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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Eur J Med Chem ; 200: 112341, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32505848

RESUMO

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections in both the community and healthcare settings challenges the limited options of effective antibiotics and motivates the search for alternative therapeutic solutions, such as antibacterial photodynamic therapy (aPDT). While many publications have described the promising anti-bacterial activities of PDT in vitro, its applications in vivo and in the clinic have been very limited. This limited availability may in part be due to variabilities in the selected photosensitizing agents (PS), the variable testing conditions used to examine anti-bacterial activities and their effectiveness in treating MRSA infections. We thus sought to systematically review and examine the evidence from existing studies on aPDT associated with MRSA and to critically appraise its current state of development and areas to be addressed in future studies. In 2018, we developed and registered a review protocol in the International Prospective Register of Systematic Reviews (PROSPERO) with registration No: CRD42018086736. Three bibliographical databases were consulted (PUBMED, MEDLINE, and EMBASE), and a total of 113 studies were included in this systematic review based on our eligibility criteria. Many variables, such as the use of a wide range of solvents, pre-irradiation times, irradiation times, light sources and light doses, have been used in the methods reported by researchers, which significantly affect the inter-study comparability and results. On another note, new approaches of linking immunoglobulin G (IgG), antibodies, efflux pump inhibitors, and bacteriophages with photosensitizers (PSs) and the incorporation of PSs into nano-scale delivery systems exert a direct effect on improving aPDT. Enhanced activities have also been achieved by optimizing the physicochemical properties of the PSs, such as the introduction of highly lipophilic, poly-cationic and site-specific modifications of the compounds. However, few in vivo studies (n = 17) have been conducted to translate aPDT into preclinical studies. We anticipate that further standardization of the experimental conditions and assessing the efficacy in vivo would allow this technology to be further applied in preclinical trials, so that aPDT would develop to become a sustainable, alternative therapeutic option against MRSA infection in the future.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia/métodos , Infecções Estafilocócicas/terapia , Anticorpos Antibacterianos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Fotoquimioterapia/normas , Fármacos Fotossensibilizantes/uso terapêutico
8.
Cell Prolif ; 53(5): e12821, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32364266

RESUMO

OBJECTIVES: Photodynamic therapy (PDT) is a promising approach for cancer treatment, and the underlying signalling pathway changes has been carried out for studying the PDT mechanisms, but is majorly limited to organic photosensitizers (PSs). For the emerging nano-PSs typically possessing higher 1 O2 quantum yield, few mechanistic studies were carried out, which limited their further applications in clinical therapeutics. PI3K/Akt signalling pathway, a most frequently activated signalling network in cancers, could promote cancer cell survival, but was seldom reported in previous PDT studies mediated by nano-PSs. MATERIALS AND METHODS: Sulphur doped carbon dots (S-CDs) was prepared via a hydrothermal synthetic route and was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy and so on. CCK-8 assay and Annexin V/PI staining were performed to demonstrate the death of cancer cells, Western blot, RT-PCR and immunofluorescence were employed to explore the underlying mechanism, and variation of PI3K/Akt and other signalling pathways was detected by Western blot. RESULTS: S-CDs was successfully synthesized, and it was much more efficient compared with classic organic PSs. S-CDs could induce cancer cell death through mitochondria mediated cell apoptosis with the imbalance of Bcl-2 family proteins and caspase cascade via several signalling pathways. Low concentration of S-CDs could effectively inhibit PI3K/Akt pathway and promote p38/JNK pathway, on one way inhibiting cancer cell survival and on the other way promoting cell apoptosis. CONCLUSIONS: Herein, we found that S-CDs acted as an inhibitor of the PI3K/Akt pathway for efficient cancer cell killing, thus yielding in a higher PDT performance over the existing photosensitizers.


Assuntos
Carbono/farmacologia , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Enxofre/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
9.
PLoS One ; 15(5): e0232775, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374766

RESUMO

Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.


