects.PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls.Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

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Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

2012-09-01

Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.

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Ekmekci, Hakan; Kaptan, Hulagu

2016-01-01

Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.

Factors to Consider in Selecting an Organisational Improvement Initiative: Survey Results

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Mohammad Musli

2017-01-01

Full Text Available Organisations should select the appropriate improvement initiative that will fit with the context of organisation and provide value to the organisation. This paper presents 18 factors to be considered when selecting an organisational improvement initiative. Organisational improvement initiatives are approaches, management systems, tools and/or techniques that can be used for managing and improving organisations, such as Lean, ISO9001, Six Sigma and Improvement Team. A survey was conducted to identify the level of importance of these 18 factors as criteria for selecting an improvement initiative. Purposive sampling was used for this survey involving practitioners, managers, engineers, executives, consultants and/or academicians, who have been involved in the selection and/or implementation of organisational improvement initiatives in Malaysia. Two factors were rated as ‘very high importance’, which involve: (1 The ability to gain top management commitment and support to introduce and implement the initiative successfully, and (2 The initiative is aligned to the vision, mission and/or purpose of the organisation. All these factors can be adopted by the organisations as decision criteria to assist in the selection of the most appropriate improvement initiative based on rational decision making.

Modern management of epilepsy: Vagus nerve stimulation.

Science.gov (United States)

Ben-Menachem, E

1996-12-01

Vagus nerve stimulation (VNS) was first tried as a treatment for seizure patients in 1988. The idea to stimulate the vagus nerve and disrupt or prevent seizures was proposed by Jacob Zabarra. He observed a consistent finding among several animal studies which indicated that stimulation of the vagus nerve could alter the brain wave patterns of the animals under study. His hypothesis formed the basis for the development of the vagus nerve stimulator, an implantable device similar to a pacemaker, which is implanted in the left chest and attached to the left vagus nerve via a stimulating lead. Once implanted, the stimulator is programmed by a physician to deliver regular stimulation 24 hours a day regardless of seizure activity. Patients can also activate extra 'on-demand' stimulation with a handheld magnet. Clinical studies have demonstrated VNS therapy to be a safe and effective mode of treatment when added to the existing regimen of severe, refractory patients with epilepsy. Efficacy ranges from seizure free to no response with the majority of patients (> 50%) reporting at least a 50% improvement in number of seizures after 1.5 years of treatment. The side-effect profile is unique and mostly includes stimulation-related sensations in the neck and throat. The mechanism of action for VNS is not clearly understood although two theories have emerged. First, the direct connection theory hypothesizes that the anticonvulsant action of VNS is caused by a threshold raising effect of the connections to the nucleus of the solitary tract and on to other structures. The second is the concept that chronic stimulation of the vagus nerve increases the amount of inhibitory neurotransmitters and decreases the amount of excitatory neurotransmitters. Additional research into the optimal use of VNS is ongoing. Animal and clinical research have produced some interesting new data suggesting there are numerous ways to improve the clinical performance of vagus nerve stimulation as a

Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation Outcome: Evaluation Using the MMPI-2-RF.

Science.gov (United States)

Block, Andrew R; Marek, Ryan J; Ben-Porath, Yossef S; Kukal, Deborah

2017-01-01

Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic pain. Previous research has demonstrated that psychosocial factors are associated with diminished results of SCS. The objective of this investigation is to examine associations between pre-implant psychological functioning as measured by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF and measures of pain, emotional distress, and functional ability as part of a pre-implant psychological evaluation. At an average of 5 months post-implant, patients completed the measures of pain and emotional distress a second time. Poorer SCS outcomes and poorer patient satisfaction were associated with higher pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction, somatic/cognitive complaints, and interpersonal problems. Ways through which pre-implant psychological evaluations of spinal cord stimulator candidates can be informed by MMPI-2-RF findings are discussed. © The Author(s) 2015.

Phytoplankton stimulation in frontal regions of Benguela upwelling filaments by internal factors

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Norbert Wasmund

2016-11-01

Full Text Available Filaments are intrusions of upwelling water into the sea, separated from the surrounding water by fronts. Current knowledge explains the enhanced primary production and phytoplankton growth found in frontal areas by external factors like nutrient input. The question is whether this enhancement is also caused by intrinsic factors, i.e. simple mixing without external forcing. In order to study the direct effect of frontal mixing on organisms, disturbing external influx has to be excluded. Therefore mixing was simulated by joining waters originating from inside and outside the filament in mesocosms (tanks. These experiments were conducted during two cruises in the northern Benguela upwelling system in September 2013 and January 2014. The mixed waters reached a much higher net primary production and chlorophyll a (chla concentration than the original waters already 2-3 days after their merging. The peak in phytoplankton biomass stays longer than the chla peak. After their maxima, primary production rates decreased quickly due to depletion of the nutrients. The increase in colored dissolved organic matter (CDOM may indicate excretion and degradation. Zooplankton is not quickly reacting on the changed conditions. We conclude that already simple mixing of two water bodies, which occurs generally at fronts between upwelled and ambient water, leads to a short-term stimulation of the phytoplankton growth. However, after the exhaustion of the nutrient stock, external nutrient supply is necessary to maintain the enhanced phytoplankton growth in the frontal area. Based on these data, some generally important ecological factors are discussed as for example nutrient ratios and limitations, silicate requirements and growth rates.

Paediatricians' decision making about prescribing stimulant medications for children with attention-deficit/hyperactivity disorder.

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Chow, S-J; Sciberras, E; Gillam, L H; Green, J; Efron, D

2014-05-01

Attention-deficit/hyperactivity disorder (ADHD) is now the most common reason for a child to present to a paediatrician in Australia. Stimulant medications are commonly prescribed for children with ADHD, to reduce symptoms and improve function. In this study we investigated the factors that influence paediatricians' decisions about prescribing stimulant medications. In-depth, semi-structured interviews were conducted with paediatricians (n = 13) who were purposively recruited so as to sample a broad demographic of paediatricians working in diverse clinical settings. Paediatricians were recruited from public outpatient and private paediatrician clinics in Victoria, Australia. The interviews were audio-recorded and transcribed verbatim for thematic analysis. Paediatricians also completed a questionnaire describing their demographic and practice characteristics. Our findings showed that the decision to prescribe is a dynamic process involving two key domains: (1) weighing up clinical factors; and (2) interacting with parents and the patient along the journey to prescribing. Five themes relating to this process emerged from data analysis: comprehensive assessments that include history, examination and information from others; influencing factors such as functional impairment and social inclusion; previous success; facilitating parental understanding including addressing myths and parental confusion; and decision-making model. Paediatricians' decisions to prescribe stimulant medications are influenced by multiple factors that operate concurrently and interdependently. Paediatricians do not make decisions about prescribing in isolation; rather, they actively involve parents, teachers and patients, to arrive at a collective, well-informed decision. © 2013 John Wiley & Sons Ltd.

