Navegação Periódicos - Artigos por Autores IPEN "CABRAL, FERNANDA V."

Classificar por: Ordenar: Resultados:

  • IPEN-DOC 29637

    YOSHIMURA, TANIA M. ; CABRAL, FERNANDA V. ; SELLERA, FABIO P.; POZZO, LORENA ; RIBEIRO, MARTHA S. . Could light-based technologies improve stem cell therapy for skin wounds?: A systematic review and meta-analysis of preclinical studies. Photochemistry and Photobiology, v. 99, n. 2, p. 519-528, 2023. DOI: 10.1111/php.13702

    Abstract: Several diseases or conditions cause dermatological disorders that hinder the process of skin repair. The search for novel technologies has inspired the combination of stem cell (SC) and light-based therapies to ameliorate skin wound repair. Herein, we systematically revised the impact of photobiomodulation therapy (PBM) combined with SCs in animal models of skin wounds and quantitatively evaluated this effect through a meta-analysis. For inclusion, SCs should be irradiated in vitro or in vivo, before or after being implanted in animals, respectively. The search resulted in nine eligible articles, which were assessed for risk of bias. For the meta-analysis, studies were included only when PBM was applied in vivo, five regarding wound closure, and three to wound strength. Overall, a positive influence of SC + PBM on wound closure (mean difference: 9.69; 95% CI: 5.78–13.61, P < 0.00001) and strength (standardized mean difference: 1.7, 95% CI: 0.68–2.72, P = 0.001) was detected, although studies have shown moderate to high heterogeneity and a lack of information regarding some bias domains. Altogether, PBM seems to be an enabling technology able to be applied postimplantation of SCs for cutaneous regeneration. Our findings may guide future laboratory and clinical studies in hopes of offering wound care patients a better quality of life.

    Palavras-Chave: skin diseases; therapy; stem cells; biological repair

  • IPEN-DOC 26934

    CABRAL, FERNANDA V. ; SILVA, CAMILA R. ; SAUTER, ISMAEL P.; SABINO, CAETANO P. ; YOSHIMURA, TANIA M. ; CORTEZ, MAURO; RIBEIRO, MARTHA S. . Efeito da terapia fotodinâmica no tratamento de leishmaniose cutânea em um modelo murino. Anais da SBBN, v. 3, p. 67-77, 2016.

    Abstract: Leishmanioses são doenças parasitárias desenvolvidas por protozoários do gênero Leishmania. A forma cutânea abrange lesões destrutivas e ulceradas com diversas limitações no tratamento. Terapias alternativas são fundamentais devido à grande relevância da doença e elevada incidência. Nesse contexto, a terapia fotodinâmica (PDT) tem sido introduzida devido ao baixo custo, baixa toxicidade, praticidade e sem relatos de resistência na literatura. Neste trabalho, dezesseis camundongos BALB/c foram infectados com 1.106 parasitos de Leishmania(L) amazonensisno membro posterior esquerdo e acompanhados por 4 semanas até o surgimento da lesão. Após esse período, os animais foram submetidos à PDT usando um diodo emissor de luz (λ=660 ±22 nm) e azul de metileno (100 μM), com fluências de 50, 100 e 150J/cm² e acompanhados durante 3 semanas. Animais controle não receberam tratamento. O tamanho da lesão e escala de dor foram mensurados utilizando um paquímetro e filamentos von Frey, respectivamente. A quantificação da carga parasitária foi realizada através do método de diluição limitante. Os resultados demonstraram que, nas semanas 2 e 3 após tratamento, ocorreu diminuição da lesão e alívio de dor nos animais que receberam 150J/cm², sugerindo que a PDT promoveu melhora clínica através da modulação do processo inflamatório.

    Palavras-Chave: photosensitivity; methylene blue; parasites; parasitic diseases; biological models; epithelium; light sources; light emitting diodes; therapy; skin diseases

  • IPEN-DOC 27775

    SOUZA, TIAGO H.S.; ANDRADE, CAMILA G.; CABRAL, FERNANDA V. ; SARMENTO-NETO, JOSE F.; REBOUÇAS, JULIO S.; SANTOS, BEATE S.; RIBEIRO, MARTHA S. ; FIGUEIREDO, REGINA C.B.Q.; FONTES, ADRIANA. Efficient photodynamic inactivation of Leishmania parasites mediated by lipophilic water-soluble Zn(II) porphyrin ZnTnHex-2-PyP4+. BBA - General Subjects, v. 1865, n. 7, p. 1-10, 2021. DOI: 10.1016/j.bbagen.2021.129897

