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1.
Neuroendocrinology ; 113(3): 319-331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36037793

RESUMO

INTRODUCTION: Hyperalgesia frequently occurs after surgery and is associated with adverse effects on surgical outcomes. Thus, we aimed to examine whether the hypothalamus-pituitary-adrenal (HPA) axis function after surgery is involved in the development of postoperative hyperalgesia. METHODS: Surgery- and pain-related variables were measured 24 and 48 h after the first and second total knee arthroplasties (TKAs) in postmenopausal patients undergoing 1-week-interval staged bilateral TKA. Two sets of saliva samples were consecutively collected from patients before (pre-T1) and 1 week after (post-T1) the first TKA (n = 69). HPA axis function was analyzed in a subgroup of 20 patients with a typical cortisol awakening response (CAR) in both the sets of saliva samples. RESULTS: Surgery-related variables were comparable between the first and second TKAs. However, pain-related variables (pain ratings and the amount of opioid analgesics consumed) were greater after the second than the first TKA. Cortisol and dehydroepiandrosterone (DHEA) secretion during the post-awakening period (CARauc and Daucawk, respectively) was higher at post-T1 than at pre-T1, but the molar CARauc/Daucawk ratio was comparable between the time points examined. No relationship was observed between the pre-T1 CARauc and pain ratings after the first TKA. However, post-T1 CARauc showed a positive correlation with pain ratings after the second TKA. Postoperative pain ratings were negatively correlated with Daucawk and positively correlated with the molar CARauc/Daucawk ratio at all examined time points. DISCUSSION/CONCLUSION: The results suggest that adrenocortical steroidogenic activity favoring the production of cortisol over DHEA after surgery may contribute to the development of hyperalgesia during the early postoperative period.


Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Hidrocortisona , Hiperalgesia , Saliva , Dor , Desidroepiandrosterona
2.
Dermatology ; 238(3): 554-561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34535604

RESUMO

BACKGROUND: Periodontitis is a chronic inflammatory disorder involving the periodontium. The precise nature of the association between periodontitis and psoriasis has not been determined. OBJECTIVE: This nationwide population-based study investigated the relationship between periodontitis and the risk of psoriasis. METHODS: A health screening database, which is a sub-dataset of the Korean National Health Insurance System database, was used in this study. Subjects with (n = 1,063,004) and without (n = 8,655,587) periodontitis who underwent health examinations from January to December 2009 were followed for 9 years. RESULTS: In multivariable analysis, compared to the non-periodontitis group, periodontitis patients had a significantly higher risk of developing psoriasis (hazard ratio 1.116, 95% confidence interval 1.101-1.13). Non-smokers with periodontitis had an 11% increase in risk of psoriasis and smokers with periodontitis had a 26.5% increase in risk of psoriasis compared to non-smokers without periodontitis. CONCLUSION: Our study highlights periodontitis as a potential independent risk factor for psoriasis, increasing awareness of the synergistic role of smoking and periodontitis in the pathogenesis of psoriasis.


Assuntos
Periodontite , Psoríase , Estudos de Coortes , Humanos , Periodontite/epidemiologia , Psoríase/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia
3.
Int J Mol Sci ; 22(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671948

RESUMO

Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Amidoidrolases/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Periodontite/tratamento farmacológico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Animais , Reabsorção Óssea/tratamento farmacológico , Células Cultivadas , Modelos Animais de Doenças , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Resultado do Tratamento
4.
Angew Chem Int Ed Engl ; 60(25): 13847-13852, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33857346

RESUMO

Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. Despite tremendous advances in imaging devices, surprisingly only a few dyes are currently available in the clinic. Previous fluorophores, ZW800-1A and ZW800-1C, significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.


