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1.
BMJ Open ; 11(7): e050252, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266844

RESUMO

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.


Assuntos
Fotoquimioterapia , Pólipos , Inibidores da Angiogênese/uso terapêutico , Corioide/diagnóstico por imagem , Angiofluoresceinografia , Seguimentos , Humanos , Injeções Intravítreas , Fármacos Fotossensibilizantes/uso terapêutico , Pólipos/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Singapura , Tomografia de Coerência Óptica , Resultado do Tratamento , Triazenos , Acuidade Visual
2.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299302

RESUMO

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.


Assuntos
Acetatos/farmacologia , Quimiocina CCL2/biossíntese , Ácidos Graxos Voláteis/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Acetatos/administração & dosagem , Quimiocina CCL2/genética , Coenzima A Ligases/antagonistas & inibidores , Coenzima A Ligases/metabolismo , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Ácidos Graxos Voláteis/administração & dosagem , Humanos , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Monócitos/imunologia , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células THP-1 , Triazenos/farmacologia , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/farmacologia
3.
Biomater Sci ; 9(15): 5302-5318, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34184011

RESUMO

To achieve synergistic photodynamic-photothermic therapy, we fabricate the novel phycocyanin (PC)-functionalized black phosphorus quantum dots (BPQDs) referred as PC@BPQDs through a one-step stirring method. PC@BPQDs are characterized by the feature of possessing both near-infrared (NIR) induced photothermal and photodynamic activity. The PC layer not only effectively alleviates plasma protein adsorption onto BPQDs, but also functionally boosts the photothermal therapy efficiency by enhanced ROS release, resulting in increased apoptosis in vitro. Moreover, PC@BPQDs eradicate tumors with high efficacy and low toxicity in vivo. Thus, PC@BPQDs have a promising potential in future therapeutic implications.


Assuntos
Fotoquimioterapia , Pontos Quânticos , Dano ao DNA , Fósforo , Ficocianina , Espécies Reativas de Oxigênio , Triazenos
4.
Photodiagnosis Photodyn Ther ; 35: 102387, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34107318

RESUMO

Erosive adenomatosis of the nipple (EAN) is an uncommon, benign neoplasm that involves the nipple. Traditional treatments include complete surgical excision, limited forms of complete surgical excision and Mohs micrographic surgery. Here, we report a case of a 40-year-old woman with a 2-year history of asymptomatic erosion, papillomatous hyperplasia and intermittent serosanguineous discharge on her right nipple. Histopathological examination confirmed the diagnosis of EAN. She was treated with 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) for 2 sessions with 2 weeks intervals. No recurrence occurred within 6 months. Therefore, our report suggested that ALA-PDT is a possible method to treat EAN, especially in patients who have the need of breastfeeding and cosmetic appearance, but this needs to be examined in a larger clinical trial.


Assuntos
Papiloma , Fotoquimioterapia , Adenoma , Adulto , Ácido Aminolevulínico/uso terapêutico , Neoplasias da Mama , Feminino , Humanos , Mamilos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Triazenos
5.
Photodiagnosis Photodyn Ther ; 35: 102393, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34116251

RESUMO

Basal cell carcinoma (BCC) is a common non-melanoma skin malignancy arising in sun exposure area. Patients with multiple BCCs have a high-risk factor for recurrence and are very difficult to  treat with current methods. 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) treat superficial type of BCCs with superior efficacy and an excellent cosmetic result, but deep tumor success is limited. Herein, a case of numerous nodular BCCs scattered on the face and head, which was treated with the combination of topical curettage and modified ALA-PDT is reported. Curettage was to rapidly scalp away nodular tumors and contributed to ALA transdermal depth to the tumor base. Modified ALA-PDT as an advanced treatment was nearly painless and can cure multiple BCCs of face and head combing curettage.


