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1.
Angew Chem Int Ed Engl ; 61(28): e202205429, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35532958

RESUMO

The clinical application of photodynamic therapy is hindered by the high glutathione concentration, poor cancer-targeting properties, poor drug loading into delivery systems, and an inefficient activation of the cell death machinery in cancer cells. To overcome these limitations, herein, the formulation of a promising IrIII complex into a biodegradable coordination polymer (IrS NPs) is presented. The nanoparticles were found to remain stable under physiological conditions but deplete glutathione and disintegrate into the monomeric metal complexes in the tumor microenvironment, causing an enhanced therapeutic effect. The nanoparticles were found to selectively accumulate in the mitochondria where these trigger cell death by hybrid apoptosis and ferroptosis pathways through the photoinduced production of singlet oxygen and superoxide anion radicals. This study presents the first example of a coordination polymer that can efficiently cause cancer cell death by apoptosis and ferroptosis upon irradiation, providing an innovative approach for cancer therapy.


Assuntos
Complexos de Coordenação , Ferroptose , Fotoquimioterapia , Apoptose , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Glutationa , Irídio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/farmacologia
2.
Inorg Chem ; 58(18): 12422-12432, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31483641

RESUMO

Fluorescence imaging is a powerful tool in biomedical research. It has been frequently used to uncover or better understand physiological mechanisms in disease-related processes such as cancer. The majority of chromophores used for imaging are based on a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) scaffold. However, their applications are limited due to their poor water solubility as well as poor cancer cell selectivity. To circumvent these drawbacks, we present herein the use of bis(dipyrrinato)zinc(II) complexes. As this class of compounds is associated with a quenching effect of the excited state in water, the lead compound of this study (3) was encapsulated in a polymer matrix with biotin as a targeting moiety (3-NP). This encapsulation improved the water solubility, overcame the quenching effects in water, as well as allowed selective accumulation in the lysosomes with a bright fluorescence signal in monolayer cells as well as 3D multicellular tumor spheroids (MCTS). As a benefit from the biotin targeting moiety, the nanoparticles were majorly taken up by the sodium dependent multivitamin transporter (SMVT) which is overexpressed in various cancers cells and selectively accumulated in cancerous cells over noncancerous cells.


Assuntos
Corantes Fluorescentes/química , Lisossomos/patologia , Nanopartículas/química , Neoplasias/patologia , Polímeros/química , Pirróis/química , Zinco/química , Células A549 , Linhagem Celular , Complexos de Coordenação/química , Células HeLa , Humanos , Lisossomos/ultraestrutura , Microscopia Confocal/métodos , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos
3.
Angew Chem Int Ed Engl ; 58(40): 14334-14340, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386250

RESUMO

The use of photodynamic therapy (PDT) to treat cancer has received increasing attention over the last years. However, the clinically used photosensitisers (PSs) have some limitations that include poor aqueous solubility, hepatotoxicity, photobleaching, aggregation, and slow clearance from the body, so the design of new classes of PSs is of great interest. We present the use of bis(dipyrrinato)zinc(II) complexes with exceptionally long lifetimes as efficient PDT PSs. Based on the heavy-atom effect, intersystem crossing of these complexes changes the excited state from singlet to a triplet state, thereby enabling singlet oxygen generation. To overcome the limitation of quenching effects in water and improve water solubility, the lead compound 3 was encapsulated in a polymer matrix. It showed impressive phototoxicity upon irradiation at 500 nm in various monolayer cancer cells as well as 3D multicellular tumour spheroids, without observed dark toxicity.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Polímeros/química , Polímeros/farmacologia , Pirróis/química , Pirróis/farmacologia , Células Tumorais Cultivadas , Zinco/química , Zinco/farmacologia
4.
Int J Med Sci ; 12(9): 742-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26392812