Percutaneous implantation of peripheral blood mononuclear cells mobilized with granulocyte colony stimulating factor in osteoarthritis of the knee. First case reported in Cuba

International Nuclear Information System (INIS)

Baganet Cobas, Aymara Maria; Hernandez Ramirez, Porfirio; Fernandez Delgado, Norma

2010-01-01

The degenerative joint disease, also known as osteoarthrosis affects to 10% of elderlies aged 60. It is mainly characterized by pain in the involved joint, crepitation, morning stiff and a progressive limitation of movement of that joint leading to a partial or total wear of articular cartilage. The treatment of the knee osteoarthrosis is a great challenge. The recent advances in use of regenerative medicine suggest that adult stem cells could represent a promisor alternative in the treatment of this entity. In a female patient aged 61 presenting with knee osteoarthrosis authors placed a percutaneous implant of autologous mononuclear cells mobilized to peripheral blood by granulocyte colony-stimulating factor achieving a fast clinical and radiological improvement. This result suggests that the procedure used is a feasible, simple, safe and less expensive method for treatment of articular degenerative lesions

The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report

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Sergio Matarasso

2009-01-01

Full Text Available Cyclic Neutropenia (CN is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC was ≥500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth (PD≤4 mm and an improvement of the oral hygiene conditions recorded at 6-month follow-up.

Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

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Rigatelli, Gianluca; Barbiero, Mario; Rigatelli, Giorgio; Riccardi, Roberto; Cobelli, Franco; Cotogni, Angelo; Bandello, Attilio; Carraro, Ugo

2003-01-01

Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, Pactuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.

Cochlear Implant Spatial Selectivity with Monopolar, Bipolar and Tripolar Stimulation

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Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

2011-01-01

Sharp spatial selectivity is critical to auditory performance, particularly in pitch related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear implant performance. PMID:22138630

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

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Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

The receptor for Granulocyte-colony stimulating factor (G-CSF is expressed in radial glia during development of the nervous system

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Krüger Carola

2008-03-01

Full Text Available Abstract Background Granulocyte colony-stimulating (G-CSF factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo. Results Outside the central nervous system (CNS we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells. Conclusion Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.

Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.

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Shah, Faraaz Ali; Singamsetty, Srikanth; Guo, Lanping; Chuan, Byron W; McDonald, Sherie; Cooper, Bryce A; O'Donnell, Brett J; Stefanovski, Darko; Wice, Burton; Zhang, Yingze; O'Donnell, Christopher P; McVerry, Bryan J

2018-03-01

Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis. Published by Elsevier Inc.

Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

LENUS (Irish Health Repository)

McCourt, M

2012-02-03

BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

Clinical outcome after stem cell mobilization with granulocyte-colony-stimulating factor after acute ST-elevation myocardial infarction:

DEFF Research Database (Denmark)

Ripa, Rasmus S; Jørgensen, Erik; Kastrup, Jens

2013-01-01

Background. Granulocyte-colony-stimulating factor (G-CSF) has been investigated in trials aiming to promote recovery of myocardial function after myocardial infarction. Long-term safety-data have never been reported. A few studies indicated an increased risk of in-stent re-stenosis. We aimed to i.......8; 0.3). Conclusions. We found no indication of increased risk of adverse events up to 5 years after G-CSF treatment. These results support the continued investigation of G-CSF for cardiac therapy....

Effects of bacterial lipopolysaccharide and X-irradiation on the production of colony-stimulating factor and the maintenance of granulopoiesis in bone marrow culture

International Nuclear Information System (INIS)

Izumi, H.; Miyanomae, T.; Tsurusawa, M.; Fujita, J.; Mori, K.

1984-01-01

Effects of bacterial lipopolysaccharide (LPS) and X-irradiation on CSF production and granulopoiesis in long-term bone marrow cultures were studied. Levels of colony-stimulating factor (CSF) increased soon after the refeeding of the culture, but the activity was undetectable at day 7. Addition of LPS induced a significant increase in CSF levels in the culture, followed by an elevated granulopoiesis. The increase in CSF levels was suppressed when culture medium that had been harvested at refeeding on day 7 was added. Although irradiation did not increase CSF production, granulopoiesis was markedly stimulated shortly after irradiation. Thus granulopoiesis in long-term bone marrow culture may also be regulated by humoral factors such as CSF, and the culture system may represent the in vivo response to haemopoietic stimuli. (author)

Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.

Science.gov (United States)

Anzinger, Joshua J; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco J; Park, Bum-Chan; Greene, Lois E; Kruth, Howard S

2010-10-01

To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders.

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Sofuoglu, Mehmet; DeVito, Elise E; Waters, Andrew J; Carroll, Kathleen M

2016-01-01

Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% to 73%, with the most common being mood disorders (13% to 64%) and anxiety disorders (21% to 50%), as well as non-substance-induced psychotic disorders (addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible transdiagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors

Theory of feedback controlled brain stimulations for Parkinson's disease

Science.gov (United States)

Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

2016-01-01

Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

Granulocyte colony-stimulating factor in toxic epidermal necrolysis (TEN) and Chelsea & Westminster TEN management protocol [corrected].

Science.gov (United States)

de Sica-Chapman, A; Williams, G; Soni, N; Bunker, C B

2010-04-01

Toxic epidermal necrolysis (TEN) is a rare but life-threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. We observed that in two cases of severe TEN, dramatic re-epithelialization and recovery coincided with the introduction of granulocyte colony-stimulating factor (G-CSF) for neutropenia. We explain how addition of the G-CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re-epithelialization. G-CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G-CSF should be considered in treating severe TEN irrespective of the severity of neutropenia.

Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

DEFF Research Database (Denmark)

Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

2009-01-01

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

Machine Learning Approach to Optimizing Combined Stimulation and Medication Therapies for Parkinson's Disease.

Science.gov (United States)

Shamir, Reuben R; Dolber, Trygve; Noecker, Angela M; Walter, Benjamin L; McIntyre, Cameron C

2015-01-01

Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naïve Bayes, and random forest. Measures of medication dosages, time factors, and symptom-specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P < 0.05) and their effect on outcomes was of similar magnitude to that of DBS. Using those results, the combined machine learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

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Gen Kuroyanagi

2014-10-01

Full Text Available It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2 on osteoprotegerin (OPG synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK, and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.

Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays

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Xile Wei

2017-11-01

Full Text Available Multi-coil arrays applied in transcranial magnetic stimulation (TMS are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF. Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest

Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays.

Science.gov (United States)

Wei, Xile; Li, Yao; Lu, Meili; Wang, Jiang; Yi, Guosheng

2017-11-14

Multi-coil arrays applied in transcranial magnetic stimulation (TMS) are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF). Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest that there is a

High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture

DEFF Research Database (Denmark)

Shin, Yun-Ji; Hong, Shin-Young; Kwon, Tae-Ho

2003-01-01

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) has been previously produced in tobacco cell suspension cultures. However, the amount of hGM-CSF accumulated in the culture medium dropped quickly from its maximum of 150 microg/L at 5 d after incubation. To overcome...... of recombinant hGM-CSF in transgenic rice cell suspension culture and protease activity of this culture medium was low compared to that of tobacco culture system....