    Abstract: Background Photodynamic inactivation (PDI) is emerging as a promising alternative for cutaneous leishmaniasis (CL). The chemotherapy currently used presents adverse effects and cases of drug resistance have been reported. ZnTnHex-2-PyP4+ is a porphyrin with a high potential as a photosensitizer (PS) for PDI, due to its photophysical properties, structural stability, and cationic/amphiphilic character that can enhance interaction with cells. This study aimed to investigate the photodynamic effects mediated by ZnTnHex-2-PyP4+ on Leishmania parasites. Methods ZnTnHex-2-PyP4+ stability was evaluated using accelerated solvolysis conditions. The photodynamic action on promastigotes was assessed by (i) viability assays, (ii) mitochondrial membrane potential evaluation, and (iii) morphological analysis. The PS-promastigote interaction was studied. PDI on amastigotes and the cytotoxicity on macrophages were also analyzed. Results ZnTnHex-2-PyP4+, under submicromolar concentration, led to immediate inactivation of more than 95% of promastigotes. PDI promoted intense mitochondrial depolarization, loss of the fusiform shape, and plasma membrane wrinkling in promastigotes. Fluorescence microscopy revealed a punctate PS labeling in the parasite cytoplasm. PDI also led to reductions of ca. 64% in the number of amastigotes/macrophage and 70% in the infection index after a single treatment session. No noteworthy toxicity was observed on mammalian cells. Conclusions ZnTnHex-2-PyP4+ is stable against demetallation and more efficient as PS than the ethyl analogue ZnTE-2-PyP4+, indicating readiness for evaluation in in vivo studies as an alternative approach to CL. General significance This report highlighted promising photodynamic effects mediated by ZnTnHex-2-PyP4+ on Leishmania parasites, opening up perspectives for applications in CL pre-clinical assays and PDI of other microorganisms.

    Palavras-Chave: inactivation; photosensitivity; photochemistry; antimicrobial agents; therapy; parasites; parasitic diseases; porphyrins

  • IPEN-DOC 23565

    SILVA, CAMILA R. ; CABRAL, FERNANDA V. ; CAMARGO, CLAUDINEI F.M. de ; NUNEZ, SILVIA C. ; YOSHIMURA, TANIA M. ; LUNA, ARTHUR C. de L.; MARIA, DURVANEI A.; RIBEIRO, MARTHA S. . Exploring the effects of low-level laser therapy on fibroblasts and tumor cells following gamma radiation exposure. Journal of Biophotonics, v. 9, n. 11-12, p. 1157-1166, 2016. DOI: 10.1002/jbio.201600107

    Abstract: Ionizing radiation (IR) induces DNA damage and low-level laser therapy (LLLT) has been investigated to prevent or repair detrimental outcomes resulting from IR exposure. Few in vitro studies, however, explore the biological mechanisms underlying those LLLT benefits. Thus, in this work, fibroblasts and tumor cells are submitted to IR with doses of 2.5 Gy and 10 Gy. After twenty-four-h, the cells are exposed to LLLT with fluences of 30 J cm–2, 90 J cm–2, and 150 J cm–2. Cellular viability, cell cycle phases, cell proliferation index and senescence are evaluated on days 1 and 4 after LLLT irradiation. For fibroblasts, LLLT promotes – in a fluence-dependent manner – increments in cell viability and proliferation, while a reduction in the senescence was observed. Regarding tumor cells, no influences of LLLT on cell viability are noticed. Whereas LLLT enhances cell populations in S and G2/M cell cycle phases for both cellular lines, a decrease in proliferation and increase in senescence was verified only for tumor cells. Putting together, the results suggest that fibroblasts and tumor cells present different responses to LLLT following exposure to gamma-radiation, and these promising results should stimulate further investigations. Senescence of tumor cells and fibroblasts on the 4th day after ionizing radiation (IR) and low-level laser therapy (LLLT) exposures. The number of senescent cells increased significantly for tumor cells (a) while for fibroblasts no increment was observed (b). The blue collor indicates senescence activity.

    Palavras-Chave: gamma radiation; tumor cells; ionizing radiations; laser radiation; mammary glands; neoplasms; tumor cells; therapy; radiotherapy; levels

  • IPEN-DOC 29091

    CABRAL, FERNANDA V. ; SELLERA, FABIO P.; RIBEIRO, MARTHA S. . Feline sporotrichosis successfully treated with methylene blue-mediated antimicrobial photodynamic therapy and low doses of itraconazole. Photodiagnosis and Photodynamic Therapy, v. 40, p. 1-3, 2022. DOI: 10.1016/j.pdpdt.2022.103154

    Abstract: Sporotrichosis is a mycotic infection of humans and animals caused by different fungal species of the genus Sporothrix. Feline sporotrichosis presents a broad spectrum of clinical manifestations and its treatment with classic antifungal drugs is often long and frustrating. Methylene blue-mediated antimicrobial photodynamic therapy (MB-APDT) comes to light as an interesting approach against fungal infections, including sporotrichosis. In this case report, a 1-year-old male cat was diagnosed with sporotrichosis, being confirmed by fungal culture. The cat was treated by MB-APDT combined with oral administration of itraconazole. Following 2 weeks after the end of treatment, the animal was clinically cured, and an additional fungal culture was negative for Sporothrix spp., confirming the total remission of sporotrichosis. No side effects and recurrences were observed after a 3-moth follow-up. MB-APDT is a promising strategy against feline sporotrichosis, however large-scale studies are welcome to confirm its potential.