Assuntos
Adaptação Biológica/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Streptococcus mutans/efeitos dos fármacos , Adaptação Biológica/efeitos da radiação , Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/efeitos da radiação , Biofilmes/efeitos da radiação , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Higiene Bucal/métodos , Periodontite/tratamento farmacológico , Streptococcus mutans/efeitos da radiação
10.
Am J Ophthalmol ; 217: 104-113, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32360342

RESUMO

PURPOSE: To study the early anatomic choroidal alterations in eyes with chronic central serous chorioretinopathy (CSCR) undergoing photodynamic therapy (PDT). DESIGN: Multicenter retrospective cohort study. METHODS: A total of 77 patients and 81 eyes with chronic CSCR treated with PDT and 64 untreated fellow eyes were evaluated. Central macular thickness (CMT) and choroidal features including subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were analyzed. Choroidal vascularity index (CVI) was calculated in all study eyes at baseline and at 1- and 3-months post-PDT. RESULTS: In eyes receiving PDT, Snellen visual acuity (VA) significantly improved at months 1 and 3 (P < .001). CMT and SFCT showed a significant reduction from baseline at months 1 and 3 (P < .001), whereas TCA and LCA showed a significant decrease only at the 1-month follow-up visit. Baseline mean TCA and LCA were 2.30 ± 1.41 mm2 and 1.23 ± 0.73 mm2, respectively, and decreased to 2.07 ± 1.21 mm2 and 1.08 ± 0.63 mm2 at the 1-month follow-up visit, respectively (P = .01). No significant changes were recorded for SCA and CVI. In the fellow eye group, VA, CMT, and all choroidal parameters showed no differences between baseline and any follow-up visits (all P > .05). CONCLUSIONS: After PDT for chronic CSCR we observed sustained reductions in CMT and SFCT, while reductions in TCA and LCA were only noted at the 1-month follow-up interval. These choroidal parameters may provide additional quantitative biomarkers to evaluate the anatomic response to therapy but await further prospective validation.


Assuntos
Coriorretinopatia Serosa Central/diagnóstico , Corioide/patologia , Fotoquimioterapia/métodos , Verteporfina/uso terapêutico , Acuidade Visual , Coriorretinopatia Serosa Central/tratamento farmacológico , Doença Crônica , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Macula Lutea/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
11.
Photodiagnosis Photodyn Ther ; 31: 101804, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32437972

RESUMO

•The World today is facing a great effort for the control of infections.•Nowadays COVID-19 is the large global outbreak and is the major public health issue.•This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Infecções Respiratórias/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias , Fármacos Fotossensibilizantes
12.
Photodiagnosis Photodyn Ther ; 31: 101804, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-356604

RESUMO

•The World today is facing a great effort for the control of infections.•Nowadays COVID-19 is the large global outbreak and is the major public health issue.•This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Infecções Respiratórias/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias , Fármacos Fotossensibilizantes
13.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276405

RESUMO

Since their invention, periodic mesoporous organosilicas (PMOs), an innovative class of materials based on organic as well as inorganic hybrid nanocomposites, have gathered enormous interest owing to their advantageous physicochemical attributes over the pristine mesoporous silica nanoparticles (MSNs). To further increase the interactions with the therapeutic guest species and subsequent compatibility as well as the physicochemical properties of PMOs, we demonstrate the post-hydroxylation of benzene-bridged PMO-based nanoparticles for photodynamic therapy (PDT). Initially, the hydrophobic benzene group in the PMO framework is modified through electrophilic substitution-assisted hydroxylation mediated by Fenton as well as Fenton-like reactions utilizing divalent and trivalent metal salts, respectively. These post-grafted PMOs with tuned hydrophobicity resulted in improved biocompatibility as well as drug loading efficiency through governing the interactions in host-guest chemistry by changing the physicochemical properties of the PMO frameworks. Furthermore, the photosensitizer, protoporphyrin IX (PpIX) molecules, encapsulated in the PMO frameworks showed a significant PDT effect in colon carcinoma (HT-29 cell line) and Gram-negative bacterial strain, Escherichia coli (E. coli). Furthermore, the light-induced cytotoxic properties in vitro are confirmed by various tests, including lactate dehydrogenase (LDH) assay for cell membrane damage and caspase assay for apoptosis determination. Indeed, the delivered PpIX molecules from PMOs generated deadly singlet oxygen species intracellularly under visible light irradiation, resulting in cell death through concomitantly triggered apoptotic caspases. Together, our findings demonstrate that this post-modified PMO design is highly advantageous and can be used as an effective PDT platform.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Nanopartículas , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Células HT29 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Dióxido de Silício/química
14.
Mutat Res ; 852: 503160, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32265045

