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1.
Photodiagnosis Photodyn Ther ; 42: 103590, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37142073

RESUMO

BACKGROUND: Novel combination of Toluidine Blue O (TBO) embedded silicone catheter with domestic/household LED bulb has a potential in clinical infection such as prevention of multi drug resistant catheter-associated urinary tract infections (CAUTIs) through photodynamic therapy. MATERIAL AND METHODS: Preliminarily, TBO was entrapped into silicone catheter by swell-encapsulation-shrink method. Further, in vitro study was carried out to check the antimicrobial photodynamic efficacy of TBO with domestic/household LED light. Antibiofilm activity was evaluated by scanning electron microscopy. RESULTS: The results showed that these modified TBO embedded silicone catheters showed significant antimicrobial and antibiofilm activity against vancomycin resistant Staphylococcus aureus VRSA. Small piece (1 cm) of TBO-embedded silicone catheter (700 µM) showed 6 log10 reduction in the viable count when exposed for only 5 min of domestic/household LED bulb, while 1 cm piece of 500 µM and 700 µM concentration of TBO-embedded catheter eradicated all bacterial load when exposed to 15 min of light. Segment of medical grade TBO-embedded silicone catheters were used to carry out investigation of reactive oxygen species generation mainly singlet oxygen that contributes to type II phototoxicity. CONCLUSION: These modified catheter provides cost effective, easy to manage and less time consuming therapy to eliminate CAUTIs.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Infecções Urinárias , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Silicones/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/prevenção & controle , Cateteres , Biofilmes
2.
J Orthop Surg Res ; 17(1): 447, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224572

RESUMO

BACKGROUND: Previous studies have demonstrated that by injecting uPA into the lumbar facet joints (LFJ) of normal rats, a rat LFJOA animal model can be successfully established. However, there is no evidence that intraarticular injection of uPA can induce or much serious osteoarthritis in bipedal rats, which biomechanics is much more similar to human than normal rats. To investigate whether intraarticular injection of urinary plasminogen activator (uPA) can induce LFJOA and low back pain symptoms in bipedal rats. METHODS: An experimental study on the construction of a modified animal model of lumbar facet joints osteoarthritis (LFJOA) which biomechanics is similar to human. Sprague-Dawley rats were treated with intraarticular injection of uPA in the L5-L6 facet joints (uPA group, n = 15) or saline (saline group, n = 15). The forelimbs of both two group rats were amputated. Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin-eosin staining, and immunohistochemical examination of the LFJ was performed. RESULTS: The saline group rats have not demonstrated significant osteoarthritis in rats LFJ after surgery. The uPA group has not been induced significantly higher mechanical and thermal hyperalgesia in comparison with the saline group. But intraarticular injection of uPA in biped rats induced significantly stronger articular cartilage damage, synovitis, and proliferation of synovial cells in the LFJ. Inflammatory factors such as iNOS, IL-1ß, and TNF-a were more significantly expressed in bipedal rat injected with uPA (p < 0.05). CONCLUSIONS: Intraarticular injection of uPA can induce LFJOA in bipedal rats, while upright posture does not induce osteoarthritis in rats LFJ in the short term.


Assuntos
Osteoartrite , Articulação Zigapofisária , Animais , Modelos Animais de Doenças , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/uso terapêutico , Humanos , Hiperalgesia , Injeções Intra-Articulares , Osteoartrite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Cloreto de Tolônio/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico
3.
Fitoterapia ; 162: 105278, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35970410

RESUMO

Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.


Assuntos
Alcaloides , Asma , Quinolizidinas , Alcaloides/metabolismo , Alcaloides/farmacologia , Animais , Antioxidantes/farmacologia , Asma/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Imunoglobulina E , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Interleucina-5/metabolismo , Interleucina-5/farmacologia , Interleucina-5/uso terapêutico , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Mucinas/metabolismo , Mucinas/farmacologia , Mucinas/uso terapêutico , Muco/metabolismo , Ovalbumina/metabolismo , Ácido Periódico/metabolismo , Ácido Periódico/farmacologia , Ácido Periódico/uso terapêutico , Quinolizidinas/farmacologia , RNA Mensageiro/metabolismo , Cloreto de Tolônio/metabolismo , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/farmacologia , Fator de Transcrição AP-1/uso terapêutico
4.
Chem Biol Interact ; 366: 110126, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36027949

