RESUMO
We report here a new class of biological reagents derived from luminescent rhenium(I) polypyridine complexes modified with a poly(ethylene glycol) (PEG) pendant. The PEG-amine complexes [Re(N(^)N)(CO)(3)(py-PEG-NH(2))](PF(6)) (py-PEG-NH(2) = 3-amino-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine, MW(PEG) = 5000 Da, PDI(PEG) < 1.08; N(^)N = 1,10-phenanthroline (phen) (1-PEG-NH(2)), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)-phen) (2-PEG-NH(2)), 4,7-diphenyl-1,10-phenanthroline (Ph(2)-phen) (3-PEG-NH(2))) and [Re(bpy-PEG)(CO)(3)(py-NH(2))](PF(6)) (bpy-PEG = 4-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine; py-NH(2) = 3-aminopyridine) (4-PEG-NH(2)) have been synthesized and characterized. The photophysical properties, lipophilicity, water solubility, cytotoxic activity, and cellular uptake properties of these complexes have been compared to those of their PEG-free counterparts [Re(N(^)N)(CO)(3)(py-Et-NH(2))](PF(6)) (py-Et-NH(2) = 3-amino-5-(N-(ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-Et-NH(2)), Me(4)-phen (2-Et-NH(2)), Ph(2)-phen (3-Et-NH(2))) and [Re(bpy-Et)(CO)(3)(py-NH(2))](PF(6)) (bpy-Et = 4-(N-(ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine) (4-Et-NH(2)). The PEG complexes exhibited significantly higher water solubility and lower cytotoxicity (IC(50) = 6.6 to 1152 µM) than their PEG-free counterparts (IC(50) = 3.6 to 159 µM), indicating that the covalent attachment of a PEG pendant to rhenium(I) polypyridine complexes is an effective way to increase their biocompatibility. The amine complexes 1-PEG-NH(2)-4-PEG-NH(2) have been activated with thiophosgene to yield the isothiocyanate complexes [Re(N(^)N)(CO)(3)(py-PEG-NCS)](PF(6)) (py-PEG-NCS = 3-isothiocyanato-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-NCS), Me(4)-phen (2-PEG-NCS), Ph(2)-phen (3-PEG-NCS)), and [Re(bpy-PEG)(CO)(3)(py-NCS)](PF(6)) (py-NCS = 3-isothiocyanatopyridine) (4-PEG-NCS) as a new class of luminescent PEGylation reagents. To examine their PEGylation properties, these isothiocyanate complexes have been reacted with a model substrate n-butylamine, resulting in the formation of the thiourea complexes [Re(N(^)N)(CO)(3)(py-PEG-Bu)](PF(6)) (py-PEG-Bu = 3-n-butylthioureidyl-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-Bu), Me(4)-phen (2-PEG-Bu), Ph(2)-phen (3-PEG-Bu)), and [Re(bpy-PEG)(CO)(3)(py-Bu)](PF(6)) (py-Bu = 3-n-butylthioureidylpyridine) (4-PEG-Bu). Additionally, bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with the isothiocyanate complexes to yield bioconjugates 1-PEG-BSA-4-PEG-BSA and 1-PEG-PEI-4-PEG-PEI, respectively. Upon irradiation, all the PEGylated BSA and PEI conjugates exhibited intense and long-lived emission in aqueous buffer under ambient conditions. The DNA-binding and polyplex-formation properties of conjugate 3-PEG-PEI have been studied and compared with those of unmodified PEI. Furthermore, the in vivo toxicity of complex 3-PEG-NH(2) and its PEG-free counterpart 3-Et-NH(2) has been investigated using zebrafish embryos as an animal model. Embryos treated with the PEG complex at high concentrations revealed delayed hatching, which has been ascribed to hypoxia as a result of adhering of the complex to the external surface of the chorion.
