RESUMO
Objective: To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children's Hospital from January 2018 to December 2019 was retrospectively analyzed. Results: A total of 16 patients were included in this study, including 13 males and 3 females, aged[M(Q1,Q3)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (P=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection. Conclusions: RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.
Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Idoso , Asparaginase , Criança , Doxorrubicina/análogos & derivados , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Metilprednisolona/uso terapêutico , Nitrilas , Polietilenoglicóis , Pirazóis , Pirimidinas , Estudos RetrospectivosRESUMO
Appropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle protein 22α (SM22α) were found to be suitable indicators of functional AF cell induction. In vitro 2D culture of human AF cells showed that transforming growth factor ß1 (TGF-ß1) upregulated the expression of the functional AF markers and increased cell contractility, indicating that TGF-ß1-pre-treated AF cells were an appropriate cell source for AF tissue regeneration. Furthermore, a tissue engineered construct, composed of polyurethane (PU) scaffold with a TGF-ß1-supplemented collagen type I hydrogel and human AF cells, was evaluated with in vitro 3D culture and ex vivo preclinical bioreactor-loaded organ culture models. The collagen type I hydrogel helped maintaining the AF functional phenotype. TGF-ß1 supplement within the collagen I hydrogel further promoted cell proliferation and matrix production of AF cells within in vitro 3D culture. In the ex vivo IVD organ culture model with physiologically relevant mechanical loading, TGF-ß1 supplement in the transplanted constructs induced the functional AF cell phenotype and enhanced collagen matrix synthesis. In conclusion, TGF-ß1-containing collagen-PU constructs can induce the functional cell phenotype of human AF cells in vitro and in situ. This combined cellular, biomaterial and bioactive agent therapy has a great potential for AF tissue regeneration and rupture repair.
Assuntos
Anel Fibroso/patologia , Colágeno/farmacologia , Poliuretanos/farmacologia , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/farmacologia , Cicatrização/efeitos dos fármacos , Adulto , Animais , Anel Fibroso/efeitos dos fármacos , Biomarcadores/metabolismo , Bovinos , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ruptura , Cicatrização/genéticaRESUMO
OBJECTIVE: To investigate the BRAF gene mutations in ameloblastic fibroma (AF), and to further analyze the relationship between the BRAF mutation and clinical characteristics so as to provide new reference to the study of AF's molecular pathology. METHODS: Sixteen cases diagnosed as AF at the Department of Oral Pathology, Peking University School of Stomatology between January 1990 and December 2017 were collected. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues using the QIAamp DNA Mini Kit (Qiagen, Germany) according to the manufacturer's instructions. Polymerase chain reaction (PCR) and direct sequencings were used to detect the BRAF gene mutations. The clinicopathological data, such as the age, location of the lesion, symptoms and treatments were retrospectively analyzed. RESULTS: The sixteen cases of AF involved nine women and seven men aged 2-67 years. Three lesions occurred in the maxilla and thirteen in the mandible. The most common presenting symptom of AF was a painless slowly enlarging mass with swelling. Ten patients received conservative treatment and the other six patients received radical surgery. Three cases relapsed during the study period. BRAF gene mutation was found in sixteen of all the sixteen samples analyzed (100%). The BRAF mutation was a point mutation with a thymine-adenine transversion at nucleotide 1 799 of 15 exons, resulting in a change at residue 600 that substituted glutamine for valine. This mutation was the strongest activator of the downstream RAS/RAF/MEK/ERK-MAPK signaling pathway. This helped to bring about a gain-of-function mutation due to a V600E substitution. Many studies identified that BRAF regulated survival, apoptosis, and proliferation of cells by inducing MAPK pathways activation. For the existing cases, none of the age, sex, location, recurrence and treatments had a statistically significant correlation with BRAF mutation. CONCLUSION: Our findings demonstrated high prevalence of BRAF V600E mutation in AF. The pathogenic role remains to be clarifiedï¼.
