1,721,021 research outputs found
Adipose derived stem cells reduce fibrosis and promote nerve regeneration in rats
No full textPeripheral nerve regeneration is critical and challenging in the adult humans. High level of collagen infiltration (i.e., scar tissue), in the niche of injury, impedes axonal regeneration and path finding. Unfortunately, studies focusing on the modulation of scar tissue in the nerves are scarce. To address part of this problem, we have evaluated the differentiated adipose derived stem cells (dASCs) for their anti-fibrotic and regenerative effects in a 10 mm nerve gap model in rats. Three different animal groups (n=5) were treated with fibrin nerve conduits (empty), or seeded with dASCs (F+dASCs) and autograft respectively. Histological analysis of regenerated nerves, at 12 weeks post-operatively, reveled the high levels of collagen infiltration (i.e., 21.5%±6.1% and 24.1%±2.9%) in the middle and distal segment of empty conduit groups in comparison with stem cells treated (16.6%±2.1% and 12.1%±2.9%) and autograft (15.0%±1.7% and 12.8%±1.0%) animals. Thus, the dASCs treatment resulted in significant reduction of fibrotic tissue formation. Consequently, enhanced axonal regeneration and re-myelination was found in the animals treated with dASCs. Interestingly, these effects of dASCs appeared to be equivalent to that of autograft treatment. Thus, the dASCs hold great potential for preventing the scar tissue formation and for promoting nerve regeneration in the adult organisms. Future experiments will focus on the validation of these findings in a critical nerve injury model. This article is protected by copyright. All rights reserved
Repair and Regeneration of Peripheral Nerve Fibrosis
Get PDFTwenty million Americans suffer from peripheral nerve injury (PNI) and is undoubtedly one of the major unmet medical needs. Approximately $150 billion is spent annually in the United States for Nerve Injuries. Moreover, 50,000 cases of PNI repairs are performed annually in the United States with even less than 42% experiencing satisfactory sensory recovery. Despite extensive medical research, there aren’t any approved small molecule antifibrotic treatment pertaining to nerve injuries. Peripheral nerve fibrosis (PNF) associated with chronic inflammation, perineural adhesions and scarring are often reported in patients with nerve injury. Surgical interventions including external neurolysis is the common available option. Unfortunately, postsurgical adhesions and fibrosis, often lead to aberrated wound healing and impairment of nerve functions. Though, various treatment strategies have been tried including use
of grafts, biomaterials, no treatment modality seems to be promising as of now.
The aim of this study was to investigate the effects of L-Alanine-L-Glutamine (L-Ala-L-Gln) and Pirfenidone (PFD) on hypoxic and TGF-ß1 stimulated fibroblasts and their ability to induce anti-fibrotic phenotype. Rat perineurial derived fibroblasts were exposed to hypoxic conditions or externally activated by TGF-ß1 and expression of hypoxic and pro-fibrotic markers were assessed following treatment with L-Ala-L-Gln (0-100mM) or with PFD (0-0.25 mg/ml). PFD was found to act through targeted downregulation of the TGF-ß pathway and significantly reduced pro-fibrotic and celladhesion inducing factors at the protein and RNA level. In rat perineurial derived fibroblasts, L-Ala-L-Gln and PFD modulated several pro-fibrotic factors and associated
pathways to induce an anti-fibrotic phenotype. In conclusion, our results showed that L-Ala-L-Gln and PFD suppressed fibrotic phenotype and might prove to be effective anti-fibrotic agents for neural fibrosis. These promising results will lead to identification of a non-invasive biomarker for the assessment of neural fibrosis. These results can easily be translated into the clinical settings and we expect our discoveries to assist
clinicians to identify a novel therapeutic strategy for neural fibrosis and support invasive surgical applications
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
New therapeutic approaches for peripheral compression neuropathies
Get PDFChronic peripheral nerve compression injuries, a distinct type of neuropathies, are characterized by paresthesia, pain, numbness and tingling. These neuropathies are caused by the entrapment or the compression of a nerve or its root. Some of the common compression neuropathies include carpal tunnel syndrome, cubital tunnel syndrome or meralgia paraesthetica, sciatica and low back pain. Current treatment options include corticosteroids, muscle relaxants and non-steroidal anti-inflammatory drugs that can be supplemented with physical and massage therapies. These therapeutic approaches are associated with several limitations and are regularly followed by a surgery to release the nerve from the compression injury. Unfortunately, these surgeries are not effective and moreover, surgeries often result in detrimental outcomes such as scar complication, muscle weakness and pillar pain. Given the facts on the growing number of nerve injuries and the inefficient current treatments, there is a clear need for new and innovative therapeutic strategies. Thus, the aim of the present research work is to develop a compression injury model with a defined setting (i.e., compression depth and time) and to investigate various therapeutic strategies that may pave the way for the novel and effective therapeutic developments.