RESUMO

Professor Barbara Tudek received the Frits Sobels Award in 2019 from the European Environmental Mutagenesis and Genomics Society (EEMGS). This article presents her outstanding character and most important lines of research. The focus of her studies covered alkylative and oxidative damage to DNA bases, in particular mutagenic and carcinogenic properties of purines with an open imidazole ring and 8-oxo-7,8-dihydroguanine (8-oxoGua). They also included analysis of mutagenic properties and pathways for the repair of DNA adducts of lipid peroxidation (LPO) products arising in large quantities during inflammation. Professor Tudek did all of this in the hope of deciphering the mechanisms of DNA damage removal, in particular by the base excision repair (BER) pathway. Some lines of research aimed at discovering factors that can modulate the activity of DNA damage repair in hope to enhance existing anti-cancer therapies. The group's ongoing research aims at deciphering the resistance mechanisms of cancer cell lines acquired following prolonged exposure to photodynamic therapy (PDT) and the possibility of re-sensitizing cells to PDT in order to increase the application of this minimally invasive therapeutic method.


Assuntos
Carcinogênese/metabolismo , Reparo do DNA , Guanina/análogos & derivados , Neoplasias/história , Fotoquimioterapia/história , Radiossensibilizantes/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Adutos de DNA/química , Adutos de DNA/metabolismo , Dano ao DNA , Guanina/metabolismo , História do Século XX , História do Século XXI , Humanos , Peroxidação de Lipídeos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Fotoquimioterapia/métodos
15.
Medicine (Baltimore) ; 99(14): e19429, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243363

RESUMO

It is known that the presence of orthodontic brackets predisposes for a change in the biofilm, facilitating the development of gingivits. The sites are difficult to access with a toothbrush and periodontal curette, worsening inflammation, in addition, a gingival hyperplasia is associated with poor hygiene. The objective of this study is to evaluate the impact of photodinamyc therapy (PDT) as an adjuvant treatment, considering clinical immunoregulatory and microbiological parameters. This randomized, controlled, double-blind clinical study will include 34 patients, both genders, having used fixed appliance for more than 12 months, with gingivitis. Participants will be divided into two groups: G1 (n = 17)- Scaling and Root Planing + PDT placebo and G2 (n = 17)- Scaling and Root Planing + PDT. In G2 the following dosimetric parameters will be used: methylene blue 0.005%, λ= 660 nanometers (nm), 9 Joules (J) per site, irradiance= 3.5Watts (W)/ centimeters (cm), radiant exposure= 318J/cm. All participants will receive oral hygiene guidance prior the curetes scaling. The clinical periodontal data to be analyzed are plaque index, gingival index and probing depth. Crevicular fluid, from 4 pre-determined sites and saliva, will be collected and analysed for IL-6, IL-1ß, IL-8, TNF-α and IL-10 cytokines using ELISA (Enzyme immunoabsorption assay) method. Total Bacteria count will also be performed, by qPCR and Universal16SrRNA gene. All analysis will be realized using in the baseline (T0), 7 (T1) and 21 (T2) days after treatment. Oral health-related quality of life will be assessed using the OHIP-14 questionnaire at times T0 and T2. If sample distribution is normal, the Student T-test will be applied if it is not normal, the Mann-Whitney test will be used. The data will be presented in terms of ±â€ŠPD and The significance level will be set at p < 0.05. Our results may improve quality of life and add data to establish a therapeutic alternative for gingivitis during the orthodontic treatment. Registration: clinicaltrials.gov NCT04037709. https://clinicaltrials.gov/ct2/show/NCT04037709 - Registered in July 2019.


Assuntos
Gengivite/terapia , Mediadores da Inflamação/metabolismo , Azul de Metileno/uso terapêutico , Aparelhos Ortodônticos Fixos , Fotoquimioterapia/métodos , Adolescente , Adulto , Criança , Terapia Combinada , Raspagem Dentária/métodos , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Gengivite/tratamento farmacológico , Gengivite/microbiologia , Humanos , Masculino , Índice Periodontal , Qualidade de Vida , Adulto Jovem
16.
Int J Nanomedicine ; 15: 1903-1914, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256067