RESUMO

Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of amyloid-ß peptide (Aß), intracellular neurofibrillary tangles containing hyperphosphorylated tau protein and neuronal loss. Most of the FDA-approved AD drugs currently on the market are cholinesterase inhibitors, which are only effective in relieving the symptoms of AD. However, recent studies in AD drug discovery focus on multi-targeted strategies, including anti-amyloid and anti-tau therapy. In the current study, we have investigated the effects of toluidine blue O (TBO), a cholinesterase inhibitor, on amyloid precursor protein (APP) processing, tau phosphorylation, and tau kinases/phosphatase in N2a mouse neuroblastoma cells stably expressing the Swedish mutation of human APP695 (N2a-APPSwe). The results demonstrated that TBO reduces Aß40/42 levels by decreasing expression levels of ß-secretase 1 (BACE1), presenilin 1 (PS1) and total APP without causing cytotoxic effects in N2a-APPSwe cells. TBO also decreased the levels of both total tau and phosphorylated tau at residues Ser202/Thr205, Thr181, Ser396 and Ser 396/Ser404. Moreover, when the possible mechanisms underlying its effects on tau pathology were explored, TBO was found to decrease tau phosphorylation at those sites by reducing the expression levels of Akt, GSK-3ß, Cdk5, inactive p-PP2A and increasing the expression levels of p-Akt Ser473 and inactive p-GSK-3ß Ser9. Our new data support the idea that TBO may be a promising multi-target drug candidate for the treatment of AD.


Assuntos
Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Inibidores da Colinesterase/uso terapêutico , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação , Presenilina-1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Proteínas tau/metabolismo
5.
Biochem Pharmacol ; 205: 115155, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35820500

RESUMO

Osteoarthritis (OA) is a degenerative disease caused by the progressive destruction of cartilage and subchondral bone [1]. Studies have shown that by inhibiting the degradation of cartilage cells and the loss of subchondral bone, OA can be prevented and treated. Neratinib, as a small molecule compound with anti-inflammatory and anti-tumor properties, is a very effective inhibitor of IL-1ß-induced chondrocyte inflammation and anabolic metabolism. By investigating the effect of neratinib in ATDC5 chondrocytes, the study finds that neratinib reduces inflammation by inhibiting the MAPK and NF-κB signaling pathways, and at the same time reduces pyrolysis (indicated by the results of reverse transcription quantitative PCR and western blotting). For anabolic metabolism, after high-density cell culture, IL-1ß-induced catalytic changes and degradation of the extracellular matrix were evaluated by toluidine blue staining. Since osteoclasts are key participants in the process of subchondral bone remodeling in OA, we also studied the effect of neratinib on the maturation of osteoclasts. The results showed that neratinib also acts as an anti-osteoclast agent in vitro. By inhibiting the NF-κB and MAPK pathways, it reduces the expression of osteoclast-related genes, thereby inhibiting RANKL-induced osteoclastogenesis. The results of in vivo animal experiments supported the conclusions from the experiments in vitro. Neratinib inhibited both the destruction of medial meniscus induced cartilage degradation and osteoclast formation, which proves that neratinib has a dual effect, protecting cartilage and inhibiting osteoclast formation. These results indicate that neratinib can be a brand-new latent strategy for the treatment of OA.


Assuntos
NF-kappa B , Osteoartrite , Animais , NF-kappa B/metabolismo , Cloreto de Tolônio/metabolismo , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Osteoartrite/patologia , Condrócitos , Cartilagem/metabolismo , Interleucina-1beta/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia
6.
Sci Rep ; 11(1): 24464, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34961769

