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1.
J Indian Soc Pedod Prev Dent ; 38(3): 304-310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33004730

RESUMO

Background: Despite endodontic infections being a common problem in the primary dentition, some of the infected primary teeth can remain functional until the exfoliation through endodontic treatment. The primary endodontic treatment goal must be to optimize root canal disinfection and to prevent reinfection. Aim: The aim of this study is to compare the antifungal efficacy of antimicrobial photodynamic therapy, LASER, and 1% clotrimazole as irrigants by reducing the colony-forming units (CFU) of Candida albicans in the infected root canals of primary teeth. Materials and Methods: Pulp therapy was performed on deciduous mandibular second molars of 20 healthy children aged 5-8 years, which were divided into four groups of intracanal disinfection protocols: Group 1 (n = 5) - Sodium Hypochlorite, Group 2 (n = 5) - Photodynamic, Group 3 (n = 5) - Normal saline with LASER, and Group 4 - (n = 5) Antifungal. Disinfection potential was compared by collecting samples one just after access opening and the other after the experimental groups using paper points. The samples were cultured and incubated for 48 h to check change in CFU of the fungi. Results: Data were analyzed statistically using the Shapiro-Wilk's test, Mann-Whitney U-test; Kruskal-Wallis test, and Wilcoxon signed-ranks test. No significant difference (P > 0.05) was found between the different groups. However, complete inhibition of C. albicans CFU was seen with Group 4. Conclusion: One percent Clotrimazole (antifungal) can be utilized as an adjunct in the endodontic irrigation protocol for better success of pulpectomy in children.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Antifúngicos , Candida albicans , Criança , Pré-Escolar , Cavidade Pulpar , Desinfecção , Humanos , Projetos Piloto , Irrigantes do Canal Radicular/uso terapêutico , Preparo de Canal Radicular , Dente Decíduo
2.
Wiad Lek ; 73(8): 1655-1658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33055328

RESUMO

OBJECTIVE: The aim: To follow-up nitric oxide content values in rat serum at the development of Staphylococcus aureus infected radiation skin injuries and their photodynamic therapy. PATIENTS AND METHODS: Materials and methods: Eighty WAG male rats were studied in an experiment. Four groups were identified for evaluation. Group 1 included unaffected intact rats (n=20). Group 2 involved rats (n=20) with a modeled radiation-induced ulcer of the skin. The rats (n=20) with a modeled radiation-induced skin ulcer followed by infecting with Staphylococcus aureus were referred to group 3. Group 4 included rats (n=20) with Staphylococcus aureus infected radiation skin ulcer exposed to photodynamic therapy. Rats of groups 1-4 were sampled for biochemical blood examination on days 7, 14, 21, 30 and 45. Total nitric oxide metabolites (nitrites and nitrates) were measured according to V.A. Metelskaya et al. method. RESULTS: Results: Infectious agent (Staphylococcus aureus) present in skin ulcer impairs nitric oxide metabolism in rat blood serum that manifested in decreased total nitric oxide metabolites content on day 7, followed by its increase within days 14 to 45. While photodynamic therapy exposed on the Staphylococcus aureus infected radiation skin ulcer, total nitric oxide metabolites in blood serum had increased by day 7, but days 14 to 45 level was compliant with physiological norm. CONCLUSION: Conclusions: Infecting radiation skin ulcers with Staphylococcus aureus causes impaired nitric oxide metabolism, while photodynamic therapy helps to normalize the metabolism of the above-mentioned chemical compound that can improve healing of radiation skin ulcers.


Assuntos
Fotoquimioterapia , Animais , Masculino , Óxido Nítrico , Ratos , Pele , Staphylococcus aureus , Cicatrização
3.
Arch Esp Urol ; 73(8): 724-734, 2020 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-33025917

RESUMO

OBJECTIVES: In recent years, there has been a rise concerning the research and development of focal prostate cancer therapies as a consequence of the high percentage of low-risk and localized prostate cancers. These focal therapies aim at preserving the gland in selected patients to avoid overtreatment. The application of lasers for focal ablation and photodynamic therapy has shown promising results in exchange for a minimal rate of adverse events compared to radical treatments. MATERIAL AND METHODS: An extensive review of the available literature on focal laser treatments for localized prostate cancer was conducted. A search in PubMed and Embase was carried out by the following keywords: "Localised prostate cancer", "Low-risk prostate cancer", "Focal therapy", "Magnetic Resonance in localized prostate cancer", "Focal laser ablation" , "Photodynamic therapy" and "TOOKAD". RESULTS: Photodynamic therapy with TOOKAD is the only focal therapy evaluated in a phase III clinical trial,showing a lower rate of progression and a longer time to progression compared to active surveillance. Other studies carried out have revealed a percentage up to 80% of negative biopsies 6 months after TOOKAD. Likewise, the quality of life of patients treated using focal laser ablation techniques and photodynamic therapy has been minimally altered, as most adverse effects have been shown to be mild and transient, with dysuria and hematuria being the most frequent. CONCLUSIONS: Despite the fact that focal therapies are still not recommended outside the context of clinical trials and the lack of comparative studies between the different techniques, laser focal therapies seem to havea future within the new approaches for localized prostate cancer.