RESUMO

OBJECTIVE: The aim of this study was to detect the prevalence of oral H.pylori among adults and to investigate the correlation between H.pylori infection and common oral diseases. STUDY DESIGN: A cross-sectional study was performed among adults Chinese who took their annual oral healthy examination at The First Affiliated Hospital, Zhejiang University School of Medicine, China. RESULTS: The study included 1050 subjects in total and oral H.pylori infection occurred in 60.29% of the subjects. The prevalence rates of oral H.pylori in patients with periodontal diseases (63.42%) and caries (66.91%) were significantly increased than those without oral diseases (54.07%), respectively (P < 0.05), while the difference between subjects with recurrent aphthous stomatitis and controls was not significant. In addition, the differences of positive rates of H.pylori with or without history of gastric ulcer were statistically significant (69.47% vs 58.26%, P<0.05). Presenting with periodontal diseases (OR 1.473;95% CI 1.021 to 2.124), caries (OR 1.717; 1.127 to 2.618), and having history of gastric ulcer (OR 1.631; 1.164 to 2.285) increased the risk of H.pylori infection. CONCLUSIONS: Oral H.pylori infection is common in adult Chinese, which is significantly associated with oral diseases including periodontal diseases and caries.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Doenças da Boca/epidemiologia , Saliva/microbiologia , Adulto , China/epidemiologia , Estudos Transversais , Cárie Dentária/epidemiologia , Cárie Dentária/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/microbiologia , Doenças Periodontais/epidemiologia , Doenças Periodontais/microbiologia , Fatores de Risco , Úlcera Gástrica/microbiologia , Estomatite/epidemiologia , Estomatite/microbiologia
5.
Angew Chem Int Ed Engl ; 54(47): 14049-52, 2015 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-26447888

RESUMO

Photodynamic therapy (PDT) is a noninvasive medical technique that has received increasing attention over the last years and been applied for the treatment of certain types of cancer. However, the currently clinically used PDT agents have several limitations, such as low water solubility, poor photostability, and limited selectivity towards cancer cells, aside from having very low two-photon cross-sections around 800 nm, which limits their potential use in TP-PDT. To tackle these drawbacks, three highly positively charged ruthenium(II) polypyridyl complexes were synthesized. These complexes selectively localize in the lysosomes, an ideal localization for PDT purposes. One of these complexes showed an impressive phototoxicity index upon irradiation at 800 nm in 3D HeLa multicellular tumor spheroids and thus holds great promise for applications in two-photon photodynamic therapy.


Assuntos
Complexos de Coordenação/farmacologia , Lisossomos/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Piridinas/química , Rutênio/química , Morte Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Células HeLa , Humanos , Lisossomos/química , Fótons , Fármacos Fotossensibilizantes/síntese química , Polímeros/química , Polímeros/farmacologia , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rutênio/farmacologia
6.
Int J Biol Macromol ; 267(Pt 2): 131657, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636753

RESUMO

Porous starch (PS) is a modified starch with commendable biodegradable and adsorption properties. PS exhibits poor thermal stability, and the aqueous solution casting method is conventionally used for PS-activated packaging films. This approach limits the large-scale production of films and makes it difficult to play the functions of porous pores. In this study, PS was prepared by enzymatic digestion combined with freeze-drying and adsorbed with clove essential oil (CEO) after cross-linking with sodium trimetaphosphate. Subsequently, a novel PLA/PBAT/TPS/ScPS-CEO sustained release active packaging film was prepared by blending PLA, PBAT, TPS, and ScPS-CEO using industrial melt extrusion. Compared with PS, ScPS effectively slowed down the release of CEO from the film, with the maximum release of active substances at equilibrium increasing by approximately 100 %, which significantly enhanced the persistence of the antimicrobial and antioxidant properties. The polylactic acid/poly (butylene adipate-co-terephthalate)/thermoplastic starch/trimetaphosphate-crosslinked porous starch incorporated with clove essential oil (PLA/PBAT/TPS/ScPS-CEO) film could reduce the proteolysis, lipid oxidation and microbial growth of salmon, extending its shelf life by approximately 100 % at 4 °C. These results indicate that the ScPS can be used in fresh packaging material in practical applications.