RESUMO

Diabetic foot infection caused by multidrug-resistant bacteria, is becoming serious problem. Moreover, polymicrobial biofilms contribute significantly to the persistent infections. In the present study, we investigated the effectiveness of novel toluidine blue conjugated chitosan coated gold-silver core-shell nanoparticles (TBO-chit-Au-AgNPs) mediated photodynamic therapy and demonstrate their use as a nontoxic antibacterial therapy to combat diabetic foot ulcer (DFU) caused by multi-drug resistant strains both in monomicrobial and polymicrobial state of infection. In vitro efficacy of TBO-chit-Au-AgNPs mediated photodynamic therapy (PDT) against polymicrobial biofilms was determined using standard plate count method and compared with that of monomicrobial biofilms of each species. Different anti-biofilm assays and microscopic studies were performed to check the efficacy of TBO-chit-Au-AgNPs mediated PDT, displayed significant decrease in the formation of biofilm. Finally, its therapeutic potential was validated in vivo type-2DFU. Cytokines level was found reduced, using nano-phototheranostic approach, indicating infection control. Expression profile of growth factors confirmed both the pathogenesis and healing of DFU. Hence, we conclude that TBO-chit-Au-AgNPs mediated PDT is a promising anti-bacterial therapeutic approach which leads to a synergistic healing of DFU caused by MDR bacterial strains.


Assuntos
Antibacterianos/uso terapêutico , Pé Diabético/tratamento farmacológico , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Prata/uso terapêutico , Cloreto de Tolônio/uso terapêutico , Animais , Biofilmes/efeitos dos fármacos , Pé Diabético/microbiologia , Masculino , Fotoquimioterapia , Ratos Wistar
7.
Lasers Med Sci ; 36(3): 675-680, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32808146

RESUMO

This study aimed to evaluate the effects of toluidine blue-mediated photodynamic therapy (TB-PDT) on the periodontitis-induced bone resorption in periodontitis in rats. Periodontal disease was induced by cotton ligature around the right second maxillary molar in 64 rats. After 4 weeks, the rats were randomly divided into four groups: sterile saline solution (control group); laser therapy (laser group); TB (100 µg/mL); TB plus laser (0.15 W/cm2) irradiation every other day for 240 s (PDT group). All rats were euthanized at 15 days postoperatively. Eight gingival tissue samples were collected from each group. The expressions of receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG) in gingival tissue samples were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The maxillae from the rest of the rats were taken for histological examination. In the PDT group, the analysis revealed less bone loss than in the control treatment (P < 0.05). No significant difference was found among the control group, TB group, and laser group (P > 0.05). Significantly higher and lower expressions of RANKL and OPG were revealed in the PDT group than that in control group, respectively (P < 0.01). When compared with the control group, the expression of RANKL was significantly reduced by 40.0% in periodontitis in rats treated with TB-PDT for 15 days (P < 0.01). The expression of OPG was increased in the PDT group with TB-PDT for 15 days, when compared with the control group (P < 0.05). TB-PDT treatment significantly reverses the abnormal expression of RANKL and OPG in periodontitis in rats.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Periodontite/complicações , Fotoquimioterapia , Perda do Osso Alveolar/tratamento farmacológico , Animais , Reabsorção Óssea/genética , Regulação da Expressão Gênica , Masculino , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Periodontite/genética , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Cloreto de Tolônio/uso terapêutico
8.
Photodiagnosis Photodyn Ther ; 31: 101936, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791295

RESUMO

BACKGROUND: There is no reliable treatment procedure for peri-implant disease, despite the rise in its incidence. This study sought to evaluate the short-term safety and efficacy of antimicrobial photodynamic therapy (a-PDT) on peri-implantitis by assessing the volume of pus discharge after a-PDT. METHODS: Patients with pus discharge from a peri-implant pocket were recruited from December 1st, 2019 to April 30th, 2020. The enrolled implants were randomly assigned to one of two groups, the irrigation and a-PDT groups. Their peri-implant pocket was irrigated with normal saline in the irrigation group, and a saline irrigation and subsequent a-PDT with toluidine blue (TB) was performed in the a-PDT group. The safety and efficacy of a-PDT were assessed 7 days after treatment. RESULTS: Twenty-five implants in 21 patients (irrigation group; 13 implants, a-PDT group; 12 implants) were registered. No complication was observed after a-PDT. Pus discharge was decreased in 7 of 12 implants (58.3 %) in the a-PDT group, and in 2 of 13 implants (15.4 %) in the irrigation group. According to Fisher's exact test, a-PDT resulted in a statistically significant decrease in pus discharge compared to irrigation alone (p = 0.0414). CONCLUSIONS: a-PDT was confirmed to be a safe treatment for peri-implantitis, and the short-term efficacy of a-PDT with TB on peri-implantitis was clarified. Nevertheless, its efficacy remains restricted, and a new combination therapy of a-PDT and decontamination procedures is expected to be developed in future.