Assuntos
Corantes Fluorescentes/química , Polietilenoglicóis/química , Humanos , Imagem Óptica , Terapia Fototérmica , Espectroscopia de Luz Próxima ao Infravermelho
5.
FASEB J ; 33(12): 13412-13422, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31545910

RESUMO

Among the main bacteria implicated in the pathology of periodontal disease, Aggregatibacter actinomycetemcomitans (Aa) is well known for causing loss of periodontal attachment and systemic disease. Recent studies have suggested that secreted extracellular RNAs (exRNAs) from several bacteria may be important in periodontitis, although their role is unclear. Emerging evidence indicates that exRNAs circulate in nanosized bilayered and membranous extracellular vesicles (EVs) known as outer membrane vesicles (OMVs) in gram-negative bacteria. In this study, we analyzed the small RNA expression profiles in activated human macrophage-like cells (U937) infected with OMVs from Aa and investigated whether these cells can harbor exRNAs of bacterial origin that have been loaded into the host RNA-induced silencing complex, thus regulating host target transcripts. Our results provide evidence for the cytoplasmic delivery and activity of microbial EV-derived small exRNAs in host gene regulation. The production of TNF-α was promoted by exRNAs via the TLR-8 and NF-κB signaling pathways. Numerous studies have linked periodontal disease to neuroinflammatory diseases but without elucidating specific mechanisms for the connection. We show here that intracardiac injection of Aa OMVs in mice showed successful delivery to the brain after crossing the blood-brain barrier, the exRNA cargos increasing expression of TNF-α in the mouse brain. The current study indicates that host gene regulation by microRNAs originating from OMVs of the periodontal pathogen Aa is a novel mechanism for host gene regulation and that the transfer of OMV exRNAs to the brain may cause neuroinflammatory diseases like Alzheimer's.-Han, E.-C., Choi, S.-Y., Lee, Y., Park, J.-W., Hong, S.-H., Lee, H.-J. Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-α production in human macrophages and cross the blood-brain barrier in mice.


Assuntos
Membrana Externa Bacteriana/metabolismo , Barreira Hematoencefálica/metabolismo , Vesículas Extracelulares/genética , Macrófagos/metabolismo , Doenças Periodontais/metabolismo , Pequeno RNA não Traduzido/genética , Fator de Necrose Tumoral alfa/metabolismo , Aggregatibacter actinomycetemcomitans/química , Aggregatibacter actinomycetemcomitans/genética , Animais , Vesículas Extracelulares/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Doenças Periodontais/microbiologia , Doenças Periodontais/patologia , RNA Bacteriano/genética , Células U937
6.
J Periodontal Res ; 55(2): 247-257, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31797379

RESUMO

BACKGROUND AND OBJECTIVE: After tooth extraction, the extraction socket undergoes several steps of soft and hard tissue healing. The healing process of the extraction socket is modulated by a range of signaling factors and biochemical agents. It has been reported that resveratrol, a polyphenolic compound, exhibits various biological effects, including anti-inflammatory, anti-carcinogenic, antioxidant, and anti-aging effects, and protects cardiovascular and bone tissues. In this study, we examined the cellular effects of resveratrol on human periodontal ligament (hPDL) cells and osteoblast-like (MC3T3-E1) cells and evaluated the bone-healing capacity of tooth extraction sockets in mice. MATERIAL AND METHODS: Resveratrol was applied to hPDL and MC3T3-E1 cells to detect cell proliferation and alkaline phosphatase (ALP) activity, and qPCR was employed to understand the gene expression level in vitro. For in vivo experiment, six-week-old C57BL/6 male mice were randomly divided into control (n = 15) and experimental (n = 15) groups and maxillary first molars were extracted by surgery. Experimental groups received 50-µM resveratrol on extraction sockets and analyzed the degree of new bone formation. RESULTS: Treatment of hPDL and MC3T3-E1 cells with resveratrol increased the cell proliferation and ALP activity and enhanced the expression of ALP, BMP-2, BMP-4, and OC genes. Resveratrol enhanced new bone formation in the lingual extraction socket in mice. CONCLUSION: These results suggest that resveratrol increases the cellular physiology of PDL and osteoblast including their proliferation and differentiation and may play an important role in bone-healing capacity after tooth extraction.


