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OBJECTIVE: To study the effect of bone morphogenetic protein (BMP) antagonist Gremlin 1 (GREM1) on the function of stem cells from apical papilla (SCAPs) and explore its mechanism. METHODS: After isolation and culturing of stem cells from apical papilla in vitro, immunofluorescent staining was done to examine the subcellular localization of GREM1 in SCAPs. Transfection with lentiviral GREM1 shRNA was done to knock-down the GREM1. The SCAPs were subjected to osteogenic induction in both the GREM1 knockdown group and the control group, and the knockdown effect of GREM1 was examined using real time-PCR and Western blot. Two groups of cells were collected and the alkaline phosphatase (ALP) activity was measured 7 d after osteogenic induction. Alizarin red staining was done 3 weeks after osteogenic/odontogenic induction and real time-PCR was done after 0, 1, 2, 3 weeks of osteogenic induction to examine the expression of osteogenic/odontogenic marker genes, including osteocalcin ( OCN), osteopontin ( OPN), bone sialoprotein ( BSP), dentin matrix protein 1 ( DMP1), dentin sialophosphoprotein ( DSPP) and and the critical transcription factor osterix ( OSX), Runt-related transcription factor 2 ( RUNX2), and distal-less homebox 2 ( DLX2). Two groups of cells were collected, and CCK-8 and CFSE assay were used to evaluate changes in cell proliferation. In addition, real time-PCR was used to examine the expression of senescence-related genes p53 and wide-type activated factor 1 ( Waf1), a regulatory factor of the cell cycle, stemness associated gene krupple-like factor 4 ( KLF4), and SRY related HMG box-2 ( SOX2), and the expression of bone morphogenetic protein ( BMP) 2, 4, 5, 6, 7, 9 after GREM1 knockdown. RESULTS: Immunofluorescence staining showed that the expression of GREM1 in the nucleus was higher than that in the cytoplasm. Real time-PCR and Western blot affirmed that GREM1 was knocked down steadily. The ALP activity of the GREM1 knockdown group was higher than that of the control group ( P<0.05), and the alizarin red staining was lighter than that of the control group. The expression of OCN and DMP1 increased in the first, second and third week, OPN was increased in the second week, BSP increased in the third week, DSPP increased in the first week, and the difference was statistically significant ( P<0.05). The key osteogenic transcription factors RUNX2, OSX, and DLX2 all increased at different stages, and the difference was statistically significant ( P<0.05). CCK-8 and CFSE assay showed that the proliferation ability of the GREM1 knockdown group decreased ( P<0.05). In the GREM1 knockdown group, the expression of BMP2, 6, and 7 increased, the expression of SOX2 and KLF4 increased, while the expression of p53 and Waf1 decreased ( P<0.05). CONCLUSIONS: The knockdown of GREM1 enhanced the osteogenic/odontogenic differentiation and stemness of SCAPs and inhibited the proliferation and senescence of SCAPs. Effects of GREM1 on the function of SCAPs maybe achieved through regulating the gene expression of BMP2, BMP6, and BMP7 at the mRNA level.
