RESUMO
Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment. While the excess production of melanin causes hyperpigmentation of human skin, hypopigmentation results in medical conditions like vitiligo. Tyrosinase inhibitors could be used as efficient skin whitening agents and tyrosinase agonists could be used for enhanced melanin synthesis and skin protection from UV exposure. Among a wide range of tyrosinase-regulating compounds, natural and synthetic derivatives of furochromenones, such as 8-methoxypsoralen (8-MOP), are known to both activate and inhibit tyrosinase. We recently reported a synthetic approach to generate a variety of dihydrofuro[3,2-c]chromenones and furo[3,2-c]chromenones in a metal-free condition. In the present study, we investigated these compounds for their potential as antagonists or agonists of tyrosinase. Using fungal tyrosinase-based in vitro biochemical assay, we obtained one compound (3k) which could inhibit tyrosinase activity, and the other compound (4f) that stimulated tyrosinase activity. The kinetic studies revealed that compound 3k caused 'mixed' type tyrosinase inhibition and 4f stimulated the catalytic efficiency. Studying the mechanisms of these compounds may provide a basis for the development of new effective tyrosinase inhibitors or activators.
Assuntos
Inibidores Enzimáticos , Monofenol Mono-Oxigenase , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Cinética , Humanos , Metoxaleno/farmacologia , Metoxaleno/química , Ativadores de Enzimas/química , Ativadores de Enzimas/farmacologiaRESUMO
BACKGROUND: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone. METHODS AND ANALYSIS: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials. ETHICS AND DISSEMINATION: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number 2022-002659-20; ISRCTN 10615985.
Assuntos
Transplante de Pulmão , Fotoferese , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aloenxertos , Rejeição de Enxerto , Pulmão/fisiopatologia , Metoxaleno/uso terapêutico , Estudos Multicêntricos como Assunto , Fotoferese/métodos , Disfunção Primária do Enxerto/terapia , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Reino UnidoRESUMO
This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4'=C5' epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP.
Assuntos
Furocumarinas , Metoxaleno , Metoxaleno/farmacologia , Simulação de Acoplamento Molecular , Metabolismo Secundário , Furocumarinas/farmacologia , Compostos de EpóxiRESUMO
New coumarin derivatives were designed using a 2-(2-oxo-2H-chromen-4-yl)acetic acid scaffold conjugated with amino acid esters or tyramine. The anti-tyrosinase and anti-lipid peroxidation activities of the synthesized compounds were investigated. Coumarin derivatives 7,9, 11-13, 15-18 showed strong anti-lipid peroxidation activity. Compound 13 exhibited uncompetitive tyrosinase inhibitory activity with an IC50 value of 68.86 µM. Compound 14 (% activity = 123.41) showed stronger tyrosinase activating activity than 8-methoxypsolaren (8-MOP, % activity = 109.46). In silico studies revealed different poses between the inhibitors and activators near the tyrosinase catalytic site. Compounds 13 (25-50 µM) and 14 (25-100 µM) did not show cytotoxicity against B16F10 cells. In contrast to the tyrosinase inhibition assay, compound 13 (50 µM) suppressed melanogenesis in B16F10 cells with two times higher potency than KA (100 µM). Compound 14 at 100 µM showed melanogenesis enhancement in B16F10 cells in a dose-dependent manner, however, inferior to the 8-MOP. Based on the findings, compound 13 and 14 offer potential for development as skin-lightening agents and vitiligo therapy agents, respectively.