Assuntos
Osteoblastos/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Resveratrol/uso terapêutico , Extração Dentária , Alvéolo Dental/efeitos dos fármacos , Células 3T3 , Animais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese , Ligamento Periodontal/citologia , Cicatrização
7.
BMC Anesthesiol ; 20(1): 28, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996130

RESUMO

BACKGROUND: The effort to improve tracheal intubation process is clinically valuable. We hypothesized that a preoperative brief exercise therapy would increase mouth opening and neck extension, enhancing intubation conditions during general anesthesia. METHODS: Patients undergoing general anesthesia were randomized into two groups. The exercise group performed the exercise regimen including masseter muscle massage and stretching of jaw and neck joints before anesthetic induction, while the control did not. Before (baseline) and after the intervention, we evaluated Mallampati score, mouth aperture size, and sternomental distance. After tracheal intubation, intubation difficulty scale with direct laryngoscope and oropharyngeal soft tissue injury were also evaluated. RESULTS: A total of 138 patients completed the analysis (control = 68, exercise = 70). Baseline characteristics did not differ between groups. At anesthetic induction, there was a significant difference in Mallampati score between the two groups (P = 0.039) and the incidence of Mallampati scores of 1 was higher in the exercise group (odds ratio [95% CI]: 2.1 [1.0-4.3], P = 0.043). Mouth opening after the intervention was greater in the exercise group than in the control group (estimated difference [95% CI]: - 2.4 [- 4.8 - -0.1], P = 0.042) and sternomental distance was similar between the two groups (estimated difference [95% CI]: - 3.7 [- 9.0-1.7, P = 0.175). The exercise group showed less soft tissue injuries (odds ratio [95% CI]: 0.2 [0.1-0.8], P = 0.009), however, intubation difficulty scale did not differ between the study groups (P = 0.112). CONCLUSIONS: The brief pre-anesthetic exercise improved intubation conditions and enabled faster tracheal intubation with less injury to oropharyngeal soft tissue. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0002618), registered at December 28, 2017.


Assuntos
Anestesia Geral , Terapia por Exercício/métodos , Intubação Intratraqueal/métodos , Arcada Osseodentária/fisiopatologia , Boca/fisiopatologia , Pescoço/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Feminino , Humanos , Masculino , Massagem/métodos , Músculo Masseter/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Tempo , Resultado do Tratamento
8.
J Nanosci Nanotechnol ; 18(2): 887-892, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448511

RESUMO

Percutaneous delivery of growth factors is often used to treat wounds, and for cosmetic purposes, as a way of accelerating healing and skin regeneration, respectively. However, the therapeutic effects of growth factors are diminished by their poor absorption when delivered percutaneously, in addition to their rapid degradation by proteinases. To overcome these obstacles, we constructed two skin-permeable compounds. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) were both genetically paired with low-molecular-weight protamine (LMWP), to yield the compounds LMWP-bFGF and LMWP-VEGF-A, respectively. The molecular weights and N-terminal amino acid sequences of LMWP-bFGF and LMWP-VEGF-A confirmed that the N-terminus-specific conjugation of LMWP with bFGF and VEGF-A had been successful. The biological abilities of the native factors to stimulate human fibroblast (CCD-986sk) and endothelial cell proliferation were preserved. Both compounds significantly promoted wound (scratch) recovery and enhanced procollagen type I C-peptide synthesis in CCD-986sk cells (to levels 184 and 133% those of the native compounds, respectively). The LMWP-conjugated growth factors were significantly more permeable than the native forms (by 7.29- and 29.22-fold, respectively). Finally, encapsulation of the compounds in positively charged elastic nanoliposomes (115 ± 1.54 nm in diameter with a zeta potential of 57.2 ± 3.05 mV) further improved both permeation and stability. Thus, nanoliposomes loaded with LMWP-conjugated growth factors are expected to enhance skin regeneration; the materials will find applications in wound-healing therapies and anti-wrinkle cosmetics.