Assuntos
Carcinoma Basocelular , Fotoquimioterapia , Neoplasias Cutâneas , Ácido Aminolevulínico/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/cirurgia , Curetagem , Síndrome do Hamartoma Múltiplo , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento , Triazenos
6.
Photodiagnosis Photodyn Ther ; 35: 102395, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34126243

RESUMO

5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a non-invasive treatment modality for premalignant and malignant skin lesions. It has the advantage of better tolerance and providing better cosmetic outcomes than conventional treatment methods. Herein, we report a patient who suffered from multiple cutaneous squamous cell carcinoma (cSCC) in situ and actinic keratosis (AK) scattered in the body's sun-exposed areas, which had led him to undergo multiple surgical resections since the age of 16. Next-generation sequencing-based on a targeted gene capture panel revealed compound heterozygous mutations c.G559A and c.G1389A in the TMC8 gene. Combined with the typical clinical manifestations and mutation analysis, the patient was diagnosed with Epidermodysplasia verruciformis (EV). Due to the multiple AK and cSCC in situ lesions, ALA-PDT was applied. After 8 courses of ALA-PDT all lesions were successfully cleared without causing any scarring. Therefore, the use of ALA-PDT treatment may constitute a very promising and effective therapeutic modality for multiple cSCC in situ and AK secondary to EV.


Assuntos
Carcinoma de Células Escamosas , Epidermodisplasia Verruciforme , Ceratose Actínica , Fotoquimioterapia , Neoplasias Cutâneas , Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Epidermodisplasia Verruciforme/tratamento farmacológico , Humanos , Ceratose Actínica/tratamento farmacológico , Masculino , Proteínas de Membrana , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento , Triazenos
7.
Photodiagnosis Photodyn Ther ; 35: 102396, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34133960

RESUMO

BACKGROUND: Different therapies have been used for dissecting cellulitis of the scalp (DCS) with poor results. Topical 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is effective for many inflammatory skin diseases. OBJECTIVES: To evaluate the efficacy and safety of fire micro-needling plus 5% ALA-PDT on DCS. METHODS: Forty-two male DCS patients were enrolled and treated by four sessions of fire micro-needling plus 5% ALA-PDT (occlusion time: 3 h, 100 mW/cm2 for 20-32 min, 633 ± 10 nm LED) with an interval of 1-2 weeks. The reduction of lesions was evaluated at each follow-up visit. The patients` symptoms were evaluated by Dermatology Life Quality Index (DLQI). All of the side effects were recorded. RESULTS: Forty-one DCS patients finished the treatments and the marked effective rate (MER) reached 65.85%. Ten patients (24.39%) were cured and 17 patients (41.46%) achieved excellent improvement. The median of lesion numbers decreased significantly from 25 to 7 (p < 0.001) with DLQI from 13 to 2 (p < 0.001). Although all the ten cured patients had a relapse during the 12-month follow-up, 5/10 patients had a remission of more than 6 months. All the patients tolerated PDT well with mild adverse effects. CONCLUSIONS: Fire micro-needling plus 5% ALA-PDT is effective for Chinese male DCS patients without the need to take systemic drugs.


Assuntos
Fotoquimioterapia , Ácido Aminolevulínico , Celulite (Flegmão) , Humanos , Masculino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Dermatoses do Couro Cabeludo , Dermatopatias Genéticas , Resultado do Tratamento , Triazenos
8.
Photodiagnosis Photodyn Ther ; 34: 102322, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33962059

RESUMO

BACKGROUND: Medicinal therapies such as systemic retinoids and antibiotics have shown efficacy in the treatment of dissecting cellulitis of the scalp (DCS), but refractory cases are common. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been successfully used in medicine-resistant cases in recent years. METHODS: A total of 12 patients who received ALA-PDT in addition to formally failed medicinal therapies were interviewed by telephone regarding improvement of symptoms, satisfaction, and side effects. RESULTS: Overall, 58.3 % patients achieved greater than 50 % improvement of at least one symptom, and 16.7 % had little improvement for any symptom. The proportion of patients who had greater than 50 % improvement for pain, pruritus, swelling and suppuration were 36.4 %, 66.7 %, 33.3 % and 58.3 % respectively. 41.7 % patients were either satisfied or very satisfied with the ALA-PDT. The side effects were mainly pain and crusting that were mostly mild and recovered quickly. CONCLUSION: ALA-PDT was safe and partially effective in reducing DCS symptoms as an adjunct to systemic medicinal therapies.