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Odontogénesis , Osteogénesis , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Células MadreRESUMEN
PURPOSE: The complex physiological barriers impose extremely conflicting demands on systemic drug delivery, so both particle size and surface charge of the nanoplatforms become vital factors. As a carbon-based nanomaterial with excellent optical properties, carbon dots are not suitable for direct systemic transport in vivo, which limits their application in the field of biomedical imaging, especially in the areas of diagnosis and cancer treatment. Liposomes have been developed as universal nanocarriers for various drugs. In this study, we aimed to build a highly precise and penetrative drug delivery system (DDS) using carbon dots encapsulated by liposomes. METHODS: Carbon dots (CDs) were synthesized by the hydrothermal method using citric acid and ethylenediamine. Furthermore, simian virus 40 large T-antigen derived the nuclear targeting sequence (NLS) was bonded on the surface of CDs to obtain CDs-NLS. The antitumor drug doxorubicin was loaded onto the CDs-NLS through an acid-labile hydrazine bond to obtain DOX@CDs. Finally, DOX@CDs were encapsulated in aqueous centers of folate-coated and pH-sensitive liposomes, named pHSL-FA. RESULTS: In this paper, a nucleus-targeted nanocomposite (DOX@CDs), which bonds with the nuclear targeting sequence (NLS) and the anticancer drug doxorubicin (DOX), has physicochemical properties of particle size of about 3.8 nm, zeta potential of +31.8 mV and high quantum yield of 64.53%. The negatively charged folate-coated and pH-sensitive liposomes (pHSL-FA) are used as a carrier to reverse the surface charge of DOX@CDs. Compared to free DOX@CDs, pHSL-FA show higher tumor accumulation in 4 T1 tumor-bearing mice and further improve cytotoxicity to tumor cells. CONCLUSIONS: This work proposes a unique nanomedical approach that enables the precise delivery of chemotherapy drugs and significantly reduces side effects, which is promising for clinical translation.
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Antibióticos Antineoplásicos/administración & dosificación , Carbono/química , Doxorrubicina/administración & dosificación , Ácido Fólico/metabolismo , Lípidos/química , Neoplasias/tratamiento farmacológico , Puntos Cuánticos , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Composición de Medicamentos , Femenino , Ácido Fólico/química , Transportadores de Ácido Fólico/metabolismo , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Inyecciones Intravenosas , Liposomas , Ratones Endogámicos BALB C , Neoplasias/metabolismo , Neoplasias/patología , Propiedades de Superficie , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Malignant glioma is the most common and deadliest brain cancer due to the obstacle from indistinct tumor margins for surgical excision and blood brain barrier (BBB) for chemotherapy. Here, we designed and prepared multifunctional polyethylenimine-entrapped gold nanoparticles (Au PENPs) for targeted SPECT/CT imaging and radionuclide therapy of glioma. RESULTS: Polyethylenimine was selected as a template for sequential modification with polyethylene glycol (PEG), glioma-specific peptide (chlorotoxin, CTX) and 3-(4-hydroxyphenyl)propionic acid-OSu (HPAO), and were then used to entrap gold nanoparticles (Au NPs). After 131I radiolabeling via HPAO, the 131I-labeded CTX-functionalized Au PENPs as a multifunctional glioma-targeting nanoprobe were generated. Before 131I radiolabeling, the CTX-functionalized Au PENPs exhibited a uniform size distribution, favorable X-ray attenuation property, desired water solubility, and cytocompatibility in the given Au concentration range. The 131I-labeled CTX-functionalized Au PENPs showed high radiochemical purity and stability, and could be used as a nanoprobe for the targeted SPECT/CT imaging and radionuclide therapy of glioma cells in vitro and in vivo in a subcutaneous tumor model. Owing to the unique biological properties of CTX, the developed nanoprobe was able to cross the BBB and specifically target glioma cells in a rat intracranial glioma model. CONCLUSIONS: Our results indicated that the formed nanosystem had the significant potential to be applied for glioma targeted diagnosis and therapy.