    Palavras-Chave: veterinary medicine; fungal diseases; photodynamic therapy; antimicrobial agents; fungi; cats; methylene blue

  • IPEN-DOC 28146

    CABRAL, FERNANDA V. ; SELLERA, FABIO P.; RIBEIRO, MARTHA S. . Methylene blue-mediated antimicrobial photodynamic therapy for canine dermatophytosis caused by Microsporum canis: a successful case report with 6 months follow-up. Photodiagnosis and Photodynamic Therapy, v. 36, p. 1-3, 2021. DOI: 10.1016/j.pdpdt.2021.102602

    Abstract: Dermatophytosis is a superficial skin infection that widely effects companion animals. Miscrosporum canis is one of the most prevalent species isolated from dogs and cats, and because of the serious zoonotic potential, short-term treatment regimens are preferred to prevent the spread of disease either by direct contact or through contamination of the environment. Antimicrobial photodynamic therapy (APDT) has emerged as a promising strategy able to kill effectively a wide range of pathogens in a short period with minimal morbidity . In this case report, a 7-year-old male dog was diagnosed with dermatophytosis caused by M. canis. Methylene blue-mediated antimicrobial photodynamic therapy (MB-APDT) was applied over the lesions in two sessions with an interval of 7 days. The dog successfully healed, achieving a complete clinical cure after 21 days, without reports of recurrence after a follow-up period of 6 months. Therefore, MB-APDT could be a potential ally of small animal clinicians to treat superficial fungal diseases and should be further explored in Veterinary Medicine.

    Palavras-Chave: antimicrobial agents; methylene blue; veterinary medicine; therapy; skin diseases; tinea

  • IPEN-DOC 25800

    DIMMER, JESICA; CABRAL, FERNANDA V. ; SABINO, CAETANO P. ; SILVA, CAMILA R. ; NUNEZ-MONTOYA, SUSANA C.; CABRERA, JOSE L.; RIBEIRO, MARTHA S. . Natural anthraquinones as novel photosentizers for antiparasitic photodynamic inactivation. Phytomedicine, v. 61, n. 152894, p. 1-7, 2019. DOI: 10.1016/j.phymed.2019.152894

    Abstract: Background: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by obligate protist parasites from the genus Leishmania. The potential toxicity as well as the increased resistance of standard treatments has encouraged the development of new therapeutical strategies. Photodynamic inactivation (PDI) combines the use of a photosensitizer and light to generate reactive oxygen species and kill cells, including microorganisms. Vegetal kingdom constitutes an important source of bioactive compounds that deserve to be investigated in the search of naturally occurring drugs with leishmanicidal activity. Purpose: The purpose of this study was to test the antiparasitic activity of PDI (ApPDI) of five natural anthraquinones (AQs) obtained from Heterophyllaea lycioides (Rusby) Sandwith (Rubiacae). To support our results, effect of AQ mediated-PDI on parasite´s morphology and AQ uptake were studied. Cytotoxicity on fibroblasts was also evaluated. Study design/Methods: Two monomers, soranjidiol (Sor) and 5-chlorosoranjidiol (5-ClSor) plus three bi-anthraquinones (bi-AQs), bisoranjidiol (Bisor), 7-chlorobisoranjidiol (7-ClBisor) and Lycionine (Lyc) were selected for this study. Recombinant L. amazonensis promastigote strain expressing luciferase was subjected to AQs and LED treatment. Following irradiation with variable light parameters, cell viability was quantified by bioluminescence. Alteration on parasite's morphology was analyzed by scanning electron microscopy (SEM). In addition, we verified the AQ uptake in Leishmania cells by fluorescence and their toxicity on fibroblasts by using MTT assay. Results: Bisor, Sor and 5-ClSor exhibited photodynamic effect on L. amazonensis. SEM showed that promastigotes treated with Bisor-mediated PDI exhibited a significant alteration in shape and size. Sor and 5-ClSor presented higher uptake levels than bi-AQs (Bisor, Lyc and 7-ClBisor). Finally, Sor and Bisor presented the lowest toxic activity against fibroblasts. Conclusion: Taking together, our results indicate that Sor presents the highest specificity towards Leishmania cells with no toxicity on fibroblasts.

    Palavras-Chave: parasitic diseases; anthraquinones; antimitotic drugs; therapy; photosensitivity; inactivation; monomers

  • IPEN-DOC 29884

    SILVA, ABDENEGO R. ; CABRAL, FERNANDA V. ; SILVA, CAMILA R. ; SILVA, DANIELA F.T. ; FREITAS, ANDERSON Z. ; FONTES, ADRIANA; RIBEIRO, MARTHA S. . New insights in phenothiazinium-mediated photodynamic inactivation of candida auris. Journal of Fungi, v. 9, n. 7, p. 1-16, 2023. DOI: 10.3390/jof9070717

    Abstract: n recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) combined with a red LED against C. auris. To evaluate the photoinactivation of yeasts, we quantified colony-forming units and monitored ROS production. To gain some insights into the differences between MB and DMMB, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm). After, we verified the effectiveness of DMMB against biofilms by measuring metabolic activity and biomass, and the structures were analyzed through scanning electron microscopy and optical coherence tomography. We also evaluated the cytotoxicity in mammalian cells. DMMB-PDI successfully eradicated C. auris yeasts at 3 μM regardless of the light dose. In contrast, MB (100 μM) killed cells only when exposed to the highest dose of light. DMMB-PDI promoted higher ROS, LPO and ΔΨm levels than those of MB. Furthermore, DMMB-PDI was able to inhibit biofilm formation and destroy mature biofilms, with no observed toxicity in fibroblasts. We conclude that DMMB-PDI holds great potential to combat the global threat posed by C. auris. © 2023 by the authors.