Assuntos
Implantes Dentários , Peri-Implantite , Fotoquimioterapia , Antibacterianos/uso terapêutico , Humanos , Peri-Implantite/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Cloreto de Tolônio/uso terapêutico
9.
Transl Vis Sci Technol ; 9(3): 13, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32714639

RESUMO

Objective: The objective of this study was to evaluate the effect of toluidine blue-mediated photodynamic therapy on experimental bacterial keratitis in rabbits. Methods: Bacterial keratitis was induced in rabbits by the injection of 200 µl Staphylococcus aureus (S. aureus) solution into the anterior stroma of the right cornea. Rabbits were randomly divided into four groups: toluidine blue O and red light (TBOR), levofloxacin eye drops (LEV), the combination of TBOR and LEV (TBOR + LEV), and a control group. Clinical manifestations, histopathology, and transmission electron microscopy were analyzed at various time points. Results: Conjunctival injection and surface area of the corneal ulcer in the TBOR group and the TBOR + LEV group showed significant improvement from baseline after 7 days of treatment. Compared to baseline, the depth of corneal infiltration was decreased at day 14 in the TBOR and TBOR + LEV groups. Microscopic analysis of the TBOR and TBOR + LEV groups showed that the structure of each layer was intact, and there were no inflammatory cells in the corneal stroma. Additionally, IL-1ß and TNF-α were highly expressed in the LEV and control groups but were lower in the TBOR and TBOR + LEV groups. Under transmission electron microscopy, the corneas in the TBOR and TBOR + LEV groups were intact, whereas in the LEV and control groups, double-walled structures corresponding to S.aureus were found in the superficial stromal layer. Conclusions: TBOR demonstrated in vivo antibacterial efficacy against S.aureus. Translational Relevance: This study found in vivo antibacterial efficacy of toluidine blue-mediated photodynamic therapy on rabbit experimental bacterial keratitis, thus providing an additional new option for clinical treatment of bacterial keratitis.


Assuntos
Infecções Oculares Bacterianas , Ceratite , Fotoquimioterapia , Animais , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Coelhos , Staphylococcus aureus , Cloreto de Tolônio/uso terapêutico
10.
Medicina (Kaunas) ; 56(7)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635245

RESUMO

Background and objectives: Transoral laser microsurgery (TLM) is widely accepted for its advantages, which consist of a brief hospital stay, rapid functional recovery, low management costs and the fact that it can be easily repeated in cases of recurrence. However, a high incidence of positive or narrow surgical margins has been reported in the literature, even if controversy still exists on the prognostic significance of positive resection margins. The aim of the study was to evaluate the utility of toluidine blue staining in defining the resection margins of early glottic cancer (T1a-T2) treated with TLM. Materials and Methods: This retrospective study was conducted on patients with early glottic cancer (T1a-T2) managed by TLM. A group of patients treated between 2010 and 2014 underwent toluidine blue staining (TB group) of the lesions before starting the cordectomy by TLM, and a group of patients treated by TLM between 2006 and 2009 was considered the control group. Results: A total of 44 subjects were included in this study: 41 were men, and 3 were women. The mean age was 58 ± 9.0 years (median 59.0, range 41-77). Twenty-three of the 44 patients were included in the TB group and 21 in the case control group. In the TB group, only the positivity of the deep margin was a predictor of local recurrence (p = 0.037), while in the control group, positive or close margins and the type of cordectomy were predictive factors of local recurrence (p = 0.049). Considering the TB group and control cases, the 5-year local recurrence-free survival was 95.6% and 80.9%, respectively (p = 0.14). Conclusions: From this first study, toluidine blue staining seems to be a useful modality to improve the rate of the negative resection margins of early glottic cancer (T1a-T2) treated by TLM.