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Sistemas de Liberación de Medicamentos , Glioma/diagnóstico por imagen , Glioma/radioterapia , Nanopartículas del Metal , Venenos de Escorpión , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Oro , Humanos , Masculino , Ratones , Péptidos , Polietileneimina , Ratas , Ratas Sprague-Dawley , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
PURPOSE: The addition of a braided bio-absorbable vicryl coating to the surface of radioactive seeds used for low dose rate (LDR) prostate brachytherapy is intended to reduce the incidence of seed movement and migration. Here, we present a single-institution study of the frequency and severity of seed slippage (initial seed movement) of coated seeds in comparison with uncoated seeds. METHODS: Forty-seven patients received permanent prostate brachytherapy, with either coated (n = 26) or uncoated (n = 21) seeds. AgX100 125 I seeds, coated or uncoated, and uncoated Model 200 103 Pd seeds were used. During the ultrasound-guided implantation procedure, each implanted seed was categorized as having remained in the implanted position after being placed, having moved slightly, or having left the ultrasound field of view. RESULTS: 3.1% of the coated seeds (AgX100 seeds, n = 70) and 6.9% of the uncoated seeds (AgX100 and Model 200 seeds, n = 128) were observed to have moved at least 2 mm from their initial implant positions, respectively. The difference in incidence of this movement was 54.4% (P = 0.0026). Coated AgX100 seeds demonstrated a 66.7% lower rate of movement of at least 2 mm than that for uncoated AgX100 seeds (P = 0.038), and a 49.0% lower rate than that for Model 200 seeds (P = 0.021). While no significant differences were noted in prescription dose coverage of the prostate or the studied dosimetric parameters for the organs at risk between the coated and uncoated seeds (P > 0.05) in the CT-based Day-0 postoperative plans, the limited sample size and differences in energies between the 125 I and 103 Pd seeds make further analysis of postoperative dosimetric coverage difficult without additional data directly comparing the coated and uncoated 125 I seeds. CONCLUSION: When the vicryl coating is used, seeds have a significantly lower propensity to slip from their initial implant locations. This may help maintain dosimetric integrity, warranting further study of postoperative dosimetry.
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Braquiterapia/instrumentación , Radioisótopos de Yodo/uso terapéutico , Movimiento (Física) , Siembra Neoplásica , Polímeros/química , Neoplasias de la Próstata/radioterapia , Prótesis e Implantes , Anciano , Estudios de Seguimiento , Migración de Cuerpo Extraño/diagnóstico por imagen , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Ultrasonografía/métodosRESUMEN
The effects of Tip-Edge plus appliance in the treatment of Angle II(1) malocclusion and the mechanism were investigated. Fifty-two Angle II(1) children, aged from 12.3-14.2 years, with mandibular retrusion in permanent dentition were selected and treated with Tip-Edge plus appliance. Lateral cephalometric films taken before and after treatment were analyzed. The arithmetic mean and standard deviation were calculated for each variable. Paired t-test was performed to evaluate the significant treatment change. Results showed that the average treatment time was 16 months. Normal overjet and overbite were established with retroclination of upper incisors and proclination of lower incisors. U1-NA was decreased by 15.4° (P<0.01). ANB and Y axial angle were decreased significantly (P<0.05). Soft tissue measurements showed that FCA and UL-E were decreased dramatically (P<0.05), and LL-E was increased significantly (P<0.05). Remarkable soft tissue change was noted after the treatment and convex facial profile changed to the straight profile. In conclusion, Tip-Edge plus technique can quickly and efficiently correct anterior bite and lateral outlook.
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Maloclusión Clase II de Angle/terapia , Aparatos Ortodóncicos , Adolescente , Niño , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To compare the difference of clinical and technical processes of full-crown restorations by using traditional and Triple-tray impression techniques, consumed materials and time estimated in every procedure of these two methods. METHODS: Four veteran clinicians were selected to carry out full-crown restorative treatment for 124 patients (130 crowns). From one impression, dentists could make casts of prepared teeth and the opposing dentition and register the interocclusal relationship.After tooth preparation,Impregum Penta polyether impression was fabricated for 76 cases(80 crowns) by Triple-tray method and 48 cases (50 crowns)by conventional method. During the whole processes, the consumption of impression materials and plaster, the time of fitting on the articulator, manufacturing procedure and try-in in clinical practice were recorded. The differences of material and time consumption in every procedure of these two methods were evaluated by Independent-Samples t test. RESULTS: The consumption of impression materials and plaster of Triple-tray impression technique was significantly less than that of traditional impression technique(P<0.01), and average time in every procedure of Triple-tray impression technique was remarkablely reduced compared with that of the traditional impression technique (P<0.01). Triple-tray impression technique reduces operating costs and the possibility of error. CONCLUSION: Compared with traditional impression technique, Triple-tray impression technique could reduce the consumption of time and materials in clinical and technical processes.