  • IPEN-DOC 29930

    CABRAL, FERNANDA V. ; CERONE, MICHELA; PERSHEYEV, SAYDULLA; LIAN, CHENG; SAMUEL, IFOR D.W.; RIBEIRO, MARTHA S. ; SMITH, TERRY K.. New insights in photodynamic inactivation of Leishmania amazonensis:: A focus on lipidomics and resistance. PLoS ONE, v. 18, n. 9, p. 1-23, 2023. DOI: 10.1371/journal.pone.0289492

    Abstract: The emergence of drug resistance in cutaneous leishmaniasis (CL) has become a major problem over the past decades. The spread of resistant phenotypes has been attributed to the wide misuse of current antileishmanial chemotherapy, which is a serious threat to global health. Photodynamic therapy (PDT) has been shown to be effective against a wide spectrum of drug-resistant pathogens. Due to its multi-target approach and immediate effects, it may be an attractive strategy for treatment of drug-resistant Leishmania species. In this study, we sought to evaluate the activity of PDT in vitro using the photosensitizer 1,9-dimethyl methylene blue (DMMB), against promastigotes of two Leishmania amazonensis strains: the wild-type (WT) and a lab induced miltefosine-resistant (MFR) strain. The underlying mechanisms of DMMB-PDT action upon the parasites was focused on the changes in the lipid metabolism of both strains, which was conducted by a quantitative lipidomics analysis. We also assessed the production of ROS, mitochondrial labeling and lipid droplets accumulation after DMMB-PDT. Our results show that DMMB-PDT produced high levels of ROS, promoting mitochondrial membrane depolarization due to the loss of membrane potential. In addition, both untreated strains revealed some differences in the lipid content, in which MFR parasites showed increased levels of phosphatidylcholine, hence suggesting this could also be related to their mechanism of resistance to miltefosine. Moreover, the oxidative stress and consequent lipid peroxidation led to significant phospholipid alterations, thereby resulting in cellular dysfunction and parasite death. Thus, our results demonstrated that DMMB-mediated PDT is effective to kill L. amazonensis MFR strain and should be further studied as a potential strategy to overcome antileishmanial drug resistance.

  • IPEN-DOC 26478

    CABRAL, FERNANDA V. ; PELEGRINO, MILENA T.; SAUTER, ISMAEL P.; SEABRA, AMEDEA B.; CORTEZ, MAURO; RIBEIRO, MARTHA S. . Nitric oxide-loaded chitosan nanoparticles as an innovative antileishmanial platform. Nitric Oxide, v. 93, p. 25-33, 2019. DOI: 10.1016/j.niox.2019.09.007

    Abstract: Leishmaniasis is a neglected tropical disease that demands for new therapeutic strategies due to adverse side effects and resistance development promoted by current drugs. Nitric oxide (NO)-donors show potential to kill Leishmania spp. but their use is limited because of their instability. In this work, we synthesize, characterize, and encapsulate S-nitroso-mercaptosuccinic acid into chitosan nanoparticles (NONPs) and investigate their activity on promastigotes and intracellular amastigotes of Leishmania (Leishmania) amazonensis. Cytotoxicity on macrophages was also evaluated. We verified that NONPs reduced both forms of the parasite in a single treatment. We also noticed reduction of parasitophorous vacuoles as an evidence of inhibition of parasite growth and resolution of infection. No substantial cytotoxicity was detected on macrophages. NONPs were able to provide a sustained parasite killing for both L. (L.) amazonensis infective stages with no toxicity on macrophages, representing a promising nanoplatform for cutaneous leishmaniasis.

    Palavras-Chave: chitin; nanoparticles; nitric oxide; protozoa; parasitic diseases; bioluminescence; fluorescence; macrophages; antimitotic drugs; antimicrobial agents

  • IPEN-DOC 28137

    CABRAL, FERNANDA V. ; PELEGRINO, MILENA T.; SEABRA, AMEDEA B.; RIBEIRO, MARTHA S. . Nitric-oxide releasing chitosan nanoparticles towards effective treatment of cutaneous leishmaniasis. Nitric Oxide, v. 113-114, p. 31-38, 2021. DOI: 10.1016/j.niox.2021.04.008

    Abstract: Cutaneous leishmaniasis (CL) is a major public health problem caused by Leishmania parasites that produce destructive and disfiguring skin conditions. There is an urgent need for alternative topical therapies due to the limitations of current systemic treatments. Recently, we have synthesized nitric oxide-releasing chitosan nanoparticles (NONPs) and shown their potential in vitro against Leishmania amazonensis. Herein we evaluated the application of NONPs for the treatment of CL on infected BALB/c mice. Mice were treated with topical administration of increasing concentrations of NONPs and disease progression was investigated regarding parasite load, lesion thickness, and pain score. As a result, we observed a dose-dependent NONPs effect. Parasite burden and lesion thickness were substantially lower on animals receiving NONPs at a 2 mM concentration compared to untreated control. Moreover, the clinical presentation of the lesions did not show any visible signs of ulcer, suggesting clinical healing in these animals. This successful outcome was sustained for at least 21 days after therapy even in one single dose. Thus, we demonstrate that NONPs are suitable for topical administration, and represent an attractive approach to treat CL.