Assuntos
Terapia a Laser , Fotoquimioterapia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Qualidade de Vida
4.
Molecules ; 25(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977525

RESUMO

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10-15 years in order to identify the most promising areas.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Porfirinas/farmacologia , Antivirais/química , Humanos , Indóis/química , Indóis/farmacologia , Pandemias , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Ligação Viral/efeitos dos fármacos
5.
Nat Commun ; 11(1): 4530, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913195

RESUMO

Various cancer cells have been demonstrated to have the capacity to form plasmonic gold nanoparticles when chloroauric acid is introduced to their cellular microenvironment. But their biomedical applications are limited, particularly considering the millimolar concentrations and longer incubation period of ionic gold. Here, we describe a simplistic method of intracellular biomineralization to produce plasmonic gold nanoparticles at micromolar concentrations within 30 min of application utilizing polyethylene glycol as delivery vector for ionic gold. We have characterized this process for intracellular gold nanoparticle formation, which progressively accumulates proteins as the ionic gold clusters migrate to the nucleus. This nano-vectorized application of ionic gold emphasizes its potential biomedical opportunities while reducing the quantity of ionic gold and required incubation time. To demonstrate its biomedical potential, we further induce in-situ biosynthesis of gold nanoparticles within MCF7 tumor mouse xenografts which is followed by its photothermal remediation.


Assuntos
Cloretos/administração & dosagem , Portadores de Fármacos/química , Compostos de Ouro/administração & dosagem , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Animais , Biomineralização/efeitos da radiação , Feminino , Ouro/efeitos da radiação , Humanos , Hipertermia Induzida/métodos , Íons , Células MCF-7 , Nanopartículas Metálicas/efeitos da radiação , Camundongos , Fotoquimioterapia/métodos , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
6.
PLoS One ; 15(9): e0237851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877414

RESUMO

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 µM) decreased the number of P. aeruginosa colony-forming units by 4.2 log10. Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.


Assuntos
Antibacterianos/uso terapêutico , Fotoquimioterapia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/efeitos da radiação , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Etilenodiaminas/uso terapêutico , Feminino , Luz , Camundongos , Camundongos Endogâmicos BALB C , Viabilidade Microbiana/efeitos dos fármacos , Modelos Biológicos , Células NIH 3T3 , Fotodegradação , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/farmacologia , Protoporfirinas/uso terapêutico , Pseudomonas aeruginosa/efeitos da radiação , Cicatrização/efeitos dos fármacos
7.
Int J Nanomedicine ; 15: 5803-5811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821102

RESUMO

Introduction: Photodynamic therapy (PDT), which induces tissue damage by exposing tissue to a specific wavelength of light in the presence of a photosensitizer and oxygen, is a promising alternative treatment that could be used as an adjunct to chemotherapy and surgery in oncology. Cell-penetrating peptides (CPPs) with high arginine content, such as protamine, have membrane translocation and lysosome localization activities. They have been used in an extensive range of drug delivery applications. Methods: We conjugated cell-penetrating peptides (CPPs) with methylene blue (MB) and then purification by FPLC. Synthesis structure was characterized by the absorbance spectrum, FPLC, Maldi-TOF, and then evaluated cell viability by cytotoxicity assay after photodynamic therapy (PDT) assay. An uptake imaging assay was used to determine the sites of MB and MB-Pro in subcellular compartments. Results: In vitro assays showed that MB-Pro has more efficient photodynamic activities than MB alone for the colon cancer cells, owing to lysosome rupture causing the rapid necrotic cell death. In this study, we coupled protamine with MB for high efficacy PDT. The conjugates localized in the lysosomes and enhanced the efficiency of PDT by inducing necrotic cell death, whereas PDT with non-coupled MB resulted in only apoptotic processes. Discussion: Our research aimed to enhance PDT by engineering the photosensitizers using CPPs coupled with methylene blue (MB). MB alone permeates through the cell membrane and distributes into the cytoplasm, whereas coupling of MB dye with CPPs localizes the MB through an endocytic mechanism to a specific organelle where the localized conjugates enhance the generation of reactive oxygen species (ROS) and induce cell damage.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Azul de Metileno/farmacologia , Fotoquimioterapia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Células HT29 , Humanos , Imageamento Tridimensional , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Azul de Metileno/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
8.
Int J Nanomedicine ; 15: 5459-5471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801700