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Coronas , Materiales de Impresión Dental/química , Técnica de Impresión Dental , Humanos , Modelos Dentales , Factores de TiempoRESUMEN
OBJECTIVE: To observe the short-term effect of clinical application of Cerec 3D anterior crowns. METHODS: A total of 16 patients were restored with 31 Cerec 3D anterior crowns. All restorations were stained before cementation. The evaluation started 1 week after luting. The restorations were examined in accordance with the modified US Public Health Service (USPHS) criteria at baseline and every 6 - 12 months. RESULTS: The observation period of 31 Cerec 3D anterior crowns varied from 8 to 33 months. The mean observation period was 22 months. All restorations scored A or B by modified USPHS standard. And 22 out of 31 restorations scored A for all criteria while 8 restorations scored B in color matching. Slight differences of translucency and chroma could be observed. Between baseline and follow-up examinations, insignificant shift from A-to B-rating occurred. CONCLUSION: Cerec 3D anterior crowns may achieve favorable short-term esthetic effects.
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Coronas , Porcelana Dental , Reparación de Prótesis Dental/métodos , Estética Dental , Adolescente , Adulto , Diseño Asistido por Computadora , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
This study focused on the fouling characteristics evaluation of the sludge in a membrane bioreactor integrated with microbial fuel cell (MFC-MBR) to reveal the mechanisms of membrane fouling mitigation. The filtration of soluble microbial products (SMPs) in MFC-MBR showed lower flux decline rate than those in the control system (C-MBR). Based on the extended Derjaguin-Landau-Verwey-Overbeek analysis, decreases in free energies of adhesion between the SMPs and clean membrane or SMP-fouled membrane were observed in MFC-MBR. When approaching the clean membrane or SMP-fouled membrane, the SMPs in MFC-MBR had to overcome a higher energy barrier compared to those in C-MBR, indicating the inhibition of adsorption of SMPs on the membrane surface in MFC-MBR. Additionally, sludge flocs in MFC-MBR exhibited lower hydrophobicity and were less negative surface charged in comparison to those in the C-MBR. In MFC-MBR, the sludge flocs approaching the clean membrane, SMP-fouled membrane and cake layer all experienced higher energy barriers and lower secondary energy minimums compared to those in C-MBR, exhibiting the lower potential of cake layer formation. These results confirmed that decreases of the fouling potentials of SMPs and sludge flocs were essential for the membrane fouling mitigation in the MFC-MBR.
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Fuentes de Energía Bioeléctrica , Reactores Biológicos , Filtración , Interacciones Hidrofóbicas e Hidrofílicas , Membranas Artificiales , Aguas del Alcantarillado/análisisRESUMEN
In the present study, isoelectronic focusing with different pH gradients (pH 3-5, 2-6) or migrating distances (8.5, 12 and 17 cm) and SDS-PAGE was used to separate continuous erythropoietin receptor activator (CERA), recombinant human erythropoietin (rhEPO), darbepoetin and endogenous EPO spiked in human urine with 37 degrees C overnight incubation. Double blotting and chemiluminescent visualization were used to detect the IEF and SDS-PAGE profiles. The bands of CERA profile were detected and well separated from the endogenous EPO and the other two EPO preparations with both SDS-PAGE and the IEF method using a gradient pH 3-5 and a migrating distance of 17 cm, and a significant particular band of CERA profile was found in the IEF result. These preliminary results indicated that the methods were reliable and reproducible for detecting CERA, and could be used as a routine procedure for anti-doping analysis.
