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[PMID]:29486746
[Au] Autor:Rosentreter A; Lappas A; Widder RA; Alnawaiseh M; Dietlein TS
[Ad] Endereço:Department of Ophthalmology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. andre.rosentreter@googlemail.com.
[Ti] Título:Conjunctival repair after glaucoma drainage device exposure using collagen-glycosaminoglycane matrices.
[So] Source:BMC Ophthalmol;18(1):60, 2018 Feb 27.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: To report the results of the repair of conjunctival erosions resulting from glaucoma drainage device surgery using collagen-glycosaminoglycane matrices (CGM). METHODS: Case series of 8 patients who underwent revision surgery due to conjunctival defects with exposed tubes through necrosis of the overlying scleral flap and conjunctiva after Baerveldt drainage device surgery. The defects were repaired by lateral displacement of the tube towards the sclera, with a slice of a CGM as a patch, covered by adjacent conjunctiva. RESULT: Successful, lasting closure (follow-up of 12 to 42 months) of the conjunctival defects was achieved without any side-effects or complications in all eight cases. CONCLUSIONS: Erosion of the drainage tube, creating buttonholes in the conjunctiva after implantation of glaucoma drainage devices, is a potentially serious problem. It can be managed successfully using a biodegradable CGM as a patch.
[Mh] Termos MeSH primário: Colágeno/uso terapêutico
Túnica Conjuntiva/lesões
Túnica Conjuntiva/cirurgia
Implantes para Drenagem de Glaucoma/efeitos adversos
Glaucoma/cirurgia
Glicosaminoglicanos/uso terapêutico
Procedimentos Cirúrgicos Oftalmológicos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
Feminino
Seres Humanos
Pressão Intraocular
Masculino
Meia-Idade
Complicações Pós-Operatórias/cirurgia
Reoperação
Estudos Retrospectivos
Esclera/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycosaminoglycans); 9007-34-5 (Collagen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0721-6


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[PMID]:28463693
[Au] Autor:Jeon EY; Choi BH; Jung D; Hwang BH; Cha HJ
[Ad] Endereço:Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 790-784, South Korea.
[Ti] Título:Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration.
[So] Source:Biomaterials;134:154-165, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Skin scarring after deep dermal injuries is a major clinical problem due to the current therapies limited to established scars with poor understanding of healing mechanisms. From investigation of aberrations within the extracellular matrix involved in pathophysiologic scarring, it was revealed that one of the main factors responsible for impaired healing is abnormal collagen reorganization. Here, inspired by the fundamental roles of decorin, a collagen-targeting proteoglycan, in collagen remodeling, we created a scar-preventive collagen-targeting glue consisting of a newly designed collagen-binding mussel adhesive protein and a specific glycosaminoglycan. The collagen-targeting glue specifically bound to type I collagen in a dose-dependent manner and regulated the rate and the degree of fibrillogenesis. In a rat skin excisional model, the collagen-targeting glue successfully accelerated initial wound regeneration as defined by effective reepithelialization, neovascularization, and rapid collagen synthesis. Moreover, the improved dermal collagen architecture was demonstrated by uniform size of collagen fibrils, their regular packing, and a restoration of healthy tissue component. Collectively, our natural healing-inspired collagen-targeting glue may be a promising therapeutic option for improving the healing rate with high-quality and effective scar inhibition.
[Mh] Termos MeSH primário: Colágeno/química
Hidrogel de Polietilenoglicol-Dimetacrilato/química
Adesivos Teciduais/química
Adesivos Teciduais/uso terapêutico
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Colágeno Tipo I/química
Colágeno Tipo I/uso terapêutico
Decorina/química
Decorina/uso terapêutico
Eletroforese em Gel de Poliacrilamida
Feminino
Glicosaminoglicanos
Seres Humanos
Camundongos
Microscopia Eletrônica de Transmissão
Células NIH 3T3
Proteínas/química
Proteínas/uso terapêutico
Proteoglicanas/química
Proteoglicanas/uso terapêutico
Ratos
Ratos Sprague-Dawley
Pele/efeitos dos fármacos
Pele/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type I); 0 (Decorin); 0 (Glycosaminoglycans); 0 (Proteins); 0 (Proteoglycans); 0 (Tissue Adhesives); 0 (adhesive protein, mussel); 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate); 9007-34-5 (Collagen)
[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:170503
[St] Status:MEDLINE


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[PMID]:28460335
[Au] Autor:Feng Y; Li Q; Wu D; Niu Y; Yang C; Dong L; Wang C
[Ad] Endereço:State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
[Ti] Título:A macrophage-activating, injectable hydrogel to sequester endogenous growth factors for in situ angiogenesis.