Assuntos
Melanogênese , Monofenol Mono-Oxigenase , Antioxidantes/farmacologia , Metoxaleno , Cumarínicos/farmacologiaRESUMO
The use of plants such as giant hogweed as raw materials for the manufacture of dosage forms has been little explored. In this study, we utilized furanocoumarins from the Heracleum sosnowskyi plant to create an experimental emulsion dosage form (EmFHS). The EmFHS was finely dispersed (481.8 nm ± 71.1 nm), shelf-stable, and contained predominantly 8-methoxypsoralen at a concentration of 1 mg/ml. Phototoxicity analysis of EmFHS for THP-1 cells under UV (365 nm) irradiation showed an IC50 of 19.1 µg/ml (24 h) and 6.3 µg/ml (48 h). In relation to spheroids (L929), EmFHS exhibited a phototoxic effect in the concentration range of 31.25-125 µg/ml8-MOP. A full phototoxic effect was observed 48 h after UV irradiation. The phototoxic effect of EmFHS in vitro was dose-dependent and comparable to the effect of emulsion synthetic 8-methoxypsoralen and chlorin e6 solution. EmFHS cytotoxicity was caused solely by UV radiation, and toxicity in the dark was minimal. EmFHS, administered at a dose of 3 mg/kg8-MOP, was found to be safe after a single intravenous administration to rats. It had a photosensitizing effect in the form of local photodermatitis when exposed to UV irradiation at a dose of 44 J/cm2. The biokinetics of emulsion furanocoumarins showed that the phototoxic effect of EmFHS is due to the high penetration ability of the emulsion into cells of spheroids. At the same time, it has a low degree of cumulation when administered intravenously. The obtained data suggest that EmFHS may be a promising treatment for PUVA therapy of various dermatological diseases. Additionally, the plant Heracleum sosnowskyi shows potential as a basis for creating new dosage forms with phototherapeutic effects.
Assuntos
Furocumarinas , Heracleum , Ratos , Animais , Fármacos Fotossensibilizantes , Metoxaleno , EmulsõesRESUMO
INTRODUCTION: Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Previous studies showed that cotinine-supported self-administration in rats and rats with a history of cotinine self-administration exhibited relapse-like drug-seeking behavior, suggesting that cotinine may also be reinforcing. To date, whether cotinine may contribute to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1/2 enzymes in rats and methoxsalen is a potent CYP2B1/2 inhibitor. AIMS AND METHODS: The study examined nicotine metabolism, self-administration, and locomotor activity. The hypothesis is that methoxsalen inhibits nicotine self-administration and cotinine replacement attenuates the inhibitory effects of methoxsalen in male rats. RESULTS: Methoxsalen decreased plasma cotinine levels following a subcutaneous nicotine injection. Repeated daily methoxsalen treatments reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, lower nicotine intake, and lower plasma cotinine levels. However, methoxsalen did not alter the maintenance of nicotine self-administration despite a significant reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. CONCLUSIONS: These results indicate that methoxsalen inhibition of cotinine formation impaired the acquisition of nicotine self-administration, and cotinine replacement attenuated the inhibitory effects of methoxsalen on the acquisition of self-administration, suggesting that cotinine may contribute to the initial development of nicotine reinforcement. IMPLICATIONS: Smoking cessation medications targeting nicotine's effects are only moderately effective, making it imperative to better understand the mechanisms of nicotine misuse. Methoxsalen inhibited nicotine metabolism to cotinine and impaired the acquisition of nicotine self-administration. Cotinine replacement restored plasma cotinine and attenuated the methoxsalen inhibition of nicotine self-administration in rats. These results suggest that (1) the inhibition of nicotine metabolism may be a viable strategy in reducing the development of nicotine reinforcement, (2) methoxsalen may be translationally valuable, and (3) cotinine may be a potential pharmacological target for therapeutic development given its important role in the initial development of nicotine reinforcement.
Assuntos
Cotinina , Metoxaleno , Nicotina , Autoadministração , Animais , Masculino , Cotinina/sangue , Ratos , Nicotina/farmacologia , Nicotina/administração & dosagem , Metoxaleno/farmacologia , Ratos Sprague-Dawley , Comportamento de Procura de Droga/efeitos dos fármacosRESUMO
Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.
Assuntos
Lipopolissacarídeos , Metoxaleno , Sepse , Animais , Camundongos , Inflamação/metabolismo , Macrófagos , Metoxaleno/análogos & derivados , Camundongos Endogâmicos C57BL , Sepse/induzido quimicamente , Sepse/tratamento farmacológico , Ubiquitinação , Ubiquitinas/metabolismoRESUMO
Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.
