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Estudos da dinâmica de fototransformação do agente antibacteriano Nitrofurantoína e da formação das espécies ativas durante sua fototransformação; Studies of the dynamics of phototransformation of Nitrofurantoin antibacterial agent and the formation of active species during its phototransformation

Parra, Gustavo Gimenez
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 05/11/2010 PT
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A fotoquimioterapia (FQT) é uma técnica de tratamento de doenças graves, inclusive o câncer, que utiliza que utiliza compostos que, sendo introduzidos dentro de um organismo, não possuem alguma atividade contra ele e quando são excitados, através de luz na região espectral de 320 até 800 nm, produzem espécies reativas que induzem a morte celular. Dentre as formas desenvolvidas em FQT, a de maior destaque, e a que vem sendo mais utilizada em clínica, é a Terapia Fotodinâmica (TFD). Apesar das vantagens do uso da TFD, esta técnica possui limitações em sua eficiência, pois seu mecanismo está associado com à formação dos estados excitados do FS e do oxigênio molecular e, por isso, depende dos tempos de vida e rendimentos quânticos destes estados. Outro fator que limita a ampla aplicação da FQT na clínica é o alto custo dos FS utilizados atualmente. No grupo de fotobiofísica do Departamento de Física e Matemática da FCLRP-USP, tem-se trabalhado na busca de novos FS que possuam espécies reativas não excitados como, por exemplo, os radicais livres (peróxidos, ânion superóxido, radical hidroxila etc.), e que sejam mais viáveis economicamente em relação a outros FS já existentes no mercado. Os derivados de nitrofurano são fármacos já utilizados na rotina clínica que possuem as características promissoras para aplicação em FQT. Este trabalho dá continuidade à busca de novos FS. Escolhemos dentre inúmeros derivados de nitrofurano a Nitrofurantoína (NFT)...

Ação da terapia fotodinâmica (TFD) sobre o biofilme dentário humano; The action of photodynamic therapy on human dental plaque

Tessarolli, Vanessa
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 29/11/2010 PT
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Entre os métodos de prevenção da cárie dentária, os controles mecânico e químico do biofilme dentário são de grande relevância neste processo. O controle mecânico é eficaz desde que executado diariamente e sistematicamente envolver todas as superfícies dentárias expostas ao meio bucal. Ele pode ser realizado pelo odontólogo por meio da profilaxia profissional e pelo próprio paciente pela escovação dentária. O controle químico do biofilme dentário deve ser empregado de forma suplementar, quando o controle mecânico não puder ser realizado diariamente ou se for realizado de forma inadequada acarretando o risco do acúmulo do biofilme dentário e como consequência, a ocorrência de lesões de cárie dentária e/ou da doença periodontal. O ideal seria associar ambos os métodos, para que um compense a deficiência do outro. É nesta direção que inúmeros estudos são feitos nos últimos anos. Para o controle químico, são relatadas na literatura inúmeras substâncias antimicrobianas. Dentre os agentes químicos recomendados, a clorexidina (CLX) tem se mostrado eficiente para esta finalidade, porém, sua aplicação apresenta limitações como: manchamento de áreas desmineralizadas dos dentes e perda do paladar...

Interação de pontos quânticos com fotossensibilizadores orgânicos na presença de estruturas nano-organizadas; Interaction of quantum dots with organic photosensitizers in the presence of nano-organized structures