    Palavras-Chave: parasitic diseases; therapy; bioluminescence; nitric oxide; skin; oligosaccharides

  • IPEN-DOC 28354

    CABRAL, FERNANDA V. ; LIAN, CHENG; PERSHEYEV, SAYDULLA; SMITH, TERRY K.; RIBEIRO, MARTHA S. ; SAMUEL, IFOR D.W.. Organic light-emitting diodes as an innovative approach for treating cutaneous leishmaniasis. Advanced Materials Technologies, v. 6, n. 11, p. 1-9, 2021. DOI: 10.1002/admt.202100395

    Abstract: Antimicrobial photodynamic therapy (APDT) has been studied as a noninvasive therapy for treating cutaneous leishmaniasis to overcome challenges with current treatment, such as toxicity, resistance, and need for in-patient hospital treatment. Organic light-emitting diodes (OLEDs) have emerged as an attractive technology that can provide wearable light-emitting materials that are conformable to human skin. This makes OLEDs ideal candidates for APDT by light-bandages for ambulatory care. In this work, suitable OLEDs are successfully developed to match the absorbance of three photosensitizers: methylene blue, new methylene blue, and 1,9-dimethyl-methylene blue to inactivate two Leishmania species in vitro: Leishmania major and Leishmania amazonensis. Parasites are treated either by LED (20 mW cm−2) or OLED (6.5 mW cm−2) at increasing photosensitizer concentrations at a radiant exposure of 50 J cm−2. 1,9-Dimethyl-methylene blue is the most potent photosensitizer, killing both strains at nanomolar concentrations. The effect of different intensities from the OLEDs (0.7, 1.5, and 6.5 mW cm−2) are also explored and it is shown that effective killing of Leishmania occurs even at a very low intensity. These findings demonstrate the great potential of OLEDs as a new approach for ambulatory treatment of cutaneous leishmaniasis by APDT.

    Palavras-Chave: antibiotics; antimicrobial agents; light emitting diodes; organic compounds; parasites; photosensitivity

  • IPEN-DOC 29710

    CABRAL, FERNANDA V. ; YOSHIMURA, TANIA M. ; SILVA, DANIELA de F.T. da ; CORTEZ, MAURO; RIBEIRO, MARTHA S. . Photodynamic therapy mediated by a red LED and methylene blue inactivates resistant leishmania amazonensis. Journal of the Optical Society of America A, v. 40, n. 5, p. 996-1005, 2023. DOI: 10.1364/JOSAA.482314

    Abstract: Cutaneous leishmaniasis is a neglected parasitic disease that leads to destructive lesions. The emergence of drug resistance has been a global concern over the past years. Photodynamic therapy (PDT) mediated by a red LED and methylene blue (MB) involves the overproduction of oxidative stress, which oxidizes several cellular biomolecules and prevents the selection of resistant strains. Herein, we investigated the potential of PDT mediated by MB against wild-type and miltefosine-resistant strains of Leishmania amazonensis. As a result, both strains were susceptible to PDT, thus encouraging us to seek the best conditions to overcome the drug resistance problem in cutaneous leishmaniasis.

    Palavras-Chave: protozoa; parasitic diseases; skin diseases; photodynamic therapy; methylene blue; light emitting diodes

  • IPEN-DOC 29924

    CABRAL, FERNANDA V. ; SANTANA, BIANCA de M.; LANGE, CAMILA N.; BATISTA, BRUNO L.; SEABRA, AMEDEA B.; RIBEIRO, MARTHA S . Pluronic F-127 hydrogels containing copper oxide nanoparticles and a nitric oxide donor to treat skin cancer. Pharmaceutics, v. 15, n. 1971, p. 1-19, 2023. DOI: 10.3390/ pharmaceutics15071971

    Abstract: Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.

  • IPEN-DOC 26678

    CABRAL, FERNANDA V. ; SABINO, CAETANO P.; DIMMER, JESICA A.; SAUTER, ISMAEL P. ; CORTEZ, MAURO J.; RIBEIRO, MARTHA S. . Preclinical investigation of methylene blue-mediated antimicrobial photodynamic therapy on Leishmania parasites using real-time bioluminescence. Photochemistry and Photobiology, v. 96, n. 3, p. 604-610, 2020. DOI: 10.1111/php.13188