Assuntos
Vesículas Extracelulares , Fotoferese , Neoplasias Cutâneas , Humanos , Metoxaleno/farmacologia , Raios Ultravioleta , Neoplasias Cutâneas/etiologiaRESUMO
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Assuntos
Ciclosporinas , Neoplasias Hematológicas , Neoplasias , Humanos , Etoposídeo , Metoxaleno , Azatioprina , Melfalan , Bussulfano , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Ciclofosfamida , Preparações FarmacêuticasRESUMO
Abstract: Pigmented purpuric dermatoses are chronic vascular inflammatory conditions characterized by the presence of pigmented macules. Among its different presentations, lichen aureus is distinguished by the lichenoid conformation of its plaques and the predilection for lower limb involvement. Its segmented form is rare and difficult to control, especially in cases of symptomatic lesions. We report a rare case of segmental lichen aureus with six years of evolution associated with light itching. We also discuss the main therapeutic approaches to control the disease.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Erupções Liquenoides/patologia , Luz Solar , Betametasona/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Erupções Liquenoides/terapia , Glucocorticoides/uso terapêutico , Metoxaleno/uso terapêuticoRESUMO
Catecóis são derivados do benzeno, podendo apresentar citotoxicidade, que pode constituir um modelo experimental útil para o desenvolvimento de novos fármacos. No bioma brasileiro inúmeras plantas produzem metabólitos com atividades diversas, como antioxidantes, ou inibidores do crescimento celular. No Brasil, as neoplasias são a segunda causa de óbito, especialmente aquelas derivadas do sistema nervoso, aumentando o interesse por novos antineoplásicos e agentes neuroprotetores. Este trabalho caracteriza efeitos citotóxicos do 1,2-dihidroxibenzeno (CAT) e discretamina (DSC) em células do sistema nervoso in vitro. Determinou-se a EC50 de CAT e DSC usando brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium (MTT), investigou-se sua auto-oxidação por espectrofotometria, avaliou-se mudanças morfológicas e condensação/fragmentação nuclear por microscopia. Avaliou-se a proteção de DSC e 8-metoxipsoraleno (8-MOP) contra a citotoxicidade do CAT. O padrão de morte celular foi analisado por citometria de fluxo. A espoliação de glutation reduzido (GSH) foi analisada usando monoclorobimano. A toxicidade do CAT para células SH-SY5Y e C6 depende da dose e associa-se à formação de quinonas. Houve mudanças morfológicas, condensação/fragmentação da cromatina e morte apoptótica, não relacionada à espoliação de GSH. DSC não foi tóxica para células SH-SY5Y, porém protegeu contra os efeitos do CAT em baixas concentrações. DSC mostrou-se citotóxica para células de glioma (GL-15 e C6) e potencializou o CAT. Pré-tratamento por 30 minutos com DSC protegeu contra a ação do CAT após 72 horas. 8-MOP potencializou os efeitos do CAT, não revertendo seus efeitos na viabilidade celular, morfologia celular, condensação/fragmentação nuclear, e espoliação de GSH. Esses resultados caracterizam um modelo de citotoxicidade que pode ser aplicado no desenvolvimento de novos agentes farmacológicos. Estudos complementares são necessários para elucidar a proteção da DSC.
Catechols are benzene derivatives, which may exhibit cytotoxic activity that can be employed to develop new drugs. Plants are important sources of metabolites with pharmacological activities such as antioxidants, or cell growth inhibitors. In Brazil, cancer is the second leading cause of death, especially those derived from the nervous system, which increase the interest for new antineoplastic and neuroprotective drugs. The cytotoxic effects promoted by 1,2-dihydroxybenzene (CAT) and discretamine (DSC) in nervous system cells were characterized in vitro. The protective effects of DSC and 8-methoxypsoralen (8-MOP) against CAT-induced cytotoxicity were also evaluated. CAT and DSC EC50 was determined by using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT). CAT auto-oxidation was investigated by spectrophotometry. Morphological changes and nuclear condensation/ fragmentation were evaluated by microscopy. The pattern of cell death was obtained by flow cytometry. Reduced glutathione (GSH) depletion was analyzed by using monochlorobimane. CAT induced a dose-dependent toxicity to SH-SY5Y and C6 cells, associated with reactive quinones formation. It also induced morphological changes, nuclear condensation/fragmentation, and apoptotic death not caused by GSH depletion. DSC was not toxic to SH-SY5Y cells, but protected against CAT effects at low concentrations. DSC was be cytotoxic to glioma cells (GL-15 and C6) and potentiated CAT effects. However, pretreatment for 30 minutes with DSC protected them against CAT after 72 hours. 8-MOP also potentiated CAT effects instead to protect cells. These results characterize an experimental model useful for studies searching new pharmacological agents. However, further studies are needed to elucidate the DSC protective effects.