Due to lack of consistent nerve compression model with the established sensory and motor pathologies in the literature, the first objective of the present thesis work is set to establish a model that would mirror chronic peripheral nerve compression injury in terms of function and anatomy. The first manuscript is describing that attempt of a reproducible model that was achieved by the entrapment of the rat sciatic nerve using a modified hemostatic clip. This chronic injury model is giving functional and histomorphological markers for the evaluation the impairment caused by different levels of compression.
Chronic peripheral nerve compression injuries, a distinct type of neuropathies, are characterized by paresthesia, pain, numbness and tingling. These neuropathies are caused by the entrapment or the compression of a nerve or its root. Some of the common compression neuropathies include carpal tunnel syndrome, cubital tunnel syndrome or meralgia paraesthetica, sciatica and low back pain. Current treatment options include corticosteroids, muscle relaxants and non-steroidal anti-inflammatory drugs that can be supplemented with physical and massage therapies. These therapeutic approaches are associated with several limitations and are regularly followed by a surgery to release the nerve from the compression injury. Unfortunately, these surgeries are not effective and moreover, surgeries often result in detrimental outcomes such as scar complication, muscle weakness and pillar pain. Given the facts on the growing number of nerve injuries and the inefficient current treatments, there is a clear need for new and innovative therapeutic strategies. Thus, the aim of the present research work is to develop a compression injury model with a defined setting (i.e., compression depth and time) and to investigate various therapeutic strategies that may pave the way for the novel and effective therapeutic developments.
Due to lack of consistent nerve compression model with the established sensory and motor pathologies in the literature, the first objective of the present thesis work is set to establish a model that would mirror chronic peripheral nerve compression injury in terms of function and anatomy. Thus, the first manuscript describes anatomical and functional changes in response to the controlled chronic nerve compression that would enable pharmaceutical drug targeting and development. For this, we first prepared custom made surgical instrument that leaves a vascular clip with a predefined lumen volume (i.e., 400μm, 250μm, 100μm and 0μm). Animals were randomized into 4 groups (n=6) and the left sciatic nerve were exposed and compressed at 10mm proximal from the nerve branching resulting in controlled degree nerve damage. The titanium compression clip was left on the sciatic nerve over 6 weeks. Post-operatively, anatomical (histomorphology), sensory and motor functions (electrophysiology) were analyzed. Resulting data and observations revealed the compression-depth dependent sensory and motor pathologies. Further, quantitative measurements revealed compression depth dependent decline in myelin, myelin sheath thickness, axonal surface and muscle weight. Sensory and motor functional dynamics were evident in response to differential injury severity. In short, such controlled compression nerve injury model would enable the investigation of basic mechanisms and repair avenues.
In the second manuscript, we explored the immunomodulation-based treatment strategy, for repair and regeneration of chronic nerve compression injuries. Within this context, three molecules, i.e., Cyclosporine, FK506 and Rapamycin, were evaluated in an in vitro model involving a serum-free culture of embryonic dorsal root ganglia (DRG) followed by in an in vivo model of chronic sciatic nerve compression. Axonal outgrowth analysis confirmed the growth promoting properties of all 3 different drug molecules, which are comparable with NGF. Drug treated animals exhibited the ability to prevent from injury induced neuromuscular degeneration and to restore the function. Among all the drug molecules, cyclosporine appeared to be more effective to support animals as evidenced by significantly preserved structure and function. Further studies are required to assess the effects of sustained local release of cyclosporine for treating the chronic nerve injuries.
In the search for new therapeutic strategies to treat chronic peripheral nerve compressions, two neuroactive synthetic molecules based on the natural paecilomycine A (PSM) have attracted attention. Thus, the third manuscript covers the neurotrophic and neuroprotective potential of PSM in vitro using embryonic dorsal root ganglia (DRG) and further translated into a rat model of chronic nerve compression. In vitro analysis of neuronal survival and axonal outgrowth in response to paecilomycine diverted synthetic molecule 1 (PSM1) and 2 (PSM2) at various concentrations (10µM and 100µM) suggested their neurotrophic capacity that is comparable to standard NGF. Furthermore, low doses of the molecules, systemically administered, appeared to protect the neuromuscular structures and function. PSM1 appeared to have a stronger effect than PSM2 in terms of neuroprotection as evidenced by significantly improved anatomy and behavioral recovery. Together these findings and observations indicate neurotrophic and neuroprotective activity for both molecules while the former is being more neurotrophic and the other one is being more neuroprotective.
In conclusion, the present thesis work produced relevant new knowledge and data in the field of neuropathies paving the way for innovative treatment options for peripheral compression neuropathies
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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