Assuntos
Antioxidantes , Poliésteres , Amido , Amido/química , Poliésteres/química , Antioxidantes/química , Antioxidantes/farmacologia , Porosidade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Preparações de Ação Retardada/farmacologia , Embalagem de Alimentos/métodos , Temperatura
7.
Medicine (Baltimore) ; 100(47): e28019, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964798

RESUMO

ABSTRACT: The water quality of dental unit waterlines (DUWLs) is associated with patient safety. No program for DUWL water quality improvement has been formulated since the time they were established 20 years ago. This study provides an improvement program for the quality of dental unit water. The improvement program was implemented step by step: discharge of DUWLs for 5 minutes in the morning before clinical service to flush out the water left in the pipeline overnight; weekly disinfection of the handpiece connector with 75% alcohol and replacement of the old connector when the water quality of the same dental chair unit (DCU) was continuously found to be unqualified; monthly disinfection of the water supply system and pipeline; and establishment of DCU maintenance work standards and staff education and training. From 2016 to 2018, the water quality of 18 DCUs was tested by microorganism culture. The colonies >200 colony forming unit were categorized as unqualified. This program was divided into a pre-test phase, Phase 1, a maintenance phase, and Phase 2. A Chi-square test was used to calculate the difference of unqualified water quality numbers between each phase of the improvement program. In the pre-test phase, the water quality rate (high quality number/high-quality number + low-quality number) was 58.3%. In Phase 1, the quality rate before and after the intervention was 64.8% (35/54) and 92.2% (83/90) (P < .001), respectively. After Phase 1, the quality rate reached 100%. However, the quality rate dropped to 75% during the maintenance phase. Then, we proceeded into Phase 2 of the improvement program by further monthly disinfection to DUWLs. In Phase 2, the quality rate was 62/73 (84.9%) and improved to 142/144 (98.6%) after the intervention (P < .001). The quality rate reached 100% once again and was maintained at 100% thereafter. In conclusion, the 4 steps of the improvement program improved the water quality of the DUWL, which is important for patient safety.


Assuntos
Equipamentos Odontológicos/microbiologia , Desinfecção , Contaminação de Equipamentos/prevenção & controle , Microbiologia da Água , Qualidade da Água , Abastecimento de Água/normas , Biofilmes , Contagem de Colônia Microbiana , Desinfetantes/uso terapêutico , Hospitais , Humanos , Desenvolvimento de Programas , Melhoria de Qualidade
8.
ACS Appl Mater Interfaces ; 12(49): 54433-54444, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33238711

RESUMO

Photodynamic therapy is a medical technique, which is gaining increasing attention to treat various types of cancer. Among the investigated classes of photosensitizers (PSs), the use of Ru(II) polypyridine complexes is gaining momentum. However, the currently investigated compounds generally show poor cancer cell selectivity. As a consequence, high drug doses are needed, which can cause side effects. To overcome this limitation, there is a need for the development of a suitable drug delivery system to increase the amount of PS delivered to the tumor. Herein, we report the encapsulation of a promising Ru(II) polypyridyl complex into polymeric nanoparticles with terminal biotin groups. Thanks to this design, the particles showed much higher selectivity for cancer cells in comparison to noncancerous cells in a 2D monolayer and 3D multicellular tumor spheroid model. As a highlight, upon intravenous injection of an identical amount of the Ru(II) polypyridine complex of the nanoparticle formulation, an improved accumulation inside an adenocarcinomic human alveolar basal epithelial tumor of a mouse up to a factor of 8.7 compared to the Ru complex itself was determined. The nanoparticles were found to have a high phototoxic effect upon one-photon (500 nm) or two-photon (800 nm) excitation with eradication of adenocarcinomic human alveolar basal epithelial tumor inside a mouse model. Overall, this work describes, to the best of our knowledge, the first in vivo study demonstrating the cancer cell selectivity of a very promising Ru(II)-based PDT photosensitizer encapsulated into polymeric nanoparticles with terminal biotin groups.