Effect of soluble factors derived from oral cancer cells on the production of interferon-γ from peripheral blood mononuclear cells following stimulation with OK-432.

Science.gov (United States)

Ohe, Go; Sasai, Akiko; Uchida, Daisuke; Tamatani, Tetsuya; Nagai, Hirokazu; Miyamoto, Youji

2013-08-01

The streptococcal antitumor agent OK-432 is commonly used as an immunopotentiator for immunotherapy in various types of malignant tumors including oral cancer. It has been demonstrated that OK-432 elicits an antitumor effect by stimulating immunocompetent cells, thereby inducing multiple cytokines including interferon (IFN)-γ, interleukin (IL)-2 and IL-12. Serum concentrations of IFN-γ in patients with oral cancer were examined 24 h after administration of OK-432. Serum concentrations of IFN-γ in patients with advanced cancer were significantly lower than those in patients with early cancer. These results suggested that some soluble factors produced by cancer cells may inhibit IFN-γ production with OK-432. Thus, in the present study, an in vitro simulation model was established for the immune status of patients with oral cancer by adding conditioned medium (CM) derived from oral cancer cell lines into a culture of peripheral blood mononuclear cells (PBMCs) derived from a healthy volunteer. We investigated whether soluble factors derived from oral cancer cells affected IFN-γ production from PBMCs following stimulation with OK-432. PBMCs stimulated with OK-432 produced a large amount of IFN-γ; however, both IFN-γ production and cytotoxic activity from PBMCs induced by OK-432 were inhibited by the addition of CM in a dose-dependent manner. In order to examine these inhibitory effects against IFN-γ production, the contribution of inhibitory cytokines such as IL-4, IL-6, IL-10, transforming growth factor-β and vascular endothelial growth factor was investigated. However, neutralization of these inhibitory cytokines did not recover IFN-γ production inhibited by CM. These results indicated that unknown molecules may inhibit IFN-γ production from PBMCs following stimulation with OK-432.

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke.

Science.gov (United States)

Niimi, Masachika; Hashimoto, Kenji; Kakuda, Wataru; Miyano, Satoshi; Momosaki, Ryo; Ishima, Tamaki; Abo, Masahiro

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.

Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

Directory of Open Access Journals (Sweden)

Hyoungshin Park

2010-01-01

Full Text Available Low-intensity ultrasound (LIUS treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12 and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo.

Cochlear-implant spatial selectivity with monopolar, bipolar and tripolar stimulation.

Science.gov (United States)

Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

2012-01-01

Sharp spatial selectivity is critical to auditory performance, particularly in pitch-related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear-implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear-implant performance. Copyright © 2011 Elsevier B.V. All rights reserved.

Technological Advances in Deep Brain Stimulation.

Science.gov (United States)

Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

2015-01-01

Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware.

Electrical Stimulation of the Upper Limb in Stroke: Stimulation of the Extensors of the Hand vs. Alternate Stimulation of Flexors and Extensors

NARCIS (Netherlands)

de Kroon, J.R.; IJzerman, Maarten Joost; Lankhorst, G.J.; Zilvold, G.

2004-01-01

Objective: To investigate whether there is a difference in functional improvement in the affected arm of chronic stroke patients when comparing two methods of electrical stimulation. Design: Explanatory trial in which 30 chronic stroke patients with impaired arm function were randomly allocated to

Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture.

Science.gov (United States)

Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y

1992-05-01

We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

Factor analysis improves the selection of prescribing indicators

DEFF Research Database (Denmark)

Rasmussen, Hanne Marie Skyggedal; Søndergaard, Jens; Sokolowski, Ineta

2006-01-01

OBJECTIVE: To test a method for improving the selection of indicators of general practitioners' prescribing. METHODS: We conducted a prescription database study including all 180 general practices in the County of Funen, Denmark, approximately 472,000 inhabitants. Principal factor analysis was us...... appropriate and inappropriate prescribing, as revealed by the correlation of the indicators in the first factor. CONCLUSION: Correlation and factor analysis is a feasible method that assists the selection of indicators and gives better insight into prescribing patterns....

Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.

Science.gov (United States)

Willand, Michael P; Holmes, Michael; Bain, James R; de Bruin, Hubert; Fahnestock, Margaret

2014-11-01

Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. All treatment groups had significantly higher muscle weight (pstimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.

Effect of transcutaneous electrical nerve stimulation induced parotid stimulation on salivary flow

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Sreenivasulu Pattipati

2013-01-01

Full Text Available Aims and Objectives: The main objective of this study was to evaluate the duration of stimulation over the parotid salivary flow following the use of transcutaneous electric nerve stimulation (TENS in different age groups. Materials and Methods: The study was carried out in three different age groups. Under group A individuals from 21 to 35 years of age, group B 36-50 years and group C above 51 years were considered. In each group 30 subjects were taken of whom 15 were males and 15 were females. The placement of pads was approximated bilaterally over the parotid glands. The working parameters of TENS unit were fixed at 50 Hz and the unit was in normal mode. Results: Subjects belonging to group B were showing statistically significant increases in the duration of stimulated parotid salivary flow following the use of TENS. Conclusion: TENS can be considered as a non-pharmacological alternative to improve salivation for longer period in xerostomia patients.

Transcranial direct current stimulation versus user training on improving online myoelectric control for amputees

Science.gov (United States)

Pan, Lizhi; Zhang, Dingguo; Jiang, Ning; Sheng, Xinjun; Zhu, Xiangyang

2017-08-01

Objective. Transcranial direct current stimulation (tDCS) and user training (UT) are two types of methods to improve myoelectric control performance for amputees. In this study, we compared the independent effect between tDCS and UT, and investigated the combined effect of tDCS and UT. Approach. An online paradigm of simultaneous and proportional control (SPC) based on electromyography (EMG) was adopted. The proposed experiments were conducted on six naïve unilateral trans-radial amputees. The subjects each received three types of 20 min interventions: active tDCS with motor training (tDCS  +  UT), active tDCS with quiet sitting (tDCS), and sham tDCS with motor training (UT). The interventions were applied at one week intervals in a randomized order. The subjects performed online control of a feedback arrow with two degrees of freedom (DoFs) to accomplish target reaching motor tasks in pre-sessions and post-sessions. We compared the performance, measured by completion rate, completion time, and efficiency coefficient, between pre-sessions and post-sessions. Main results. The results showed that the intervention tDCS  +  UT and tDCS significantly improved the online SPC performance (i.e. improved the completion rate; reduced the completion time; and improved the efficiency coefficient), while intervention UT did not significantly change the performance. The results also showed that the online SPC performance after intervention tDCS  +  UT and tDCS was not significantly different, but both were significantly better than that after intervention UT. Significance. tDCS could be an effective intervention to improve the online SPC performance in a short time.

Long-term effects of stimulant treatment on ADHD symptoms, social-emotional functioning, and cognition.

