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[PMID]:28453954
[Au] Autor:Pakulska MM; Tator CH; Shoichet MS
[Ad] Endereço:Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.
[Ti] Título:Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1α promotes functional repair in the injured rat spinal cord.
[So] Source:Biomaterials;134:13-21, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradation of the glial scar, using chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells (NPCs), using stromal cell-derived factor 1α (SDF). To test this hypothesis, we designed a crosslinked methylcellulose hydrogel (XMC) for minimally invasive, localized, and sustained intrathecal drug delivery. ChABC was released from XMC using protein-peptide affinity interactions while SDF was delivered by electrostatic affinity interactions from polymeric nanoparticles embedded in XMC. Rats with SCI were treated acutely with a combination of SDF and ChABC, SDF alone, ChABC alone, or vehicle alone, and compared to injury only. Treatment with ChABC, both alone and in combination with SDF, resulted in faster and more sustained behavioural improvement over time than other groups. The significantly reduced chondroitin sulfate proteoglycan levels and greater distribution of NPCs throughout the spinal cord tissue with ChABC delivery, both alone and in combination with SDF, may explain the improved locomotor function. Treatment with SDF alone had no apparent effect on NPC number or distribution nor synergistic effect with ChABC delivery. Thus, in this model of SCI, tissue and functional repair is attributed to ChABC.
[Mh] Termos MeSH primário: Quimiocina CXCL12/química
Condroitina ABC Liase/metabolismo
Traumatismos da Medula Espinal/metabolismo
[Mh] Termos MeSH secundário: Animais
Quimiocina CXCL12/metabolismo
Quimiocina CXCL12/uso terapêutico
Condroitina ABC Liase/química
Proteoglicanas de Sulfatos de Condroitina/química
Ensaio de Imunoadsorção Enzimática
Feminino
Hidrogel de Polietilenoglicol-Dimetacrilato/química
Imuno-Histoquímica
Metilcelulose/química
Células-Tronco Neurais/citologia
Células-Tronco Neurais/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Traumatismos da Medula Espinal/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chemokine CXCL12); 0 (Chondroitin Sulfate Proteoglycans); 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate); 9004-67-5 (Methylcellulose); EC 4.2.2.20 (Chondroitin ABC Lyase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29228020
[Au] Autor:Carwardine D; Prager J; Neeves J; Muir EM; Uney J; Granger N; Wong LF
[Ad] Endereço:School of Veterinary Sciences, University of Bristol, Bristol, United Kingdom.
[Ti] Título:Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury.
[So] Source:PLoS One;12(12):e0188967, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients.
[Mh] Termos MeSH primário: Axônios
Condroitina ABC Liase/biossíntese
Proteoglicanas de Sulfatos de Condroitina/metabolismo
Doenças do Cão/metabolismo
Mucosa Olfatória/transplante
Traumatismos da Medula Espinal/veterinária
[Mh] Termos MeSH secundário: Animais
Doenças do Cão/patologia
Cães
Mucosa Olfatória/citologia
Mucosa Olfatória/metabolismo
Traumatismos da Medula Espinal/metabolismo
Traumatismos da Medula Espinal/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chondroitin Sulfate Proteoglycans); EC 4.2.2.20 (Chondroitin ABC Lyase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188967