Assuntos
Ácido Aminolevulínico , Fotoquimioterapia , Ácido Aminolevulínico/efeitos adversos , Celulite (Flegmão) , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Estudos Retrospectivos , Dermatoses do Couro Cabeludo , Dermatopatias Genéticas , Resultado do Tratamento , Triazenos
9.
Photodiagnosis Photodyn Ther ; 35: 102328, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34004363

RESUMO

BACKGROUND: Majocchi's granuloma (MG) is a deep persistent suppurative granulomatous perifolliculitis which might be caused by Trichophyton tonsurans (T. tonsurans). Conventional treatment for MG is oral administration of systematic antifungal drugs, associated with a low cure rate and a high relapse rate. ALA-PDT is a new approach for fungal infection. METHODS: A case of refractory MG was treated by 3 times of ALA-PDT. At the same time, T. tonsurans strains isolated from the lesions of the patient were used for an in vitro inhibition experiment and an in vivo experiment in guinea pig model to furtherly verify the effectiveness and investigate the mechanism of ALA-PDT for T. tonsurans. RESULTS: After 3 times of ALA-PDT, the lesions of MG were eliminated. And the mycological and pathological examination showed a disappearance of fungi in follicles. In vitro and in vivo experiment both demonstrated that ALA-PDT could obviously inhibit the growth of T. tonsurans partly by directly destroying the structure of fungal cells and recruiting CD4 + T cells. CONCLUSION: ALA-PDT is a potentially effective noninvasive method for the treatment of MG with mechanisms of direct killing and with CD4+ T cell-mediated immune response.


Assuntos
Fotoquimioterapia , Linfócitos T , Animais , Arthrodermataceae , Cobaias , Homicídio , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Tinha , Triazenos
10.
Photodiagnosis Photodyn Ther ; 34: 102277, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33819685

RESUMO

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive disorder. Individuals with EV are more susceptible to the development of cutaneous neoplasia in sun-exposed regions. This disease should be closely observed for cutaneous squamous cell carcinoma (cSCC) or pre-cancerous lesions - if neoplasia is found, it should be removed. A 68-year-old woman with EV had a post-operative recurrent, invasive cSCC growing on her upper-left eyelid. Although the standard treatment for cSCC is surgical excision, it is challenging to reach the deepest regions. Herein, we reported a case of a recurrent, invasive cSCC effectively treated by a combination of non-invasive 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and deep-penetrative holmium laser. The results were satisfactory without any adverse effects to the patient.


Assuntos
Carcinoma de Células Escamosas , Epidermodisplasia Verruciforme , Lasers de Estado Sólido , Fotoquimioterapia , Neoplasias Cutâneas , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Epidermodisplasia Verruciforme/tratamento farmacológico , Pálpebras , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Triazenos
11.
Sci Rep ; 11(1): 7290, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790399

RESUMO

Cancer can develop into a recurrent metastatic disease with latency periods of years to decades. Dormant cancer cells, which represent a major cause of recurrent cancer, are relatively insensitive to most chemotherapeutic drugs and radiation. We previously demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner. Dormant cancer cells exhibited increased porphyrin metabolism and sensitivity to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). However, the metabolic changes in dormant cancer cells or the factors that enhance porphyrin metabolism have not been fully clarified. In this study, we revealed that lipid metabolism was increased in dormant cancer cells, leading to ALA-PDT sensitivity. We performed microarray analysis in non-dormant and dormant cancer cells and revealed that lipid metabolism was remarkably enhanced in dormant cancer cells. In addition, triacsin C, a potent inhibitor of acyl-CoA synthetases (ACSs), reduced protoporphyrin IX (PpIX) accumulation and decreased ALA-PDT sensitivity. We demonstrated that lipid metabolism including ACS expression was positively associated with PpIX accumulation. This research suggested that the enhancement of lipid metabolism in cancer cells induces PpIX accumulation and ALA-PDT sensitivity.