Science.gov (United States)

Schweren, Lizanne; Hoekstra, Pieter; van Lieshout, Marloes; Oosterlaan, Jaap; Lambregts-Rommelse, Nanda; Buitelaar, Jan; Franke, Barbara; Hartman, Catharina

2018-03-13

Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social-emotional functioning or cognition, measured after medication wash-out. ADHD symptoms, social-emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n = 148, 58% male, age = 11.1). A matched healthy control group was included for reference. All but two outcome measures (emotional problems and prosocial behaviour) improved between baseline and follow-up. Improvement over time in the stimulant-treated group did not differ from improvement in the not stimulant-treated group on any outcome measure. Stimulant treatment is not associated with the long-term developmental course of ADHD symptoms, social-emotional functioning, motor control, timing or verbal working memory. Adolescence is characterised by clinical improvement regardless of stimulant treatment during that time. These findings are an important source to inform the scientific and public debate.

Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

Energy Technology Data Exchange (ETDEWEB)

Buck, P.A.

1986-01-01

Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

Enhanced motor skill acquisition in the non-dominant upper extremity using intermittent theta burst stimulation and transcranial direct current stimulation.

Science.gov (United States)

Butts, Raymond J; Kolar, Melissa B; Newman-Norlund, Roger D

2014-01-01

Individuals suffering from motor impairments often require physical therapy (PT) to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS) and bihemispheric transcranial direct current stimulation (tDCS) may increase the speed and extent of motor learning/relearning. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-h, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15) or control group (n = 12). iTBS (20 trains of 10 pulse triplets each delivered at 80% active motor threshold (AMT) / 50 Hz over 191.84 s) and bihemispheric tDCS (1.0 ma for 20 min) were used as a primer to, and in conjunction with, 20 min of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function (JTHF) test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-h post training (p = 0.055), and were significant at 7-days post training (p iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

Staurosporine potentiates platelet activating factor stimulated phospholipase C activity in rabbit platelets but does not block desensitization by platelet activating factor

International Nuclear Information System (INIS)

Morrison, W.J.; Dhar, A.; Shukla, S.D.

1989-01-01

The possible involvement of protein kinase C activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets. PAF stimulated incorporation of 32 P into proteins and caused [ 3 H]InsP 3 levels to increase about 260% of control. These responses were compared after platelets were pretreated with either PAF, phorbol 12-myristate 13-acetate (PMA) or staurosporine and also after pretreatments with staurosporine followed by PAF or PMA. Pretreating platelets with staurosporine potentiated PAF-stimulated [ 3 H]InsP 3 levels by 54% and blocked protein phosphorylation. Pretreatments with PAF and PMA caused PAF-stimulated [ 3 H]InsP 3 levels to decrease to 115 and 136%, respectively. Staurosporine pretreatment blocked the decrease caused by the PMA pretreatment but not that by PAF. This study demonstrates that PAF-stimulated PLC activity is negatively affected by protein kinase C (PKC) activation and that inhibition of PKC activity did not prevent desensitization of PLC by PAF

Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

Science.gov (United States)

Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

2015-01-01

Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance During Adaptation to Visuomotor and Somatosensory Distortion.

Science.gov (United States)

Temple, David R; De Dios, Yiri E; Layne, Charles S; Bloomberg, Jacob J; Mulavara, Ajitkumar P

2018-01-01

Astronauts exposed to microgravity face sensorimotor challenges affecting balance control when readapting to Earth's gravity upon return from spaceflight. Small amounts of electrical noise applied to the vestibular system have been shown to improve balance control during standing and walking under discordant sensory conditions in healthy subjects, likely by enhancing information transfer through the phenomenon of stochastic resonance. The purpose of this study was to test the hypothesis that imperceptible levels of stochastic vestibular stimulation (SVS) could improve short-term adaptation to a locomotor task in a novel sensory discordant environment. Healthy subjects (14 males, 10 females, age = 28.7 ± 5.3 years, height = 167.2 ± 9.6 cm, weight = 71.0 ± 12.8 kg) were tested for perceptual thresholds to sinusoidal currents applied across the mastoids. Subjects were then randomly and blindly assigned to an SVS group receiving a 0-30 Hz Gaussian white noise electrical stimulus at 50% of their perceptual threshold (stim) or a control group receiving zero stimulation during Functional Mobility Tests (FMTs), nine trials of which were done under conditions of visual discordance (wearing up/down vision reversing goggles). Time to complete the course (TCC) was used to test the effect of SVS between the two groups across the trials. Adaptation rates from the normalized TCCs were also compared utilizing exponent values of power fit trendline equations. A one-tailed independent-samples t -test indicated these adaptation rates were significantly faster in the stim group ( n = 12) than the control ( n = 12) group [ t (16.18) = 2.00, p = 0.031]. When a secondary analysis was performed comparing "responders" (subjects who showed faster adaptation rates) of the stim ( n = 7) group to the control group ( n = 12), independent-samples t -tests revealed significantly faster trial times for the last five trials with goggles in the stim group "responders" than the controls. The data

Improvement of uncorrected visual acuity (UCVA and contrast sensitivity (UCCS with perceptual learning and transcranial random noise stimulation (tRNS in individuals with mild myopia

Directory of Open Access Journals (Sweden)

Rebecca eCamilleri

2014-10-01

Full Text Available Perceptual learning has been shown to produce an improvement of visual acuity (VA and contrast sensitivity (CS both in subjects with amblyopia and refractive defects such as myopia or presbyopia. Transcranial random noise stimulation (tRNS has proven to be efficacious in accelerating neural plasticity and boosting perceptual learning in healthy participants. In this study we investigated whether a short behavioural training regime using a contrast detection task combined with online tRNS was as effective in improving visual functions in participants with mild myopia compared to a two-month behavioural training regime without tRNS (Camilleri et al., 2014. After two weeks of perceptual training in combination with tRNS, participants showed an improvement of 0.15 LogMAR in uncorrected VA (UCVA that was comparable with that obtained after eight weeks of training with no tRNS, and an improvement in uncorrected CS (UCCS at various spatial frequencies (whereas no UCCS improvement was seen after eight weeks of training with no tRNS. On the other hand, a control group that trained for two weeks without stimulation did not show any significant UCVA or UCCS improvement. These results suggest that the combination of behavioural and neuromodulatory techniques can be fast and efficacious in improving sight in individuals with mild myopia.

Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs

Directory of Open Access Journals (Sweden)

Lei Du

2016-01-01

Full Text Available Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses (0.7 V, 5 Hz were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oculomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.

Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

Science.gov (United States)

Stafford, Jason H.; Hirai, Takahisa; Deng, Lei; Chernikova, Sophia B.; Urata, Kimiko; West, Brian L.; Brown, J. Martin

2016-01-01

Background Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. Methods To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. Results GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. Conclusion CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy. PMID:26538619

Exogenous ciliary neurotrophic factor (CNTF) reduces synaptic depression during repetitive stimulation.