Assuntos
Complexos de Coordenação/síntese química , Polietilenoglicóis/química , Rênio/química , Água/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Embrião não Mamífero/efeitos dos fármacos , Células HeLa , Humanos , Concentração Inibidora 50 , Luminescência , Microscopia Confocal , Modelos Animais , Estrutura Molecular , Fotoquímica , Solubilidade , Peixe-ZebraRESUMO
The temporomandibular joint (TMJ) is a synovial joint involved in sliding and hinge movements of lower jaw in mammals. Studies on TMJ development in embryos have been mainly performed using rodents. However, the TMJ structure in rodents differs in several aspects from that in humans. There are few studies on the embryonic development of TMJ in large mammals. In the present study, we investigated the embryonic developmental characteristics of the TMJ in pigs histologically. Embryonic day 35 (E35), E45, E55, E75, E90, and postnatal day 1(P1) embryos/fetuses from the pigs were used for the study. The results showed condensation of mesenchymal cells on E35. The inferior articular cavity was formed on E45, together with a narrow crack in the superior articular cavity region. The superior and inferior articular cavities and articular disc of the TMJ were completely formed on E55. On E75, the condyle showed an obvious conical shape and the superior and inferior joint cavities were enlarged. Furthermore, the mandibular ramus and mandibular body under the neck of the condyle were ossified from E75 to P1 day. The chondrocyte layer of the condyle was significantly thinner from E75 to P1. It is speculated that the spatiotemporal development of the TMJ in miniature pig embryos is similar to that in humans. Embryonic development of the pig TMJ is an important bridge for translating the results of rodent research to medical applications.
Assuntos
Arcada Osseodentária , Articulação Temporomandibular , Animais , Condrócitos , Osteogênese , Suínos , Porco MiniaturaRESUMO
We report the synthesis, characterization, and photophysical properties of a new class of luminescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N--C)(2)(N--N)](PF(6)) (HN--C=Hppy (2-phenylpyridine), N--N=bpy-CONH-PEG1 (bpy=2,2'-bipyridine; 1a), bpy-CONH-PEG3 (1b); HN--C=Hpq (2-phenylquinoline), N--N=bpy-CONH-PEG1 (2a), bpy-CONH-PEG3 (2b); HN--C=Hpba (4-(2-pyridyl)benzaldehyde), N--N=bpy-CONH-PEG1 (3)) and their PEG-free counterparts (N--N=bpy-CONH-Et, HN--C=Hppy (1c); HN--C=Hpq (2c)). The cytotoxicity and cellular uptake of these complexes have been investigated by the MTT assay, ICPMS, laser-scanning confocal microscopy, and flow cytometry. The results showed that the complexes supported by the water-soluble PEG can act as biological probes and labels with considerably reduced cytotoxicity. Because the aldehyde groups of complex 3 are reactive toward primary amines, the complex has been utilized as the first luminescent PEGylation reagent. Bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with this complex, and the resulting conjugates have been isolated, purified, and their photophysical properties studied. The DNA-binding and gene-delivery properties of the luminescent PEI conjugate 3-PEI have also been investigated.
Assuntos
Irídio/química , Compostos Organometálicos/síntese química , Polietilenoglicóis/química , Polímeros/química , Soroalbumina Bovina/química , Animais , Bovinos , Eletroquímica , Irídio/toxicidade , Luminescência , Estrutura Molecular , Compostos Organometálicos/química , Compostos Organometálicos/toxicidade , Polietilenoglicóis/toxicidade , Ligação Proteica , Soroalbumina Bovina/metabolismoRESUMO
Luminescent dendritic cyclometalated iridium(III) polypyridine complexes [{Ir(N--C)(2)}(n)(bpy-n)](PF(6))(n) (HN--C = 2-phenylpyridine, Hppy, n = 8 (ppy-8), 4 (ppy-4), 3 (ppy-3); HN--C = 2-phenylquinoline, Hpq, n = 8 (pq-8), 4 (pq-4), 3 (pq-3)) have been designed and synthesized. The properties of these dendrimers have been compared to those of their monomeric counterparts [Ir(N--C)(2)(bpy-1)](PF(6)) (HN--C = Hppy (ppy-1), Hpq (pq-1)). Cyclic voltammetric studies revealed that the iridium(IV/III) oxidation and bpy-based reduction occurred at about +1.24 to +1.29 V and -1.21 to -1.27 V versus SCE, respectively, for all the complexes. The molar absorptivity of the dendritic iridium(III) complexes is approximately proportional to the number of [Ir(N--C)(2)(N--N)] moieties in one complex molecule. However, the emission lifetimes and quantum yields are relatively independent of the number of [Ir(N--C)(2)(N--N)] units, suggesting negligible electronic communications between these units. Upon photoexcitation, the complexes displayed triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(bpy-n)) emission. The interaction of these complexes with plasmid DNA has been investigated by agarose gel retardation assays. The results showed that the dendritic iridium(III) complexes, unlike their monomeric counterparts, bound to the plasmid, and the interaction was electrostatic in nature. The lipophilicity of all the complexes has been determined by reversed-phase high-performance liquid chromatography (HPLC). Additionally, the cellular uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cell line has been examined by inductively coupled plasma mass spectrometry (ICP-MS), laser-scanning confocal microscopy, and flow cytometry. Upon internalization, all the complexes were localized in the perinuclear region, forming very sharp luminescent rings surrounding the nuclei. Interestingly, in addition to these rings, HeLa cells treated with the dendritic iridium(III) complexes showed specific labeled compartments, which have been identified to be the Golgi apparatus. Furthermore, the cytotoxicity of these iridium(III) complexes has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.