Assuntos
Ácido Aminolevulínico/farmacologia , Metabolismo dos Lipídeos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Próstata/metabolismo , Coenzima A Ligases/antagonistas & inibidores , Coenzima A Ligases/metabolismo , Humanos , Masculino , Células PC-3 , Porfirinas/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Triazenos/farmacologia
12.
Small ; 17(21): e2100398, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33885221

RESUMO

Small molecular dye that simultaneously exerts dual PDT/PTT effects as well as florescence imaging triggered by a single NIR-II light has never been reported to date. Apart from the huge challenge in pushing absorption profile into NIR-II region, fine-tuning dyes' excited state via rational structure design to meet all three functions, especially oxygen photosensitization, remains the most prominent throttle. Herein, five novel NIR-II dyes (BHs) are productively developed by strategically conjugating dyad innovative xanthonium with sequentially extended polymethine bridges, enabling intense absorption from 890 to 1206 nm, significantly 400 nm longer than conventional cyanine dyes with same polymethines. More importantly, owning to high resonance and favorable excited state energy population induced by greater rigidity via ring-fused amino, BH 1024 exhibits best singlet oxygen generation capability, moderate photothermal heating, and considerable fluorescence under 1064 nm laser irradiation. Furthermore, BH 1024 is encapsulated into folate-functionalized polymer, which demonstrated a synergetic PDT/PTT effect in vitro and in vivo, eventually achieving solid tumors elimination under NIR-II fluorescence guide. As far as it is known, this is the first time small molecular dyes for NIR-II PDT or NIR-II PDT/PTT are explored and designed.


Assuntos
Neoplasias , Fotoquimioterapia , Corantes/uso terapêutico , Humanos , Indóis , Lasers , Neoplasias/tratamento farmacológico , Triazenos
13.
Photodiagnosis Photodyn Ther ; 34: 102273, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33798749

RESUMO

Antimicrobial Photodynamic Therapy (A-PDT) is a modern and non-invasive therapeutic modality. Nanostructures like the polymeric nanocapsules (NC) has proved to be a system that has enormous potential to improve current antimicrobial therapeutic practice. NC of Zinc phenyl-thio-phthalocyanine and Amphotericin B association (NC/ZnS4Pc + AMB) built with poly(lactide-co-glycolide) (PLGA) 50:50 using the preformed polymer interfacial deposition method were developed at a 0.05 mg mL- 1 theoretical concentration to improve antifungal activity with two actives association and assistance from PDTa. It showed an average particle diameter of 253.8 ±â€¯17.3, an average polydispersity index of 0.36 ±â€¯0.01, and a negative Zeta potential average of -31.03 ±â€¯5.54 for 158 days. UV-vis absorption and emission spectroscopy analyses did not show changes in photophysical properties in the steady-state of NC/ZnS4Pc + AMB counterparts free ZnS4Pc. The encapsulation percentage of actives was 89.24 % and 7.40 % for ZnS4Pc and AMB, respectively. Cell viability assay using NIH/3T3 ATCC® CRL-1658 ™ cells line showed no cytotoxicity for the concentrations tested. The photodynamic activity assay using NC/ZnS4Pc + AMB diluted showed fungal toxicity against Candida albicans yeast with energetic fluences of 12 J.cm-2 and 25 J.cm-2 by a decrease in cell viability. The MFC assay demonstrated a fungistatic activity for the conditions employed in the PDTa assay. The results show that NC/ZnS4Pc + AMB is a promising nanomaterial for antimicrobial inactivation using PDT.