    Abstract: Cutaneous leishmaniasis (CL) is a neglected disease that promotes destructive lesions. Difficulties in treatment are related to accessibility of drugs, resistance and toxicity. Antimicrobial photodynamic therapy (APDT) has been emerging as a promising treatment for CL. In this work, we evaluated methylene blue (MB)-mediated APDT (MB-APDT) on Leishmania amazonensis in vitro and in vivo by bioluminescence technique. In vitro, MB-APDT was performed using a red LED (k = 660 11 nm, 100 mW cm 2) and MB (100 μM) at different light doses. In vivo, mice were infected and 4 weeks later, randomly divided into three groups: control, APDT 1 (single session) and APDT 2 (two sessions of MB-APDT). MB was used at 100 μM and energy dose was established at 150 J cm 2. Parasite burden, lesion size and pain were evaluated weekly for 4 weeks. In vitro, lethal dose for 90% parasite inactivation was achieved at 48.8 J cm 2. In vivo, although APDT 1 and APDT 2 groups have showed similar parasite burden after 4 weeks, two sessions were clinically better, especially considering the inflammatory process associated to CL. Our findings reinforce MB-APDT as a costeffective treatment to combat CL.

    Palavras-Chave: antimicrobial agents; therapy; photosensitivity; methylene blue; parasites; bioluminescence; photochemistry; in vivo; in vitro; mice

  • IPEN-DOC 29840

    CABRAL, FERNANDA V. ; SOUZA, TIAGO H. dos S.; SALLERA, FABIO P.; FONTES, ADRIANA; RIBEIRO, MARTHA S. . Strengthening collaborations at the Biology‑Physics interface: trends in antimicrobial photodynamic therapy. Biophysical Reviews, v. 15, n. 4, p. 685-697, 2023. DOI: 10.1007/s12551-023-01066-5

    Abstract: The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and efective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT feld involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an efective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat diferent infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers.

    Palavras-Chave: antimicrobial agents; methylene blue; inactivation; photodynamic therapy; photosensitivity; porphyrins; zinc

  • IPEN-DOC 28315

    SELLERA, FABIO P.; SABINO, CAETANO P.; CABRAL, FERNANDA V. ; RIBEIRO, MARTHA S. . A systematic scoping review of ultraviolet C (UVC) light systems for SARS-CoV-2 inactivation. Journal of Photochemistry and Photobiology, v. 8, p. 1-6, 2021. DOI: 10.1016/j.jpap.2021.100068

    Abstract: A significant amount of epidemiological evidence has underlined that human-to-human transmission due to close contacts is considered the main pathway of transmission, however since the SARS-CoV-2 can also survive in aerosols, water, and surfaces, the development and implementation of effective decontamination strategies are urgently required. In this regard, ultraviolet germicidal irradiation (UVGI) using ultraviolet C (UVC) has been proposed to disinfect different environments and surfaces contaminated by SARS-CoV-2. Herein, we performed a systematic scoping review strictly focused on peer-reviewed studies published in English that reported experimental results of UVC-based technologies against the SARS-CoV-2 virus. Studies were retrieved from PubMed and the Web of Science database. After our criterious screening, we identified 13 eligible articles that used UVC-based systems to inactivate SARS-CoV-2. We noticed the use of different UVC wavelengths, technologies, and light doses. The initial viral titer was also heterogeneous among studies. Most studies reported virus inactivation in well plates, even though virus persistence on N95 respirators and different surfaces were also evaluated. SARS-CoV-2 inactivation reached from 90% to 100% depending on experimental conditions. We concluded that there is sufficient evidence to support the use of UVC-based technologies against SARS-CoV-2. However, appropriate implementation is required to guarantee the efficacy and safety of UVC strategies to control the COVID-19 pandemic.

    Palavras-Chave: coronaviruses; inactivation; germicides; ultraviolet radiation; photoreactivation

  • IPEN-DOC 28857

    COLLINA, GABRIELA A. da; CABRAL, FERNANDA V. ; MONTEIRO, CAROLINA M.; MACHADO, GABRIELA B.; GONCALVES, JOSE M.L.A.; FREIRE, FERNANDA; PRATES, RENATO A.; RIBEIRO, MARTHA S. ; PAVANI, CHRISTIANE. The importance of combining methods to assess Candida albicans biofilms following photodynamic inactivation. Photodiagnosis and Photodynamic Therapy, v. 38, p. 1-6, 2022. DOI: 10.1016/j.pdpdt.2022.102769

    Abstract: Background: Methylene blue (MB)-mediated photodynamic inactivation (PDI) has shown good results in killing Candida spp. Although MB solutions are commonly used, new formulations have been designed to improve PDI. However, chemical substances in the formulation may interfere with the PDI outcome. In this sense, different methodologies should be used to evaluate PDI in vitro. Herein, we report different methodologies to evaluate the effects of PDI with an oral formulation (OF) containing 0.005% MB on Candida albicans biofilm. Methods: Biofilms were treated using the MB-OF, with 5 min pre-irradiation time and exposure to a 640 nm LED device (4.7 J/cm2). PDI was evaluated by the XTT reduction test, counting the colony forming units (CFU), a filamentation assay, crystal violet (CV) staining, and scanning electronic microscopy (SEM). Results: PDI was able to reduce around 1.5 log10 CFU/mL, even though no significant differences were noted in metabolic activity in comparison to the control immediately after PDI. A significant decrease in yeast to hyphae transition was observed after PDI, while the biofilm exhibited flattened cells and a reduced number of yeasts in SEM. The CV assay showed increased biomass. Conclusion: MB-OF-mediated PDI was effective in C. albicans biofilms, as it significantly reduced the CFU/mL and the virulence of surviving cells. The CV data were inconclusive, since the OF components interacted with the CV, making the data useless. Taken together, our data suggest that the association of different methods allows complementary responses to assess how PDI mediated by a formulation impacts biofilms.