Assuntos
Complexos de Coordenação/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Rutênio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Feminino , Humanos , Luz , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fótons , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Piridinas/química , Oxigênio Singlete/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Distribuição Tecidual , Transplante Heterólogo
9.
Shanghai Kou Qiang Yi Xue ; 29(2): 213-216, 2020 Apr.
Artigo em Zh | MEDLINE | ID: mdl-32626888

RESUMO

PURPOSE: To investigate the efficacy of autologous dentin particles combined with platelet-rich fibrin membrane (PRF) in the treatment of root bifurcation lesions of mandibular first molar. METHODS: Ninety-three patients (93 teeth) with mandibular first molar root bifurcation lesions were selected from our department from February 2016 to October 2017. They were randomly divided into 2 groups. Forty-six patients with 46 teeth in the experimental group underwent autologous dentin particles combined with platelet-rich fibrin membrane, while patents in the control group (47 patients with 47 teeth) were treated with Bio-Oss implanted in the bone defect area covered with collagen membrane. The patients were revisted at 1, 3, 6 and 12 months after operation. The success rate of the operation group, the depth of periodontal pocket (PD), the loss of attachment (AL), the depth of penetration of the root bifurcation (HPD), and the bone density of the root bifurcation area before and after treatment. The data were recorded and compared with SPSS25.0 software package. RESULTS: The success rate was 97.83%(45/46) in the experimental group, 85.11%(40/47) in the control group, the difference between the two groups was significant(P<0.05). After treatment, PD, AL and HPD decreased significantly (P<0.05), and MGVs increased gradually. There was no significant difference in MGVs before treatment and 1 month after treatment in the experimental group (P>0.05). MGVs at other time points were significantly higher than those of the control group (P<0.05). PD, AL and HPD of the experimental group were lower significantly than the control group at each time point after treatment (P<0.05), and MGVs value was significantly higher than the control group (P<0.05). There was no significant difference in the incidence of complications(4.35% vs 6.38%, χ2=0.189, P>0.05). CONCLUSIONS: Autologous dentin particles combined with platelet-rich fibrin membrane is effective for the treatment of root bifurcation lesions of mandibular first molar, which is worthy of wide application.


Assuntos
Fibrina Rica em Plaquetas , Densidade Óssea , Dentina , Humanos , Dente Molar , Bolsa Periodontal
10.
Medicine (Baltimore) ; 98(8): e14634, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30813202

RESUMO

BACKGROUND: The purpose of this meta-analysis was to compare the effectiveness and safety of cemented versus uncemented hemiarthroplasty for displaced femoral neck fractures. METHODS: We searched PUBMED, EMBASE, Cochrane Library, and Google Scholar from their inception to February 2016. All RCTs comparing cemented with uncemented hemiarthroplasty for displaced femoral neck fractures were eligible. The participants who underwent primary hemiarthroplasty for unilateral femoral neck fracture were older than 55 and the mean age of more than 75 years old. For the trials before 2006 used old designed prostheses, so we excluded trails before 2006 which used old designed prostheses. Outcomes of interest include postoperative hip function, Harris hip score (HHS), mortality, reoperation rate, complications, operation time, intraoperative blood loss. Two reviewers independently evaluated the included studies and extracted data into RevMan. Quality Assessments were classified by agreement of 2 authors based on the Cochrane tool. RESULTS: Seven trials were eligible. Postoperative hip function at 12 months cemented hemiarthroplasty was better than that in uncemented hemiarthroplasty (OR = 0.52, 95% CI, 0.31-0.88; P = .01). Postoperative fractures rates in cemented hemiarthroplasty were lower than that in uncemented hemiarthroplasty (OR = 0.09, 95% CI, 0.02-0.38; P = .001). Also, the interoperative fracture rates in cemented hemiarthroplasty were lower than that in uncemented hemiarthroplasty (OR = 0.29, 95% CI, 0.13-0.68; P = .004). Shorter operation time was achieved in uncemented hemiarthroplasty than that in cemented hemiarthroplasty (WMD = 8.22 min, 95% CI, 5.57-10.86 min; P<.00001). There was no significant difference between the 2 groups with HHS, mortality, wound infection, dislocation, general complications, reoperation rate, and intraoperative blood loss. CONCLUSION: The available evidence indicates that compared with uncemented hemiarthroplasty cemented hemiarthroplasty achieved better postoperative hip function, less postoperative, and interoperative fractures in displaced femoral neck fracture. Uncemented hemiarthroplasty achieved shorter operation time. There was no difference between the 2 groups with HHS at 1 year, mortality, and complications.