RESUMO

Purpose: Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. Methods and Results: PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG ("PEG-BSA-AgNP/ICG"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. Conclusion: Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Difusão Dinâmica da Luz , Meia-Vida , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Melanoma Experimental/tratamento farmacológico , Camundongos Endogâmicos ICR , Camundongos Nus , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/química , Soroalbumina Bovina/química , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier
9.
PLoS One ; 15(8): e0237330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32780752

RESUMO

We investigated whether response to photodynamic therapy (PDT) with intravitreal aflibercept injection (IAI) for polypoidal choroidal vasculopathy (PCV) differs depending on fellow eye condition. A retrospective review was conducted for consecutive 60 eyes with PCV treated with PDT combined with IAI as well as 2-years of follow-up data. Fellow eyes were divided into 4 groups; Group 0: no drusen, Group 1; pachydrusen, Group 2; soft drusen, Group 3: PCV/fibrovascular scarring. Best-corrected visual acuity improved at 24-months irrespective of groups and there were no significant differences in visual improvement among treated eyes among the 4 groups. Within 2-years, 35 (58.3%) required the retreatment. The need for retreatment including additional injection and the combination therapy was significantly less in Group 1(12.5%) compared to the others (P = 0.0038) and mean number of additional IAI was also less in Group 1 compared to the others (P = 0.017). The retreatment-free period from the initial combination therapy was longest in Group 1 (23.6±1.1 months) (P = 0.0055, Group 0: 19.1±6.9, Group 2: 12.8±7.9, Group 3: 11.5±9.9). The need for retreatment was significantly different according to fellow-eye condition. Among PCV patients, pachydrusen in fellow eyes appear to be a predictive characteristic for a decreased treatment burden at 2 years.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Fotoquimioterapia/métodos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Drusas Retinianas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/efeitos dos fármacos , Neovascularização de Coroide/diagnóstico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Drusas Retinianas/diagnóstico , Retratamento/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
10.
Photodiagnosis Photodyn Ther ; 31: 101943, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32763473

RESUMO

BACKGROUND: To review the effect of ultraviolet germicidal irradiation (UVGI) as a disinfection method for filtering facepiece respirators (FFRs) to facilitate reuse during COVID-19 pandemic. METHODS: Systematic review of the research concerning UVGI for FFRs disinfection to facilitate reuse (also termed limited reuse) during respiratory infectious diseases where aerosol transmission is considered possible. RESULTS: UVGI is one possible method for respiratory disinfection to facilitate the reuse of dwindling supplies. Appropriate dose UVGI exposition could provide enough energy to effectively decontaminate respiratory viral agents and maintain respirator's integrity for reuse. There was not currently sufficient research evidence on the effect of UVGI to inactivate coronaviruses SARS-CoV-2, and the practical application of UVGI is still unclear. . CONCLUSION: Appropriate dose UVGI exposition could provide enough energy to effectively decontaminate respiratory viral agents and maintain respirator's integrity for reuse. Further evidence concerning UVGI as a decontamination technique specifically for SARS-CoV-2 isneeded.


Assuntos
Infecções por Coronavirus/prevenção & controle , Descontaminação/métodos , Contaminação de Equipamentos/prevenção & controle , Pandemias/prevenção & controle , Fotoquimioterapia/métodos , Pneumonia Viral/prevenção & controle , Terapia Ultravioleta/métodos , Ventiladores Mecânicos/virologia , Infecções por Coronavirus/epidemiologia , Reutilização de Equipamento/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Pneumonia Viral/epidemiologia
13.
J Nippon Med Sch ; 87(3): 110-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655090

RESUMO

BACKGROUND: Cutaneous wound healing is a complex, dynamic physiological process. Traditional methods of promoting wound healing are not always effective. Consequently, alternative modalities, such as photodynamic therapy (PDT), are needed. We examined the effectiveness and underlying mechanisms of PDT in a murine model of acute wound healing. METHODS: Two excisional wounds were produced, one on each side of the midline, in C57bL/6J mice. Methyl 5-aminolevulinate hydrochloride (MAL) was applied to the right-side wound. After 1 to 3 hours of incubation, the wound was irradiated with red light. The left-side wound was not treated with MAL or red light. On Day 14, the wounds were excised and subjected to histological and immunohistochemical analysis. RESULTS: During the first week, no difference was seen between the two sides. However, at week 2, PDT-treated wounds exhibited delayed re-epithelialization. On Day 14, hematoxylin and eosin (HE) staining showed a continuous epithelial lining in untreated wounds. In contrast, PDT-treated wounds partially lacked epithelium in the wound bed. Masson's Trichrome (MTC) staining showed a thicker dermis and more collagen fibers and inflammatory cells in PDT-treated wounds than in untreated wounds. Immunohistochemical analyses showed significantly fewer CD31+ blood vessels and greater collagen III density in PDT-treated wounds than in untreated wounds. However, treated and untreated wounds did not differ in collagen I density. CONCLUSIONS: PDT delayed acute wound healing in a murine model of secondary intention wound healing.