Assuntos
Fibroma , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Éxons , Feminino , Fibroma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The efficacy and outcomes of aspirin in local defects and the use of platelet-rich fibrin (PRF) in periodontal defects were investigated. Whether the PRF/aspirin complex is a suitable scaffold and delivery system to carry sustained-release aspirin/salicylic acid to promote periodontal bone regeneration was determined. MATERIAL AND METHODS: PRF and PRF/aspirin complex were prepared. The concentrations of aspirin/salicylic acid released from the PRF/aspirin complex were calculated at 37°C. Periodontal ligament mesenchymal cells were cultured on six-well plates with PRF or PRF/aspirin complex gel to analyze proliferation and migration. The alveolar bone between the inferior buccal mesial root and anterior buccal distal root of the first maxillary molar was removed in 15 rats randomly divided into three groups: no treatment, PRF or PRF/aspirin complex. Twelve weeks post-transplantation, 2D/3D micro-computed tomography and histomorphometric technique were used for quantitative analyses. RESULTS: The PRF/aspirin complex provided a sustained-release aspirin/salicylic acid. Peak concentrations occurred 4 hours after transplantation and were sustained to 48 hours at 37°C; the total concentration of released aspirin/salicylic acid was 83.5 mg/mL, respectively. The sustained-release promoted the proliferation and migration of periodontal ligament mesenchymal cells. Micro-computed tomography and histological data showed that both the PRF and PRF/aspirin complex enhanced periodontal bone formation (P<.05). Moreover, the new bone formation was two times greater in the PRF/aspirin complex group than the PRF group. CONCLUSION: Aspirin/salicylic acid could be sustained-released from PRF/aspirin complex, which could inhibit inflammation and improve the function of mesenchymal cells. The data might provide a new safe and easy clinical therapeutic strategy to promote periodontal bone reparation.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Regeneração Óssea/efeitos dos fármacos , Fibrina Rica em Plaquetas , Processo Alveolar/citologia , Processo Alveolar/diagnóstico por imagem , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Preparações de Ação Retardada , Regeneração Tecidual Guiada Periodontal , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Modelos Animais , Ligamento Periodontal/citologia , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
AIMS: To identify the contributions of various mechanical factors related to cast posts in a root filled tooth by integration of finite element analysis and the Taguchi method. The investigated factors included post-length (Post-L), post-diameter (Post-D), ferrule height (Ferrule-H) and periodontal bone loss (Bone-H). METHODOLOGY: Three-dimensional finite element models of a mandibular premolar were developed to simulate a root filled tooth. For each investigated factor, three levels and values were selected, and based on a Taguchi orthogonal array, nine models were established. An inclination load of 100 N was applied on the buccal cusp tip, and the dentine peak von Mises stress was used as the evaluation index. RESULTS: Among the four investigated factors, Bone-H was the predominant mechanical factor, with a contribution of more than 97%. Among the other three controllable factors of post-design, Post-D was the primary contributing factor and was almost five times more substantial than the least contributing factor, Ferrule-H. CONCLUSION: Bone-H was the predominant factor influencing the stress of the dentine on a post-restored root filled tooth, followed by the Post-D, Post-L and Ferrule-H. For patients with severe periodontal bone loss, a large post-diameter is essential for endodontic post-restoration treatment.
Assuntos
Dente Pré-Molar/cirurgia , Análise do Estresse Dentário/métodos , Técnica para Retentor Intrarradicular , Tratamento do Canal Radicular , Análise de Elementos Finitos , Humanos , Mandíbula , Tratamento do Canal Radicular/métodosRESUMO
Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.
Assuntos
Catarata/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Análise Mutacional de DNA , Genes Ligados ao Cromossomo X , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença , Humanos , MutaçãoRESUMO
The coxsackievirus B4 (CVB4) belongs to human enterovirus B species within the family Picornaviridae. Here we report a novel complete genome sequence of a recombinant CVB4 strain, CVB4/GX/10, which was isolated from a patient with a fatal case of hand, foot, and mouth disease in China. The complete genome consists of 7,293 nucleotides, excluding the 3' poly(A) tail, and has an open reading frame that maps between nucleotide positions 742 and 7293 and encodes a 2,183-amino-acid polyprotein. Phylogenetic analysis based on different genome regions reveals that CVB4/GX/10 is closest to a CVB4 strain, EPIHFMD-CLOSE CONTACT-16, in the 5' half (VP4â¼2B) of the genome, although it is closer to a Chinese CVB5 strain, CVB5/Henan/2010, in the 3' half (2Câ¼3D) of the genome. Furthermore, similar bootscan analysis based on the whole genomes demonstrates that recombination has possibly occurred within the 2C domain and that CVB4/GX/10 is a possible progeny of intertypic recombination of the CVB4 strain EPIHFMD-CLOSE CONTACT-16 and CVB5/Henan/2010 that occurred during their cocirculation and evolution, which is a relatively common phenomenon in enteroviruses.