[So] Source:Biomaterials;134:128-142, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Biomaterials scaffolds designed for many regenerative applications are expected to support neo-vascularisation, which is now being hampered by two limitations - the instability of exogenous growth factors (GFs) that are delivered to promote angiogenesis; and the loss of extracellular matrix components that bind and stabilise GFs. Here, we report the design and evaluation of an injectable hydrogel system aimed at restoring a GF-binding microenvironment to enhance the pro-angiogenic functions of endogenous GFs. This gel comprises two polysaccharides with their unique bioactivities: Konjac glucomannan (KGM) as the building block of the gel scaffold, for its demonstrated capacity to activate macrophages/monocytes to secrete pro-angiogenic/-mitogenic GFs; and heparin (Hep), a representative glycosaminoglycan molecule that binds numerous pro-angiogenic GFs, as functional moieties to sequester the macrophage-produced GFs. Modified with tyramine (TA) groups, the two polysaccharides can be co-polymerised and rapidly form into hydrogel upon enzyme catalysis. The designed KGM-TA/Hep-TA hydrogel successfully preserves the macrophage-activating function and GF-binding affinity of the two components, respectively, and, once subcutaneously implanted, effectively sequestered the locally-produced GFs in situ and promote the formation and maturation of blood vessels in mice. In summary, the designed hydrogel system demonstrates a feasible approach to stimulate the production and harness the function of endogenous GFs for inducing blood vessel formation in vivo, without the addition of any exogenous proteins. This design may provide an innovative, open platform to promote vascularisation for various regenerative purposes.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Materiais Biocompatíveis/farmacologia
Hidrogel de Polietilenoglicol-Dimetacrilato/química
Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Indutores da Angiogênese/química
Indutores da Angiogênese/farmacologia
Animais
Glicosaminoglicanos/metabolismo
Seres Humanos
Integrina beta1/metabolismo
Lectinas Tipo C/metabolismo
Masculino
Mananas/metabolismo
Lectinas de Ligação a Manose/metabolismo
Camundongos
Neovascularização Fisiológica/efeitos dos fármacos
Polissacarídeos/metabolismo
Células RAW 264.7
Receptores de Superfície Celular/metabolismo
Células THP-1
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inducing Agents); 0 (Biocompatible Materials); 0 (Glycosaminoglycans); 0 (Integrin beta1); 0 (Intercellular Signaling Peptides and Proteins); 0 (Lectins, C-Type); 0 (Mannans); 0 (Mannose-Binding Lectins); 0 (Polysaccharides); 0 (Receptors, Cell Surface); 0 (mannose receptor); 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate); 36W3E5TAMG ((1-6)-alpha-glucomannan)
[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:170502
[St] Status:MEDLINE


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[PMID]:29381716
[Au] Autor:Paul CPL; Smit TH; de Graaf M; Holewijn RM; Bisschop A; van de Ven PM; Mullender MG; Helder MN; Strijkers GJ
[Ad] Endereço:Department of Orthopedic Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
[Ti] Título:Quantitative MRI in early intervertebral disc degeneration: T1rho correlates better than T2 and ADC with biomechanics, histology and matrix content.