Science.gov (United States)

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Priego, Mercedes; Obis, Teresa; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2012-09-01

It has been shown that ciliary neurotrophic factor (CNTF) has trophic and maintenance effects on several types of peripheral and central neurons, glia, and cells outside the nervous system. Both CNTF and its receptor, CNTF-Rα, are expressed in the muscle. We use confocal immunocytochemistry to show that the trophic cytokine and its receptor are present in the pre- and post-synaptic sites of the neuromuscular junctions (NMJs). Applied CNTF (7.5-200 ng/ml, 60 min-3 h) does not acutely affect spontaneous potentials (size or frequency) or quantal content of the evoked acetylcholine release from post-natal (in weak or strong axonal inputs on dually innervated end plates or in the most mature singly innervated synapses at P6) or adult (P30) NMJ of Levator auris longus muscle of the mice. However, CNTF reduces roughly 50% the depression produced by repetitive stimulation (40 Hz, 2 min) on the adult NMJs. Our findings indicate that, unlike neurotrophins, exogenous CNTF does not acutely modulate transmitter release locally at the mammalian neuromuscular synapse but can protect mature end plates from activity-induced synaptic depression. © 2012 Peripheral Nerve Society.

[Noopept improves the spatial memory and stimulates prefibrillar beta-amyloid(25-35) antibody production in mice].

Science.gov (United States)

Bobkova, N V; Gruden', M A; Samokhin, A N; Medvinskaia, N I; Morozova-Roch, L; Uudasheva, T A; Ostrovskaia, R U; Seredinin, S B

2005-01-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

Science.gov (United States)

Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

2018-03-01

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Perceived Factors Associated with Sustained Improvement Following Participation in a Multicenter Quality Improvement Collaborative.

Science.gov (United States)

Stone, Sohini; Lee, Henry C; Sharek, Paul J

2016-07-01

The California Perinatal Quality Care Collaborative led the Breastmilk Nutrition Quality Improvement Collaborative from October 2009 to September 2010 to increase the percentage of very low birth weight infants receiving breast milk at discharge in 11 collaborative neonatal ICUs (NICUs). Observed increases in breast milk feeding and decreases in necrotizing enterocolitis persisted for 6 months after the collaborative ended. Eighteen to 24 months after the end of the collaborative, some sites maintained or further increased their gains, while others trended back toward baseline. A study was conducted to assess the qualitative factors that affect sustained improvement following participation. Collaborative leaders at each of the 11 NICUs that participated in the Breastmilk Nutrition Quality Improvement Collaborative were invited to participate in a site-specific one-hour phone interview. Interviews were recorded and transcribed and then analyzed using qualitative research analysis software to identify themes associated with sustained improvement. Eight of 11 invited centers agreed to participate in the interviews. Thematic saturation was achieved by the sixth interview, so further interviews were not pursued. Factors contributing to sustainability included physician involvement within the multidisciplinary teams, continuous education, incorporation of interventions into the daily work flow, and integration of a data-driven feedback system. Early consideration by site leaders of how to integrate best-practice interventions into the daily work flow, and ensuring physician commitment and ongoing education based in continuous data review, should enhance the likelihood of sustaining improvements. To maximize sustained success, future collaborative design should consider proactively identifying and supporting these factors at participating sites.

Computational electromagnetic methods for transcranial magnetic stimulation

Science.gov (United States)

Gomez, Luis J.

Transcranial magnetic stimulation (TMS) is a noninvasive technique used both as a research tool for cognitive neuroscience and as a FDA approved treatment for depression. During TMS, coils positioned near the scalp generate electric fields and activate targeted brain regions. In this thesis, several computational electromagnetics methods that improve the analysis, design, and uncertainty quantification of TMS systems were developed. Analysis: A new fast direct technique for solving the large and sparse linear system of equations (LSEs) arising from the finite difference (FD) discretization of Maxwell's quasi-static equations was developed. Following a factorization step, the solver permits computation of TMS fields inside realistic brain models in seconds, allowing for patient-specific real-time usage during TMS. The solver is an alternative to iterative methods for solving FD LSEs, often requiring run-times of minutes. A new integral equation (IE) method for analyzing TMS fields was developed. The human head is highly-heterogeneous and characterized by high-relative permittivities (107). IE techniques for analyzing electromagnetic interactions with such media suffer from high-contrast and low-frequency breakdowns. The novel high-permittivity and low-frequency stable internally combined volume-surface IE method developed. The method not only applies to the analysis of high-permittivity objects, but it is also the first IE tool that is stable when analyzing highly-inhomogeneous negative permittivity plasmas. Design: TMS applications call for electric fields to be sharply focused on regions that lie deep inside the brain. Unfortunately, fields generated by present-day Figure-8 coils stimulate relatively large regions near the brain surface. An optimization method for designing single feed TMS coil-arrays capable of producing more localized and deeper stimulation was developed. Results show that the coil-arrays stimulate 2.4 cm into the head while stimulating 3

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

Science.gov (United States)

Aleman, André; Enriquez-Geppert, Stefanie; Knegtering, Henderikus; Dlabac-de Lange, Jozarni J

2018-06-01

Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests. For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of

Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

NARCIS (Netherlands)

Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

2002-01-01

Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

Insulin-stimulating diets during the weaning-to-estrus interval do not improve fetal and placental development and uniformity in high-prolific multiparous sows

NARCIS (Netherlands)

Wientjes, J.G.M.; Soede, N.M.; Laurenssen, B.F.A.; Koopmanschap, R.E.; Brand, van den H.; Kemp, B.

2013-01-01

Piglet birth weight and litter uniformity are important for piglet survival. Insulin-stimulating sow diets before mating may improve subsequent piglet birth weights and litter uniformity, but the physiological mechanisms involved are not clear. This study evaluated effects of different levels of

Does interscalene catheter placement with stimulating catheters improve postoperative pain or functional outcome after shoulder surgery? A prospective, randomized and double-blinded trial

NARCIS (Netherlands)

Stevens, Markus F.; Werdehausen, Robert; Golla, Elisabeth; Braun, Sebastian; Hermanns, Henning; Ilg, Ansgar; Willers, Reinhardt; Lipfert, Peter

2007-01-01

BACKGROUND: In this prospective, randomized, double-blind trial we investigated the use of stimulating catheters in patients during and after shoulder surgery; functional improvement being the primary outcome measurement. METHODS: After eliciting an adequate muscular twitch at

Anhedonia and amotivation in psychiatric outpatients with fully remitted stimulant use disorder.

Science.gov (United States)

Leventhal, Adam M; Kahler, Christopher W; Ray, Lara A; Stone, Kristen; Young, Diane; Chelminski, Iwona; Zimmerman, Mark

2008-01-01

This study evaluated whether psychiatric outpatients with a past stimulant use disorder in full remission for >/= 2 months (STIM+, n = 204) and those with no history of stimulant use disorder (STIM-, n = 2070) differed in the prevalence of current anhedonia and amotivation. Results showed that a significantly greater proportion of STIM+ participants reported anhedonia and amotivation than STIM- participants. The relation between stimulant use disorder history and anhedonia remained robust after controlling for other relevant clinical and demographic factors. These findings suggest that anhedonia may be a preexisting risk factor or protracted effect of stimulant misuse.

Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution

International Nuclear Information System (INIS)

Chen, Liqing; Wang, Yujun; Wells, David; Toh, Diana; Harold, Hunt; Zhou, Jing; DiGiammarino, Enrico; Meehan, Edward J.

2006-01-01

The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 Å. The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein–protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12–72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 Å. The overall structure shows a characteristic SH3 fold consisting of two perpendicular β-sheets that form a β-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors

Stimulation site within the MRI-defined STN predicts postoperative motor outcome.

Science.gov (United States)

Wodarg, Fritz; Herzog, Jan; Reese, René; Falk, Daniela; Pinsker, Markus O; Steigerwald, Frank; Jansen, Olav; Deuschl, Günther; Mehdorn, H Maximillian; Volkmann, Jens

2012-06-01

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is highly effective in treating motor symptoms in Parkinson's disease (PD) and medication side effects as well as in improving quality of life. Despite preoperative screening for patients as eligible candidates for this treatment, electrode position may furthermore influence treatment quality. Here, we investigated the relationship between the anatomical site of stimulation within the MRI-defined STN and the outcome of PD patients after STN-HFS. In 30 PD patients with bilateral STN stimulation, we retrospectively defined the boundaries of the STN within the axial target plane of the stereotactic T2-weighted MRI and determined the position of the active electrode contact in relation to the border of the STN. The position of the active contact within the STN was the only variable to predict the outcome of STN stimulation. In contrast, covariates such as age, disease duration, symptom severity, and response to levodopa had no effect. The lateral position of the stimulation contact within the STN led to significantly better clinical improvement, lower stimulation parameters, and less need for postoperative dopaminergic medication. The outcome of patients with stimulation contacts within the medial region of the STN was significantly worse. Precise targeting of the lateral region of the STN is essential for achieving sufficient stimulation efficacy. Preoperative T2-weighted MRI might be a useful component of the targeting procedure to improve the outcome of PD patients. Copyright © 2012 Movement Disorder Society.

Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

DEFF Research Database (Denmark)

Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

2003-01-01

BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

Regulation of granulocyte colony-stimulating factor receptor-mediated granulocytic differentiation by C-mannosylation.

Science.gov (United States)

Otani, Kei; Niwa, Yuki; Suzuki, Takehiro; Sato, Natsumi; Sasazawa, Yukiko; Dohmae, Naoshi; Simizu, Siro

2018-04-06

Granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is a type I cytokine receptor which is involved in hematopoietic cell maturation. G-CSFR has three putative C-mannosylation sites at W253, W318, and W446; however, it is not elucidated whether G-CSFR is C-mannosylated or not. In this study, we first demonstrated that G-CSFR was C-mannosylated at only W318. We also revealed that C-mannosylation of G-CSFR affects G-CSF-dependent downstream signaling through changing ligand binding capability but not cell surface localization. Moreover, C-mannosylation of G-CSFR was functional and regulated granulocytic differentiation in myeloid 32D cells. In conclusion, we found that G-CSFR is C-mannosylated at W318 and that this C-mannosylation has role(s) for myeloid cell differentiation through regulating downstream signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

Science.gov (United States)

Yun, Sanghee; Reynolds, Ryan P; Petrof, Iraklis; White, Alicia; Rivera, Phillip D; Segev, Amir; Gibson, Adam D; Suarez, Maiko; DeSalle, Matthew J; Ito, Naoki; Mukherjee, Shibani; Richardson, Devon R; Kang, Catherine E; Ahrens-Nicklas, Rebecca C; Soler, Ivan; Chetkovich, Dane M; Kourrich, Saïd; Coulter, Douglas A; Eisch, Amelia J

2018-04-16

Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

Structural insights into the backbone-circularized granulocyte colony-stimulating factor containing a short connector.

Science.gov (United States)

Miyafusa, Takamitsu; Shibuya, Risa; Honda, Shinya

2018-06-02

Backbone circularization is a powerful approach for enhancing the structural stability of polypeptides. Herein, we present the crystal structure of the circularized variant of the granulocyte colony-stimulating factor (G-CSF) in which the terminal helical region was circularized using a short, two-amino acid connector. The structure revealed that the N- and C-termini were indeed connected by a peptide bond. The local structure of the C-terminal region transited from an α helix to 3 10 helix with a bend close to the N-terminal region, indicating that the structural change offset the insufficient length of the connector. This is the first-ever report of a crystal structure of the backbone of a circularized protein. It will facilitate the development of backbone circularization methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

Using of gamma rays in stimulation and improvement of mushroom spawns plerotus ostreatus

International Nuclear Information System (INIS)

Hussein, O.S.; Atia, A.I.

2009-01-01

The objective of this work was activation and stimulation of plerotus ostreatus growth and increasing their yields by using of gamma rays, in addition to improvement of mushroom quality and shelf life.Exposing plerotus ostreatus to different doses of gamma rays 2.5, 5, 10 and 15 Gy to determine some of the basic composition of mushroom fruits achieved significant increase in yields and basic composition of resulted mushrooms. Also, increase in carbohydrates content, most of amino acids content and fatty acids content, mainly unsaturated fatty acid i.e., (C 16:1) and (C 18:1,2), which are essential for human nutrition as antioxidant. Whereas, there was a significant decrease in the total phenols content of the resulted fruits, which affected the quality and shelf life of mushroom fruits. All gamma rays doses used increased mushroom yield in fresh and dry wt basis. The recommended dose for spawn irradiation was 10 Gy to increase mushroom yields and its chemical components

Cognitive Function as a Trans-Diagnostic Treatment Target in Stimulant Use Disorders

Science.gov (United States)

Sofuoglu, Mehmet; DeVito, Elise E.; Waters, Andrew J.; Carroll, Kathleen M.

2016-01-01

Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive

Transcranial direct current stimulation, implicit alcohol associations and craving

NARCIS (Netherlands)

den Uijl, T.E.; Gladwin, T.E.; Wiers, R.W.

2015-01-01

Previous research has shown that stimulation of the left dorsolateral prefrontal cortex (DLPFC) enhances working memory (e.g. in the n-back task), and reduces craving for cigarettes and alcohol. Stimulation of the right inferior frontal gyrus (IFG) improves response inhibition. The underlying

An evaluation of factors affecting duration of treatment with repetitive transcranial magnetic stimulation for depression

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Roni Broder Cohen

2007-12-01

Full Text Available Objective: To investigate the effects of repetitive transcranialmagnetic stimulation in patients with major depression who weresubmitted to this treatment during the period from 2000 to 2006.Methods: A retrospective study with 204 patients who underwenttreatment with repetitive transcranial magnetic stimulation, collectingdata from those who experienced remission (defined as a HDRS scoreequal to or lower than 7. The patients were followed for up to 6 monthsafter treatment. Mean duration of remission for this cohort of patientswas 70.2 (± 58.4 days. Results: The only variable associated withthe duration of remission in the linear regression model was numberof repetitive transcranial magnetic stimulation sessions. Conclusion:Our findings suggest that the greater the number of sessions, the longerthe duration of repetitive transcranial magnetic stimulation effects.Consequently, future research investigating the effects of repetitivetranscranial magnetic stimulation should explore this variable in orderto maximize the therapeutic effects of this new brain stimulationtechnique.