Assuntos
Enterovirus/genética , Genoma Viral , Doença de Mão, Pé e Boca/etnologia , Doença de Mão, Pé e Boca/virologia , China , Humanos , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
Apical periodontitis is an inflammatory condition that is considered an immunological reaction of the periapical tissue to invading bacteria and their pathogenic components. Recent research has revealed that NLR family pyrin domain containing 3 (NLRP3) is crucial to the pathogenesis of apical periodontitis and serves as a link between innate and adaptive immunity. The balance between regulatory T-cell (Treg) and T helper cell 17 (Th17 cell) determines the direction of the inflammatory response. Therefore, this study aimed to investigate whether NLRP3 exacerbated periapical inflammation by disturbing Treg/Th17 balance and the underlying regulatory mechanisms. In the present study, NLRP3 was raised in apical periodontitis tissues as opposed to healthy pulp tissues. Low NLRP3 expression in dendritic cells (DCs) increased transforming growth factor ß secretion while decreasing interleukin (IL)-1ß and IL-6 production. The Treg ratio and IL-10 secretion rose when CD4+ T cells were cocultured with DCs primed with IL-1ß neutralizing antibody (anti-IL-1ß) and specific small interfering RNA (siRNA) targeting NLRP3 (siRNA NLRP3), but the proportion of Th17 cells and IL-17 release dropped. Furthermore, siRNA NLRP3-mediated suppression of NLRP3 expression aided Treg differentiation and elevated Foxp3 expression as well as IL-10 production in CD4+ T cells. Inhibition of NLRP3 activity by MCC950 boosted the percentage of Tregs while decreasing the ratio of Th17 cells, leading to reduced periapical inflammation and bone resorption. Nigericin administration, however, exacerbated periapical inflammation and bone destruction with an unbalanced Treg/Th17 response. These findings demonstrate that NLRP3 is a pivotal regulator by regulating the release of inflammatory cytokines from DCs or directly suppressing Foxp3 expression to disturb Treg/Th17 balance, thus exacerbating apical periodontitis.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Periodontite Periapical , Linfócitos T Reguladores , Humanos , Fatores de Transcrição Forkhead , Inflamação , Interleucina-10 , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Interferente Pequeno , Células Th17RESUMO
Coxsackievirus (CV) strains CVA2, CVA4, CVA5, and CVA10 were isolated from patients with hand, foot, and mouth disease during a 2009 outbreak in China. Full genome sequences for four representative strains, CVA2/SD/CHN/09 (A2SD09), CVA4/SZ/CHN/09 (A4SZ09), CVA5/SD/CHN/09 (A5SD09), and CVA10/SD/CHN/09 (A10SD09), were determined. Phylogenetic and recombination analyses of the isolates by comparison with human enterovirus A prototype strains revealed that genetic recombination occurred during cocirculation of the viruses. The A2SD09 and A4SZ09 strains were most closely related to their corresponding prototype strains in the capsid region but shared noncapsid sequences with each other. Similarly, strains A5SD09 and A10SD09 had serotype-specific homology for the capsid proteins but shared noncapsid sequences with each other. Phylogenetic analyses of the four isolates with homotypic strains showed that CVA2 strains were divided into five genotypes. The A2SD09 strain clustered with Mongolia strains isolated in 2003, forming genotype V. The A4SZ09 strain and other isolates from mainland China and Taiwan clustered with genotype III strains and are likely related to strains that circulated in Europe and Mongolia. The A5SD09 strain is closely related to other Chinese strains isolated in 2008. The A10SD09 isolate, together with other Chinese strains isolated since 2004, formed a distinct lineage that was likely imported from Japan and South Korea. This study shows that natural recombination is a frequent event in human enterovirus A evolution. More comprehensive surveillance of enteroviruses that focus not only on EV71 or CVA16 is needed for us to understand the molecular epidemiology of enteroviruses and to track recombination events which may ultimately affect the virulence of viruses during outbreaks.