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Eritropoyetina/orina , Electroforesis en Gel de Poliacrilamida , Humanos , Focalización Isoeléctrica/métodos , Polietilenglicoles , Proteínas RecombinantesRESUMEN
Potential anti-cancer drugs are frequently of low efficacy in clinics due to the lack of predictive models or the insufficient employment of existing preclinical test systems. Three-dimensional (3D) in vitro engineered tumor models can better predict the efficacy of novel drugs by reproducing the in vivo tumor microenvironment. In this study, three sources of scaffolds (decellularized lung scaffold, chitosan/gelatin scaffold, and poly-L-lactic acid scaffold) incorporated with breast cancer cells (MCF-7, 4T1) were bioengineered as a platform to study in vitro solid tumor development. The good biocompatibility of three scaffolds favored cell growth and proliferation. Cells in 3D scaffolds were less sensitive to chemotherapy and exhibited characteristics of higher malignancy compared to their 2D counterparts. The expression of breast cancer biomarkers in MCF-7 cells markedly up-regulated in 3D scaffolds in comparison with those in 2D cultures. Cells grown in 3D scaffolds were found to be more tumorigenic and angiogenic in BABL/c mice xenografts than cells grown from monolayers. The results demonstrate that 3D engineered tumor model can better mimic in vivo tumor and can serve as a more appropriate platform for the study and screening of novel cancer therapeutics.
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Materiales Biocompatibles/farmacología , Ingeniería de Tejidos , Animales , Materiales Biocompatibles/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quitosano/química , Resistencia a Antineoplásicos/efectos de los fármacos , Matriz Extracelular/metabolismo , Fluorouracilo/farmacología , Gelatina/química , Humanos , Pulmón/citología , Ratones , Poliésteres/química , Porcinos , Andamios del Tejido , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy. Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I). Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo. Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.
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Oro/química , Radioisótopos de Yodo/química , Nanopartículas del Metal/química , Polietileneimina/química , Radiofármacos/uso terapéutico , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Coloides/química , Glioma/patología , Glioma/radioterapia , Humanos , Nanopartículas del Metal/ultraestructura , Ratones Endogámicos BALB C , Ratones Desnudos , Especificidad de Órganos , Tamaño de la Partícula , Propionatos/química , Venenos de Escorpión/toxicidadRESUMEN
BACKGROUND: This study assessed the impact of closed suction drains and evaluated whether the intraoperative use of a fibrin sealant decreased time to drain removal and wound complications in melanoma patients undergoing inguino-femoral lymph node dissection. METHODS: A pilot study (n = 18) assessed the impact of a closed suction drain following inguino-femoral lymph node dissection. A single-institution, prospective trial was then performed in which patients were randomized to a group that received intraoperative application of a fibrin sealant following inguino-femoral lymph node dissection or to a control group that did not receive sealant. RESULTS: The majority of the patients enrolled felt the drains caused moderate or severe discomfort and difficulties with activities of daily living. Thirty patients were then randomized; the median time to drain removal in the control group (n = 14) was 30 days (range, 13-74) compared to 29 days (range, 11-45) in the fibrin sealant group (n = 16; P = 0.6). Major and minor complications were similar in the two groups. CONCLUSION: Postoperative closed suction drains were associated with major patient inconvenience. Applying a fibrin sealant at the time of inguino-femoral lymph node dissection in melanoma patients did not reduce the time to drain removal or postoperative morbidity. Alternative strategies are needed.