Parra, Gustavo Gimenez
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 19/01/2015 PT
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O sucesso de tratamento de câncer depende do seu diagnóstico e tratamento nas etapas iniciais da doença. Isso estimula a busca de novos métodos de diagnóstico e de tratamento sensíveis e tecnicamente simples. Entre esses métodos, o diagnóstico por fluorescência (DPF) e a fotoquimioterapia (FQT) atraem uma atenção especial, sendo não invasivos, sensíveis e fácil de usar. Os fotossensibilizadores (FS) atualmente utilizados em DPF e FQT são corantes orgânicos, os quais possuem algumas desvantagens, tais como instabilidade fotoquímica e baixa seletividade. Os pontos quânticos (PQ) são candidatos promissores para substituírem os FS clássicos por serem fotoestáveis, apresentarem amplo e intenso espectro de absorção óptica e luminescência com alto rendimento quântico. Contudo a iteração entre FS clássicos e os PQ pode aumentar a eficiência de ambos devido a transferência de energia entre eles. O objetivo geral deste trabalho foi estudar os processos da interação de FS orgânicos (as porfirinas PPh, TMPyP e TPPS4) com PQs (CdTe e CdSe/ZnS), funcionalizados com diferentes grupos, em solução aquosa e na presença de modelos nano-organizados de estruturas biológicas com a finalidade de avaliar seu potencial para aplicação em Fotoquimioterapia e Diagnóstico por Fluorescência. Dedicamos especial atenção aos processos de transferência de energia e de carga entre os PQs e os FS. Os PQs interagem efetivamente com as PPh...

Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T-cell lymphoma.

Di Renzo, M; Rubegni, P; De Aloe, G; Paulesu, L; Pasqui, A L; Andreassi, L; Auteri, A; Fimiani, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1997 EN
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Extracorporeal photochemotherapy (ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage-dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non-toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC) in eight patients with early stage (Ib) cutaneous T-cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)-stimulated proliferation and production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) as well as lipopolysaccharide (LPS)-induced production of IL-12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL-4 and lower levels of IFN-gamma and IL-12 than those of healthy control subjects. After 1 year of ECP, IL-4, IFN-gamma and IL-12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that early-stage CTCL patients show a predominantly type-2 immune response that might be responsible for several immunological abnormalities found in this disease. We have demonstrated that ECP reverses the T-helper type 1/T-helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modifier.

Influence of prophylactic photochemotherapy on incidence of relapse of psoriasis cleared initially with dithranol.

Marks, J M; Lawrence, C M; Corbett, M; Coburn, P; Parker, S; Shuster, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 14/01/1984 EN
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Forty one patients whose psoriasis cleared with dithranol were given prophylatic photochemotherapy with psoralens and ultraviolet A once a week. With life table analysis the chance of remaining in remission for 16 months was shown to be 42% for these patients, compared with 13% for a group of patients who were not given prophylactic photochemotherapy.

Relapse rate and long-term management of plaque psoriasis after treatment with photochemotherapy and dithranol.

Vella Briffa, D; Greaves, M W; Warin, A P; Rogers, S; Marks, J; Shuster, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 21/03/1981 EN
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The relapse rate of plaque psoriasis after initial clearing with the "Ingram" dithranol regimen or photochemotherapy was comparable when no maintenance treatment was given. It was estimated that psoriasis recurs to half of its pretreatment extent after about six months in half the patients. Maintenance treatment with photochemotherapy once a week or once every three weeks was useful in reducing the relapse rate. This study failed to show any statistical difference in relapse rates between these two maintenance schedules. If this finding turns out to be true over longer periods of study the maintenance schedule entailing treatment once every three weeks with its lower cumulative dose of long-wave ultraviolet light will clearly be preferable. The psoriasis in most patients was under better overall control with maintenance treatment than with intermittant clearing courses given when the extent of the psoriasis had become unacceptable to them. There was, however, a group of roughly one-fifth of patients who remained in satisfactory remission for over 16 months after initial clearing. Regular maintenance treatment was unnecessary in them. Much more information is needed on response to treatment in subgroups of patients to permit recognition from the start of which patients are likely to have long remission and which are not.

Photochemotherapy in mycosis fungoides.

Hodge, L; Warin, A P; Gange, R W; Bleehen, S; Vella Briffa, D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 12/11/1977 EN
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Six patients with mycosis fungoides were treated with methoxsalen and long-wave ultraviolet light. They were assessed clinically and histologically before and after treatment. All six patients showed clinical improvement. Histological clearing of both epidermis and dermis occurred in three patients, and epidermal clearing alone occurred in two. Photochemotherapy may have a place in the treatment of the early and intermediate stages of mycosis fungoides, and it may also be useful as an adjunct to other forms of treatment in the more advanced stages.

Morphologic studies of bladder tumors treated with hematoporphyrin derivative photochemotherapy.