Assuntos
Sistemas de Liberação de Medicamentos , Lipossomos , Nanocompostos , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Cicatrização , Humanos , Protaminas , Pele , Absorção Cutânea , Fator A de Crescimento do Endotélio Vascular/farmacocinética
9.
Hum Genomics ; 10(1): 28, 2016 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-27531006

RESUMO

BACKGROUND: Periodontitis is the most common chronic inflammatory disease caused by complex interaction between the microbial biofilm and host immune responses. In the present study, high-throughput RNA sequencing was utilized to systemically and precisely identify gene expression profiles and alternative splicing. METHODS: The pooled RNAs of 10 gingival tissues from both healthy and periodontitis patients were analyzed by deep sequencing followed by computational annotation and quantification of mRNA structures. RESULTS: The differential expression analysis designated 400 up-regulated genes in periodontitis tissues especially in the pathways of defense/immunity protein, receptor, protease, and signaling molecules. The top 10 most up-regulated genes were CSF3, MAFA, CR2, GLDC, SAA1, LBP, MME, MMP3, MME-AS1, and SAA4. The 62 down-regulated genes in periodontitis were mainly cytoskeletal and structural proteins. The top 10 most down-regulated genes were SERPINA12, MT4, H19, KRT2, DSC1, PSORS1C2, KRT27, LCE3C, AQ5, and LCE6A. The differential alternative splicing analysis revealed unique transcription variants in periodontitis tissues. The EDB exon was predominantly included in FN1, while exon 2 was mostly skipped in BCL2A1. CONCLUSIONS: These findings using RNA sequencing provide novel insights into the pathogenesis mechanism of periodontitis in terms of gene expression and alternative splicing.


Assuntos
Periodontite Crônica/metabolismo , Transcriptoma , Processamento Alternativo , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Periodontite Crônica/diagnóstico , Periodontite Crônica/genética , Perfilação da Expressão Gênica , Gengiva/metabolismo , Gengiva/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
10.
J Nanosci Nanotechnol ; 17(4): 2363-369, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29641166

RESUMO

Topical administration of growth factors has been suggested as a promising strategy for promoting the healing process and skin regeneration in wound management. However, several restrictions hinder their successful clinical use; specifically, limited percutaneous absorption causes inconsistent efficacy, and various growth factors with specific functionalities are required at different stages of healing. To overcome these shortcomings, previously we have constructed highly skin-permeable analogues of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor-A (PDGF-A) (LMWP-EGF, LMWP-IGF-I and LMWP-PDGF-A) by genetically conjugating the low-molecular-weight protamine (LMWP) to their N-terminus. In the present study, we determined the optimal concentration ratio of these growth factors by investigating In Vitro cell proliferation and the scratch wound repairing assay. After confirming synergetic effects of growth factors in combinations, we developed a topical delivery system consisting of a nanoemulsion (NE)-dispersed polyvinylpyrrolidone hydrogel loaded with all three growth factors. In Vitro permeability studies were also performed to assess whether the LMWP-conjugated growth factors in the formulation enhanced their skin permeation compared to native growth factors. Combinations of native or LMWP-fused growth factors significantly promoted fibroblast proliferation and scratch wound recovery, and the synergy of LMWP-EGF, LMWP-IGF-I and LMWP-PDGF-A was optimal at a ratio of 100:100:10 by concentration. The growth factor combination-loaded NE appeared to be spherical under cryo-transmission electron microscopy and the average droplet diameter was 127±4.30 nm. The LMWP-conjugated growth factors allowed significantly higher skin permeation than native growth factors from the NE-dispersed hydrogel. Thus, the LMWP-conjugated growth factor combination-loaded NE-dispersed hydrogel is expected to induce more rapid and prolonged wound healing.