[So] Source:PLoS One;13(1):e0191442, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Low-back pain (LBP) has been correlated to the presence of intervertebral disc (IVD) degeneration on T2-weighted (T2w) MRI. It remains challenging, however, to accurately stage degenerative disc disease (DDD) based on T2w MRI and measurements of IVD height, particularly for early DDD. Several quantitative MRI techniques have been introduced to detect changes in matrix composition signifying early DDD. In this study, we correlated quantitative T2, T1rho and Apparent Diffusion Coefficient (ADC) values to disc mechanical behavior and gold standard early DDD markers in a graded degenerated lumbar IVD caprine model, to assess their potential for early DDD detection. METHODS: Lumbar caprine IVDs were injected with either 0.25 U/ml or 0.5 U/ml Chondroïtinase ABC (Cabc) to trigger early DDD-like degeneration. Injection with phosphate-buffered saline (PBS) served as control. IVDs were cultured in a bioreactor for 20 days under axial physiological loading. High-resolution 9.4 T MR images were obtained prior to intervention and after culture. Quantitative MR results were correlated to recovery behavior, histological degeneration grading, and the content of glycosaminoglycans (GAGs) and water. RESULTS: Cabc-injected IVDs showed aberrancies in biomechanics and loss of GAGs without changes in water-content. All MR sequences detected changes in matrix composition, with T1rho showing largest changes pre-to-post in the nucleus, and significantly more than T2 and ADC. Histologically, degeneration due to Cabc injection was mild. T1rho nucleus values correlated strongest with altered biomechanics, histological degeneration score, and loss of GAGs. CONCLUSIONS: T2- and T1rho quantitative MR-mapping detected early DDD changes. T1rho nucleus values correlated better than T2 and ADC with biomechanical, histological, and GAG changes. Clinical implementation of quantitative MRI, T1rho particularly, could aid in distinguishing DDD more reliably at an earlier stage in the degenerative process.
[Mh] Termos MeSH primário: Degeneração do Disco Intervertebral/diagnóstico por imagem
Degeneração do Disco Intervertebral/patologia
Imagem por Ressonância Magnética
Fenômenos Mecânicos
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Progressão da Doença
Feminino
Glicosaminoglicanos/metabolismo
Cabras
Degeneração do Disco Intervertebral/metabolismo
Degeneração do Disco Intervertebral/fisiopatologia
Razão Sinal-Ruído
Fatores de Tempo
Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glycosaminoglycans); 059QF0KO0R (Water)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191442


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[PMID]:28457855
[Au] Autor:Tan CW; Sam IC; Chong WL; Lee VS; Chan YF
[Ad] Endereço:Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tancw86@gmail.com.
[Ti] Título:Polysulfonate suramin inhibits Zika virus infection.
[So] Source:Antiviral Res;143:186-194, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log PFU viral reduction with IC value of ∼2.5-5 µg/ml (1.93 µM-3.85 µM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Infecção pelo Zika virus/prevenção & controle
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais
Cercopithecus aethiops
Cloratos/farmacologia
DNA Helicases/metabolismo
Sulfato de Dextrana/antagonistas & inibidores
Flavivirus/efeitos dos fármacos
Glicosaminoglicanos/farmacologia
Heparina/análogos & derivados
Heparina/química
Heparina/farmacologia
Heparitina Sulfato/farmacologia
Concentração Inibidora 50
Camundongos
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Suramina/administração & dosagem
Células Vero
Proteínas do Envelope Viral/metabolismo
Proteínas não Estruturais Virais/química
Proteínas não Estruturais Virais/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/fisiologia
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Chlorates); 0 (Glycosaminoglycans); 0 (NS3 protein, flavivirus); 0 (Viral Envelope Proteins); 0 (Viral Nonstructural Proteins); 6032D45BEM (Suramin); 9005-49-6 (Heparin); 9042-14-2 (Dextran Sulfate); 9050-30-0 (Heparitin Sulfate); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.- (DNA Helicases); EC 3.6.4.13 (RNA Helicases); T95DR77GMR (sodium chlorate)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28464847
[Au] Autor:Rajas O; Quirós LM; Ortega M; Vazquez-Espinosa E; Merayo-Lloves J; Vazquez F; García B
[Ad] Endereço:Pneumology Service, Hospital La Princesa, Institute for Health Research (IP), Hospital Universitario de La Princesa, Madrid, Spain.