Assuntos
Terapia a Laser/métodos , Cloreto de Tolônio/uso terapêutico , Neoplasias da Língua/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Corantes/uso terapêutico , Feminino , Humanos , Terapia a Laser/instrumentação , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Neoplasias da Língua/tratamento farmacológico
11.
Photodiagnosis Photodyn Ther ; 31: 101868, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32526374

RESUMO

AIM: This study evaluated three concentrations of butyl toluidine blue (BuTB) for antimicrobial photodynamic therapy (aPDT) in experimental periodontitis (EP) in rats. MATERIAL AND METHODS: EP was ligature-induced at the first mandibular molar in 105 rats. Ligature was removed after 7 days and animals were distributed into the following treatments: SRP, scaling and root planing (SRP) plus saline solution; BuTB-0.1, SRP plus BuTB at 0.1 mg/mL; aPDT-0.1, SRP plus BuTB at 0.1 mg/mL and InGaAlP diode laser (DL) irradiation; BuTB-0.5, SRP plus BuTB at 0.5 mg/mL; aPDT-0.5, SRP plus BuTB at 0.5 mg/mL and DL irradiation; BuTB-2.0, SRP plus BuTB at 2 mg/mL; aPDT-2.0, SRP plus BuTB at 2 mg/mL and DL irradiation. Five animals from each group were submitted to euthanasia at 7, 15 and 30 days post-treatment. The furcation area was submitted to histological, histometric and immunohistochemical (TGF-ß1, OCN and TRAP) analyses. RESULTS: aPDT-0.5 group presented a better tissue remodeling in all periods, resolution of the inflammatory response and bone neoformation areas at 30 days. aPDT-0.5 also resulted in higher immunolabeling patterns of TGF-ß1 at all periods (p < 0.05) and of OCN at 30 days (p < 0.05). CONCLUSION: aPDT-0.5 showed the best benefits for inflammatory response and periodontal repair process.


Assuntos
Perda do Osso Alveolar , Anti-Infecciosos , Periodontite , Fotoquimioterapia , Animais , Anti-Infecciosos/uso terapêutico , Terapia Combinada , Raspagem Dentária , Periodontite/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ratos , Ratos Wistar , Aplainamento Radicular , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico
12.
Photodiagnosis Photodyn Ther ; 31: 101888, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593778

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a minimally invasive method for the treatment of oral leukoplakia (OL) through the activation of a photosensitizer, after exposure to a specific wavelength light source. METHODS: To investigate the effectiveness of toluidine blue as topical photosensitizer. Eleven patients participated in this study; fifteen oral leukoplakia lesions were treated, in several sessions, with 2.5 % toluidine blue and an LED source of 630 nm wavelength. Patients were evaluated at baseline (t0), at the end of treatment cycles (t1) and one year from the end of treatment (t2). All the treated sites were photographed at each visit. Images were processed with ImageJ 1.52 software in order to obtain the areas (mm2) of the treated lesions. Comparison between data at different follow-up was performed using a paired T-test. RESULTS: At t1, complete response was obtained in six lesions, partial response in seven lesions while only two lesions showed no response. At t2, a further improvement was observed in two patients. The analysis of the areas showed significant reduction of the lesion size from t0 to t1 (p = 0.003), and from t1 to t2 (p = 0.01). CONCLUSION: Toluidine blue appears to be a promising photosensitizer in the photodynamic therapy of oral leukoplakia.


Assuntos
Fotoquimioterapia , Cloreto de Tolônio , Humanos , Leucoplasia Oral/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Cloreto de Tolônio/uso terapêutico
13.
Lasers Med Sci ; 35(1): 79-85, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31081523