Assuntos
Cimentos Ósseos/uso terapêutico , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia , Complicações Pós-Operatórias , Fraturas Mal-Unidas , Hemiartroplastia/efeitos adversos , Hemiartroplastia/métodos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Gastroenterol Hepatol ; 23(2): 283-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17645475

RESUMO

BACKGROUND AND AIM: To elucidate the epidemiology of gastroesophageal reflux disease (GERD) symptoms in outpatients from the Department of Medicine in 10 hospitals in Zhejiang Province, east China. METHODS: A cross-sectional survey in the cluster random sample was conducted from November 2004 to June 2005 using a validated Chinese version of the reflux disease questionnaire and other items recording the demographic characteristics for GERD symptoms. The statistical analysis was performed with SPSS 13.0 programs. RESULTS: A total of 15,283 outpatients from the Department of Medicine were investigated. The prevalence of GERD symptoms was 7.28% (95% confidence interval [CI], 6.87%, and 7.69%) with the prevalence rate increasing with age (P < 0.001), which was higher in men (7.79%, 95% CI: 7.20%, 8.38%) than in women (6.73%, 95% CI: 6.18%, 7.28%; chi2 = 5.81, P < 0.05). The prevalence rate of the gastrointestinal symptoms in GERD symptoms, including epigastric discomfort, nausea, retrosternal pain, belching, globus sensation, loss of appetite, excessive salivation, vomiting, wheezing cough, weight loss, and dysphagia were all higher than the non-GERD patients (P < 0.0001). In the GERD patients, the prevalence of diseases, such as pharyngolaryngitis, snoring, bronchitis, liver disease, and gallbladder disease were all higher than the non-GERD patients (P < 0.01). The multiple logistic regression analysis showed that old age, night-shift work, heavy work burdens, single or divorced people, increase intake of greasy or sweet foods, excessive eating, and constipation were independent risk factors associated with GERD symptoms. CONCLUSION: GERD has a high prevalence in China and its main associated factors include respiratory, laryngopharyngeal and dental disorders, sex, anthropometrical variables, and social-psychological characteristics.


Assuntos
Refluxo Gastroesofágico/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/complicações , Doenças Faríngeas/epidemiologia , Prevalência , Doenças Respiratórias/complicações , Doenças Respiratórias/epidemiologia , Fatores de Risco , Distribuição por Sexo , Doenças Estomatognáticas/complicações , Doenças Estomatognáticas/epidemiologia , Inquéritos e Questionários
12.
Shanghai Kou Qiang Yi Xue ; 26(3): 297-301, 2017 Jun.
Artigo em Zh | MEDLINE | ID: mdl-29098250

RESUMO

PURPOSE: To compare the clinical efficacy of MTA apical barrier technique and Vitapex apexification in treatment of young permanent teeth with periapical inflammation, and to evaluate the satisfaction of patients. METHODS: Seventy-five cases of young permanent teeth with periapical inflammation were randomly divided into control group (n=37) and experimental group (n=38). Patients in the control group were treated with Vitapex apexification, while patients in the experimental group were treated with MTA apical barrier technique. The clinical efficacy of the two groups was compared at 3, 6, 9 months and 1 year after treatment, and the average treatment time and average treatment period were compared between 2 groups. The difference of patients' satisfaction with medical environment, health care service, late health care guidance, treatment cost, treatment period and treatment effect were compared between 2 groups. The clinical efficacy, treatment times and period, satisfaction of 2 groups were recorded and analyzed by using SPSS 19.0 software package. RESULTS: At 3 month and 6 month of revisit, the clinical efficacy of the experimental group was better than the control group, but there was no significant difference between 2 groups (P>0.05). At 9 months and 1 year of revisit, the total efficiency of the experimental group was significantly better than the control group (78.38%:94.74%, P=0.037;75.68%∶97.37%, P=0.006). The treatment time and treatment period of the experimental group were significantly lower than the control group (P<0.05), the values were (3.24±0.39) times, (0.68±0.23) months and (7.78±0.65) times, (8.24±2.95) months. Patients' satisfaction with medical treatment environment, health care service, late health care guidance and treatment period was not significant different between 2 groups (P>0.05). However, patients' satisfaction with treatment cost and treatment effect in the experimental group was significantly higher than the control group (P<0.05). CONCLUSIONS: MTA apical barrier technique has better clinical efficacy, less treatment time, shorter treatment period and higher satisfaction than Vitapex apexification. It is suitable for clinical application.