    Palavras-Chave: antimicrobial agents; methylene blue; chemotherapy; photodynamic therapy

  • IPEN-DOC 28366

    CABRAL, FERNANDA V. ; SOUZA, TIAGO H. dos S.; SELLERA, FABIO P.; FONTES, ADRIANA; RIBEIRO, MARTHA S. . Towards effective cutaneous leishmaniasis treatment with light-based technologies. A systematic review and meta-analysis of preclinical studies. Journal of Photochemistry and Photobiology B: Biology, v. 221, p. 1-8, 2021. DOI: 10.1016/j.jphotobiol.2021.112236

    Abstract: Cutaneous leishmaniasis (CL) is a neglected disease that represents a serious global public health concern. We performed a systematic review with meta-analysis targeting the use of light-based therapies on CL in preclinical studies since they are essential to identify the benefits, challenges, and limitations of proposing new technologies to fight CL. We searched Pubmed and Web of Science to include original preclinical researches in English that used light-based technologies to fight CL. Inclusion criteria encompassed any animal model for CL induction, an untreated infected group as the comparator, reliable and consistent methodology to develop and treat CL, focus on an antimicrobial therapeutic approach, and data for lesion size and/or parasite load in the infection site. We identified eight eligible articles, and all of them used photodynamic therapy (PDT). For the meta-analysis, three studies were included regarding the parasite load in the infection site and four comprised the lesion size. No overall statistically significant differences were observed between untreated control and PDT groups for parasite load. Differently, PDT significantly reduced the lesion size regardless of the protocol used to treat CL (in mm, SMD: -1.90; 95% CI: −3.74 to −0.07, p = 0.04). This finding is particularly encouraging since CL promotes disfiguring lesions that profoundly affect the quality of life of patients. We conclude that PDT is a new promising technology able to be topically used against CL if applied in more than one session, making it a promising ally for the management of CL.

    Palavras-Chave: protozoa; antimicrobial agents; therapy; photosensitivity

A pesquisa no RD utiliza os recursos de busca da maioria das bases de dados. No entanto algumas dicas podem auxiliar para obter um resultado mais pertinente.

É possível efetuar a busca de um autor ou um termo em todo o RD, por meio do Buscar no Repositório , isto é, o termo solicitado será localizado em qualquer campo do RD. No entanto esse tipo de pesquisa não é recomendada a não ser que se deseje um resultado amplo e generalizado.

A pesquisa apresentará melhor resultado selecionando um dos filtros disponíveis em Navegar

Os filtros disponíveis em Navegar tais como: Coleções, Ano de publicação, Títulos, Assuntos, Autores, Revista, Tipo de publicação são autoexplicativos. O filtro, Autores IPEN apresenta uma relação com os autores vinculados ao IPEN; o ID Autor IPEN diz respeito ao número único de identificação de cada autor constante no RD e sob o qual estão agrupados todos os seus trabalhos independente das variáveis do seu nome; Tipo de acesso diz respeito à acessibilidade do documento, isto é , sujeito as leis de direitos autorais, ID RT apresenta a relação dos relatórios técnicos, restritos para consulta das comunidades indicadas.

A opção Busca avançada utiliza os conectores da lógica boleana, é o melhor recurso para combinar chaves de busca e obter documentos relevantes à sua pesquisa, utilize os filtros apresentados na caixa de seleção para refinar o resultado de busca. Pode-se adicionar vários filtros a uma mesma busca.

Exemplo:

Buscar os artigos apresentados em um evento internacional de 2015, sobre loss of coolant, do autor Maprelian.

Autor: Maprelian

Título: loss of coolant

Tipo de publicação: Texto completo de evento

Ano de publicação: 2015

Para indexação dos documentos é utilizado o Thesaurus do INIS, especializado na área nuclear e utilizado em todos os países membros da International Atomic Energy Agency – IAEA , por esse motivo, utilize os termos de busca de assunto em inglês; isto não exclui a busca livre por palavras, apenas o resultado pode não ser tão relevante ou pertinente.

95% do RD apresenta o texto completo do documento com livre acesso, para aqueles que apresentam o significa que e o documento está sujeito as leis de direitos autorais, solicita-se nesses casos contatar a Biblioteca do IPEN, bibl@ipen.br .

Ao efetuar a busca por um autor o RD apresentará uma relação de todos os trabalhos depositados no RD. No lado direito da tela são apresentados os coautores com o número de trabalhos produzidos em conjunto bem como os assuntos abordados e os respectivos anos de publicação agrupados.

O RD disponibiliza um quadro estatístico de produtividade, onde é possível visualizar o número dos trabalhos agrupados por tipo de coleção, a medida que estão sendo depositados no RD.