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

Directory of Open Access Journals (Sweden)

Bryan Howell

Full Text Available 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

Granulocyte colony-stimulating factor mobilizes dormant hematopoietic stem cells without proliferation in mice.

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Bernitz, Jeffrey M; Daniel, Michael G; Fstkchyan, Yesai S; Moore, Kateri

2017-04-06

Granulocyte colony-stimulating factor (G-CSF) is used clinically to treat leukopenia and to enforce hematopoietic stem cell (HSC) mobilization to the peripheral blood (PB). However, G-CSF is also produced in response to infection, and excessive exposure reduces HSC repopulation capacity. Previous work has shown that dormant HSCs contain all the long-term repopulation potential in the bone marrow (BM), and that as HSCs accumulate a divisional history, they progressively lose regenerative potential. As G-CSF treatment also induces HSC proliferation, we sought to examine whether G-CSF-mediated repopulation defects are a result of increased proliferative history. To do so, we used an established H2BGFP label retaining system to track HSC divisions in response to G-CSF. Our results show that dormant HSCs are preferentially mobilized to the PB on G-CSF treatment. We find that this mobilization does not result in H2BGFP label dilution of dormant HSCs, suggesting that G-CSF does not stimulate dormant HSC proliferation. Instead, we find that proliferation within the HSC compartment is restricted to CD41-expressing cells that function with short-term, and primarily myeloid, regenerative potential. Finally, we show CD41 expression is up-regulated within the BM HSC compartment in response to G-CSF treatment. This emergent CD41 Hi HSC fraction demonstrates no observable engraftment potential, but directly matures into megakaryocytes when placed in culture. Together, our results demonstrate that dormant HSCs mobilize in response to G-CSF treatment without dividing, and that G-CSF-mediated proliferation is restricted to cells with limited regenerative potential found within the HSC compartment. © 2017 by The American Society of Hematology.

Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder.

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Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L

2018-03-01

Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.

High Expression of Colony-Stimulating Factor 1 Receptor Associates with Unfavorable Cancer-Specific Survival of Patients with Clear Cell Renal Cell Carcinoma.

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Yang, Liu; Liu, Yidong; An, Huimin; Chang, Yuan; Zhang, Weijuan; Zhu, Yu; Xu, Le; Xu, Jiejie

2016-03-01

Colony-stimulating factor 1 receptor (CSF-1R), a single-pass type III transmembrane tyrosine-protein kinase, is mainly involved in inflammation and immune regulation to facilitate the progression of solid tumors. This study aimed to evaluate the impact of CSF-1R expression on clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) after surgery. We retrospectively enrolled 268 patients with ccRCC undergoing nephrectomy between 2001 and 2004. Clinicopathologic features and cancer-specific survival (CSS) were collected. Western blot analysis was performed in the pairwise comparisons of CSF-1R expression in peritumor and tumor tissues of patients with ccRCC. Immunohistochemistry was conducted to determine CSF-1R expression level in tumor specimens. Survival analysis was performed by the Kaplan-Meier method. Cox regression models were used to evaluate the impact of prognostic factors on CSS. A concordance index was calculated to measure prognostic accuracy. A prognostic nomogram was constructed on the basis of the identified independent prognostic factors. CSF-1R expression in tumor tissues was higher than in peritumor tissues in 71.4% (5 of 7) patients. CSF-1R expression of tumor tissues was positively associated with metastasis, tumor, node, metastasis classification system (TNM) stage, Eastern Cooperative Oncology Group performance status score and poor CSS. CSF-1R expression was determined as an independent prognostic factor for CSS in patients with ccRCC. Furthermore, extension of the well-established prognostic models with CSF-1R expression presented significantly improved prognostic accuracy. An efficient prognostic nomogram was constructed on the basis of the independent prognostic factors. High CSF-1R expression is a potential independent adverse prognostic factor for CSS in patients with ccRCC.

Clinical improvement in patients with borderline personality disorder after treatment with repetitive transcranial magnetic stimulation: preliminary results.

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Reyes-López, Julian; Ricardo-Garcell, Josefina; Armas-Castañeda, Gabriela; García-Anaya, María; Arango-De Montis, Iván; González-Olvera, Jorge J; Pellicer, Francisco

2018-01-01

Current treatment of borderline personality disorder (BPD) consists of psychotherapy and pharmacological interventions. However, the use of repetitive transcranial magnetic stimulation (rTMS) could be beneficial to improve some BPD symptoms. The objective of this study was to evaluate clinical improvement in patients with BPD after application of rTMS over the right or left dorsolateral prefrontal cortex (DLPFC). Twenty-nine patients with BPD from the National Institute of Psychiatry, Mexico, were randomized in two groups to receive 15 sessions of rTMS applied over the right (1 Hz, n=15) or left (5 Hz, n=14) DLPFC. Improvement was measured by the Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity Over Time (BEST), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), and Barratt Impulsiveness Scale (BIS). Intragroup comparison showed significant (p < 0.05) reductions in every psychopathologic domain of the CGI-BPD and in the total scores of all scales in both groups. Both protocols produced global improvement in severity and symptoms of BPD, particularly in impulsiveness, affective instability, and anger. Further studies are warranted to explore the therapeutic effect of rTMS in BPD. NCT02273674

What interventions can improve quality of life or psychosocial factors of individuals with knee osteoarthritis? A systematic review with meta-analysis of primary outcomes from randomised controlled trials.

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Briani, Ronaldo Valdir; Ferreira, Amanda Schenatto; Pazzinatto, Marcella Ferraz; Pappas, Evangelos; De Oliveira Silva, Danilo; Azevedo, Fábio Mícolis de

2018-03-16

To systematically review evidence of primary outcomes from randomised controlled trials (RCTs) examining the effect of treatment strategies on quality of life (QoL) or psychosocial factors in individuals with knee osteoarthritis (OA). Systematic review with meta-analysis. Medline, Embase, SPORTDiscus, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science were searched from inception to November 2017. We included RCTs investigating the effect of conservative interventions on QoL or psychosocial factors in individuals with knee OA. Only RCTs considering these outcomes as primary were included. Pooled data supported the use of exercise therapy compared with controls for improving health-related and knee-related QoL. There was limited evidence that a combined treatment of yoga, transcutaneous electrical stimulation and ultrasound may be effective in improving QoL. Limited evidence supported the use of cognitive behavioural therapies (with or without being combined with exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress. Exercise therapy (with or without being combined with other interventions) seems to be effective in improving health-related and knee-related QoL or psychosocial factors of individuals with knee OA. In addition, evidence supports the use of cognitive behavioural therapies (with or without exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress in individuals with knee OA. CRD42016047602. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Adenosine Receptor Stimulation Improves Glucocorticoid-Induced Osteoporosis in a Rat Model