[Ti] Título:Glycosaminoglycans are involved in bacterial adherence to lung cells.
[So] Source:BMC Infect Dis;17(1):319, 2017 05 02.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Lower respiratory infections are among the top ten causes of death worldwide. Since pathogen to cell adhesion is a crucial step in the infection progress, blocking the interaction between eukaryotic receptors and bacterial ligands may enable the pathogenesis process to be stopped. Cell surface glycosaminoglycans (GAGs) are known to be mediators in the adhesion of diverse bacteria to different cell types, making it of interest to examine their involvement in the attachment of various pathogenic bacteria to lung cells, including epithelial cells and fibroblasts. METHODS: The function of cell surface GAGs in bacterial adhesion was studied by reducing their levels through inhibiting their biosynthesis and enzymatic degradation, as well as in binding competition experiments with various species of GAGs. The participation of the different bacterial adhesins in attachment was evaluated through competition with two peptides, both containing consensus heparin binding sequences. Blocking inhibition assays using anti-syndecans and the enzymatic removal of glypicans were conducted to test their involvement in bacterial adhesion. The importance of the fine structure of GAGs in the interaction with pathogens was investigated in competition experiments with specifically desulfated heparins. RESULTS: The binding of all bacteria tested decreased when GAG levels in cell surface of both lung cells were diminished. Competition experiments with different types of GAGs showed that heparan sulfate chains are the main species involved. Blocking or removal of cell surface proteoglycans evidenced that syndecans play a more important role than glypicans. The binding was partially inhibited by peptides including heparin binding sequences. Desulfated heparins also reduced bacterial adhesion to different extents depending on the bacterium and the sulfated residue, especially in fibroblast cells. CONCLUSIONS: Taken together, these data demonstrate that the GAG chains of the cell surface are involved in the adhesion of bacterial adhesins to lung cells. Heparan sulfate seems to be the main species implicated, and binding is dependent on the sulfation pattern of the molecule. These data could facilitate the development of new anti-infective strategies, enabling the development of new procedures for blocking the interaction between pathogens and lung cells more effectively.
[Mh] Termos MeSH primário: Aderência Bacteriana/fisiologia
Glicosaminoglicanos/metabolismo
Bactérias Gram-Positivas/patogenicidade
[Mh] Termos MeSH secundário: Linhagem Celular
Células Epiteliais/microbiologia
Fibroblastos/microbiologia
Heparina/metabolismo
Heparitina Sulfato/metabolismo
Seres Humanos
Pulmão/citologia
Pulmão/microbiologia
Proteoglicanas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glycosaminoglycans); 0 (Proteoglycans); 9005-49-6 (Heparin); 9050-30-0 (Heparitin Sulfate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180120
[Lr] Data última revisão:
180120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2418-5


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[PMID]:29049735
[Au] Autor:Song M; Lee S; Choe D; Kim S; Roh YH; Rho S
[Ad] Endereço:Department of Food Biotechnology, Silla University, Busan, Republic of Korea.
[Ti] Título:Clinical and Biological Evaluations of Biodegradable Collagen Matrices for Glaucoma Drainage Device Implantation.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5329-5335, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To characterize the clinical and biological properties of biodegradable collagen matrices (BCMs) for possible glaucoma drainage device implantation. Methods: A total of 68 refractory glaucoma eyes, followed up postoperatively for at least 6 months, were consecutively enrolled after retrospective chart review. The BCM-augmented Ahmed valve implantations (BAAVI) using our Ologen-6 and Ologen-7 valves were performed and compared with a conventional method. Complete surgical success was defined as an IOP of ≤21 mm Hg (IOP 1) or ≤17 mm Hg (IOP 2) without antiglaucoma medications. Qualified success was defined as an IOP ≤21 mm Hg with or without antiglaucoma medications. The biological properties of each BCM were assessed by enzymatic degradation rates via collagenase under ocular physiological conditions. Results: The mean ages and preoperative IOPs were similar for the groups. In the conventional, BAAVI with Ologen-6, and BAAVI with Ologen-7 groups, complete success rates with target IOP 1 were 29.2%, 40.0%, and 66.7%; those with target IOP 2 were 12.5%, 30.0%, and 45.8%; qualified success rates were 45.8%, 55.0%, and 75.0%, respectively. The enzymatic degradation rate of Ologen-7 was significantly slower than that of Ologen-6 (12.5 × 10-3 vs. 28.8 × 10-3). Conclusions: The surgical success rate was highest in the Ologen-7 BAAVI group, with the lowest dependency on postoperative antiglaucoma medication use compared with the conventional and Ologen-6 BAAVI groups. The clinical results correlated with the different biological and physicochemical properties based on the degree of enzymatic degradation and on the structural morphology.