Assuntos
Fotoquimioterapia/efeitos adversos , Fenômenos Fisiológicos da Pele , Cicatrização/efeitos da radiação , Animais , Colágeno/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pele/metabolismo , Fatores de Tempo , Cicatrização/fisiologia , Infecção dos Ferimentos
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(3): 283-288, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32616121

RESUMO

Objective To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on Propionibacterium acnes (P.acnes) biofilm. Methods P.acnes biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm2),ALA-PDT2 group (100 J/cm2),ALA-PDT3 group (200 J/cm2)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. Results CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(md=0.003, P=1.000)and LED group(md=-0.025, P=1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (md=-0.162, P<0.001),ALA-PDT2 group (md=-0.254, P<0.001),and ALA-PDT3 group (md=-0.352, P<0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(md=-0.044, P=1.000)and LED groups (md=-0.020, P=1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (md=1.175, P<0.001),ALA-PDT2 group (md=1.942, P<0.001),and ALA-PDT3 group (md=-0.352, md=2.742, P<0.001). Conclusions ALA-PDT has an inhibitory effect on P.acnes biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.


Assuntos
Biofilmes , Ácido Aminolevulínico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Propionibacterium acnes
15.
Cochrane Database Syst Rev ; 7: CD008946, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632956

RESUMO

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions. OBJECTIVES: To assess the effects of interventions for MF in all stages of the disease. SEARCH METHODS: We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines. MAIN RESULTS: This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs. AUTHORS' CONCLUSIONS: ​​There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.


Assuntos
Micose Fungoide/terapia , Neoplasias Cutâneas/terapia , Acitretina/efeitos adversos , Acitretina/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bexaroteno/uso terapêutico , Terapia Combinada/métodos , Humanos , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Micose Fungoide/patologia , Estadiamento de Neoplasias/métodos , Terapia PUVA/métodos , Fotoquimioterapia/métodos , Fotoferese/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Cutâneas/patologia
17.
Photodiagnosis Photodyn Ther ; 31: 101914, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645436

RESUMO

BACKGROUND: Actinic keratosis (AK) affects one quarter of over 60  year olds in Europe with the risk of transforming into invasive squamous cell carcinoma. Daylight photodynamic therapy (dPDT) is an effective and patient preferred treatment that uses sunlight to clear AK. Currently, there is no standardised method for measuring the light received during treatment. METHODS: SmartPDT® is a smartphone-based application and web-portal, developed by siHealth Ltd, enabling remote delivery of dPDT. It uses satellite imagery and computational algorithms to provide real-time determination of exposure to PpIX-effective solar radiation ("light dose"). The application also provides forecast of expected radiant exposures for 24- and 48-hs prior to the treatment period. Validation of the real-time and forecasted radiant exposure algorithms was performed against direct ground-based measurement under all weather conditions in Chilton, UK. RESULTS: Agreement between direct ground measurements and satellite-determined radiant exposure for 2-h treatment was excellent at -0.1 % ± 5.1 % (mean ±â€¯standard deviation). There was also excellent agreement between weather forecasted radiant exposure and ground measurement, 1.8 % ± 17.7 % at 24-hs and 1.6 % ± 25.2 % at 48-hs. Relative Root Mean Square of the Error (RMSEr) demonstrated that agreement improved as time to treatment reduced (RMSEr = 22.5 % (48 -hs), 11.2 % (24-hs), 5.2 % (real-time)). CONCLUSION: Agreement between satellite-determined, weather-forecasted and ground-measured radiant exposure was better than any existing published literature for dPDT. The SmartPDT® application and web-portal has excellent potential to assist with remote delivery of dPDT, an important factor in reducing risk in an elderly patient population during the Covid-19 pandemic.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Radiometria/métodos , Smartphone/estatística & dados numéricos , Idoso , Ritmo Circadiano , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Ceratose Actínica/diagnóstico , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Medição de Risco , Luz Solar , Resultado do Tratamento , Reino Unido
18.
PLoS One ; 15(6): e0235213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579608

RESUMO

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Doenças da Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Corioide/fisiologia , Doenças da Coroide/patologia , Terapia Combinada , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Lasers , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Verteporfina/uso terapêutico , Acuidade Visual
19.
Nat Commun ; 11(1): 3262, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591538

RESUMO

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.


Assuntos
Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Fotoquimioterapia , Fótons , Rutênio/química , Animais , Proliferação de Células , Sobrevivência Celular , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Feminino , Células HeLa , Humanos , Camundongos Nus , Oxigênio Singlete/química , Análise Espectral , Esferoides Celulares/patologia
20.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
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