RESUMO

Chagas disease is endemic in Latin America and increasingly found in non-endemic countries. Its treatment is limited due to the variable efficacy and several side effects of benznidazole. Photodynamic antimicrobial chemotherapy (PACT) may be an attractive approach for treating Chagas disease. Here, the trypanocidal activity of PACT was investigated in vitro using phenothiazine derivatives. The cytotoxicity of both, methylene blue (MB) and toluidine blue (TBO), was determined on macrophages cultures using AlamarBlue method. The trypanocidal activity of the two photosensitizers was initially evaluated by determining their IC50 values against trypomastigote forms. After this, the trypanocidal effect was evaluated in cultures of infected macrophages using an automatized image analysis protocol. All experiments were performed in the dark and in the clear phase (after a photodynamic exposure). The compounds showed no cytotoxicity in both phases at the tested concentrations. The IC50 values for the sole use of MB and TBO were 2.6 and 1.2 µM, respectively. The photoactivation of the compounds using a fixed energy density (J/cm2) caused a reduction of the IC50 values to 1.0 and 0.9 µM, respectively. It was found that, on infected macrophage, the use of TBO significantly reduced the number of infected cells and parasitic load, and this effect was increased in the presence of light. The results of the present study are indicative that PACT may be considered as both selective and effective therapeutic intervention for treating Chagas disease.


Assuntos
Antiparasitários/farmacologia , Fenotiazinas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Antiparasitários/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Doença de Chagas/tratamento farmacológico , Humanos , Luz , Azul de Metileno/química , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Camundongos Endogâmicos BALB C , Carga Parasitária , Fenotiazinas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Cloreto de Tolônio/química , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Trypanosoma cruzi/efeitos da radiação
14.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 27-33. DENTAL SUPPLEMENT, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538447

RESUMO

Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.


Assuntos
Líquen Plano Bucal/tratamento farmacológico , Fotoquimioterapia , Cloreto de Tolônio/uso terapêutico , Doença Crônica , Humanos , Fármacos Fotossensibilizantes
15.
Oral Dis ; 25(8): 1954-1963, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478283

RESUMO

OBJECTIVE: In this study, the effect of photodynamic therapy with topical corticosteroid in oral lichen planus patients was compared. MATERIAL AND METHODS: In this randomized, double-blind clinical trial, eight patients with bilateral oral OLP lesions were recruited. Toluidine blue was applied on the lesions of both sides; a 660-nm diode laser InGaAlP was irradiated for 10 min (power: 25 mW, fluence: 19.23 J/cm2 , probe cross section: 0.78 cm2 ) for three sessions. In the control side of the oral mucosa, only sham laser was used. Follow-up sessions were held on weeks 3 and 7. In week 3, oral paste triamcinolone acetonide 0.1% was prescribed. Response rates were assessed clinically by VAS, Thongprasom sign scoring, clinical severity index, efficacy indices, and the amount of reduction in the size of the lesions. The Mann-Whitney test was used to evaluate the treatment outcomes. RESULTS: In spite of the control side, all scores improved significantly between sessions 0 and 4 for the intervention side. The differences between the changes in almost all scores between sessions 0 and 4 in both the intervention and control sides were significantly considerable (p value < .05). CONCLUSION: Photodynamic therapy can be used as an alternative therapy alongside standard methods or as a new modality for refractory OLP.


Assuntos
Corticosteroides/uso terapêutico , Líquen Plano Bucal/terapia , Terapia com Luz de Baixa Intensidade/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Cloreto de Tolônio/uso terapêutico , Administração Tópica , Corticosteroides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Photodiagnosis Photodyn Ther ; 28: 221-225, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31394297

RESUMO

BACKGROUND: Orthodontics involves diagnosis and treatment of dental and skeletal malocclusions. Orthodontic apparatus may repair these malocclusions but may also impair oral hygiene making patients prone to develop both periodontal diseases and caries. Antimicrobial agents may be used to prevent this.To avoid increased antimicrobial resistance to available drugs, A-PDT (Antimicrobial Photodynamic Therapy) appears as a viable alternative. OBJECTIVE: This work aimed to evaluate the efficacy of A-PDT on reducing the number of colony forming units (CFU) through the use of phenothiazine compound (methylene blue+ toluidine blue) as a photosensitizer, associated with red LED (λ640±5ηm) irradiation in orthodontic patients. METHODOLOGY: Twenty-one patients consented to participate in the study. Three biofilm collections were performed around the brackets and gums of the inferior central incisors; first before any intervention (Control); second after 5min of pre-irradiation and the last one immediately after AmPDT. Subsequently, a microbiological routine for microorganism growth period were performed and CFU counting after a 24h done. RESULTS: The data showed that the AmPDT was able to reduce CFU count around 90% when compared to Control group (p=0.007) and also between the A-PDT and Photosensitizer groups (p=0.010). However, there were no differences between the Control and Photosensitizer groups. CONCLUSION: A-PDT associated with the use of phenothiazine compounds and red LED was able to significantly reduce the number of CFUs in orthodontic patients.