Assuntos
Compostos de Cálcio , Satisfação do Paciente , Materiais Restauradores do Canal Radicular , Preparo de Canal Radicular , Compostos de Alumínio , Combinação de Medicamentos , Humanos , Incisivo , Inflamação/terapia , Óxidos , Materiais Restauradores do Canal Radicular/uso terapêutico , Silicatos , Ápice Dentário , Resultado do Tratamento
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(3): 309-15, 2016 Mar.
Artigo em Zh | MEDLINE | ID: mdl-27063154

RESUMO

OBJECTIVE: To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. METHODS: The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. RESULTS: The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. CONCLUSION: The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.


Assuntos
Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Rifampina/administração & dosagem , Animais , Materiais Biocompatíveis/química , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos
14.
Clin Cancer Res ; 10(21): 7244-51, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15534098

RESUMO

PURPOSE: Rapid cleavage in vivo and inefficient cellular uptake limit the clinical utility of antisense oligonucleotides (AON). Liposomal formulation may promote better intratumoral AON delivery and inhibit degradation in vivo. We conducted the first clinical evaluation of this concept using a liposomal AON complementary to the c-raf-1 proto-oncogene (LErafAON). EXPERIMENTAL DESIGN: A dose escalation study was done to determine the maximum tolerated dose and to characterize the toxicities of LErafAON given as weekly intravenous infusion for 8 weeks to adults with advanced solid tumors. Pharmacokinetic analysis and evaluation of c-raf-1 target suppression in peripheral blood mononuclear cells were included. RESULTS: Twenty-two patients received LErafAON (median 7 infusions; range 1-27) at doses of 1, 2, 4, and 6 mg/kg/week. Across all dose cohorts patients experienced infusion-related hypersensitivity reactions including flushing, dyspnea, hypoxia, rigors, back pain, and hypotension. Prolonged infusion duration and pretreatment with acetaminophen, H1- and H2-antagonists, and corticosteroids reduced the frequency and severity of these reactions. Progressive thrombocytopenia was dose-limiting at 6 mg/kg/week. No objective responses were observed. Two patients treated at the maximum tolerated dose of 4 mg/kg/week had evidence of stable disease, with dosing extended beyond 8 weeks. Pharmacokinetic analysis revealed persistence of detectable circulating rafAON at 24 hours in 7 of 10 patients in the highest 2 dose cohorts. Suppression of c-raf-1 mRNA was noted in two of five patients analyzed. CONCLUSIONS: Dose-independent hypersensitivity reactions and dose-dependent thrombocytopenia limited tolerance of LErafAON. Future clinical evaluation of this approach will depend on modification of the liposome composition.


