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[PMID]:29337062
[Au] Autor:Yang Y; Zheng K; Mei W; Wang Y; Yu C; Yu B; Deng S; Hu J
[Ad] Endereço:Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
[Ti] Título:Anti-inflammatory and proresolution activities of bergapten isolated from the roots of Ficus hirta in an in vivo zebrafish model.
[So] Source:Biochem Biophys Res Commun;496(2):763-769, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bergapten (5-methoxypsoralen), a coumarin-derivate compound isolated from Ficus hirta roots, was evaluated for its anti-inflammatory and proresolution activities in a tail-cutting-induced zebrafish larvae model. Bergapten was evaluated using a caudal fin-wounded transgenic zebrafish line "Tg(corola: eGFP)" to visualize the effects of the recruitment and clearance of neutrophils and macrophages at the injury site. We found that bergapten significantly suppressed the recruitment of neutrophils and macrophages toward the injury site, as well as promoted the clearance of neutrophils and macrophages from the wound site. We also investigated the reactive oxygen species (ROS) and nitric oxide (NO) level of bergapten in a tail-cutting-induced inflammation zebrafish model. The Results revealed that bergapten effectively inhibited the tail-cutting-induced production of ROS and NO in zebrafish larvae. This study reported for the first time the potential anti-inflammatory and proresolution activities of bergapten in an in vivo zebrafish model, suggesting that bergapten may be a potential candidate for inflammation therapy.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Inflamação/tratamento farmacológico
Macrófagos/efeitos dos fármacos
Metoxaleno/análogos & derivados
Neutrófilos/efeitos dos fármacos
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/química
Modelos Animais de Doenças
Feminino
Ficus/química
Inflamação/imunologia
Macrófagos/imunologia
Masculino
Metoxaleno/química
Metoxaleno/farmacologia
Neutrófilos/imunologia
Óxido Nítrico/antagonistas & inibidores
Óxido Nítrico/imunologia
Raízes de Plantas/química
Espécies Reativas de Oxigênio/antagonistas & inibidores
Espécies Reativas de Oxigênio/imunologia
Peixe-Zebra/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Reactive Oxygen Species); 31C4KY9ESH (Nitric Oxide); 4FVK84C92X (5-methoxypsoralen); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29247925
[Au] Autor:Vostálová J; Cukr M; Zálesák B; Lichnovská R; Ulrichová J; Rajnochová Svobodová A
[Ad] Endereço:Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hnevotínská 3, 775 15 Olomouc, Czech Republic.
[Ti] Título:Comparison of various methods to analyse toxic effects in human skin explants: Rediscovery of TTC assay.
[So] Source:J Photochem Photobiol B;178:530-536, 2018 Jan.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Skin explants are a suitable model which can replace dermatological experiments on animals or human volunteers. In this study, we searched for a fast, cheap and reproducible method for screening skin explant viability after treatment with UVA radiation or/and chemical agents. We compared frequently used methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) activity assay with a rarely used 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) assay for the evaluation of UVA radiation and/or chlorpromazine and 8-methoxypsoralen effect as model agents. Histological analysis of skin explants was also performed by a simple haematoxylin-eosin method. Only the TTC assay was able to show the toxicity of model agents in a dose- and concentration-dependent manner. LDH assay was partially able to demonstrate results comparable to the TTC method, however, the agents' effect was less pronounced. The MTT and NR assays completely failed in the evaluation. Haematoxylin-eosin staining showed discrete structural changes in samples treated with UVA alone and CPZ+UVA, but only after 48h. Therefore, the method is not useful for screening of toxic or phototoxic effects either. In conclusion, the TTC assay was the most suitable for the evaluation of toxicity or phototoxicity in ex vivo skin.
[Mh] Termos MeSH primário: Bioensaio
Clorpromazina/toxicidade
Metoxaleno/toxicidade
Raios Ultravioleta
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos da radiação
Células Cultivadas
Seres Humanos
Técnicas In Vitro
L-Lactato Desidrogenase/metabolismo
Pele/citologia
Pele/efeitos dos fármacos
Pele/patologia
Sais de Tetrazólio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tetrazolium Salts); 7OL20RET2I (triphenyltetrazolium); EC 1.1.1.27 (L-Lactate Dehydrogenase); U42B7VYA4P (Chlorpromazine); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE


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[PMID]:28770976
[Au] Autor:Eccleston C; Cooper TE; Fisher E; Anderson B; Wilkinson NM
[Ad] Endereço:Centre for Pain Research, University of Bath, Claverton Down, Bath, UK.
[Ti] Título:Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.
[So] Source:Cochrane Database Syst Rev;8:CD012537, 2017 08 02.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. OBJECTIVES: To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/159; fenoprofen 0/79; ketoprofen 0/30; ibuprofen 4/45; indomethacin 0/30; meloxicam 11/147; naproxen 10/285; and rofecoxib 0/209 (very low-quality evidence).There were few or no data for our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning as defined by validated scales; and quality of life as defined by validated scales (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for our primary and secondary outcomes as very low because there were limited data from studies and no opportunity for a meta-analysis. AUTHORS' CONCLUSIONS: We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Artrite Juvenil/tratamento farmacológico
Artrite Reumatoide/tratamento farmacológico
Dor Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Anti-Inflamatórios não Esteroides/efeitos adversos
Aspirina/efeitos adversos
Aspirina/uso terapêutico
Celecoxib/efeitos adversos
Celecoxib/uso terapêutico
Criança
Pré-Escolar
Doença Crônica
Fenoprofeno/efeitos adversos
Fenoprofeno/uso terapêutico
Seres Humanos
Ibuprofeno/efeitos adversos
Ibuprofeno/uso terapêutico
Lactonas/efeitos adversos
Lactonas/uso terapêutico
Metoxaleno/efeitos adversos
Metoxaleno/uso terapêutico
Naproxeno/efeitos adversos
Naproxeno/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Sulfonas/efeitos adversos
Sulfonas/uso terapêutico
Tiazinas/efeitos adversos
Tiazinas/uso terapêutico
Tiazóis/efeitos adversos
Tiazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Lactones); 0 (Sulfones); 0 (Thiazines); 0 (Thiazoles); 0QTW8Z7MCR (rofecoxib); 57Y76R9ATQ (Naproxen); JCX84Q7J1L (Celecoxib); R16CO5Y76E (Aspirin); RA33EAC7KY (Fenoprofen); U4VJ29L7BQ (Methoxsalen); VG2QF83CGL (meloxicam); WK2XYI10QM (Ibuprofen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012537.pub2


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[PMID]:28552422
[Au] Autor:Zhao G; Xu D; Yuan Z; Jiang Z; Zhou W; Li Z; Yin M; Zhou Z; Zhang L; Wang T
[Ad] Endereço:Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
[Ti] Título:8-Methoxypsoralen disrupts MDR3-mediated phospholipids efflux and bile acid homeostasis and its relevance to hepatotoxicity.
[So] Source:Toxicology;386:40-48, 2017 Jul 01.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Since its discovery in 1987, multidrug resistance 3 P-glycoprotein (MDR3) had recognized to play a crucial role in the translocation of phospholipids from the inner to outer leaflets of bile canalicular membranes. An increasing number of reports suggest that drug-mediated functional disruption of MDR3 is responsible for drug-induced cholestasis. 8-Methoxypsoralen (8-MOP) is used clinically to treat psoriasis, vitiligo and other skin disorders. However, psoralens safety for long-term use is a concern. In the current study, we evaluate 8-MOP's potential hepatotoxicity and effects on bile formation. Sprague Dawley (SD) rats were treated daily 200mg/kg or 400mg/kg of 8-MOP orally for 28 days. The result showed a prominent decrease in biliary phospholipids output, which associated with the down-regulation of MDR3. Elevated bile acid serum level and increased biliary bile acid outputs were observed in 8-MOP-treated groups. The disturbance of bile acid homeostasis was associated with changes in enzymes and proteins involved in bile acid synthesis, regulation and transport. Human liver cell line L02 was used to determine on the mRNA and protein levels of MDR3. Cells treated with 8-MOP reveled a decrease in fluorescent PC (phosphatidylcholine) secretion into the pseudocanaliculi (formed between adjacent cells) compared with untreated cells. Our investigation represent the first evidence that 8-MOP can induce cholestatic liver injury by disturbing MDR3-mediated phospholipids efflux and bile acid homeostasis.
[Mh] Termos MeSH primário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Ácidos e Sais Biliares/metabolismo
Doença Hepática Induzida por Substâncias e Drogas/etiologia
Metoxaleno/toxicidade
Fármacos Fotossensibilizantes/toxicidade
[Mh] Termos MeSH secundário: Animais
Ácidos e Sais Biliares/sangue
Linhagem Celular
Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia
Colestase/induzido quimicamente
Colestase/patologia
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Feminino
Homeostase
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/patologia
Metoxaleno/administração & dosagem
Fosfolipídeos/metabolismo
Fármacos Fotossensibilizantes/administração & dosagem
RNA Mensageiro/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Bile Acids and Salts); 0 (Phospholipids); 0 (Photosensitizing Agents); 0 (RNA, Messenger); 0 (multidrug resistance protein 3); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE


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[PMID]:28437747
[Au] Autor:Wainwright LK; Parisi AV; Downs NJ
[Ad] Endereço:Faculty of Health, Engineering and Sciences, University of Southern Queensland, Toowoomba, Queensland 4350, Australia. Electronic address: lisa.wainwright@usq.edu.au.
[Ti] Título:Concurrent evaluation of personal damaging and beneficial UV exposures over an extended period.
[So] Source:J Photochem Photobiol B;170:188-196, 2017 May.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Personal exposure to solar ultraviolet radiation (UVR) is acknowledged as having both positive and negative effects on human health. This study aimed to measure concurrently the personal erythemal UV, UVA and vitamin D effective exposures of participants in each season of a year. Participants were all indoor office workers located at two different sites less than 6.5 km apart at the sub-tropical location of Toowoomba (27°33'S 151°55'E). The subjects wore a combined dosimeter badge horizontally on the shoulder for a minimum of one week in each season; this badge used 8-methoxypsoralen film to record the UVA waveband and polyphenylene oxide film for the erythemal and the vitamin D effective UV wavebands. The results show that median erythemal exposure was highest during the spring and lowest during winter, as was the vitamin D effective exposure. Median UVA exposures were at a similar level in winter and summer, autumn was higher (double) and spring at a lower level. The duration and time of day participants spent outdoors changed in each season; in winter, participants spent an average of 101 minutes outdoors between 10:00-14:00 h over the week, whereas in summer this fell to 79 minutes even though they were outdoors more often. The daily UVA/UVB ratio is lowest between 10:00-14:00 h and also changes with the season resulting in the differences between the distributions of exposure for each of the wavebands. Each category of exposures must be assessed individually as each season and each waveband has different distributions. The results also demonstrate that the dual film dosimeter developed and characterized with a calibration to three different biological responses, is an effective device for the concurrent measurement of erythemal UV, UVA and vitamin D effective UV exposures for periods of up to seven days.
[Mh] Termos MeSH primário: Dosimetria Fotográfica
Raios Ultravioleta
[Mh] Termos MeSH secundário: Eritema/etiologia
Seres Humanos
Metoxaleno/química
Fenóis/química
Polímeros/química
Estações do Ano
Vitamina D/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phenols); 0 (Polymers); 1406-16-2 (Vitamin D); 9041-80-9 (polyphenylene oxide); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE


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[PMID]:28321041
[Au] Autor:Yonezawa Y; Miyashita T; Ashizawa H; Hashimoto K; Nejishima H; Ogawa H
[Ad] Endereço:Pharmacokinetics and Safety Department Drug Research Center Kaken Pharmaceutical Co., Ltd.
[Ti] Título:Evaluation of a general toxicity study incorporating phototoxicity assessments in Sprague-Dawley rats.
[So] Source:J Toxicol Sci;42(2):145-157, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Previously, we showed that phototoxicity assessments in Sprague-Dawley (SD) rats can detect phototoxic potential to the same degree as those in guinea pigs. In this study, we examined whether phototoxicity assessments can be incorporated into general toxicology studies, using SD rats. Three phototoxic compounds were tested. Acridine and 8-methoxypsoralen (8-MOP) were transdermally administered, and 8-MOP and lomefloxacin were orally administered. The animals were allocated to three groups for each compound: single-dose, repeated-dose, and repeated-dose plus toxicokinetics (TK). The single-dose group was irradiated with UV-A and UV-B after a single administration of the drug. The repeated-dose and TK groups were irradiated after 8 days of repeated administration of the drug. Blood samples were also collected from the TK group on days 1 and 7 after administration. The phototoxic compounds resulted in skin reactions in all the groups, with no difference in the degree of skin reaction among the three groups. In the TK measurements, all of the phototoxic compounds were detected in the plasma samples, and the irradiation timing was close to the T . These results indicate that phototoxic potential could be evaluated in the TK group, and phototoxicity assessments could be incorporated into general toxicology studies. This reduces the number of studies and animals required, thus shortening the research and development period, and supporting the 3Rs principle of animal experiments. The study also provides information regarding appropriate irradiation timings, differences between the sexes, and dose-response, in turn enabling the phototoxic risk of the compounds to be clearly evaluated.
[Mh] Termos MeSH primário: Acridinas/toxicidade
Fluoroquinolonas/toxicidade
Metoxaleno/toxicidade
Fármacos Fotossensibilizantes/toxicidade
Testes de Toxicidade/métodos
[Mh] Termos MeSH secundário: Acridinas/análise
Acridinas/farmacocinética
Administração Cutânea
Administração Oral
Animais
Dermatite Fototóxica
Fluoroquinolonas/sangue
Fluoroquinolonas/farmacocinética
Masculino
Metoxaleno/sangue
Metoxaleno/farmacocinética
Fármacos Fotossensibilizantes/sangue
Fármacos Fotossensibilizantes/farmacocinética
Ratos Sprague-Dawley
Pele/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acridines); 0 (Fluoroquinolones); 0 (Photosensitizing Agents); L6BR2WJD8V (lomefloxacin); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.145