Assuntos
Enterovirus Humano A/classificação , Enterovirus Humano A/genética , Genoma Viral , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , RNA Viral/genética , Recombinação Genética , Proteínas do Capsídeo/genética , China/epidemiologia , Análise por Conglomerados , Enterovirus Humano A/isolamento & purificação , Evolução Molecular , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
It is widely known that smoking is a risk factor for bone loss and plays a key role in osteopenia. Despite this well-known association, the mechanisms by which smoking affects bone have not been definitively established. Since smoking increases bone loss and potentially affects bone resorption in response to mechanical force, we investigated the impact of cigarette smoke on osteoclast numbers and underlying mechanisms in a mouse model of orthodontic tooth movement (OTM). The experimental group was exposed to once-daily cigarette smoke while the control group was not, and tooth movement distance and osteoclast numbers were assessed. In addition, the effect of cigarette smoke extract (CSE) on osteoclast precursor proliferation and osteoclast apoptosis was assessed in vitro. We found that cigarette smoke exposure enhanced bone remodeling stimulated by mechanical force and increased osteoclast numbers in vivo. Also, CSE increased the number of osteoclasts by inhibiting osteoclast apoptosis via the mitochondrial reactive oxygen species/cytochrome C/caspase 3 pathway in vitro. Moreover, exposure of mice to cigarette smoke affected bone marrow cells, leading to increased formation of osteoclasts in vitro. This study identifies a previously unknown mechanism of how smoking has a detrimental impact on bone.
Assuntos
Apoptose , Osteoclastos , Animais , Remodelação Óssea , Camundongos , Fumaça/efeitos adversos , FumarRESUMO
The TGFß superfamily of proteins participates in tooth development. TGFß1 and TGFß3 regulate odontoblast differentiation and dentin extracellular matrix synthesis. Although the expression of TGFß family member ligands is well-characterized during mammalian tooth development, less is known about the TGFß receptor, which is a heteromeric complex consisting of a type I and type II receptors. The molecular mechanism of ALK5 (TGFßR1) in the dental mesenchyme is not clear. We investigated the role of ALK5 in tooth germ mesenchymal cells (TGMCs) from the lower first molar tooth germs of day 15.5 embryonic mice. Human recombinant TGFß3 protein or an ALK5 inhibitor (SD208) was added to the cells. Cell proliferation was inhibited by SD208 and promoted by TGFß3. We found that SD208 inhibited TGMCs osteogenesis and dentinogenesis. Both canonical and noncanonical TGFß signaling pathways participated in the process. TAK1, P-TAK1, p38 and P-p38 showed greater expression and SMAD4 showed less expression when ALK5 was inhibited. Our findings contribute to understanding the role of TGFß signaling for the differentiation of mesenchymal stem cells derived from dental germ and suggest possible targets for optimizing the use of stem cells of dental origin for tissue regeneration.
Assuntos
Odontogênese/fisiologia , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Germe de Dente/citologia , Dente/citologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos ICR , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Germe de Dente/metabolismo , Proteínas Wnt/metabolismoRESUMO
Exploring the subtle mechanical property changes of tooth enamel in different conditions is important for dental research. However, some experimental results can be deceptive and may lead to misunderstanding. In particular, we show the dehydration associated with increased mechanical properties of tooth enamel as monitored by Nanomechanical System Testing (NST) can be misleading. The results indicate that the friction coefficient decreased with an increase of hardness of enamel upon dehydration, which appears to imply that dehydrated enamel has better mechanical properties than hydrated enamel. However, more critical scrutiny of the actual situation, suggests dehydrated teeth enamel are more prone to damage and greater wear. To appreciate the basis for the contrast between the experimental results and reality of natural hydrated enamel, which has better resistance to wear, and is critical for an understanding of the aetiology of enamel resistance to fracture.
Assuntos
Esmalte Dentário/metabolismo , Fenômenos Mecânicos , Água/metabolismo , Animais , Fenômenos Biomecânicos , Esmalte Dentário/diagnóstico por imagem , Microscopia Eletrônica de Varredura , SuínosRESUMO
Molecular diagnosis of malignant lymphoma depends on the ability to extract high molecular weight genomic DNA. However, collection, storage, and transportation of frozen tissue is time consuming and expensive. We used a simple, low-cost lysis, storage, and transportation buffer (LST) to maintain clinical tissue samples at room temperature for up to 4 weeks before molecular analysis. Immersion of lymphoid tissue in LST at room temperature for 2 to 4 weeks was compared with snap-freezing in liquid nitrogen followed by storage at -75 degrees C. Southern blot analysis using an immunoglobulin heavy chain JH probe yielded identical results in 5 clonal and 6 nonclonal samples. The DNA recovered from the LST of a 12th sample was too degraded to be analyzed; however, the tissue had large zones of geographic necrosis. We also demonstrated that DNA extracted from tissue stored in LST is suitable for amplification by the polymerase chain reaction. Results from 4 of the snap-frozen and LST samples analyzed for rearrangements at the immunoglobulin heavy chain VDJ locus were identical. LST can be used in a clinical laboratory for storing tissue samples at room temperature up to 4 weeks before molecular analysis.