Assuntos
Dendritos/química , Irídio/química , Luminescência , Compostos Organometálicos/farmacologia , Piridinas/química , Proliferação de Células/efeitos dos fármacos , DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Complexo de Golgi/química , Células HeLa , Humanos , Organelas/efeitos dos fármacos , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Plasmídeos/efeitos dos fármacos , Polímeros/química , Relação Estrutura-AtividadeRESUMO
To resolve the problems of bacterial infections and the low efficiency of osteogenesis of implanted titanium alloys in clinical dental and bone therapy, we developed a bifunctional titanium alloy (Ti) with a nano-hydroxyapatite (HA) coating (HBD + BMP/HA-Ti), which enables the sustained release of the natural antimicrobial peptide human ß-defensin 3 (HBD-3) and bone morphogenetic protein-2 (BMP-2). Due to the poriferous nano-sized structure of the HA coating with a 20-30 µm thickness, the HBD + BMP/HA-Ti material had a high encapsulation efficiency (>74%) and exhibited synchronized slow release of HBD-3 and BMP-2. In an antibacterial test, HBD + BMP/HA-Ti prevented the growth of bacteria in an inoculated medium, and its surface remained free from viable bacteria after a continuous incubation with Gram-negative and Gram-positive strains for 7 days. Furthermore, good adhesion, proliferation and osteogenic differentiation of hBMSCs in contact with HBD + BMP/HA-Ti were achieved in 7 days. Therefore, the bifunctional titanium alloy HBD + BMP/HA-Ti has a great potential for eventual applications in the protection of implants against bacteria in the orthopaedic and dental clinic.
Assuntos
Antibacterianos , Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Hidroxiapatitas , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Titânio , Antibacterianos/química , Antibacterianos/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Hidroxiapatitas/química , Hidroxiapatitas/farmacologia , Células-Tronco Mesenquimais/citologia , Propriedades de Superfície , Titânio/química , Titânio/farmacologiaRESUMO
Two novel photoactivatable mitochondria-targeting luminescent iridium(III) poly(ethylene glycol) (PEG) complexes incorporated with a nitrobenzyl group were designed. They showed minimal cytotoxic activity in the dark, but became significantly cytotoxic upon irradiation due to the release of the PEG pendants.
Assuntos
Antineoplásicos/isolamento & purificação , Irídio/química , Mitocôndrias/efeitos dos fármacos , Nitrobenzenos/química , Polietilenoglicóis/química , Antineoplásicos/química , LuminescênciaRESUMO
We report the synthesis, characterization, photophysical and electrochemical behaviour and biological labelling applications of new phosphorogenic bioorthogonal probes derived from iridium(III) polypyridine complexes containing a 1,2,4,5-tetrazine moiety. In contrast to common luminescent cyclometallated iridium(III) polypyridine complexes, these tetrazine complexes are almost non-emissive due to effective Förster resonance energy transfer (FRET) and/or photoinduced electron transfer (PET) from the excited iridium(III) polypyridine unit to the appended tetrazine moiety. However, they exhibited significant emission enhancement upon reacting with (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) (ca. 19.5-121.9 fold) and BCN-modified bovine serum albumin (BCN-BSA) (ca. 140.8-1133.7 fold) as a result of the conversion of the tetrazine unit to a non-quenching pyridazine derivative. The complexes were applied to image azide-modified glycans in live cells using a homobifunctional crosslinker, 1,13-bis((1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonylamino)-4,7,10-trioxatridecane (bis-BCN).