Assuntos
Sistemas de Liberação de Medicamentos , Fator de Crescimento Epidérmico , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanoestruturas/química , Fator de Crescimento Derivado de Plaquetas , Administração Tópica , Animais , Emulsões/química , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/química , Fator de Crescimento Epidérmico/farmacocinética , Fator de Crescimento Epidérmico/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Camundongos , Modelos Biológicos , Células NIH 3T3 , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Fator de Crescimento Derivado de Plaquetas/química , Fator de Crescimento Derivado de Plaquetas/farmacocinética , Fator de Crescimento Derivado de Plaquetas/farmacologia , Pele/química , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
11.
Implant Dent ; 26(3): 351-356, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28288021

RESUMO

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of patients undergoing sinus membrane elevation by a minimally invasive crestal approach using a novel drilling system. MATERIALS AND METHODS: From May 2008 to November 2009, 21 implants were placed in 19 patients (10 men and 9 women) ranging from 23 to 69 years of age (average of 49.5 years). Implants were placed in maxillary premolar and molar areas that demonstrated insufficient residual bone quality; maxillary sinus membrane elevation was performed using a crestal approach with the sinus crestal approach kit (Neobiotech, Seoul, Korea). RESULTS: There was no sinus perforation or osseointegration failure. The implant survival rate was 100%. The postsurgical, augmented volume of the alveolar height ranged from 2 to 9.2 mm (average of 5.81 ± 2.06 mm). Six months after maxillary sinus elevation, the bone reduction volume ranged from 0.06 to 1.42 mm (average of 0.6 ± 0.38 mm). At final F/U, the amount of bone-height reduction ranged from 0.06 to 2.60 mm (average of 0.82 ± 0.63 mm). CONCLUSION: Sinus membrane elevation by the crestal approach using special reamers is advantageous because of the noticeable reduction in the risk of perforation and the ability to perform the surgery rapidly.


Assuntos
Implantação Dentária Endóssea/métodos , Instrumentos Odontológicos , Seio Maxilar/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Levantamento do Assoalho do Seio Maxilar/métodos , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Radiografia Panorâmica , Resultado do Tratamento
12.
Molecules ; 22(8)2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28749427

RESUMO

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.


Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Regeneração/efeitos dos fármacos , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Humanos , Pele/efeitos dos fármacos
13.
Nanotechnology ; 27(8): 085101, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26807875

RESUMO

Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function.


Assuntos
Cálcio/farmacologia , Macrófagos/efeitos dos fármacos , Nanoestruturas/química , Estrôncio/farmacologia , Titânio/farmacologia , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Biomarcadores/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/imunologia , Cátions Bivalentes , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Implantes Dentários , Expressão Gênica , Macrófagos/citologia , Macrófagos/imunologia , Camundongos , Microscopia de Força Atômica , Nanoestruturas/ultraestrutura , Fenótipo , Propriedades de Superfície , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia
14.
J Clin Periodontol ; 41(2): 181-90, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24256613

RESUMO

AIM: This study investigated the efficacy of the hypothalamic nonapeptide oxytocin (OT) by direct delivery to local defects using a microporous ß-tricalcium phosphate (TCP) as the carrier for the future applications as a method to achieve predictable bone regeneration of large osseous defects requiring sinus bone graft and guided bone regeneration procedures for implant placement. MATERIAL AND METHODS: Both the ectopic and new bone formation induced by the OT-loaded microporous ß-TCP powder was histomorphometrically compared with unloaded ß-TCP in a subcutaneous ectopic bone formation model and calvarial critical-sized defects (CSDs) in 45 rats. RESULTS: The OT-loaded ß-TCP clearly enhanced ectopic bone formation compared with the unloaded control group. A High initial OT dose (250 µg) significantly increased ectopic bone formation at an early healing time-point compared with a lower OT dose (50 µg). The OT-loaded samples displayed greater new bone formation in the rat calvarial CSDs. Extensive new bone formation was achieved in the calvarial CSDs with the higher OT dose. CONCLUSION: These results suggest that local OT delivery to bone substitute promotes new bone formation via an osteoinductive mode of action.