Assuntos
Citogenética/métodos , DNA/isolamento & purificação , Tecido Linfoide/citologia , Polietilenoglicóis , Polissorbatos , Preservação de Tecido/métodos , Trometamina , Southern Blotting , Eletroforese , Rearranjo Gênico , Genes de Imunoglobulinas , Humanos , Peso Molecular , Reação em Cadeia da PolimeraseRESUMO
There is growing evidence that proteins are early targets of reactive oxygen species, and that the altered proteins can in turn damage other biomolecules. In this study, we measured the effects of proteins on the oxidation of liposome phospholipid membranes, and the formation of protein hydroperoxides in serum and in cultured cells exposed to radiation-generated hydroxyl free radicals. Lysozyme, which did not affect liposome stability, gave 50% protection when present at 0.3 mg/ml, and virtually completely prevented lipid oxidation at 10 mg/ml. When human blood serum was irradiated, lipids were oxidized only after the destruction of ascorbate. In contrast, peroxidation of proteins proceeded immediately. Protein hydroperoxides were also generated without a lag period in hybrid mouse myeloma cells, while at the same time no lipid peroxides formed. These results are consistent with the theory that, under physiological conditions, lipid membranes are likely to be effectively protected from randomly-generated hydroxyl radicals by proteins, and that protein peroxyl radicals and hydroperoxides may constitute an important hazard to biological systems under oxidative stress.
Assuntos
Lipídeos/sangue , Lipossomos/metabolismo , Mieloma Múltiplo/metabolismo , Animais , Ácido Ascórbico/farmacologia , Relação Dose-Resposta a Droga , Humanos , Peróxido de Hidrogênio/farmacologia , Cinética , Peroxidação de Lipídeos , Camundongos , Modelos Químicos , Muramidase/metabolismo , Estresse Oxidativo , Oxigênio/metabolismo , Proteínas/metabolismo , Espécies Reativas de Oxigênio , Fatores de Tempo , Células Tumorais CultivadasRESUMO
Two kinds of synthetic biomaterial, porous tricalcium phosphate (PTCP) and magnetic porous tricalcium phosphate (MPTCP) ceramic granules were implanted in rat femur. In the period of 4 months, the assessment of serial histological sections, scanning electron microphotographs and quantitative analysis of bone formation in the sections showed that both ceramics are biocompatible and degradable in vivo. More new bone formation occurred in the MPTCP group. Endochondral ossification was seen in both groups. The quantitative analysis in this study is reliable, and may be suitable to the similar experimental models.
Assuntos
Materiais Biocompatíveis , Regeneração Óssea/fisiologia , Fosfatos de Cálcio , Próteses e Implantes , Animais , Cerâmica , Fêmur/anatomia & histologia , Fêmur/cirurgia , Processamento de Imagem Assistida por Computador , Magnetismo , Masculino , Ratos , Ratos WistarRESUMO
The macrophages mediated biodegradation of two biomaterials, collagen/hydroxylapatite (CHA) and beta-tricalcium phosphate ceramics (TCP), was studied in 24 male Kunming mice and 20 male C57BL/6 mice with histopathologic, histochemical and ultrastructural observation. It was demonstrated that macrophages infiltrated after CHA, TCP were implanted. The macrophages could be differentiated from fibroblasts and the other infiltrated cells for special cellular profile and strong acid phosphatase activity. Morphologically, monocyte-macrophages and infused multinuclear giant cell degraded CHA and TCP by phagocytosis and extracellular resorption. The carbonic anhydrase activity of macrophages was demonstrated by histochemical technique. It suggested that macrophages secreted H+ and accomplished the decalcification of calcium phosphate compound of CHA and TCP. We conclude that macrophages are the main mediating cells which degraded CHA and TCP intracellularly and extracellularly.