Assuntos
Nanocápsulas , Fotoquimioterapia , Anfotericina B , Antifúngicos/farmacologia , Candida albicans , Indóis , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polímeros , Triazenos , Zinco
14.
Photodiagnosis Photodyn Ther ; 33: 102099, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33725799

RESUMO

OBJECTIVE: To evaluate the state of psychology and quality of life of patients effected by acne and also the efficacy and safety of photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) for moderate to severe acne patients. METHODS: In the questionnaire part, a pre-designed form was filled out. The questionnaire was comprised of 2 sections related to acne including sociodemographic and disease information as well as Cardiff Acne Disability Index (CADI) and Self-Rating Anxiety Scale (SAS). In the trial part, the ALA-PDT was applied to moderate to severe acne patients. Fresh 5% ALA solution was topically applied to face or face & neck. After 1 h's incubation, a LED device was illuminated. A power density of 60-100 mW/cm2 was delivered for 20 min. All the patients finished 3-4 sessions of ALA-PDT at 7-10 days intervals. Non-invasive detections were taken for skin moisture, oil, and VISIA indexes. Adverse events were recorded during and after the treatment. RESULTS: A total of 247 acne patients finished questionnaires. Over 97 % patients were assessed as mild to severe impacts in CADI questionnaire and 37.6 % patients had various degrees of anxiety in SAS questionnaire. The higher the BMI was, the higher the CADI points were (G = 0.278, p = 0.005). The severity of acne was correlated with psychology and quality of life (CADI: G = 0.367, p = 0.000; SAS: G = 0.285, p = 0.003). A total of 116 patients with moderate or severe acne accepted ALA-PDT and completed at least 3 sessions (PDT3) or even PDT4. After 1 session of treatment (AT1) and AT2, the efficiencies of all patients were 5.2 % and 29.3 %. For patients with PDT3, the efficiencies at follow-up at 1st month after last session (FU1), FU2 and FU3 were 59.4 %, 66.7 % and 78.3 %, respectively. For patients with PDT4, the efficiencies at AT3 and FU1-3 were 51.3 %, 63.6 %, 76.5 % and 85.7 %, respectively. The efficacies of PDT4 patients showed an increasing trend from FU1 to FU3 (G = 0.480, p = 0.004). Acne lesions of mild to severe were correlated with the treatment efficacies (FU1: G = 0.354, p = 0.000; FU2: G = 0.474, p = 0.000; FU3: G = 0.397, p = 0.000). Nearly 15 % patients were followed up for 12 months and among them 52.9 % patients were able to maintain ≥90 % improvement rate. There were no statistically significant differences before and after treatment (p > 0.05) according to the skin moisture content, oil content, ultraviolet ray spots, brown spots, red areas, and purple textures measured. The adverse reactions of ALA-PDT, including local burning sensation, mild pain sensation, mild edema erythema, reactive acne, pigmentation, etc., were temporary and tolerable. CONCLUSION: In our study, 97.2 % patients were rated as impact in CADI questionnaire and 37.6 % patients had anxiety in SAS questionnaire. It is necessary to control weight and disease progression. The efficiencies of ALA-PDT for moderate and severe acne were 59.4%-85.7% at follow-ups of 1st, 2nd or 3rd month after last session. The adverse reactions of ALA-PDT were temporary and tolerable.