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[PMID]:29257018
[Au] Autor:Zhu D; Tapadia MD; Palispis W; Luu M; Wang W; Gupta R
[Ad] Endereço:Peripheral Nerve Research Laboratory, Department of Orthopaedic Surgery, University of California, Irvine, Irvine, California.
[Ti] Título:Attenuation of Robust Glial Scar Formation Facilitates Functional Recovery in Animal Models of Chronic Nerve Compression Injury.
[So] Source:J Bone Joint Surg Am;99(24):e132, 2017 Dec 20.
[Is] ISSN:1535-1386
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Late surgery for chronic nerve compression injuries usually improves sensation but rarely reverses motor atrophy. We hypothesized that a persistent glial scar after chronic nerve compression injury might account for poor motor recovery and that degradation of the glial scar as an adjunct to surgical decompression would improve functional recovery. METHODS: A previously described model of chronic nerve compression injury was created in C57BL/6 mice and Sprague-Dawley rats, and the nerves were harvested early or late after electrophysiological confirmation of the injury. Western blot, polymerase chain reaction, and quantitative immunohistochemical analyses were performed to determine levels of chondroitin sulfate proteoglycans and extracellular matrix molecules. Subsets of mice were treated either with surgical decompression alone or with decompression coupled with intraepineurial injection of a low dose (0.1 µgµL) or a high dose (0.2 µg/µL) of chondroitinase ABC at 6 weeks after injury. RESULTS: Aggrecan showed the greatest change in mRNA and protein levels at the early and late time points following creation of the chronic nerve compression injury. Quantitative immunohistochemical analysis revealed early aggrecan upregulation localized primarily to the endoneurium and late upregulation localized to the perineurium and epineurium (p < 0.0105). Quantitative immunohistochemical analysis for collagen IV, laminin-α2, and fibronectin also showed early upregulation with perineurial scarring. Quantitative immunohistochemical analysis and Western blot analysis for aggrecan demonstrated a marked increase in the endoneurium at the early time points and upregulation of expression in the epineurium and perineurium at the late time points. Decompression along with intraepineurial injection of high-dose chondroitinase ABC at 6 weeks after creation of the compression injury resulted in marked attenuation of decorin and aggrecan expression with functional improvement in nerve conduction velocity. CONCLUSIONS: Significant upregulation of chondroitin sulfate proteoglycans and other extracellular matrix components contributes to the pathogenesis of compression neuropathies in murine models. The administration of chondroitinase ABC degrades these chondroitin sulfate proteoglycans and improves functional recovery after chronic nerve compression injury; thus, it can be considered as a possible therapeutic adjunct.
[Mh] Termos MeSH primário: Condroitina ABC Liase/farmacologia
Cicatriz/prevenção & controle
Descompressão Cirúrgica/métodos
Síndromes de Compressão Nervosa/tratamento farmacológico
Traumatismos dos Nervos Periféricos/tratamento farmacológico
Traumatismos dos Nervos Periféricos/patologia
[Mh] Termos MeSH secundário: Agrecanas/farmacologia
Análise de Variância
Animais
Western Blotting
Doença Crônica
Modelos Animais de Doenças
Injeções Intralesionais
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Síndromes de Compressão Nervosa/patologia
Síndromes de Compressão Nervosa/cirurgia
Condução Nervosa/efeitos dos fármacos
Traumatismos dos Nervos Periféricos/cirurgia
RNA Mensageiro/efeitos dos fármacos
Distribuição Aleatória
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real/métodos
Recuperação de Função Fisiológica/fisiologia
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aggrecans); 0 (RNA, Messenger); EC 4.2.2.20 (Chondroitin ABC Lyase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.2106/JBJS.17.00396


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[PMID]:28771534
[Au] Autor:Suzuki H; Ahuja CS; Salewski RP; Li L; Satkunendrarajah K; Nagoshi N; Shibata S; Fehlings MG
[Ad] Endereço:Division of Genetics and Development, Krembil Research Institute, Toronto, Canada.
[Ti] Título:Neural stem cell mediated recovery is enhanced by Chondroitinase ABC pretreatment in chronic cervical spinal cord injury.
[So] Source:PLoS One;12(8):e0182339, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Traumatic spinal cord injuries (SCIs) affect millions of people worldwide; the majority of whom are in the chronic phase of their injury. Unfortunately, most current treatments target the acute/subacute injury phase as the microenvironment of chronically injured cord consists of a well-established glial scar with inhibitory chondroitin sulfate proteoglycans (CSPGs) which acts as a potent barrier to regeneration. It has been shown that CSPGs can be degraded in vivo by intrathecal Chondroitinase ABC (ChABC) to produce a more permissive environment for regeneration by endogenous cells or transplanted neural stem cells (NSCs) in the subacute phase of injury. Using a translationally-relevant clip-contusion model of cervical spinal cord injury in mice we sought to determine if ChABC pretreatment could modify the harsh chronic microenvironment to enhance subsequent regeneration by induced pluripotent stem cell-derived NSCs (iPS-NSC). Seven weeks after injury-during the chronic phase-we delivered ChABC by intrathecal osmotic pump for one week followed by intraparenchymal iPS-NSC transplant rostral and caudal to the injury epicenter. ChABC administration reduced chronic-injury scar and resulted in significantly improved iPSC-NSC survival with clear differentiation into all three neuroglial lineages. Neurons derived from transplanted cells also formed functional synapses with host circuits on patch clamp analysis. Furthermore, the combined treatment led to recovery in key functional muscle groups including forelimb grip strength and measures of forelimb/hindlimb locomotion assessed by Catwalk. This represents important proof-of-concept data that the chronically injured spinal cord can be 'unlocked' by ChABC pretreatment to produce a microenvironment conducive to regenerative iPS-NSC therapy.
[Mh] Termos MeSH primário: Condroitina ABC Liase/farmacologia
Regeneração Nervosa/efeitos dos fármacos
Traumatismos da Medula Espinal/terapia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/efeitos dos fármacos
Células Cultivadas
Medula Cervical/lesões
Doença Crônica
Cicatriz/prevenção & controle
Potenciais Evocados/fisiologia
Membro Anterior/fisiologia
Células-Tronco Pluripotentes Induzidas/citologia
Locomoção/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Células-Tronco Neurais/citologia
Células-Tronco Neurais/efeitos dos fármacos
Células-Tronco Neurais/transplante
Neurônios/citologia
Neurônios/fisiologia
Recuperação de Função Fisiológica/efeitos dos fármacos
Medula Espinal/metabolismo
Medula Espinal/fisiologia
Traumatismos da Medula Espinal/patologia
Sinapses/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 4.2.2.20 (Chondroitin ABC Lyase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182339