Assuntos
Terapia Genética/efeitos adversos , Terapia Genética/métodos , Lipossomos/metabolismo , Neoplasias/terapia , Oligonucleotídeos Antissenso/farmacologia , Proteínas Proto-Oncogênicas c-raf/genética , Adulto , Idoso , Antineoplásicos/farmacologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Técnicas de Transferência de Genes , Humanos , Hipóxia/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Transplante de Neoplasias , Proto-Oncogene Mas , RNA Mensageiro/metabolismo , Trombocitopenia/etiologia , Fatores de Tempo , Resultado do Tratamento
15.
Dalton Trans ; 44(15): 7058-65, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25785372

RESUMO

To prolong the observation time, increase the penetration depth and decrease self-absorption and phototoxicity, two-photon luminescent vectors have emerged as promising tools for tracking gene delivery in living cells. Herein, we report four new tetranuclear Ru(ii) complexes based on oligo-oxyethylene and polybenzimidazole as one- and two- photon luminescent tracking non-viral gene vectors. In such a molecular design, the oligo-oxyethylene, polybenzimidazole and Ru(ii) polypyridyl complexes were expected to render the vectors with increased cell permeability, biocompatibility, proton buffering capacity and one- and two-photon luminescence. Corresponding DNA interaction studies showed that the ability of the complexes to condense DNA decreased with increasing oligo-oxyethylene lengths. Additionally, all complexes protected DNA. The complexes were investigated as one- and two-photon tracking non-viral gene vectors in living cells and showed proper cellular uptake, good luciferase expression and low cytotoxicity.


Assuntos
Complexos de Coordenação/química , Vetores Genéticos , Rutênio/química , Benzimidazóis/química , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA/química , DNA/metabolismo , DNA/ultraestrutura , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Luminescência , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Fótons , Plasmídeos , Polietilenoglicóis/química , Polímeros/química , Rutênio/farmacologia
16.
Chem Commun (Camb) ; 50(17): 2123-5, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24418839

RESUMO

A new series of dinuclear ruthenium(II) polypyridyl complexes, which possess larger π-conjugated systems, good water solubility and pH resistance, and high photostability, were developed to act as single and two-photon luminescence cellular imaging probes.


Assuntos
Complexos de Coordenação/química , Polímeros/química , Rutênio/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Citometria de Fluxo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Microscopia Confocal , Fótons , Solubilidade , Água/química
17.
Int J Nanomedicine ; 6: 3057-64, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22162662

RESUMO

Many studies in recent years have focused on surface engineering of implant materials in order to improve their biocompatibility and other performance. Porous tantalum implants have increasingly been used in implant surgeries, due to their biocompatibility, physical stability, and good mechanical strength. In this study we functionalized the porous tantalum implant for sustained drug delivery capability via electrostatic self-assembly of polyelectrolytes of hyaluronic acid, methylated collagen, and terpolymer on the surface of a porous tantalum implant. The anticancer drug doxorubicin was encapsulated into the multilayer copolymer membranes on the porous tantalum implants. Results showed the sustained released of doxorubicin from the functionalized porous tantalum implants for up to 1 month. The drug release solutions in 1 month all had inhibitory effects on the proliferation of chondrosarcoma cell line SW1353. These results suggest that this functionalized implant could be used in reconstructive surgery for the treatment of bone tumor as a local, sustained drug delivery system.


Assuntos
Antibióticos Antineoplásicos/química , Materiais Biocompatíveis/química , Doxorrubicina/química , Implantes de Medicamento/química , Membranas Artificiais , Polímeros/química , Tantálio/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Condrossarcoma/tratamento farmacológico , Condrossarcoma/metabolismo , Preparações de Ação Retardada , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Implantes de Medicamento/administração & dosagem , Implantes de Medicamento/farmacocinética , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Ácido Hialurônico/farmacocinética , Porosidade , Eletricidade Estática , Propriedades de Superfície
18.
J Pain Symptom Manage ; 38(5): 738-46, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19748760