Assuntos
Humanos , /administração & dosagem , /análise , /farmacologia , /uso terapêutico , Metoxaleno/análise , Metoxaleno/farmacologia , Metoxaleno/uso terapêutico , Neoplasias/patologia , Neoplasias/prevenção & controleRESUMO
Duas adolescentes e uma menina com vitiligo clinicamente diagnosticado foram tratadas com 8-metoxipsoraleno a 0,2 por cento em creme Lanette com subsequente exposição solar. Um ano após, apresentaram máculas acrômicas na área do vitiligo. A biópsia de pele em um dos casos revelou melanócitos com escassa pigmentação melânica. Os achados clínicos e histológicos sugerem o diagnóstico de leucodermia punctata.
Two adolescent females and a girl, all with clinically diagnosed vitiligo, were treated with 0.2 percent 8-methoxypsoralen cream followed by exposure to solar ultraviolet light. One year later, they developed hypopigmented and achromic spots on the areas affected by the vitiligo. Biopsy of skin tissue taken from one of these cases showed a marked reduction in melanin. Clinical and histological findings point to a diagnosis of leukoderma punctata.
Assuntos
Adolescente , Criança , Feminino , Humanos , Metoxaleno/efeitos adversos , Terapia PUVA/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Transtornos da Pigmentação/etiologia , Metoxaleno/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Transtornos da Pigmentação/patologia , Vitiligo/tratamento farmacológicoRESUMO
8-Methoxy psoralen (8-MOP) exerts a short-term (24 h) mitogenic action, and a long-term (48-72 h) anti-proliferative and melanogenic action on two human melanoma cell lines, SK-Mel 28 and C32TG. An increase of intracellular calcium concentration was observed by spectrofluorometry immediately after the addition of 0.1 mM 8-MOP to both cell lines, previously incubated with calcium probe fluo-3 AM (5 µM). The intracellular Ca2+ chelator BAPTA/AM (1 µM) blocked both early (mitogenic) and late (anti-proliferative and melanogenic) 8-MOP effects on both cell lines, thus revealing the importance of the calcium signal in both short- and long-term 8-MOP-evoked responses. Long-term biological assays with 5 and 10 mM tetraethylammonium chloride (TEA, an inhibitor of Ca2+-dependent K+ channels) did not affect the responses to psoralen; however, in 24-h assays 10 mM TEA blocked the proliferative peak, indicating a modulation of Ca2+-dependent K+ channels by 8-MOP. No alteration of cAMP basal levels or forskolin-stimulated cAMP levels was promoted by 8-MOP in SK-Mel 28 cells, as determined by radioimmunoassay. However, in C32TG cells forskolin-stimulated cAMP levels were further increased in the presence of 8-MOP. In addition, assays with 1 µM protein kinase C and calcium/calmodulin-dependent kinase inhibitors, Ro 31-8220 and KN-93, respectively, excluded the participation of these kinases in the responses evoked by 8-MOP. Western blot with antibodies anti-phosphotyrosine indicated a 92 percent increase of the phosphorylated state of a 43-kDa band, suggesting that the phosphorylation of this protein is a component of the cascade that leads to the increase of tyrosinase activity.