RESUMO

Background: Cancer is one of the major causes of death and is difficult to cure using existing clinical therapies. Clinical cancer treatments [such as surgery, chemotherapy (CHT), radiotherapy (RT) and immunotherapy (IT)] are widely used but they have limited therapeutic effects and unavoidable side effects. Recently, the development of novel nanomaterials offers a platform for combinational therapy (meaning a combination of two or more therapeutic agents) which is a promising approach for cancer therapy. Recent studies have demonstrated several types of nanomaterials suitable for photothermal therapy (PTT) based on a near-infrared (NIR) light-responsive system. PTT possesses favorable properties such as being low in cost, and having high temporospatial control with minimal invasiveness. However, short NIR light penetration depth limits its functions. Methods: In this review, due to their promise, we focus on inorganic nanomaterials [such as hollow mesoporous silica nanoparticles (HMSNs), tungsten sulfide quantum dots (WS2QDs), and gold nanorods (AuNRs)] combining PTT with CHT, RT or IT in one treatment, aiming to provide a comprehensive understanding of PTT-based combinational cancer therapy. Results: This review found much evidence for the use of inorganic nanoparticles for PTT-based combinational cancer therapy. Conclusion: Under synergistic effects, inorganic nanomaterial-based combinational treatments exhibit enhanced therapeutic effects compared to PTT, CHT, RT, IT or PDT alone and should be further investigated in the cancer field.


Assuntos
Nanopartículas/uso terapêutico , Neoplasias/terapia , Animais , Terapia Combinada , Ouro/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Imunoterapia/métodos , Nanopartículas/química , Nanotubos , Fotoquimioterapia/métodos , Fototerapia/métodos , Pontos Quânticos , Radioterapia/métodos
17.
PLoS One ; 15(4): e0231439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298314

RESUMO

INTRODUCTION: The primary purpose of crosslinking is to halt the progression of ectasia. We retrospectively assessed the condition of keratoconus patients who were followed-up at least twice after the initial examination to evaluate keratoconus progression, to identify definitive factors to predict a later need for corneal crosslinking (CXL). METHODS: The medical charts of 158 eyes of 158 keratoconus patients (112 males and 46 females; mean age, 27.8 ± 11.7 years), who were followed up at the Department of Ophthalmology, Keio University School of Medicine at least twice after the initial examination to evaluate keratoconus progression were retrospectively reviewed. Best-spectacle corrected visual acuity, intraocular pressure, steepest corneal axis on the anterior float (Ks), thinnest corneal thickness according to Pentacam® HR, and corneal endothelial cell density were assessed. Gender, age, onset age of keratoconus, history of atopic dermatitis, and Pentacam® indices were also recorded. CXL was performed when the eye showed significant keratoconus progression, an increase in the steepest keratometric value, or an increase in the spherical equivalent or cylinder power of the manifest refraction by more than 1.0 D versus the respective values 2 years prior. Predictor variables and the requirement for CXL were analyzed using logistic regression. RESULTS: Fifty-eight eyes required CXL treatment. The best predictor of the requirement for CXL was patient age, followed by the Pentacam® Rmin (the minimum sagittal curvature evaluated by Pentacam®) value. The incidence of CXL was 86.4% in the < 20 years age group, with an Rmin of ≤ 5.73 mm, whereas 10.8% in the ≥ 27 years age group with an Rmin > 5.73 mm underwent treatment. CONCLUSIONS: An age of < 20 years and an Rmin value of ≤ 5.73 mm predicted keratoconus progression and the requirement for CXL treatment in the near future.


Assuntos
Ceratocone/patologia , Fotoquimioterapia/métodos , Adolescente , Adulto , Fatores Etários , Reagentes para Ligações Cruzadas/uso terapêutico , Feminino , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/epidemiologia , Ceratocone/radioterapia , Masculino , Fotoquimioterapia/normas , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Terapia Ultravioleta
18.
Am J Ophthalmol ; 216: 80-89, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32289294