Assuntos
Antiprotozoários/uso terapêutico , Biofilmes/efeitos dos fármacos , Cárie Dentária/microbiologia , Braquetes Ortodônticos , Doenças Periodontais/microbiologia , Fenotiazinas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Contagem de Colônia Microbiana , Estudos Cross-Over , Humanos , Azul de Metileno/uso terapêutico , Cloreto de Tolônio/uso terapêutico
17.
Sci Rep ; 9(1): 8248, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160615

RESUMO

Periodontitis is initiated by causative bacteria in the gingival sulcus. However, as the lesion is often deep and out of circulation system and biofilm is frequently formed on the bacteria cluster, use of antibacterial agents has been limited and the invasive method such as curettage is thought as an only treatment. Here we designed non-invasive photodynamic therapy (PDT), with the ointment which leads a photosensitizer deliverable into gingival sulcus. We assessed whether 650 nm light-emitting-diode (LED) penetrates the 3-mm soft tissue and effectively activates a photosensitizer toluidine-blue-O (TBO) through the thickness to remove Porphyromonas gingivalis and Fusobacterium nucleatum species. The oral ointment formulation was optimized to efficiently deliver the photosensitizer into gingival sulcus and its efficacy of PDT was evaluated in in vitro and in vivo models. Four weeks of TBO-formulation mediated-PDT treatment significantly attenuated periodontitis-induced alveolar bone loss and inflammatory cytokines production in rats. These results confirm that a 650 nm LED indeed penetrates the gingiva and activates our TBO formulation which is sufficiently delivered to, and retained within, the gingival sulcus; thus, it effectively kills the bacteria that reside around the gingival sulcus. Collectively, TBO-mediated PDT using LED irradiation has potential as a safe adjunctive procedure for periodontitis treatment.


Assuntos
Fusobacterium nucleatum/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Fotoquimioterapia , Porphyromonas gingivalis/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Reabsorção Óssea/patologia , Liberação Controlada de Fármacos , Inflamação/patologia , Masculino , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ratos Wistar , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Viscosidade
18.
Photodiagnosis Photodyn Ther ; 27: 167-172, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31116996

RESUMO

BACKGROUND: The persistence of periodontal pockets > 5 mm after periodontal treatments increases the risk of periodontitis recurrence and the need of periodontal surgery. This study evaluated the impact of tooth-related factors on the effectiveness of adjunctive photodynamic treatment (PDT) in the reduction of pockets > 5 mm during active periodontal treatment. METHODS: Thirty-six patients suffering from severe chronic periodontitis were evaluated in a 6-months split-mouth randomized clinical trial. Each quadrant was assigned to test (scaling and root planing (SRP) + PDT) or control (SRP alone) group. PDT was conducted using the toluidine blue O and a light-emitting diode (LED) with a red spectrum. PDT applications were performed immediately after SRP, 7 days later and at 3 months. Plaque index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), and clinical attachment level (CAL) were recorded at baseline, 3 and 6 months. RESULTS: Multilevel analysis showed a significant reduction of pockets > 5 mm in test group in comparison with control group at 3 (OR = 0.69) and 6 months (OR = 0.77). This effect was mainly observed at 6 months in initially deep sites (PPD > 6 mm) with BOP (OR = 0.57). At sites exhibiting PI > 1 no PDT effect was observed. A more moderate PDT effect was observed on mean PPD and BOP reductions at 3 months only. CONCLUSIONS: Repeated applications of PDT significantly improved SRP outcomes, reducing by more than 40% residual pockets > 5 mm in initially deep and bleeding on probing periodontal sites. PDT effect was negatively influenced by dental plaque accumulation.