Assuntos
Materiais Biocompatíveis , Fosfatos de Cálcio , Durapatita , Macrófagos/metabolismo , Próteses e Implantes , Animais , Cerâmica , Colágeno , Masculino , Camundongos , Camundongos Endogâmicos C57BL , FagocitoseRESUMO
AIM: To investigate the bioactivity of the self-designed biodegradable osteosynthetic devices made of resorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) composites. METHOD: Forty-three rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod, the duration of follow-up were 3, 6, 12, 24 and 36 weeks. Histological, scanning electron microscopic (SEM), energy dispersive X-ray (EDX) and biomechanical analyses were done. RESULTS: Active new bone formation and direct bone-bonding were seen at the bone-implant interface. Generous apatite crystals deposited and grew on the surface of the composites at 3 approximately 6 weeks postoperation. The interfacial shear strength increased significantly. CONCLUSION: Through the incorporating of resorbable HA microparticles, specific bone-bonding and active osteogenic capacity is introduced. This kind of bioactivity, together with other properties such as sufficient mechanical strength, enhanced biocompatibility and radiopacity, which are intrinsically unobtainable in totally resorbable polymer/polymer systems, make the HA/PDLLA composites become a desirable material for the internal fixation of cancellous bone.
Assuntos
Substitutos Ósseos/uso terapêutico , Durapatita/uso terapêutico , Fêmur/cirurgia , Fixadores Internos , Poliésteres/uso terapêutico , Implantes Absorvíveis , Animais , Materiais Biocompatíveis , Feminino , Seguimentos , Masculino , Microscopia Eletrônica de Varredura , Osseointegração , CoelhosRESUMO
Heparin-free hemodialysis (HFHD) is important in patient hemodialysis with ARF and CRF with hemorrhagic trend. Adsorption method HFHD was used clinically in patients in our hospital. The method showed that the positively charged hemophan membrane binds the negatively charged anticoagulant heparin. The result showed that adsorption method HFHD has good bioconcomitance, needs no special medicine and equipment, and never increase the load of heart. It is simple and has high successful rate ( > or = 90%).
Assuntos
Diálise Renal/métodos , Insuficiência Renal/terapia , Adulto , Idoso , Materiais Biocompatíveis , Celulose/análogos & derivados , Feminino , Heparina , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the effect of transforming growth factor (TGF) beta 1 gene transfection on the growth of mesenchymal stem cells(MSCs) and to evaluate a new biomimetic biodegradable polymer as scaffolds for applications in articular cartilage tissue engineering. METHODS: Principles of tissue engineering were combined organically with principles of gene therapy to produce cultured periosteum-derived MSCs transduced with the full-length rat TGF-beta 1 cDNA in vitro. These cells were then seeded onto three-dimensional porous poly-DL-lactide scaffolds modified with poly-L-lysine that mimicked cell-binding domains found on natural extracellular matrix to promote specific cell adhesion. The adhesion, proliferation, and differentiation of the transfected MSCs were examined with scanning electron microscope within 2 weeks. RESULTS: All cells adhered to the biomimetic matrices well, but more cartilage-like tissue was formed for TGF-beta 1 gene modified MSCs/scaffolds composites than for the control groups. Transfer of gene encoding TGF-beta 1 to MSCs promoted its proliferation and differentiation significantly. CONCLUSIONS: The TGF-beta 1 gene transduced MSCs/biomimetic matrix composites used in this study was the first attempt to apply the principles of molecular tissue engineering for articular cartilage repair. This new molecular tissue engineering approach could be of potential benefit to repair damaged articular cartilage, especially in osteoarthritis. The new biomimetic biodegradable polymer matrices modified with biomolecules not only have good structural compatibility, but also have better interfacial compatibility and bioactivity, and can be used as scaffolds for articular cartilage tissue engineering.
Assuntos
Materiais Biocompatíveis , Polímeros , Células-Tronco/citologia , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/farmacologia , Animais , Adesão Celular , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Divisão Celular , Ácido Láctico , Mesoderma/citologia , Coelhos , TransfecçãoRESUMO
The biocompatibility of self-designed hydroxyapatite/poly (DL-lactide) rods was evaluated both in vitro and in vivo including Ames test, micronucleus test, acute and subacute systemic toxicity test, hemolysis test, hemopexis test and long-term muscle and bone implant test. The results indicate that the material has no toxicity, no stimulation and mutation, and it does not cause hemolysis and hemopexis. Consequently, the biocompatibility of the composite was good.