[Mh] Termos MeSH primário: Implantes Absorvíveis
Colágeno
Implantes para Drenagem de Glaucoma
Glaucoma/cirurgia
Glicosaminoglicanos
[Mh] Termos MeSH secundário: Feminino
Seguimentos
Glaucoma/fisiopatologia
Seres Humanos
Pressão Intraocular/fisiologia
Masculino
Meia-Idade
Implante de Prótese
Estudos Retrospectivos
Técnicas de Sutura
Tonometria Ocular
Resultado do Tratamento
Acuidade Visual/fisiologia
Cicatrização
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycosaminoglycans); 0 (collagen-glycosaminoglycan copolymer); 9007-34-5 (Collagen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22579


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[PMID]:29045442
[Au] Autor:Skidmore MA; Mustaffa KMF; Cooper LC; Guimond SE; Yates EA; Craig AG
[Ad] Endereço:School of Biological Sciences, University of Liverpool, Crown Street, Liverpool, United Kingdom.
[Ti] Título:A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence.
[So] Source:PLoS One;12(10):e0186276, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process. One semi-synthetic, sulfated polysaccharide has been identified that is capable of inhibiting and reversing sequestration of pRBC on endothelial cells in vitro under physiological flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal effects on cell (HUVEC) viability (MTT proliferation assay). These findings suggest that carbohydrate-based anti-adhesive candidates may provide potential leads for therapeutics for severe malaria.
[Mh] Termos MeSH primário: Antimaláricos/administração & dosagem
Adesão Celular/efeitos dos fármacos
Glicosaminoglicanos/administração & dosagem
Malária Falciparum/tratamento farmacológico
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antimaláricos/síntese química
Proliferação Celular/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Eritrócitos/efeitos dos fármacos
Eritrócitos/metabolismo
Eritrócitos/patologia
Glicosaminoglicanos/efeitos adversos
Glicosaminoglicanos/síntese química
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Seres Humanos
Malária Falciparum/parasitologia
Malária Falciparum/patologia
Plasmodium falciparum/patogenicidade
Proteínas de Protozoários/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Glycosaminoglycans); 0 (Protozoan Proteins); 0 (erythrocyte membrane protein 1, Plasmodium falciparum)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186276


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[PMID]:28846132
[Au] Autor:Riedler KL; Shokrani A; Markarian A; Fisher LM; Pepper JP
[Ad] Endereço:Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, U.S.A.
[Ti] Título:Age-related histologic and biochemical changes in auricular and septal cartilage.
[So] Source:Laryngoscope;127(11):E399-E407, 2017 Nov.