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Escisión del Ganglio Linfático/efectos adversos , Melanoma/patología , Seroma/prevención & control , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Femenino , Adhesivo de Tejido de Fibrina/economía , Ingle , Humanos , Escisión del Ganglio Linfático/economía , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Seroma/etiología , Neoplasias Cutáneas/cirugía , Succión , Factores de Tiempo , Adhesivos Tisulares/economíaRESUMEN
In this study, we report the synthesis, characterization and utilization of 99mTc-labelled polyethylenimine-entrapped gold nanoparticles (99mTc-Au-PENPs) for dual mode single-photon emission computed tomography/computed tomography (SPECT/CT) imaging applications. Polyethylenimine (PEI) was selected as a platform to conjugate with diethylene triamine pentacetate acid (DTPA) and polyethylene glycol monomethyl ether to synthesize Au PENPs, followed by acetylation or hydroxylation modification of the remaining PEI surface amine groups and radiolabelling of 99mTc. The generated multifunctional 99mTc-Au-PENPs with different surface groups (acetyl or hydroxyl) were characterized via different methods. The Au PENPs before 99mTc labelling are colloidally stable, haemocompatibility and noncytotoxic at an Au concentration up to 100 µM. The 99mTc-labelled Au PENPs exhibit high radiochemical purity, good stability and SPECT/CT imaging performance of different organs and lymph node. The designed strategy to use the radionuclide labelling technique and PEI-facilitated versatile nanoplatform may be extended to develop various novel nanoprobes for precision imaging applications.
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Oro/química , Nanopartículas del Metal/química , Polietileneimina/química , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Tecnecio/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Marcaje Isotópico , Ensayo de Materiales , Ratones , Polietileneimina/farmacocinética , Polietileneimina/toxicidad , Conejos , Ganglio Linfático Centinela/diagnóstico por imagen , Distribución TisularRESUMEN
Non-invasive imaging of apoptosis in tumors induced by chemotherapy is of great value in the evaluation of therapeutic efficiency. In this study, we report the synthesis, characterization, and utilization of radionuclide technetium-99m (99mTc)-labeled dendrimer-entrapped gold nanoparticles (Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis. Generation five poly(amidoamine) (PAMAM) dendrimers (G5.NH2) were sequentially conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), polyethylene glycol (PEG) modified duramycin, PEG monomethyl ether, and fluorescein isothiocyanate (FI) to form the multifunctional dendrimers, which were then utilized as templates to entrap gold nanoparticles. Followed by acetylation of the remaining dendrimer surface amines and radiolabeling of 99mTc, the SPECT/CT dual mode nanoprobe of tumor apoptosis was constructed. The developed multifunctional Au DENPs before and after 99mTc radiolabeling were well characterized. The results demonstrate that the multifunctional Au DENPs display favorable colloidal stability under different conditions, own good cytocompatibility in the given concentration range, and can be effectively labeled by 99mTc with high radiochemical stability. Furthermore, the multifunctional nanoprobe enables the targeted SPECT/CT imaging of apoptotic cancer cells in vitro and tumor apoptosis after doxorubicin (DOX) treatment in the established subcutaneous tumor model in vivo. The designed duramycin-functionalized Au DENPs might have the potential to be employed as a nanoplatform for the detection of apoptosis and early tumor response to chemotherapy.
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Antineoplásicos/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Dendrímeros/síntesis química , Oro/química , Nanopartículas del Metal/química , Tecnecio/química , Animales , Bacteriocinas/administración & dosificación , Bacteriocinas/química , Línea Celular Tumoral , Dendrímeros/química , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Compuestos Heterocíclicos con 1 Anillo/química , Ratones , Ratones Desnudos , Péptidos/administración & dosificación , Péptidos/química , Polietilenglicoles/química , Ratas , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
At present, the majority of methods used for uric acid (UA) detection are not able to meet the detection requirements with speed, accuracy, high sensitivity, high specificity, a wide linear range or a low cost. Compared with other methods, the electrochemical method has a high sensitivity and fast detection. The present study aimed to identify an electrochemical sensor with high sensitivity, fast detection and a wide linear range for the detection of UA. A glassy carbon electrode modified with graphenemolybdenum disulfideNafion (GMoS2Nafion) composites was prepared for use as the working electrode. The morphologies and elemental compositions of the GMoS2 composites were characterized by field emission scanning electron microscopy, elemental distribution spectrometry and Xray diffraction, respectively. The electrochemical behaviors were investigated by cyclic voltammetry, linear sweep voltammetry and the amperometric it curve (it). The interference of glucose, ascorbic acid and dopamine, and the accuracy and precision of the electrochemical method were subsequently evaluated. The present study identified the following: (1) Only the reduction peak of UA was detected in human serum, indicating that the method established in the present study has a high specificity for the determination of UA in human serum; (2) UA concentration has a linear correlation with current intensity (y=0.012x+0.998; R2=0.998), wide linear range and high sensitivity (minimum detectability=13.91 µM; signaltonoise ratio=3); (3) the values of UA content in human serum were positively proportional to the clinical results (y=0.9802x+11.494; R2=0.978); (4) the average recovery rate of UA (95.28%) and the replicability assay of the it electrochemical method (coefficient of variation=2.04%), suggest that the method had a high accuracy and good precision for UA detection. Due to its characteristics of good accuracy, high sensitivity, wide linear range, good antiinterference ability and replicability, GMoS2Nafion has good prospects for UA detection in the clinical setting.