Assuntos
Acne Vulgar , Fotoquimioterapia , Acne Vulgar/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Triazenos
15.
Photodiagnosis Photodyn Ther ; 34: 102249, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33711530

RESUMO

BACKGROUND: A recently proposed synergistic photodynamic therapy protocol (s-PDT) combining advantages of both conventional- and daylight-PDT proved to be an effective and almost painless treatment for patients with actinic keratoses (AKs). This study investigated the safety and efficacy of an additional ablative fractional CO2-laser (AFXL) pretreatment. METHODS: 28 patients with AKs on the head received s-PDT using 5-aminolevulinic acid. AFXL pretreatment was conducted using the following parameters: pulse energy 8 mJ, spot density 50 spots/cm2, power 30 W, beam size 4-18 mm. Outcome was assessed by AK area and severity index (AKASI) and lesion count (LC) before and 3 months after treatment. Safety was monitored by blood pressure and pulse measurements. Intensity of pain was determined by use of a visual analog scale (VAS). RESULTS: Most patients (96.4 %) showed a significant AKASI reduction (P < 0.0001) 3 months after PDT (median AKASI 1.6 [0-2.4]) compared to baseline (5.3 [4-7.75]). Median reduction rate was 75.5 % (61.3 %-100 %). Eleven patients (39.3 %) achieved AKASI 100, three (10.7 %) AKASI 75 and ten (35.7 %) AKASI 50. Blood pressure and pulse did not change significantly throughout treatment. Median VAS for pain during irradiation was 0 (0-0), 0 (0-2) and 0 (0-2) at the beginning, in the meantime and at the end, respectively. Compared to data without AFXL pretreatment, this study showed significantly higher AKASI and LC reduction rates (75.5 % vs. 63.7 % [P = 0.023] and 91.3 % vs. 80.4 % [P = 0.043]). CONCLUSIONS: S-PDT with AFXL pretreatment represents a safe and almost painless treatment for patients with AKs on the head and improves treatment efficacy.


Assuntos
Ceratose Actínica , Lasers de Gás , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Humanos , Ceratose Actínica/tratamento farmacológico , Lasers de Gás/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Resultado do Tratamento , Triazenos
16.
Photodiagnosis Photodyn Ther ; 34: 102271, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33785444

RESUMO

BACKGROUND: Biofilm-associated Candida albicans (C. albicans) infections are hard to cure due to their high levels of resistance to antifungal agents. Photodynamic therapy (PDT) is a promising approach for controlling infections caused by C. albicans. This study was designed to explore the inhibitory activity of PDT using 5-aminolevulinic acid (ALA) as photosensitizer against C. albicans biofilms. METHODS: C. albicans cell suspensions were incubated for 48 h to form mature biofilms. ALA solution was diluted to 15 mM and incubated with C. albicans biofilms for 5 h before irradiated by red light semiconductor laser under the light intensity of 300 J/cm2 and fluence rate of 100 mW/cm2 for 50 min. The inhibitory activity was evaluated from subcellular level, molecular level and transcriptional level using transmission electron microscopy (TEM) observation, flow cytometry analysis and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) assays, respectively. RESULTS: From subcellular level, the degraded content of the cytoplasm, nuclear condensation and mitochondrial swelling were observed after ALA-PDT. From molecular level, ALA-PDT resulted in 19.4 % cell apoptosis. From transcriptional level, ALA-PDT significantly reduced the mRNA expressions of hyphae-specific genes (HWP1 and ALS3) and long-term biofilm maintenance genes (UME6 and HGC1), whereas ALA or red light alone had no significant effect. CONCLUSIONS: The inhibitory activity indicated that ALA-PDT may have the potential to serve as an antifungal strategy in eliminatingC. albicans biofilms.


Assuntos
Ácido Aminolevulínico , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Biofilmes , Candida albicans , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Triazenos
17.
Int J Pharm ; 597: 120326, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33540003