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[PMID]:28322980
[Au] Autor:Blacktop JM; Todd RP; Sorg BA
[Ad] Endereço:Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, United States. Electronic address: jordan.blacktop@wsu.edu.
[Ti] Título:Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration.
[So] Source:Neuropharmacology;118:124-136, 2017 May 15.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Addiction involves drug-induced neuroplasticity in the circuitry of motivated behavior, which includes the medial forebrain bundle and the lateral hypothalamic area. Emerging at the forefront of neuroplasticity regulation are specialized extracellular matrix (ECM) structures that form perineuronal nets (PNNs) around certain neurons, mainly parvalbumin positive (PV ), fast-spiking interneurons (FSINs), making them a promising target for the regulation of drug-induced neuroplasticity. Despite the emerging significance of PNNs in drug-induced neuroplasticity and the well-established role of the lateral hypothalamic area (LHA) in reward, reinforcement, and motivation, very little is known about how PNN-expressing neurons control drug-seeking behavior. We found that a discrete region of the anterior dorsal LHA (LHAad) exhibited robust PNN and dense ECM expression. Approximately 87% of parvalbumin positive (PV ) neurons co-expressed the PNN marker Wisteria floribunda agglutinin (WFA), while 62% of WFA positive (WFA ) neurons co-expressed PV in the LHAad of drug naïve rats. Removal of PNNs within this brain region via chrondroitinase ABC (Ch-ABC) administration abolished acquisition of cocaine-induced CPP and significantly attenuated the acquisition of cocaine self-administration (SA). Removal of LHAad PNNs did not affect locomotor activity, sucrose intake, sucrose-induced CPP, or acquisition of sucrose SA in separate groups of cocaine naïve animals. These data suggest that PNN-dependent neuroplasticity within the LHAad is critical for the acquisition of both cocaine-induced CPP and SA but is not general to all rewards, and that PNN degradation may have utility for the management of drug-associated behavioral plasticity and memory in cocaine addicts.
[Mh] Termos MeSH primário: Anestésicos Locais/farmacologia
Cocaína/farmacologia
Condicionamento Operante/efeitos dos fármacos
Matriz Extracelular/metabolismo
Região Hipotalâmica Lateral/citologia
Neurônios/fisiologia
[Mh] Termos MeSH secundário: Animais
Condroitina ABC Liase/metabolismo
Proteoglicanas de Sulfatos de Condroitina/metabolismo
Sinais (Psicologia)
Extinção Psicológica/efeitos dos fármacos
Matriz Extracelular/efeitos dos fármacos
Comportamento Alimentar/efeitos dos fármacos
Região Hipotalâmica Lateral/efeitos dos fármacos
Masculino
Neurônios/efeitos dos fármacos
Parvalbuminas/metabolismo
Lectinas de Plantas/metabolismo
Ratos
Ratos Sprague-Dawley
Receptores de N-Acetilglucosamina/metabolismo
Reforço (Psicologia)
Autoadministração
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Local); 0 (Chondroitin Sulfate Proteoglycans); 0 (Parvalbumins); 0 (Plant Lectins); 0 (Receptors, N-Acetylglucosamine); 0 (wisteria lectin); EC 4.2.2.20 (Chondroitin ABC Lyase); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE


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[PMID]:28135331
[Au] Autor:Karhula SS; Finnilä MA; Lammi MJ; Ylärinne JH; Kauppinen S; Rieppo L; Pritzker KP; Nieminen HJ; Saarakkala S
[Ad] Endereço:Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
[Ti] Título:Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography.
[So] Source:PLoS One;12(1):e0171075, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Contrast-enhanced micro-computed tomography (CEµCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEµCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEµCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEµCT method for 3D characterization of articular cartilage.
[Mh] Termos MeSH primário: Cartilagem Articular/diagnóstico por imagem
Cartilagem Articular/metabolismo
Ácido Fosfotúngstico/química
Microtomografia por Raio-X/métodos
[Mh] Termos MeSH secundário: Animais
Bovinos
Condroitina ABC Liase/metabolismo
Colagenases/metabolismo
Eletroforese em Gel de Ágar
Ácido Ioxáglico/química
Proteoglicanas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteoglycans); 12067-99-1 (Phosphotungstic Acid); EC 3.4.24.- (Collagenases); EC 4.2.2.20 (Chondroitin ABC Lyase); Z40X7EI2AF (Ioxaglic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171075


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[PMID]:28082225
[Au] Autor:Kheirollahi A; Khajeh K; Golestani A
[Ad] Endereço:Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Rigidifying flexible sites: An approach to improve stability of chondroitinase ABC I.
[So] Source:Int J Biol Macromol;97:270-278, 2017 Apr.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The stability of chondroitin ABC lyase I (cABC I) at physiological temperature is one of the current obstacles to its clinical application. In this study, we used a protein engineering approach; rigidify flexible sites, to improve stability of cABC I. B-factor analysis showed a flexible loop at the N-terminal domain of cABC I which may be involved in its thermal instability and five residues in this region were replaced with proline. Thermal inactivation and thermal denaturation analysis revealed that Glu138Pro mutation increased half-life and Tm of enzyme, respectively. The K values of mutated enzymes were slightly increased compared to the wild type enzyme. The results of limited proteolysis indicated that Glu138Pro mutant was more resistant against trypsinolysis and this variant was less quenched in both acrylamide and KI quenching experiments. Moreover, intrinsic fluorescence intensity of Glu138Pro variant was increased and its ANS fluorescence intensity was decreased, whereas no considerable changes were observed in the far-UV CD spectra. The structural analyses indicated compactness of structure of Glu138Pro enzyme which can be related to moderately enhanced stability of this mutant. This study demonstrated that rigidifying flexible residues can be considered as a possible approach to increase the stability of the protein.
[Mh] Termos MeSH primário: Condroitina ABC Liase/química
Condroitina ABC Liase/metabolismo
Mutagênese Sítio-Dirigida
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Condroitina ABC Liase/genética
Entropia
Ativação Enzimática
Estabilidade Enzimática
Cinética
Modelos Moleculares
Domínios Proteicos
Proteólise
Temperatura de Transição
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 4.2.2.20 (Chondroitin ABC Lyase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170114
[St] Status:MEDLINE


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[PMID]:28011383
[Au] Autor:Xia T; Huang B; Ni S; Gao L; Wang J; Wang J; Chen A; Zhu S; Wang B; Li G; Zhu S; Li X
[Ad] Endereço:Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China.
[Ti] Título:The combination of db-cAMP and ChABC with poly(propylene carbonate) microfibers promote axonal regenerative sprouting and functional recovery after spinal cord hemisection injury.
[So] Source:Biomed Pharmacother;86:354-362, 2017 Feb.
[Is] ISSN:1950-6007
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:This study describes the use of poly(propylene carbonate) (PPC) electrospun microfibres impregnated with a combination of dibutyryl cyclic adenosine monophosphate (db-cAMP) and chondroitinase ABC (ChABC) in the treatment of right-side hemisected spinal cord injury (SCI). Release of db-cAMP and/or ChABC from the microfibres was assessed in vitro using high-performance liquid chromatography (HPLC). Drug-impregnated microfibres were implanted into the hemisected thoracic spinal cord of rats, and treatment was evaluated using functional recovery examinations and immunohistochemistry. Our results demonstrated that the microfibres containing db-cAMP and/or ChABC displayed a stable and prolonged release of each agent. Sustained delivery of db-cAMP and/or ChABC was found to promote axonal regenerative sprouting, functional recovery, and reduced glial scar formation when compared to untreated control animals. The combination of both db-cAMP and ChABC was determined to be more effective than using either drug alone in the treatment of SCI. These findings demonstrate the feasibility of using PPC electrospun microfibres for multi-drug combination therapy in SCI.
[Mh] Termos MeSH primário: Axônios/efeitos dos fármacos
Condroitina ABC Liase/fisiologia
AMP Cíclico/farmacologia
Propano/análogos & derivados
Recuperação de Função Fisiológica/efeitos dos fármacos
Traumatismos da Medula Espinal/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Feminino
Propano/farmacologia
Ratos
Ratos Wistar
Medula Espinal/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
8D08K3S51E (propylene carbonate); E0399OZS9N (Cyclic AMP); EC 4.2.2.20 (Chondroitin ABC Lyase); T75W9911L6 (Propane)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170208
[Lr] Data última revisão:
170208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161225
[St] Status:MEDLINE