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Técnicas Biosensibles/instrumentación , Carbono/química , Disulfuros/química , Polímeros de Fluorocarbono/química , Molibdeno/química , Ácido Úrico/sangre , Adulto , Técnicas Electroquímicas/instrumentación , Electrodos , Femenino , Grafito/química , Humanos , Límite de Detección , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCOâSNPs. After the intravenous injection and subsequent concentration of the TCOâSNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope ((64)Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted (64)Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.
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Ciclooctanos/química , Glioblastoma/diagnóstico por imagen , Glioblastoma/diagnóstico , Compuestos Heterocíclicos con 1 Anillo/química , Nanopartículas/química , Tomografía de Emisión de Positrones/métodos , Animales , Radioisótopos de Cobre/administración & dosificación , Radioisótopos de Cobre/química , Dendrímeros/química , Glioblastoma/patología , Compuestos Heterocíclicos con 1 Anillo/administración & dosificación , Humanos , Inyecciones Subcutáneas , Ratones , Ratones Desnudos , Nanopartículas/ultraestructura , Trasplante de Neoplasias , Permeabilidad , Polietilenos/química , Trasplante HeterólogoRESUMEN
The objective of the study was to evaluate the relationship between the fluoride concentration of the fluoride-releasing elastomers and the acquired acid resistance of human enamel. Four kinds of fluoride concentration of the experimental fluoride-releasing elastomers were 1.25, 2.5, 3.75 and 5.0 wt%. An enamel block was cut into two smaller enamel blocks, one of which was set with an elastomer, the other as a control not set with elastomer. A plastic block that had the same shape as the small enamel block was also set with elastomer. Fluoride release and acid resistance tests were carried out. The mineral loss of the demineralized enamel was measured by microradiography. The results showed that the fluoride-releasing ability significantly increased with the increase of fluoride concentration in the elastomer (p < 0.05). The acid resistance of the enamel appeared to be enhanced greatly, however, its change was not proportional to the fluoride concentration in the elastomers.
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Cariostáticos/química , Esmalte Dental/efectos de los fármacos , Elastómeros/química , Fluoruros/química , Poliuretanos/química , Absorción , Análisis de Varianza , Cariostáticos/farmacología , Solubilidad del Esmalte Dental/efectos de los fármacos , Difusión , Microanálisis por Sonda Electrónica , Fluoruros/farmacología , Humanos , Microrradiografía , Minerales/análisis , Desmineralización Dental/metabolismoRESUMEN
The purpose of the study was to investigate the biocompatibility of experimental elastomers, E580 and E590. The experimental elastomers and the control--a clinically used elastomer--were implanted into the subcutaneous tissue of rats. The tissue reactions were examined histologically on the 3rd, 7th, 14th, 28th, and 56th day after implantation. It was found that there were some irritant responses in the tissues adjacent to the implanted elastomers during the first week. However, the inflammatory tissue reaction subsided substantially from the second week onwards. The stable fibrous capsule surrounding the elastomer was formed after eight weeks. The tissue responses of the control, E580, and E590 were similar. The results suggested that the long-term tissue irritation of the experimental elastomers was so low such that they have the potential to be applied clinically.