Assuntos
Periodontite Crônica/tratamento farmacológico , Raspagem Dentária/métodos , Bolsa Periodontal/tratamento farmacológico , Fotoquimioterapia/métodos , Adulto , Idoso , Periodontite Crônica/terapia , Terapia Combinada , Índice de Placa Dentária , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Fármacos Fotossensibilizantes/uso terapêutico , Aplainamento Radicular , Cloreto de Tolônio/uso terapêutico
19.
Lasers Med Sci ; 34(8): 1535-1545, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30825010

RESUMO

Antibiotics and photodynamic therapy (PDT) are widely employed in curing acne. However, antibiotics as an effective treatment would lead to bacterial resistance and severe side effects. In this study, we aimed to develop a novel TBO hydrogel, which could prolong the retention time of photosensitizer (TBO) at the lesion site and improve therapeutic effect. In vitro antibacterial experiments (against Staphylococcus aureus and Escherichia coli), the response surface methodology was used to optimize the formulation of TBO hydrogel. The results indicated that the optimal formulation was 0.5% (v/v) carbomer, 0.01 mg/mL TBO, 0.5% (v/v) ethanol concentration, 0.5% (v/v) Tween 80, the mass ratio of NaOH to carbomer of 0.4 (w/w). The TBO hydrogel formulation showed the strong antibacterial activity for Propionibacterium acnes. The stability, pH, and antibacterial activity of TBO hydrogel did not significantly change under 4 °C, 25 °C, and 40 °C during 6-week storage. Furthermore, TBO combined with carbomer hydrogel showed the 51.28% (4 h) and 69.80% (24 h) release. In summary, the hydrogel TBO might be a vital therapeutic strategy to promote the PDT applied in the topical therapy of acne. Graphical abstract A TBO hydrogel for photodynamic therapy in the treatment of acne.


Assuntos
Acne Vulgar/tratamento farmacológico , Hidrogéis/química , Fotoquimioterapia , Cloreto de Tolônio/uso terapêutico , Resinas Acrílicas/química , Análise de Variância , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Etanol/farmacologia , Luz , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polissorbatos/farmacologia , Hidróxido de Sódio/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Fatores de Tempo , Cloreto de Tolônio/farmacologia , Viscosidade
20.
Int J Oral Maxillofac Implants ; 33(5): 1019-1026, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30231087

RESUMO

PURPOSE: Decontamination of the rough surfaces of dental implants is a challenge in the treatment of peri-implantitis. An acceptable cleaning technique must be able to debride and detoxify the surface without traumatizing it. This study assessed the possible implant surface alterations following decontamination with laser, photodynamic therapy (PDT), and application of chlorhexidine (CHX). MATERIALS AND METHODS: Of 16 dental implants with sandblasted, large-grit, acid-etched surfaces, Aggregatibacter actinomycetemcomitans was cultured on the surfaces of 15 implants for 48 hours. These 15 implants were divided into five groups of three and were subjected to erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation, 630 nm light-emitting diode and toluidine blue O photosensitizer, 810 nm diode laser, and indocyanine green-based photosensitizer, 2% CHX, and control group (no treatment). One implant remained intact. The morphology and element/phase identification of the implants were studied using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS), respectively. RESULTS: The SEM images and EDS maps revealed that the decontamination methods did not alter the surface quality of the implants. However, in photodynamic therapy, sodium chloride that remained from rinsing liquid can make an adhesive layer on the surface of the treated implants. CONCLUSION: Er:YAG laser irradiation and PDT did not alter the surfaces of sandblasted, large-grit, acid-etched implants.


Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Biofilmes/efeitos dos fármacos , Clorexidina/uso terapêutico , Implantes Dentários/microbiologia , Lasers Semicondutores/uso terapêutico , Fotoquimioterapia/métodos , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Anti-Infecciosos Locais/uso terapêutico , Corantes/uso terapêutico , Descontaminação/métodos , Humanos , Verde de Indocianina/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Microscopia Eletrônica de Varredura , Peri-Implantite/terapia , Fármacos Fotossensibilizantes/uso terapêutico , Propriedades de Superfície , Cloreto de Tolônio/uso terapêutico
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