RESUMO

Although nanoparticles (NPs) bear a great potential in tumour therapy, just a few nanosized drug delivery systems are commercially available. Besides their advantages like passive drug targeting and stable embedment of lipophilic active pharmaceutical ingredients, targeted drug release is a major challenge for a safe therapy. While drug release of commonly used materials depends on physiological factors, nanoparticles prepared by using stimuli responsive polymers offer a promising approach. External irradiation of light-sensitive nanoparticles enables local drug release, resulting in selective accumulation and consequently more effective treatment with less side effects. In this study light-responsive nanoparticles based on a new innovative light-responsive polyester (Nip-SLrPE) combined with poly(DL-lactide-co-glycolide) (PLGA) were prepared and examined for their physicochemical characteristics and light-triggered properties. As model drug the photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorine (mTHPC) was incorporated and light-depending drug release was investigated. Furthermore, cytotoxic potential of selected formulations for PDT and intracellular accumulation of mTHPC were evaluated. In conclusion, nanoparticles based on the new light-sensitive Nip-SLrPE showed auspicious light-responsive properties, resulting in promising results for a smart drug delivery system.


Assuntos
Nanopartículas , Fotoquimioterapia , Sistemas de Liberação de Medicamentos , Fármacos Fotossensibilizantes , Poliésteres , Triazenos
18.
Photodiagnosis Photodyn Ther ; 34: 102222, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33601002

RESUMO

BACKGROUND: The behavior of mast cells, their interaction with neuronal cells or nerve fibers, the expression of neuropeptides and the distribution of skin neuronal cells or nerve fibers after ALA-PDT treated vs untreated chronic wounds were investigated. METHODS: Nineteen patients suffering from chronic venous ulcers (CVU) were enrolled in this study. Skin samples from wound bed before and after irradiation with ALA-PDT were taken. All specimens were anonymized and analyzed by immunohistochemistry. RESULTS: After completion of ALA-PDT, mast cells showed an increase of degranulation index and expression of NGF and VIP. Amongst all the neuronal mediators tested, all except for SP showed an increase of cellular expression after ALA-PDT therapy. CONCLUSION: Our study shows preliminary evidences that ALA-PDT induces rapid recruitment of mast cells around dermal fibers in chronic venous ulcers. This finding is also associated with increase in expression of multiple peripheral neuropeptides except SP by skin neuronal cells. ALA-PDT may promote healing of chronic venous ulcers via stimulation of quiescent peripheral nerves, possibly after release of inflammatory molecules by degranulating mast cells.


Assuntos
Neuropeptídeos , Fotoquimioterapia , Úlcera Varicosa , Humanos , Mastócitos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Projetos Piloto , Pele , Triazenos , Úlcera Varicosa/tratamento farmacológico
19.
Sci Rep ; 11(1): 2541, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510223

RESUMO

In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.


Assuntos
Triazenos/química , Triazenos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
20.
Photodiagnosis Photodyn Ther ; 33: 102050, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33453422

RESUMO

BACKGROUND: 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is increasingly used to control severe acne. However, its impact on skin microbiota remains uncertain. OBJECTIVES: We aimed to compare the makeup, diversity, and function of the microbiota in pilosebaceous units of patients with severe acne before and after ALA-PDT. METHODS: A longitudinal cohort study was performed on 11 participants with severe facial acne. All patients were given 5%ALA-PDT every two weeks for three sessions in total. The contents of lesions were sampled for metagenomic sequencing at baseline and two weeks after the first ALA-PDT session. RESULTS: Cutibacterium acnes was the most dominant species followed by Staphylococcus epidermidis and Pseudomonas fluorescens. Treatment with ALA-PDT led to clinical improvements in acne severity concurrent with a significant reduction in the relative abundance of C. acnes, while P. fluorescens increased significantly after ALA-PDT. No significant change was identified in other species. ALA-PDT administration was associated with an increased microbiota diversity and reductions in the relative abundance of the functional genes involved in energy metabolism and DNA replication. CONCLUSIONS: ALA-PDT plays a therapeutic role by killing C. acnes, increasing P. fluorescens and the microbiome diversity, while inhibiting the function of microbiota in pilosebaceous units of severe acne.


Assuntos
Acne Vulgar , Microbiota , Fotoquimioterapia , Acne Vulgar/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Humanos , Estudos Longitudinais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Triazenos
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