Asunto(s)
Elastómeros/toxicidad , Poliuretanos/toxicidad , Tejido Subcutáneo/efectos de los fármacos , Animales , Caproatos/toxicidad , Implantes Experimentales , Isocianatos/toxicidad , Lactonas/toxicidad , Masculino , Ratas , Ratas WistarRESUMEN
Metastatic squamous cell carcinoma (SCCA) of the anal canal is a rare malignancy for which no standard treatment algorithm exists. To determine the best approach, all patients diagnosed with metastatic SCCA of the anal canal treated at a single institution were evaluated for choice of chemotherapy and treatment outcome. A retrospective study from January 2000 to May 2012 was conducted. Electronic medical records were reviewed for diagnosis of metastatic SCCA of the anal canal. All patients were treatment naïve for metastatic disease and completed all radiographic imaging at our institution. The purpose of this study was to evaluate outcomes among patients who received systemic chemotherapy and if appropriate were referred for multidisciplinary intervention (e.g., surgery, radiofrequency ablation, etc.). Seventy-seven patients fulfilled eligibility criteria. Forty-two patients (55%) received 5-fluorouracil (5-FU) + cisplatin (PF); 24 patients (31%) received carboplatin + paclitaxel (CP); 11 patients (14%) received an alternative regimen. After a median follow-up of 42 months, the median progression-free survival (PFS) for all patients was 7 months; the median overall survival (OS) was 22 months. Thirty-three patients (43%) underwent multidisciplinary management for metastatic disease resulting in a median PFS of 16 months (95% CI: 9.2 -22.8) and median OS of 53 months (95% CI: 28.3 - 77.6). Systemic chemotherapy provides durable survival for patients with surgically unresectable metastatic SCCA of the anal canal. Multidisciplinary management for select patients with metastatic disease effectively improves survival and should be considered whenever possible.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/patología , Neoplasias del Ano/terapia , Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Paclitaxel/administración & dosificación , Cuidados Paliativos , Poliuretanos/administración & dosificación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate clinical effects of computer aided design and computer aided manufacturing (CAD/CAM) milled zirconia crown in three aspects: aesthetic, contact wear and fracture. METHODS: Sixty patients were divided into two groups.In one group, 35 full contour CAD/CAM zirconia crown were made on molars of 30 patients. The manufacturing process of zirconia crown was as follow. First, the three dimensional(3-D) data of working models, antagonist impression and check records were acquired by 3-D laser scanning Dental wings S50. Then full contour zirconia crowns, which had functional occlusal contacts with antagonistic teeth, and appropriate contact with adjacent teeth were designed with Zeno-CAD(V4.2.5.5.12919) software. ZENOSTAR Zr pure zirconia material was milled in digital controlled machine WIELAND 4030 M1.In the end, the zirconia crown were completed with the method of second sintering and polishing. After clinical try-in, the crown was cemented.In the control group, thirty gold alloy full crown were made and cemented on molars of 30 patients. According to the modified U S Public Health Service Criteria(USPHS) evaluation standard, all crowns were evaluated on the same day, at three months, half a year, one year and two years following delivery. There were three aspects we were focusing on in the evaluation: aesthetic, contact wear(restoration and antagonist), and fracture. RESULTS: In all the prosthesis we evaluated during the 24 months, no fracture was found. Contact wear of crowns varies according to different antagonist teeth. CONCLUSIONS: The zirconia crowns show privilege in aesthesis, toughness and anti-wearing.However, there is contact wear on antagonistic natural teeth. Thus it is a good choice when full zirconia crowns are indicated on two antagonistic teeth in both jaws.