Klaunig, J. E.; Selman, S. H.; Shulok, J. R.; Schafer, P. J.; Britton, S. L.; Goldblatt, P. J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1985 EN
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The morphologic changes that occurred in transplanted rat bladder tumors after treatment with hematoporphyrin derivative (HPD) and/or phototherapy were investigated. Transitional cell bladder tumors were initiated subcutaneously in male F344 rats by injection of AY27 cells. When tumors reached 1 cm in diameter, the rats received either HPD (10 mg/kg body weight) photochemotherapy, HPD only, phototherapy only, or no treatment. Tumors were sampled immediately (0 time), 1/2, 1, 2, 4, and 24 hours after phototreatment for light and electron microscopy. Tumors receiving HPD-photochemotherapy displayed progressive injury to both tumor cells and endothelial cells. Early changes (0-2 hours) included focal tumor and endothelial cell vacuolation and swelling as well as sloughing of tumor cells into papillary spaces. Tumor cells and endothelial cells displayed vacuolization and damage to cell mitochondria immediately after phototreatment. Intercellular spaces also increased in size. Lethally injured cells were apparent in papillary spaces. At 4 hours after phototherapy, tumor cells and endothelial cells exhibited extensive cell damage, including mitochondrial destruction, endoplasmic reticulum swelling, polyribosome disaggregation, and plasma membrane blebbing. By 24 hours after phototherapy...

Treatment of autoimmune disease with extracorporeal photochemotherapy: progressive systemic sclerosis.

Rook, A. H.; Freundlich, B.; Nahass, G. T.; Washko, R.; Macelis, B.; Skolnicki, M.; Bromley, P.; Witmer, W. K.; Jegasothy, B. V.
Fonte: Yale Journal of Biology and Medicine Publicador: Yale Journal of Biology and Medicine
Tipo: Artigo de Revista Científica
Publicado em //1989 EN
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In this report, we describe the use of extracorporeal photochemotherapy in n the treatment of two patients with rapidly advancing progressive systemic sclerosis. Both patients experienced improvement in the cutaneous as well as the systemic manifestations of their disease while undergoing therapy. The potential therapeutic mechanisms are discussed.

Treatment of autoimmune disease with extracorporeal photochemotherapy: pemphigus vulgaris--preliminary report.

Rook, A. H.; Heald, P. W.; Nahass, G. T.; Macey, W.; Witmer, W. K.; Lazarus, G. S.; Jegasothy, B. V.
Fonte: Yale Journal of Biology and Medicine Publicador: Yale Journal of Biology and Medicine
Tipo: Artigo de Revista Científica
Publicado em //1989 EN
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Extracorporeal photochemotherapy is a new form of immunotherapy which involves the extracorporeal photoinactivation of peripheral blood cells by 8-methoxypsoralen in the presence of ultraviolet A irradiation, followed by readministration of the cells. To explore the efficacy of this therapy in the treatment of autoimmune disease, four patients with a lengthy history of corticosteroid and immunosuppressive drug-resistant pemphigus vulgaris were initiated on extracorporeal photochemotherapy. Three patients experienced a complete remission in cutaneous disease expression, permitting discontinuation of medications in two and a substantial decrease in the third. Significant reductions in serum antiepidermal cell antibody titers occurred in all four patients. The treatments were well tolerated without the occurrence of adverse events. These results in a small number of patients suggest that extracorporeal photochemotherapy may prove to be a useful tool in the treatment of aggressive autoimmune disease.

Targeting of T/Tn Antigens with a Plant Lectin to Kill Human Leukemia Cells by Photochemotherapy

Poiroux, Guillaume; Pitié, Marguerite; Culerrier, Raphaël; Lafont, Elodie; Ségui, Bruno; Van Damme, Els J. M.; Peumans, Willy J.; Bernadou, Jean; Levade, Thierry; Rougé, Pierre; Barre, Annick; Benoist, Hervé
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 17/08/2011 EN
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Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death...

Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy

Berger, Carole; Hoffmann, Kristin; Vasquez, Juan G.; Mane, Shrikant; Lewis, Julia; Filler, Renata; Lin, Aiping; Zhao, Hongyu; Durazzo, Tyler; Baird, Abigail; Lin, William; Foss, Francine; Christensen, Inger; Girardi, Michael; Tigelaar, Robert; Edelson, Ri
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 02/12/2010 EN
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Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T-cell lymphoma, graft-versus-host disease, and allografted organ rejection. Its clinical and experimental efficacy in cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway, within a single day, without added cytokines, as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature, common to ECP-processed monocytes from normal subjects, and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway, this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances...

Treatment of Childhood Psoriasis with Phototherapy and Photochemotherapy

Lara-Corrales, Irene; Ramnarine, Sabrina; Lansang, Perla
Fonte: Libertas Academica Publicador: Libertas Academica
Tipo: Artigo de Revista Científica
Publicado em 29/07/2013 EN
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Phototherapy and photochemotherapy are well-described treatment modalities for psoriasis in adults. Like many other treatments, the experience and long-term safety of their use in children is limited. We conducted a literature search and identified publications reporting the use of phototherapy and photochemotherapy in pediatric populations. This article summarizes the existing literature on this topic. Although many studies report good improvement with these treatment modalities, long-term safety data on their use is lacking for pediatric patients.

Integrin-driven monocyte to dendritic cell conversion in modified extracorporeal photochemotherapy

Gonzalez, A L; Berger, C L; Remington, J; Girardi, M; Tigelaar, R E; Edelson, R L
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
EN
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Due to clinical efficacy and safety profile, extracorporeal photochemotherapy (ECP) is a commonly used cell treatment for patients with cutaneous T cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The capacity of ECP to induce dendritic antigen-presenting cell (DC)-mediated selective immunization or immunosuppression suggests a novel mechanism involving pivotal cell signalling processes that have yet to be clearly identified as related to this procedure. In this study we employ two model systems of ECP to dissect the role of integrin signalling and adsorbed plasma proteins in monocyte-to-DC differentiation. We demonstrate that monocytes that were passed through protein-modified ECP plates adhered transiently to plasma proteins, including fibronectin, adsorbed to the plastic ECP plate and activated signalling pathways that initiate monocyte-to-DC conversion. Plasma protein adsorption facilitated 54·2 ± 4·7% differentiation, while fibronectin supported 29·8 ± 7·2% differentiation, as detected by DC phenotypic expression of membrane CD80 and CD86, as well as CD36, human leucocyte antigen D-related (HLA-DR) and cytoplasmic CD83. Further, we demonstrate the ability of fibronectin and other plasma proteins to act through cell adhesion via the ubiquitous arginine–glycine–aspartic (RGD) motif to drive monocyte-to-DC differentiation...

Mechanistic insights into extracorporeal photochemotherapy: Efficient induction of monocyte-to-dendritic cell maturation

Edelson, Richard L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma, as well as immunomodulation of graft-versus-host disease (GVHD) and transplanted organ rejection. ECP’s mechanism encompasses large-scale physiologic platelet induction of dendritic cells (DCs). The normal bidirectional immunologic talents of DCs likely contribute heavily to ECP’s capacity to immunize against tumor antigens, while also suppressing transplant immunopathology. Our understanding of how ECP physiologically induces monocyte-to-DC maturation can enhance the treatment’s potency, potentially broaden its use to other cancers and autoimmune disorders and tailor its application to individual patients’ diseases. ECP’s next decade is filled with promise.

Induction of Monocyte-to-Dendritic Cell Maturation by Extracorporeal Photochemotherapy: Initiation via Direct Platelet Signaling

Durazzo, Tyler S.; Tigelaar, Robert E.; Filler, Renata; Hayday, Adrian; Girardi, Michael; Edelson, Richard L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Extracorporeal Photochemotherapy (ECP) is a widely used therapy for cutaneous T cell lymphoma (CTCL). Although the mechanism of clinical action of ECP is not precisely established, previous studies have shown evidence of induction of dendritic cells (DC). Here we show that, under flow conditions similar to those in post-capillary venues, ECP promotes platelet immobilization and activation, initiating stepwise receptor-ligand interactions with monocytes, which then differentiate into DC. These findings clarify how ECP directly stimulates DC maturation; suggest a new clinically applicable approach to the obtainment of DC; and identify a novel mechanism that may reflect physiological induction of DC.