Assuntos
Materiais Biocompatíveis/síntese química , Meios de Contraste/síntese química , Transferência Ressonante de Energia de Fluorescência/métodos , Irídio/química , Microscopia de Fluorescência/métodos , Desenho de Fármacos , Teste de Materiais , Coloração e Rotulagem/métodosRESUMO
PURPOSE: To summarize the clinical and imaging features of malignant tumors in parotid gland. METHODS: Four hundred and twelve cases were collected in the department of oral and maxillofacial surgery and department of otolaryngology head & neck surgery of general hospital of Chinese PLA and department of oral and maxillofacial surgery of first affiliated hospital of Dalian medical university. RESULTS: The top three malignant tumors were mucoepidermoid carcinoma, adenoid cystic carcinoma and acinic cell carcinoma in parotid gland. Of all the collected cases, 73.1% had certain symptoms or recent rapid growth, 58% had tough quality, 66.2% had poor mobility, 32.3% had unclear boundary and 36.8% had pain. Of all cases with imaging examination, 74.2% and 68.7% demonstrated irregular shapes in CT and ultrasound imaging, respectively. The accuracy was 83.7% and 91.8% for fine-needle aspiration cytology and frozen section examination in diagnosis, respectively. The accuracy was 79.4% for frozen section examination in diagnosis of highly malignant tumors in parotid gland. CONCLUSIONS: There are diverse pathological types of malignant tumors in parotid gland. The clinical and imaging features are helpful to diagnosis. The accuracy is high in diagnosis of malignant tumors in parotid gland by fine-needle aspiration cytology and frozen section examination.
Assuntos
Carcinoma Adenoide Cístico , Neoplasias Parotídeas , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Humanos , Glândula Parótida , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Estudos Retrospectivos , Cirurgia BucalRESUMO
PURPOSE: This study was to investigate the effect of the digital computer-assisted technique in orthognathic surgery. METHODS: Twelve patients from January 2008 to December 2011 with jaw malformation were treated in our department. With the help of CT and three-dimensional reconstruction technique, 12 patients underwent surgical treatment and the results were evaluated after surgery. RESULTS: Digital computer-assisted technique could clearly show the status of the jaw deformity and assist virtual surgery. After surgery all patients were satisfied with the results. CONCLUSIONS: Digital orthognathic surgery can improve the predictability of the surgical procedure, and to facilitate patients' communication, shorten operative time, and reduce patients' pain.
Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Dor Pós-Operatória/prevenção & controle , Cirurgia Assistida por ComputadorRESUMO
Osteoporosis deteriorates jaw bone quality and may compromise early implant osseointegration and early implant loading. The influence of lowmagnitude, highfrequency (LMHF) vibration on periimplant bone healing and implant integration in osteoporotic bones remains poorly understood. LMHF loading via wholebody vibration (WBV) for 8 weeks has previously been demonstrated to significantly enhance bonetoimplant contact, periimplant bone fraction and implant mechanical properties in osteoporotic rats. In the present study, LMHF loading by WBV was performed in osteoporotic rats, with a loading duration of 4 weeks during the early stages of bone healing. The results indicated that 4week LMHF loading by WBV partly reversed the negative effects of osteoporosis and accelerated early periimplant osseointegration in ovariectomized rats.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osseointegração/efeitos dos fármacos , Vibração/uso terapêutico , Animais , Densidade Óssea/efeitos dos fármacos , Feminino , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ovariectomia/métodos , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Titânio/farmacologiaRESUMO
This study was designed to investigate the effects of occlusal splints in the treatment of sagittal fractures of the mandibular condyle in children. From January 1995 to December 2011, 37 sagittal fractures of the mandibular condyle in 30 patients aged 4-8 years old were included in this study. All the patients were treated with 1-2mm occlusal splints in the molar region. The mouths of the patients were kept slightly open by the occlusal splints for 3-6 months, and we reviewed the clinical and radiological remodelling of the affected condyles after treatment. Excellent (n=20) and good (n=10) clinical outcomes were achieved with full radiological remodelling seen in 19 and partial remodelling in 11. Treatment with occlusal splints is effective in delivering good results and function with minimal morbidity in children with sagittal fractures of the condyle, while permitting ongoing remodelling and growth in the short term.