RESUMO

PURPOSE: To assess whether chronic central serous chorioretinopathy (cCSC) patients without a complete resolution of subretinal fluid (SRF) after either half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) treatment may benefit from crossover treatment. DESIGN: Multicenter prospective interventional case series. METHODS: cCSC patients with persistent SRF at the final visit of the PLACE trial were included. Patients received crossover treatment with either half-dose PDT or HSML. RESULTS: Thirty-two patients received PDT and 10 patients received HSML. At the first evaluation visit (6-8 weeks after treatment), 81% of patients in the PDT group had complete resolution of SRF, while none of the HSML-treated patients had complete resolution of SRF. At final visit (1 year after baseline), 78% (P = .030) and 67% (P = .109) of the patients, respectively, had a complete resolution of SRF. The mean retinal sensitivity in the PDT group increased from 21.7 dB (standard error [SE]: 0.9) to 23.4 dB (SE: 0.8) at evaluation visit 1 (P = .003), to 24.7dB (SE: 0.8) at final visit (P < .001), while there were no significant changes in the HSML group (23.7 dB [SE: 1.6] at baseline, 23.8 dB [SE: 1.4] at evaluation 1, and 23.3 dB [SE: 1.4] at final visit). The mean visual acuity and mean visual quality-of-life questionnaire score did not change significantly in both groups. CONCLUSIONS: Crossover to half-dose PDT after previous unsuccessful HSML treatment for cCSC may lead to improved anatomic and functional endpoints, while crossover to HSML after half-dose PDT does not seem to significantly affect these endpoints.


Assuntos
Coriorretinopatia Serosa Central/terapia , Fotocoagulação/métodos , Fotoquimioterapia/métodos , Acuidade Visual/fisiologia , Adulto , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/fisiopatologia , Coriorretinopatia Serosa Central/cirurgia , Doença Crônica , Corantes/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Lasers Semicondutores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Qualidade de Vida/psicologia , Perfil de Impacto da Doença , Líquido Sub-Retiniano , Inquéritos e Questionários , Tomografia de Coerência Óptica , Falha de Tratamento
19.
J Mycol Med ; 30(2): 100949, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32234349

RESUMO

Onychomycosis is one of the most prevalent and severe nail fungal infections, which is affecting a wide population across the globe. It leads to variations like nail thickening, disintegration and hardening. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a relapse rate of 25-30%. Due to systemic toxicity and various other disadvantages associated with oral therapy like gastrointestinal, hepatotoxicity, topical therapy is commonly used. Topical therapy improves patient compliance and reduces the cost of treatment. However, due to poor penetration of topical therapy across the nail plate, research is focused on different chemical, mechanical and physical methods to improve drug delivery. Penetration enhancers like Thioglycolic acid, Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), Sodium lauryl sulfate (SLS), carbocysteine, N-acetylcysteine etc. have shown results enhancing the drug penetration across the nail plate. Results with physical techniques such as iontophoresis, laser and Photodynamic therapy are quite promising, but the long-term suitability of these devices is in need to be determined. In this article, a brief analysis of the treatment procedures, factors affecting drug permeation across nail plate, chemical, mechanical and physical devices used to increase the drug delivery through nails for the onychomycosis management has been achieved.


Assuntos
Onicomicose/terapia , Administração Oral , Administração Tópica , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Química Farmacêutica/métodos , Terapia Combinada , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Iontoforese/métodos , Iontoforese/tendências , Terapia a Laser/métodos , Terapia a Laser/tendências , Unhas/efeitos dos fármacos , Unhas/metabolismo , Unhas/efeitos da radiação , Onicomicose/tratamento farmacológico , Onicomicose/epidemiologia , Onicomicose/microbiologia , Permeabilidade/efeitos dos fármacos , Permeabilidade/efeitos da radiação , Fotoquimioterapia/métodos , Fotoquimioterapia/tendências
20.
Chemistry ; 26(34): 7685-7691, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32294275

RESUMO

Photodynamic therapy (PDT) is a promising alternative treatment for different types of cancer due to its high selectivity, which prevents healthy tissues from being damaged. The use of nanomaterials in PDT has several advantages over classical photosensitizing agents, due to their unique properties and their capacity for functionalization. Especially interesting is the use of metallic nanoparticles, which are capable of absorbing electromagnetic radiation and either transferring this energy to oxygen molecules for the generation of reactive oxygen species (ROS) or dissipating it as heat. Although previous reports have demonstrated the capacity of Rh derivatives to serve as anti-tumor drugs, to the best of our knowledge there have been no studies on the potential use of small-sized Rh nanoparticles as photosensitizers in PDT. In this study, 5 nm Rh nanoparticles have been synthesized and their potential in PDT has been evaluated. The results show that treatment with Rh nanoparticles followed by NIR irradiation induces apoptosis in cancer cells through a p53-independent mechanism.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/química , Ródio/farmacologia , Apoptose , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes/química , Ródio/química
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