Atividades melanogênica, genotóxica e antiproliferativa de extratos de Brosimum gaudichaudii Trécul e Dorstenia brasiliensis Lam induzidas por radiação UVA.

Quevedo, Adriana Elias Pires
Fonte: Universidade Federal de Mato Grosso do Sul Publicador: Universidade Federal de Mato Grosso do Sul
Tipo: Tese de Doutorado
POR
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As furanocumarinas lineares ou psoralenos são fotossensibilizadores empregados na dermatologia associados a ultravioleta A no tratamento de doenças como o vitiligo. A fotoquimioterapia tem reações adversas imediatas (náuseas, prurido, eritema e xerodermia) e tardias (carcinogênese e, possivelmente, catarata). No Brasil, não existe medicamento fitoterápico ou medicamentos contendo extratos de plantas para tratamento do vitiligo que estejam de acordo com a legislação vigente da Agência Nacional de Vigilância Sanitária. O objetivo deste estudo foi analisar extratos de espécies do Cerrado que contêm furanocumarinas e avaliar suas atividades melanogênica, mutagênica e antiproliferativa. A quantificação das furanocumarinas por cromatografia líquida de alta eficiência acoplada a detector de arranjo de fotodiodos (CLAE-DAD) revelou 40,77 mg/g de 5-metoxipsoraleno (5-MOP) no extrato de Brosimum gaudichaudii e 85,33 mg/g de psoraleno + 5-MOP no extrato de Dorstenia brasiliensis. Foram obtidos perfis cromatográficos para controle de qualidade dos extratos em cromatografia em camada delgada (CCD) e em CLAE-DAD. A dorstenina foi identificada no extrato de D. brasiliensis por cromatografia em fase gasosa acoplada a espectrometria de massa (CG-EM). Os extratos de B. gaudichaudii e de D. brasiliensis e as furanocumarinas psoraleno...

The role of reactive oxygen species in photochemotherapy with haematoporphyrin derivative / by Kevin Lee See

Lee See, Kevin
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //1985 EN
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Thesis (M.D.)--University of Adelaide, 1985; Bibliography: leaves 144-163; xi, 163 leaves :; The complete thesis in print form is available from the University Library.

Mechanisms of lymphocytotoxicity induced by extracorporeal photochemotherapy for cutaneous T cell lymphoma.

Marks, D I; Rockman, S P; Oziemski, M A; Fox, R M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1990 EN
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Extracorporeal photochemotherapy is an effective treatment for cutaneous T cell lymphoma but its mode of action is uncertain. The reduction in viability of patients' photoirradiated buffy coat lymphocytes was correlated with a 35% increase in DNA single-strand breaks and marked decreases in cellular ATP and NAD levels (to 58 and 34% of control, respectively) immediately after photoirradiation. Complementary in vitro studies were conducted with normal human peripheral blood lymphocytes using a Therakos ultraviolet A (UVA) light box. UVA light was cytotoxic on its own but was potentiated by 8-methoxysporalen. 3-aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, mitigated the cytotoxic effect of ultraviolet A light in the presence of 8-methoxypsoralen in lymphocytes and reduced the amount of nucleotide depletion they caused. 10 J/cm2 of UVA light in the presence of 300 ng/ml 8-methoxypsoralen increased the poly (ADP-ribose) synthetase activity of peripheral blood lymphocytes. Exposing lymphocytes to deoxycoformycin and deoxyadenosine was found to induce biochemical and physical effects similar to those of photochemotherapy. In summary, we have shown that the lymphocytotoxic effect of extracorporeal photochemotherapy for cutaneous T cell lymphoma is apparently mediated by DNA damage...

Activation of GILZ gene by photoactivated 8-methoxypsoralen: Potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy

Futterleib, Jeffrey S.; Feng, Hao; Tigelaar, Robert E.; Choi, Jaehyuk; Edelson, Richard L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft-versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production...