Assuntos
Humanos , Melanoma , Metoxaleno , Fármacos Fotossensibilizantes , Canais de Potássio , Proteínas Tirosina Quinases , Indóis , Transdução de Sinais , Espectrometria de Fluorescência , Fatores de Tempo , Células Tumorais CultivadasRESUMO
FUNDAMENTOS - O tratamento normalmente usado para o vitiligo envolve a combinaçäo de 8-metoxipsoraleno (8-MOP) e radiaçäo ultravioleta A, conhecida como PUVA-terapia. Embora a estimulaçäo da proliferaçäo e diferenciaçäo de melanócitos possa explicar a eficiência da PUVA-terapia no tratamento do vitiligo, até a presente data, näo se demonstrou nenhuma interaçäo direta desse composto com melanócitos humanos normais em cultura. OBJETIVOS - Estudar a interaçäo de [3H]8-metoxipsoraleno com melanócitos humanos normais em cultura obtidos de indivíduos de cor branca e negra. MÉTODOS - Melanócitos humanos normais isolados de prepúcios de crianças e mantidos em meio MCDB-153 na ausência de soro, éster de forbol (PMA) e toxina da cólera, foram incubados com [3H]8-metoxipsoraleno para determinaçäo da ligaçäo específica a essas células. RESULTADOS - Melanócitos isolados de ambos os tipos de pele, mostraram ligaçäo com 8-MOP, embora uma maior porcentagem de ligaçäo tenha sido observada em melanócitos isolados de pessoas de cor negra. CONCLUSÖES - A capacidade proliferativa de melanócitos humanos normais varia de acordo com a cor racial. É possível que as diferenças observadas na ligaçäo do psoraleno, estejam relacionadas com diferenças quanto ao número de receptores de psoralenos entre melanócitos isolados de pele clara e escura
Assuntos
Humanos , População Negra , População Branca , Melanócitos/imunologia , Metoxaleno , Fotoquimioterapia , Terapia PUVA , Vitiligo/tratamento farmacológico , Meios de Cultura/análise , Furocumarinas/metabolismo , PeleRESUMO
Se presenta un caso de micosis fungoides en fase tumoral que ha respondido favorablemente al manajo con cobalto luego de 15 sesiones con dosis fraccionadas de 200 rads diarios. Posteriormente, se ha manejado con puvaterapia, obteniendo excelentes resultados hasta el momento
Assuntos
Humanos , Feminino , Adulto , Cobalto , Cobalto/uso terapêutico , Metoxaleno , Metoxaleno/uso terapêutico , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Terapia PUVA/estatística & dados numéricos , Dosagem RadioterapêuticaRESUMO
El vitiligo es una hipomelanosis y amelanosis idiopática adquirida de la piel que afecta un alto porcentaje de la población. La fotoquimioterapia estimula la melanogénesis, la proliferación y la migración de melonocitos. Estudios recientes han mostrado exelente repigmentación con PUVA empleando 5-Metoxipsoralen oral. Este método tiene la ventaja de que produce muy poca fototoxicidad cutánea y náuseas. Hemos tratados 30 pacientes de vitiligo localizado con fotoquimioterapia tópica, empleando una preparación líquida nueva de 5-Metoxipsoralen que ha mostrado ser efectiva en la repigmenación de un número substancial de pacientes. (76.6%)
Assuntos
Criança , Adolescente , Adulto , Humanos , Masculino , Feminino , Terapia PUVA , Vitiligo/tratamento farmacológico , Metoxaleno/administração & dosagem , Metoxaleno/uso terapêutico , Administração Oral , Administração TópicaRESUMO
Dos hombres afectados de reticuloide actinico, un de 73 y el otro de 58 anos de edad, fueron tratados con 20 mg de metoxalen por via oal y exposicion al sol. Ambos mejoraron considerablemente de los sintomas cutaneos y continuaron bien con tratamiento ambulatorio en base al mismo esquema terapeutico
Assuntos
Pessoa de Meia-Idade , Humanos , Masculino , Linfoma , Metoxaleno , Micose Fungoide , Raios UltravioletaRESUMO
Avaliacao de 8-methoxipsoraleina associada a luz ultravioleta longa (~365nm) - 8MOP-UVL na inducao de profagos em Staphylococcus aureus 609tet-r. As frequencias de inducao de profagos por UVL, na presenca de 8MOP, quando lancadas em grafico, em funcao da dose, reveleram uma curva de dose-efeito tipica, tambem conhecida para outros sistemas lisogenicos. Para as condicoes experimentais utilizadas, a frequencia maxima de inducao foi maior que aquela obtida apos irradiacao por luz ultravioleta curta (~245nm)