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[PMID]:27992393
[Au] Autor:Offiah I; Didangelos A; OʼReilly BA; McMahon SB
[Ad] Endereço:aNeurorestoration Group, Wolfson CARD, King's College London, London, United KingdombDepartment of Urogynaecology, Cork University Maternity Hospital, University College Cork, Wilton, Co. Cork, Ireland.
[Ti] Título:Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.
[So] Source:Pain;158(1):161-170, 2017 Jan.
[Is] ISSN:1872-6623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.
[Mh] Termos MeSH primário: Matriz Extracelular/metabolismo
Dor/etiologia
Dor/metabolismo
Doenças da Bexiga Urinária/complicações
[Mh] Termos MeSH secundário: Animais
Capsaicina/toxicidade
Condroitina ABC Liase/toxicidade
Modelos Animais de Doenças
Feminino
Glucuronidase/toxicidade
Glicosilação/efeitos dos fármacos
Infiltração de Neutrófilos/efeitos dos fármacos
Proteoglicanas/toxicidade
Proteínas Proto-Oncogênicas c-fos/metabolismo
Ratos
Ratos Wistar
Medula Espinal/efeitos dos fármacos
Medula Espinal/metabolismo
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária/fisiologia
Doenças da Bexiga Urinária/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteoglycans); 0 (Proto-Oncogene Proteins c-fos); EC 3.2.1.- (heparanase); EC 3.2.1.31 (Glucuronidase); EC 4.2.2.20 (Chondroitin ABC Lyase); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161220
[St] Status:MEDLINE


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[PMID]:27789329
[Au] Autor:Daneshjou S; Dabirmanesh B; Rahimi F; Khajeh K
[Ad] Endereço:Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.
[Ti] Título:Porous silicon nanoparticle as a stabilizing support for chondroitinase.
[So] Source:Int J Biol Macromol;94(Pt B):852-858, 2017 Jan.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chondroitinase ABCI (cABCI) from Proteus vulgaris is a drug enzyme that can be used to treat spinal cord injuries. One of the main problems of chondroitinase ABC1 is its low thermal stability. The objective of the current study was to stabilize the enzyme through entrapment within porous silicon (pSi) nanoparticles. pSi was prepared by an electrochemical etch of p-type silicon using hydrofluoric acid/ethanol. The size of nanoparticles were determined 180nm by dynamic light scattering and the mean pore diameter was in the range of 40-60nm obtained by scanning electron microscopy. Enzymes were immobilized on porouse silicon nanoparticles by entrapment. The capacity of matrix was 35µg enzyme per 1mg of silicon. The immobilized enzyme displayed lower V values compared to the free enzyme, but Km values were the same for both enzymes. Immobilization significantly increased the enzyme stability at various temperatures (-20, 4, 25 and 37°C). For example, at 4°C, the free enzyme (in 10mM imidazole) retained 20% of its activity after 100min, while the immobilized one retained 50% of its initial activity. Nanoparticles loading capacity and the enzyme release rate showed that the selected particles could be a pharmaceutically acceptable carrier for chondroitinase.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Condroitina ABC Liase/química
Enzimas Imobilizadas/química
Nanopartículas/química
Silício/química
[Mh] Termos MeSH secundário: Sulfatos de Condroitina/química
Liberação Controlada de Fármacos
Estabilidade Enzimática
Etanol/química
Ácido Fluorídrico/química
Cinética
Tamanho da Partícula
Porosidade
Proteus vulgaris/química
Proteus vulgaris/enzimologia
Proteínas Recombinantes/química
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Enzymes, Immobilized); 0 (Recombinant Proteins); 3K9958V90M (Ethanol); 9007-28-7 (Chondroitin Sulfates); EC 4.2.2.20 (Chondroitin ABC Lyase); RGL5YE86CZ (Hydrofluoric Acid); Z4152N8IUI (Silicon)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE



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