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Gabriele Pizzino

2017-09-01

Full Text Available Glucocorticoid-induced osteoporosis (GIO is a secondary cause of bone loss. Bisphosphonates approved for GIO, might induce jaw osteonecrosis; thus additional therapeutics are required. Adenosine receptor agonists are positive regulators of bone remodeling, thus the efficacy of adenosine receptor stimulation for treating GIO was tested. In a preventive study GIO was induced in Sprague-Dawley rats by methylprednisolone (MP for 60 days. Animals were randomly assigned to receive polydeoxyribonucleotide (PDRN, an adenosine A2 receptor agonist, or PDRN and DMPX (3,7-dimethyl-1-propargylxanthine, an A2 antagonist, or vehicle (0.9% NaCl. Another set of animals was used for a treatment study, following the 60 days of MP-induction rats were randomized to receive (for additional 60 days PDRN, or PDRN and DMPX (an adenosine A2 receptor antagonist, or zoledronate (as control for gold standard treatment, or vehicle. Control animals were administered with vehicle for either 60 or 120 days. Femurs were analyzed after treatments for histology, imaging, and breaking strength analysis. MP treatment induced severe bone loss, the concomitant use of PDRN prevented the developing of osteoporosis. In rats treated for 120 days, PDRN restored bone architecture and bone strength; increased b-ALP, osteocalcin, osteoprotegerin and stimulated the Wnt canonical and non-canonical pathway. Zoledronate reduced bone resorption and ameliorated the histological features, without significant effects on bone formation. Our results suggest that adenosine receptor stimulation might be useful for preventing and treating GIO.

Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients

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You, Dae Sang; Kim, Dae-Yul; Chun, Min Ho; Jung, Seung Eun; Park, Sung Jong

2011-01-01

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and…

Mobilization of stem cell with granulocyte-colony stimulating factor promotes recovery after traumatic brain injury in rat

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Mohsen Marzban

2010-01-01

Full Text Available Introduction: This study was designed to investigate the effects of granulocyte colony-stimulating factor (G-CSF administration in rats for 6 weeks after traumatic brain injury (TBI. Methods: Adult male Wistar rats (n = 30 were injured with controlled cortical impact device and divided into four groups. The treatment groups (n = 10 each were injected subcutaneously with recombinant human G-CSF. Vehicle group (n=10 received phosphate buffered saline (PBS and only Brdu intraperitoneally. Bromodeoxyuridine (BrdU was used for mitotic labeling. Experimental rats were injected intraperitoneally with BrdU. Rats were killed at 6th week after traumatic brain injury. Neurological functional evaluation of animals was performed before and after injury using neurological severity scores (NSS. Animals were sacrificed 42 days after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (p<0.01. This benefit was visible 7 days after TBI and persisted until 42 days (end of trial. Histological analysis showed that Brdu cell positive was more in the lesion boundary zone at treatment animal group than all injected animals. Discussion: We believe that G-CSF therapeutic protocol reported here represents an attractive strategy for the development of a clinically significant noninvasive traumatic brain injury therapy.

Stridor and dysphagia associated with subthalamic nucleus stimulation in Parkinson disease.

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Fagbami, Oluwakemi Y; Donato, Anthony A

2011-11-01

Refractory symptoms in Parkinson disease show good response to deep brain stimulation (DBS). This procedure improves United Parkinson's Disease Rating Scale scores and reduces dyskinesias, whereas speech and swallowing dysfunction typically do not improve and may even worsen. Rarely, DBS can cause idiosyncratic dystonias of muscle groups, including those of the neck and throat. The authors describe a patient experiencing stridor and dysphagia with confirmed pulmonary restriction and aspiration following subthalamic nucleus deep brain stimulator adjustment, with a resolution of symptoms and signs when the stimulator was switched off.

Graphene electrodes for stimulation of neuronal cells

International Nuclear Information System (INIS)

Koerbitzer, Berit; Nick, Christoph; Thielemann, Christiane; Krauss, Peter; Yadav, Sandeep; Schneider, Joerg J

2016-01-01

Graphene has the ability to improve the electrical interface between neuronal cells and electrodes used for recording and stimulation purposes. It provides a biocompatible coating for common electrode materials such as gold and improves the electrode properties. Graphene electrodes are also prepared on SiO 2 substrate to benefit from its optical properties like transparency. We perform electrochemical and Raman characterization of gold electrodes with graphene coating and compare them with graphene on SiO 2 substrate. It was found that the substrate plays an important role in the performance of graphene and show that graphene on SiO 2 substrate is a very promising material combination for stimulation electrodes. (paper)

Stimulation Technologies for Deep Well Completions

Energy Technology Data Exchange (ETDEWEB)

None

2003-09-30

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 is conducting a study to evaluate the stimulation of deep wells. The objective of the project is to assess U.S. deep well drilling & stimulation activity, review rock mechanics & fracture growth in deep, high pressure/temperature wells and evaluate stimulation technology in several key deep plays. An assessment of historical deep gas well drilling activity and forecast of future trends was completed during the first six months of the project; this segment of the project was covered in Technical Project Report No. 1. The second progress report covers the next six months of the project during which efforts were primarily split between summarizing rock mechanics and fracture growth in deep reservoirs and contacting operators about case studies of deep gas well stimulation.

Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma.

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Tsuzuki, H; Fujieda, S; Sunaga, H; Noda, I; Saito, H

1998-02-15

Granulocyte colony-stimulating factor receptors (G-CSFRs) have been observed on the surface of not only hematopoietic cells but also several cancer cells. The stimulation of G-CSF has been demonstrated to induce proliferation and activation of G-CSFR-positive cells. In this study, we investigated the expression of G-CSFR on the surface of tumor cells and G-CSF production in oral and mesopharyngeal squamous cell carcinoma (SCC) by an immunohistochemical approach. Of 58 oral and mesopharyngeal SCCs, 31 cases (53.4%) and 36 cases (62.1%) were positive for G-CSFR and G-CSF, respectively. There was no association between G-CSFR expression and G-CSF staining. In the group positive for G-CSFR expression, relapse was significantly more likely after primary treatment (P = 0.0069), whereas there was no association between G-CSFR expression and age, sex, tumor size, lymph node metastasis, and clinical stage. Also, the G-CSFR-positive groups had a significantly lower disease-free and overall survival rate than the G-CSFR-negative groups (P = 0.0172 and 0.0188, respectively). However, none of the clinical markers correlated significantly with G-CSF staining, nor did the status of G-CSF production influence the overall survival. The results imply that assessment of G-CSFR may prove valuable in selecting patients with oral and mesopharyngeal SCC for aggressive therapy.

Chapter 7. Assessing soil factors in wildland improvement programs

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Arthur R. Tiedemann; Carlos F. Lopez

2004-01-01

Soil factors are an important consideration for successful wildland range development or improvement programs. Even though many soil improvement and amelioration practices are not realistic for wildlands, their evaluation is an important step in selection of adapted plant materials for revegetation. This chapter presents information for wildland managers on: the...