Assuntos
Materiais Biocompatíveis/química , Doenças Ósseas/cirurgia , Fosfatos de Cálcio/química , Ossificação Heterotópica/induzido quimicamente , Ocitocina/uso terapêutico , Crânio/cirurgia , Animais , Doenças Ósseas/patologia , Regeneração Óssea/efeitos dos fármacos , Difusão , Modelos Animais de Doenças , Portadores de Fármacos , Regeneração Tecidual Guiada/métodos , Masculino , Ossificação Heterotópica/patologia , Osteogênese/efeitos dos fármacos , Ocitocina/farmacologia , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Crânio/efeitos dos fármacos , Crânio/patologia , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia , Fatores de Tempo , Cicatrização/efeitos dos fármacos
15.
Clin Oral Implants Res ; 25(5): 632-40, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23278625

RESUMO

OBJECTIVES: Bisphosphonate-related jaw necrosis (BRONJ) associated with dental implants is a rare but continuously reported complication. To verify clinical and pathological characteristics of BRONJ around dental implants, the present study analyzed clinical, radiographic and histopathological findings of these lesions. PATIENTS AND METHODS: Nineteen patients were diagnosed with osteonecrosis of the jaw associated with dental implants and treated at our institute from 2008 to 2011. The patients' medical history, demographic features, radiographic, and histopathological findings along with information on bisphosphonates (BP) administration were analyzed. RESULTS: The majority of BRONJ patients associated with dental implants used oral BP for osteoporosis. The patients were divided into two groups: BP initiation before (n = 16) and after (n = 3) implant surgery. Only three patients (15.8%) could be regarded as "implant surgery-triggered" BRONJ. Many patients (n = 9) showed successful osteointegration after fixture installation to an average of 35 months (11-82 months) until the development of osteonecrosis. The histological features of the lesion showed that the necrotic bone with empty lacunae was infiltrated by inflammatory cells and bacterial colonies. Viable osteocytes were also observed in some areas of the bony specimens. Three types of bone destruction pattern were observed: (i) complete necrosis of the bone around the implant (frozen type), (ii) extensive osteolysis around the implant with or without sequestra (osteolytic type), and (iii) sequestration of bone with an implant maintaining direct implant-bone contact (en block sequestration type). These findings could be existed at the same lesions depending on the degree of local bone destruction and the severity of the infection. CONCLUSION: These results and those of others suggested that already osseointegrated dental implants can also cause the osteonecrosis around the implant after BP administration. En block sequestration of bone with implant might be one of the characteristics of implant-related BRONJ, which is different from peri-implantitis-induced bone destruction. The possible role of microcracks in this type of bone destruction needs to be examined further.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Implantes Dentários/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia Panorâmica , Cintilografia , Tomografia Computadorizada por Raios X
16.
J Esthet Restor Dent ; 26(2): 107-18, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24344955

RESUMO

STATEMENT OF THE PROBLEM: There is a reported gap between the relative satisfaction of the clinician and patient after a root coverage procedure. In addition, there may also be a disparity between objective esthetic evaluation tools and subjective satisfaction. METHODS: This study included 58 sites in 31 patients who had undergone root coverage procedures. The percentage of root coverage and the root coverage esthetic score system were used as objective measurements. A questionnaire with a five-point ordinal scale was used for subjective evaluation. Initial recession depth and width, Miller classification, tissue biotype, treatment procedures, and follow-up periods were considered as associated factors. RESULTS: After a period of at least 6 months from the procedure, the patient-perceived outcome showed a better match with the root coverage esthetic scoring system than the percentage of root coverage alone. A lower value for objective outcome was obtained for a deeper gingival recession and higher Miller class, but the subjective outcome displayed a steady trend. All four esthetic results were at their lowest after an epithelialized free soft tissue graft. CONCLUSION: An esthetic outcome according to patient satisfaction was not always consistent with that determined by professional scoring. In addition, partial root coverage may be viewed as a positive outcome by patients and clinicians in cases of deep gingival recession and high Miller class. CLINICAL SIGNIFICANCE: This study evaluates the esthetic outcome of root coverage procedures using an objective method, including the percentage of root coverage, root coverage esthetic scoring system, and subjective assessment by patient and clinician-based questionnaires. The results will be helpful for the understanding of the differences that exist in esthetic satisfaction.