[Is] ISSN:1531-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES/HYPOTHESIS: To characterize the histologic and biochemical properties of auricular and septal cartilage and analyze age-related changes in middle-aged to older adults. STUDY DESIGN: Cross-sectional study of auricular and septal cartilage from 33 fresh cadavers. METHODS: Auricular and septal cartilage specimens were stained using Safranin O for glycosaminoglycans, Verhoeff's stain for elastin, and Masson's trichrome for collagen. Percentage of tissue stained, cell density and size were quantified. Relationships between donor characteristics and histologic properties were evaluated using mixed model analyses. RESULTS: The average donor age was 75 years (standard deviation = 11 years; range, 55-93 years). In auricular cartilage, each 1-year increase in age was associated with a 0.97% decrease in glycosaminoglycans (P < .001) and a 0.98% decrease in elastin (P < .001). In septal cartilage, glycosaminoglycans decreased 2.4% per year (P < .001). Age did not affect collagen content significantly in auricular (P = .417) or septal cartilage (P = .284). Cell density and cell size declined with age in auricular (both P < .001) and septal cartilage (P = .044, P = .032, respectively). Compared to septal cartilage in patients of all ages, auricular cartilage had more glycosaminoglycans, less collagen, higher cell density, and smaller cells. CONCLUSIONS: In auricular and septal cartilage, glycosaminoglycans, elastin, cell density, and cell size decrease significantly with age in patients over 55 years of age. Glycosaminoglycan content declines faster with age in septal cartilage than auricular cartilage. These age-related changes may affect biomechanical properties and tissue viability, and thereby have implications for graft choice in functional, aesthetic, and reconstructive nasal surgery. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E399-E407, 2017.
[Mh] Termos MeSH primário: Envelhecimento/fisiologia
Cartilagem da Orelha/patologia
Cartilagens Nasais/patologia
[Mh] Termos MeSH secundário: Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Cadáver
Estudos Transversais
Cartilagem da Orelha/metabolismo
Glicosaminoglicanos/metabolismo
Seres Humanos
Meia-Idade
Cartilagens Nasais/metabolismo
Coloração e Rotulagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycosaminoglycans)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1002/lary.26807


  10 / 21610 MEDLINE  
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[PMID]:28837619
[Au] Autor:Thomas AJ; Pulsipher A; Davis BM; Alt JA
[Ad] Endereço:Division of Head and Neck Surgery, Rhinology - Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
[Ti] Título:LL-37 causes cell death of human nasal epithelial cells, which is inhibited with a synthetic glycosaminoglycan.
[So] Source:PLoS One;12(8):e0183542, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:LL-37 is an immune peptide that regulates innate and adaptive immune responses in the upper airways. Elevated levels of LL-37 have been linked to cell death and inflammatory diseases, such as chronic rhinosinusitis (CRS). Glycosaminoglycans (GAGs) are polysaccharides that are found on respiratory epithelial cells and serve important roles in mucosal surface repair. Recent findings suggest that a synthetic glycosaminoglycan (GM-0111) can protect against LL-37-induced sinonasal mucosal inflammation and cell death in a murine model of acute RS. Herein, we elucidated the mechanisms by which LL-37 causes sinonasal inflammation and how GM-0111 can prevent these mechanisms. When challenged with LL-37, human nasal epithelial cells (HNEpCs) and mouse macrophages (J774.2) demonstrated increased release of adenosine triphosphate (ATP) and interleukin (IL)-6 and -8, as well as cell death and lysis. These cellular responses were all blocked dose-dependently by pre-treatment with GM-0111. We identified that LL-37-induced cell death is associated with caspase-1 and -8 activation, but not activation of caspase-3/7. These responses were again blocked by GM-0111. Our data suggest that LL-37 causes cellular death of HNEpCs and macrophages through the pro-inflammatory necrotic and/or pyroptotic pathways rather than apoptosis, and that a GM-0111 is capable of inhibiting these pro-inflammatory cellular events.
[Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/farmacologia
Morte Celular/efeitos dos fármacos
Glicosaminoglicanos/farmacologia
Mucosa Nasal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/secreção
Sequência de Aminoácidos
Peptídeos Catiônicos Antimicrobianos/química
Caspases/metabolismo
Linhagem Celular
Relação Dose-Resposta a Droga
Ativação Enzimática
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Interleucina-6/metabolismo
Interleucina-8/metabolismo
Mucosa Nasal/citologia
Mucosa Nasal/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Glycosaminoglycans); 0 (Interleukin-6); 0 (Interleukin-8); 143108-26-3 (CAP18 lipopolysaccharide-binding protein); 8L70Q75FXE (Adenosine Triphosphate); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183542



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