Assuntos
Côndilo Mandibular/lesões , Fraturas Mandibulares/terapia , Placas Oclusais , Remodelação Óssea/fisiologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Masculino , Mandíbula/crescimento & desenvolvimento , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/crescimento & desenvolvimento , Fraturas Mandibulares/diagnóstico por imagem , Desenho de Aparelho Ortodôntico , Radiografia Panorâmica/métodos , Amplitude de Movimento Articular/fisiologia , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/patologia , Tomografia Computadorizada Espiral/métodos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the chemical composition of the zinc modified surface of implanted titanium and to assess its effect on the antibacterial activity in vitro. METHODS: Pure commercial titanium discs were modified with zinc by plasma immersion ion implantation and deposition (PIIID) technique. The surfaces were characterized by X-ray photoelectron spectrometer. To measure the bacterial responses, S. mutans were seeded onto the surfaces of discs in 24-well culture plates at a density of 1×10(9) CFU/mL and observed by a scanning electron microscope. The statistical significance of difference was assessed by ANOVA using SPSS 13.0 software package, followed by a Bonferroni test. RESULTS: The full range XPS indicated that the main difference of zinc PIIID on the disc was the appearance of the signals of zinc and oxygen. At the same time, the relative atomic concentration of zinc increased gradually with the implanting time, the concentration of zinc in Zn-Ti-80 min group being the highest among the groups. The zinc implanted titanium could affect adherence and the form of S.mutans. The adherence amount of bacteria in Zn-Ti-60 min and -80 min group was significantly less than those in cp-Ti group, Zn-Ti-20 min and -40 min group. CONCLUSIONS: PIIID can successfully introduce zinc into pure titanium surface, which can change adherence and the form of S.mutans slightly.
Assuntos
Implantes Dentários , Titânio , Zinco , Antibacterianos , Propriedades de SuperfícieRESUMO
OBJECTIVE: To investigate the clinical results of occlusal splint in the treatment of sagittal fracture of mandibular condyle (SFMC) in children. METHODS: Thirty-nine patients (48 condyles)aged 3-8 years with sagittal fracture of mandibular condyle were included in this study. All the patients were treated by occlusal splint.Slight open occlusion was maintained by occlusal splint for 3-6 months. Clinical and radiological examination was performed six mouths and every year after treatment. RESULTS: Good mandibular function was observed in 39 patients. Maximal mouth opening over 35 mm was achieved at 6 months. But 11 of the 39 patients presented with deviation on mouth opening at 6 months. The radiology showed an complete remodeling in 32 condyles (28 patients) and partial remodeling in 16 condyles (11 patients). Poor remodelling was not observed in any patients. CONCLUSIONS: Good clinical results can be obtained by using occlusal splint in the treatment of pediatric sagittal fracture of mandibular condyle.
Assuntos
Côndilo Mandibular/lesões , Fraturas Mandibulares/terapia , Placas Oclusais , Criança , Pré-Escolar , Oclusão Dentária , Feminino , Seguimentos , Humanos , Masculino , Côndilo Mandibular/fisiologia , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/fisiopatologia , Recuperação de Função Fisiológica , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To analyze the clinical features, pathological classification, causes of misdiagnosis, treatment and prognosis of non-Hodgkin's lymphoma (NHL) originated in head and neck and to afford experience in early diagnosis and treatment. METHODS: The clinical manifestation , treatment and prognosis of 138 cases of primary head and neck NHL were studied retrospectively. RESULTS: The incidence in male was higher than that in female (male:female=1.26:1). Among non-Hodgkin's lymphomas, 86.2% were neoplasms originating from B lymphocytes,which was remarkably higher than those originating from T lymphocyte(13.8%). The early symptom was mainly painless mass(71.7%). The primary location was in the following order: cervical region, submandibular region , parotid gland, skin of face, maxilla and mandible, tongue and palate. The main treatment was multimodal therapy(chemotherapy and operations).The five- year survival rate was 59.4%. CONCLUSIONS: The clinical manifestation of head and neck NHL is not specific and has a high misdiagnosis rate,so we must pay more attention to improve the early diagnosis and treatment of NHL.