Na página inicial nas referências são sinalizados todos os autores IPEN, ao clicar nesse símbolo será aberta uma nova página correspondente à aquele autor – trata-se da página do pesquisador.

Na página do pesquisador, é possível verificar, as variações do nome, a relação de todos os trabalhos com texto completo bem como um quadro resumo numérico; há links para o Currículo Lattes e o Google Acadêmico ( quando esse for informado).

ATENÇÃO!

ESTE TEXTO "AJUDA" ESTÁ SUJEITO A ATUALIZAÇÕES CONSTANTES, A MEDIDA QUE NOVAS FUNCIONALIDADES E RECURSOS DE BUSCA FOREM SENDO DESENVOLVIDOS PELAS EQUIPES DA BIBLIOTECA E DA INFORMÁTICA.

O gerenciamento do Repositório está a cargo da Biblioteca do IPEN. Constam neste RI, até o presente momento 20.950 itens que tanto podem ser artigos de periódicos ou de eventos nacionais e internacionais, dissertações e teses, livros, capítulo de livros e relatórios técnicos. Para participar do RI-IPEN é necessário que pelo menos um dos autores tenha vínculo acadêmico ou funcional com o Instituto. Nesta primeira etapa de funcionamento do RI, a coleta das publicações é realizada periodicamente pela equipe da Biblioteca do IPEN, extraindo os dados das bases internacionais tais como a Web of Science, Scopus, INIS, SciElo além de verificar o Currículo Lattes. O RI-IPEN apresenta também um aspecto inovador no seu funcionamento. Por meio de metadados específicos ele está vinculado ao sistema de gerenciamento das atividades do Plano Diretor anual do IPEN (SIGEPI). Com o objetivo de fornecer dados numéricos para a elaboração dos indicadores da Produção Cientifica Institucional, disponibiliza uma tabela estatística registrando em tempo real a inserção de novos itens. Foi criado um metadado que contém um número único para cada integrante da comunidade científica do IPEN. Esse metadado se transformou em um filtro que ao ser acionado apresenta todos os trabalhos de um determinado autor independente das variáveis na forma de citação do seu nome.

A elaboração do projeto do RI do IPEN foi iniciado em novembro de 2013, colocado em operação interna em julho de 2014 e disponibilizado na Internet em junho de 2015. Utiliza o software livre Dspace, desenvolvido pelo Massachusetts Institute of Technology (MIT). Para descrição dos metadados adota o padrão Dublin Core. É compatível com o Protocolo de Arquivos Abertos (OAI) permitindo interoperabilidade com repositórios de âmbito nacional e internacional.

1. Portaria IPEN-CNEN/SP nº 387, que estabeleceu os princípios que nortearam a criação do RDI, clique aqui.


2. A experiência do Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP) na criação de um Repositório Digital Institucional – RDI, clique aqui.

O Repositório Digital do IPEN é um equipamento institucional de acesso aberto, criado com o objetivo de reunir, preservar, disponibilizar e conferir maior visibilidade à Produção Científica publicada pelo Instituto, desde sua criação em 1956.

Operando, inicialmente como uma base de dados referencial o Repositório foi disponibilizado na atual plataforma, em junho de 2015. No Repositório está disponível o acesso ao conteúdo digital de artigos de periódicos, eventos, nacionais e internacionais, livros, capítulos, dissertações, teses e relatórios técnicos.

A elaboração do projeto do RI do IPEN foi iniciado em novembro de 2013, colocado em operação interna em julho de 2014 e disponibilizado na Internet em junho de 2015. Utiliza o software livre Dspace, desenvolvido pelo Massachusetts Institute of Technology (MIT). Para descrição dos metadados adota o padrão Dublin Core. É compatível com o Protocolo de Arquivos Abertos (OAI) permitindo interoperabilidade com repositórios de âmbito nacional e internacional.

O gerenciamento do Repositório está a cargo da Biblioteca do IPEN. Constam neste RI, até o presente momento 20.950 itens que tanto podem ser artigos de periódicos ou de eventos nacionais e internacionais, dissertações e teses, livros, capítulo de livros e relatórios técnicos. Para participar do RI-IPEN é necessário que pelo menos um dos autores tenha vínculo acadêmico ou funcional com o Instituto. Nesta primeira etapa de funcionamento do RI, a coleta das publicações é realizada periodicamente pela equipe da Biblioteca do IPEN, extraindo os dados das bases internacionais tais como a Web of Science, Scopus, INIS, SciElo além de verificar o Currículo Lattes. O RI-IPEN apresenta também um aspecto inovador no seu funcionamento. Por meio de metadados específicos ele está vinculado ao sistema de gerenciamento das atividades do Plano Diretor anual do IPEN (SIGEPI). Com o objetivo de fornecer dados numéricos para a elaboração dos indicadores da Produção Cientifica Institucional, disponibiliza uma tabela estatística registrando em tempo real a inserção de novos itens. Foi criado um metadado que contém um número único para cada integrante da comunidade científica do IPEN. Esse metadado se transformou em um filtro que ao ser acionado apresenta todos os trabalhos de um determinado autor independente das variáveis na forma de citação do seu nome.