RESUMO

The purposes of this study were 1) to assess and describe the occurrence, frequency, severity, and distress of symptoms reported by Taiwanese pediatric cancer patients who were between 10 and 18 years of age, and 2) to use statistical analysis to determine whether the multiple dimensions (i.e., frequency, severity, or distress) of the Memorial Symptom Assessment Scale (MSAS) 10-18 alone can provide sufficient useful information for the assessment of symptoms that patients report as distressing. A total of 144 Taiwanese pediatric cancer patients and their mothers participated in this cross-sectional study. The frequency of symptoms for all patients ranged from 52% for "lack of energy" to 10% for "feeling nervous." The most common symptoms (occurrence >40%) were "lack of energy," "lack of appetite," "feeling drowsy," "sweating," "worrying," "nausea," "dry mouth," "pain," and "lack of concentration." Patients in the "on-treatment group" had more distressing symptoms than those in the "off-treatment group." The severity and distress subscales did provide the most information for symptom assessment and were the two best subscales to represent the impact of symptoms on quality of life, fatigue, and internalizing behaviors. The findings of this study suggest that revising the current format of the MSAS 10-18 into three separate instruments (one for each of the subscales) might provide more accurate data for assessments. Such a modification would change the scoring system and provide for more accurate data analysis.


Assuntos
Neoplasias/complicações , Dor/etiologia , Adolescente , Criança , Comportamento Infantil , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Neoplasias/epidemiologia , Dor/epidemiologia , Medição da Dor , Qualidade de Vida , Taiwan/epidemiologia
19.
Drug Dev Ind Pharm ; 32(5): 595-607, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16720414

RESUMO

We described to achieve the local retention of minoxidil which has penetrated the skin with minimization of its absorption into the general circulation and elimination of local irritation induced by propylene glycol. The effect of tocopheryl polyethylene glycol succinate (TPGS) on the penetration flux of minoxidil and its retention in the skin from topical minoxidil formulations consisting of water, alcohol, and polyethylene glycol 400 was characterized by an experimental design of ten solvent formulations in this study. Results show that the addition of TPGS was only able to improve the solubility of minoxidil in those solvent systems containing higher proportions of water and PEG 400, and the extent of improvement was also more profound with the addition of TPGS at concentrations higher than 5%. For those solvent systems containing a higher fraction of alcohol, an insignificant change in minoxidil solubility with increasing added amounts of TPGS was noted even with the tendency to decrease the solubility of minoxidil with higher amounts of TPGS. Increasing the amount of TPGS added gradually increased the flux and the corrected flux from solvent formulations with a lower solubility parameter, but decreased those from solvent systems with a higher solubility parameter. With the addition of TPGS, solvent formulation F6 (alcohol:PEG 400 of 50:50) was demonstrated to be the optimal choice by having an improved local effect and a reduced systemic effect compared to the reference of 2% Regaine((R)). Tocopheryl polyethylene glycol succinate (TPGS) was mainly retained locally in the stratum corneum, and the amount was proportional to the increase in the amount of TPGS added to these ten solvent formulations.


Assuntos
Minoxidil/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Vasodilatadores/farmacocinética , Vitamina E/análogos & derivados , Administração Cutânea , Algoritmos , Animais , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Etanol , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Minoxidil/administração & dosagem , Polietilenoglicóis/farmacologia , Solubilidade , Soluções , Tensoativos , Vasodilatadores/administração & dosagem , Vitamina E/farmacologia , Água
20.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 21(2): 112-4, 2005 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16011197

RESUMO

OBJECTIVE: To evaluate an island pectoralis major myocutaneous flap for immediate reconstruction of the total tongue body and the floor of the mouth after radical resection of bilateral tongue carcinoma involved. METHODS: Form October 2000 to December 2002, seven patients with bilateral tongue carcinoma were selected to treat with salvage surgery, and an island pectoralis major myocutaneous flap were applied for immediate reconstruction of total body of tongue and floor of mouth. RESULTS: Six flaps survived well. Only one flap showed a partial necrosis, with no submandibular fistula, infection, and other complications. The reconstructed tongue and floor of mouth worked well. The speaking and swallowing functions were satisfactory after 2 approximately 16 months' follow-ups. Only one patient died of lung metastasis carcinoma in 9 months after the operation. CONCLUSIONS: The island pectoralis major myocutaneous flap could be an ideal selection for the immediate reconstruction of the total tongue body and the floor of mouth.


Assuntos
Soalho Bucal/cirurgia , Músculos Peitorais/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Língua/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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