Assuntos
Estética Dentária , Retração Gengival/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
17.
Clin Oral Implants Res ; 24 Suppl A100: 145-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22251085

RESUMO

OBJECTIVE: This study assessed the osseointegration of grit-blasted titanium (Ti) implants with a hydrophilic phosphate ion-incorporated oxide surface in rabbit cancellous bone, and compared its bone healing with commercially available phosphate-incorporated clinical implants obtained by micro-arc oxidation (TiUnite, TU implant). MATERIAL AND METHODS: The hydrophilic phosphate-incorporated Ti surface (P implant) was produced by hydrothermal treatment on grit-blasted moderately rough-surfaced clinical implant. The TU surface was used as a control. The surface characteristics were evaluated by field emission-scanning electron microscopy, X-ray photoelectron spectroscopy, optical profilometry, and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Thirty-two threaded implants with lengths of 10 and 3.3 mm diameter (16 P implants and 16 TU implants) were placed in the femoral condyles of 16 New Zealand White rabbits. Histomorphometric analysis, removal torque tests, and surface analysis of the torque-tested implants were performed 4 weeks after implantation. RESULTS: The P and TU implants displayed micro-rough surface features with similar Ra values at the micron-scale. ICP-AES analysis revealed that both the P and TU implants released phosphate ions into the solution. The torque-tested P and TU implants exhibited a considerable quantity of bone attached to the surface. The P implants exhibited significantly higher bone-implant contact percentages, both in terms of the all threads region and the total lateral length of implants compared with the TU implants (P < 0.01), but no statistical difference was found for the removal torque values. CONCLUSION: These results suggest that the phosphate-incorporated Ti oxide surface obtained by hydrothermal treatment achieves rapid osseointegration in cancellous bone by increasing the degree of bone-implant contact.


Assuntos
Implantação Dentária Endóssea/métodos , Implantes Dentários , Osseointegração/fisiologia , Titânio/química , Animais , Implantes Experimentais , Íons , Masculino , Microscopia Eletrônica de Varredura , Osteotomia , Espectroscopia Fotoeletrônica , Coelhos , Espectrofotometria Atômica , Propriedades de Superfície , Torque
18.
Clin Oral Implants Res ; 24(6): 706-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22409778

RESUMO

OBJECTIVE: It is unclear whether surface bioactive chemistry or hydrophilicity plays a more dominant role in the osseointegration of micro-structured titanium implants having the same surface topography at the micrometer and submicrometer scales. To understand their comparative effect on enhancing the early osseointegration of micro-rough-surfaced implants, this study compared the bone healing-promoting effect of surface strontium (Sr) chemistry that has been shown in numerous studies to super-hydrophilicity in the early osseointegration of moderately rough-surfaced clinical oral implants (SLA(®) implant) in rabbit cancellous bone. MATERIAL AND METHODS: Hydrothermal treatment was performed to incorporate Sr ions into the surface of clinical SLA implants (SLA/Sr implant). The surface characteristics were evaluated by using field emission-scanning electron microscopy, X-ray photoelectron spectroscopy and optical profilometry. Twenty screw implants (10 control and 10 experimental) were placed in the femoral condyles of 10 New Zealand White rabbits. The early osseointegration of the SLA/Sr implant was compared with a chemically modified super-hydrophilic SLA implant (SLActive(®) implant) by histomorphometric and resonance frequency analysis after 2 weeks of implantation. RESULTS: The SLA/Sr and SLActive implants exhibited an identical surface topography and average R(a) values at the micron and submicron scales. The SLA/Sr implant displayed a high amount of surface Sr content (15.6 at.%). There was no significant difference in the implant stability quotient (ISQ) values between the two groups. However, histomorphometric analysis revealed a significantly higher bone-to-implant contact percentage in the SLA/Sr implants compared with the SLActive implants in rabbit cancellous bone (P < 0.01). CONCLUSION: The results indicate that the surface Sr chemistry surpasses the effect of super-hydrophilicity in promoting the early bone apposition of moderately rough Ti surface in cancellous bone.


Assuntos
Implantes Dentários , Osseointegração/efeitos dos fármacos , Estrôncio/química , Titânio/química , Animais , Fêmur/cirurgia , Interações Hidrofóbicas e Hidrofílicas , Masculino , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica , Coelhos , Propriedades de Superfície
19.
J Oral Maxillofac Surg ; 71(9): 1577-87, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23800674

RESUMO

PURPOSE: The purpose of the present study was to investigate whether asymmetric mandibular prognathism accompanies a fundamental difference in soft tissue thickness and whether asymmetric mandibular setback surgery would influence the contour and thickness of the soft tissue of the chin. MATERIALS AND METHODS: The present retrospective study included skeletal class III patients with significant mandibular chin deviation greater than 6 mm at the pogonion, who had undergone cone-beam computed tomography before and 6 months after surgery during a 2-year period. The predictor variables were timing (pre- and postoperatively) and side (asymmetric vs contralateral). The outcome measures were the hard and soft tissue contours and soft tissue thickness of the chin at the infradentale, B-point, and pogonion level evaluated with reformatted computed tomography images. The study variables were statistically compared using regression model and correlation analysis. RESULTS: The present study consisted of 20 patients (10 males and 10 females; average age 20.2 years; range, 18 to 25). Preoperatively, the chin deviation side showed a more prominent hard and soft tissue outline but had a thinner soft tissue thickness, which camouflaged the hard tissue asymmetry. After surgery, the hard and soft tissue outline was greatly improved, and the soft tissue thickness had become nearly symmetric. Most of the soft tissue thickness changes correlated negatively with the hard tissue changes. CONCLUSIONS: Asymmetric mandibular prognathism accompanied the 3-dimensional soft tissue contour and thickness asymmetry. Because the soft tissue responds favorably after skeletal surgery, the correction of 3-dimensional asymmetry of bone should be emphasized in patients with asymmetric mandibular prognathism.


Assuntos
Face , Assimetria Facial/cirurgia , Mandíbula/cirurgia , Prognatismo/cirurgia , Adolescente , Adulto , Cefalometria/métodos , Queixo/patologia , Tomografia Computadorizada de Feixe Cônico/métodos , Meato Acústico Externo/patologia , Assimetria Facial/patologia , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Incisivo/patologia , Masculino , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/patologia , Osso Nasal/patologia , Órbita/patologia , Osteotomia Sagital do Ramo Mandibular/métodos , Estudos Retrospectivos , Sela Túrcica/patologia , Resultado do Tratamento , Adulto Jovem
20.
J Biomater Appl ; 37(7): 1228-1242, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36205350

RESUMO

This study evaluated surface characteristics and biocompatibility of surface-modified thin titanium (Ti) foils as a regenerative barrier membrane for future application in guided bone regeneration (GBR) surgery to augment atrophic alveolar bone. Anodic oxidation and post-heat treatment were performed to prepare various Ti foil samples. Then, the in vitro soft and hard tissue compatibility of the samples was evaluated by examining the cell responses using primary human gingival fibroblasts (HGFs) and MG63 human osteoblast-like cells. Investigated Ti foil samples showed marked differences in physicochemical surface properties. Additional 400°C heat treatment applied to the anodized Ti surface led to formation of an anatase titanium dioxide structure and well-organized nanoscale protrusions, and significantly increased surface wettability. Anodization and heat treatment enhanced the growth of HGFs and MG63 cells in Ti foil samples. Additional heat treatment for 10 and 30 min further significantly improved the response of HGFs including spreading and proliferation, and upregulated the mRNA expression of cell adhesion- and maturation-related genes as well as the osteoblast differentiation of MG63 cells. Ti foil sample with thin oxide coating obtained by a 30 min heat treatment exhibited poor clinical plasticity as a regenerative barrier membrane, which showed complete coating failure in the bending test. Our results indicate that anatase Ti oxide coating of a specific film thickness with nanoscale surface protrusion morphology and hydrophilic characteristics obtained by anodization and post-heat treatment would be an effective approach as a biocompatible Ti regenerative membrane for inducing better regeneration of both gingival tissue and bone.


Assuntos
Regeneração Óssea , Titânio , Humanos , Titânio/química , Propriedades de Superfície , Adesão Celular , Óxidos/metabolismo , Osteoblastos , Proliferação de Células
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