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[PMID]:28287037
[Au] Autor:Wrzesniok D; Beberok A; Rok J; Delijewski M; Hechmann A; Oprzondek M; Rzepka Z; Bacler-Zbikowska B; Buszman E
[Ad] Endereço:a Department of Pharmaceutical Chemistry , Medical University of Silesia in Katowice , Sosnowiec , Poland.
[Ti] Título:UVA radiation augments cytotoxic activity of psoralens in melanoma cells.
[So] Source:Int J Radiat Biol;93(7):734-739, 2017 Jul.
[Is] ISSN:1362-3095
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Melanoma is an aggressive form of skin cancer. The aim of the study was to evaluate the influence of UVA radiation and psoralens: 5-methoxypsoralen (5-MOP) or 8-methoxypsoralen (8-MOP) on melanoma cells viability. MATERIALS AND METHODS: The amelanotic C32 and melanotic COLO829 human melanoma cell lines were exposed to increasing concentrations of psoralens (0.1-100 µM) in the presence or absence of UVA radiation. Cell viability was evaluated by the WST-1 assay. RESULTS: We demonstrated that 8-MOP, in contrast to 5-MOP, has no cytotoxic effect on both melanoma cell lines. Simultaneous exposure of cells to 8-MOP and UVA radiation caused significant cytotoxic response in C32 cells where the EC value was estimated to be 131.0 µM (UVA dose: 1.3 J/cm ) and 105.3 µM (UVA dose: 2.6 J/cm ). The cytotoxicity of 5-MOP on both C32 and COLO829 cells was significantly augmented by UVA radiation - the EC was estimated to be 22.7 or 7.9 µM (UVA dose: 1.3 J/cm ) and 24.2 or 7.0 µM (UVA dose: 2.6 J/cm ), respectively. CONCLUSIONS: The demonstrated high cytotoxic response after simultaneous exposure of melanoma cells to psoralens and UVA radiation in vitro suggests the usefulness of PUVA therapy to treat melanoma in vivo.
[Mh] Termos MeSH primário: Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos da radiação
Melanoma/tratamento farmacológico
Melanoma/patologia
Terapia PUVA/métodos
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Relação Dose-Resposta à Radiação
Sinergismo Farmacológico
Seres Humanos
Metoxaleno/administração & dosagem
Metoxaleno/análogos & derivados
Dosagem Radioterapêutica
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
4FVK84C92X (5-methoxypsoralen); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:170314
[St] Status:MEDLINE
[do] DOI:10.1080/09553002.2017.1297903


  8 / 2241 MEDLINE  
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[PMID]:28139335
[Au] Autor:Kubo R; Muramatsu S; Sagawa Y; Saito C; Kasuya S; Nishioka A; Nishida E; Yamazaki S; Morita A
[Ad] Endereço:Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
[Ti] Título:Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis.
[So] Source:J Dermatol Sci;86(1):46-53, 2017 Apr.
[Is] ISSN:1873-569X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis. OBJECTIVES: We examined the effects of bath-PUVA therapy on three distinct Foxp3 subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells. METHODS: We enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session. RESULTS: Levels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy. CONCLUSIONS: Bath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients.
[Mh] Termos MeSH primário: Metoxaleno/uso terapêutico
Terapia PUVA/métodos
Fármacos Fotossensibilizantes/uso terapêutico
Psoríase/tratamento farmacológico
Linfócitos T Reguladores/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Banhos
Feminino
Fatores de Transcrição Forkhead/metabolismo
Seres Humanos
Masculino
Metoxaleno/administração & dosagem
Meia-Idade
Fármacos Fotossensibilizantes/administração & dosagem
Psoríase/sangue
Índice de Gravidade de Doença
Linfócitos T Reguladores/metabolismo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); 0 (Photosensitizing Agents); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE


  9 / 2241 MEDLINE  
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[PMID]:27976780
[Au] Autor:Hähnel V; Dormann F; Nitsopoulos A; Friedle A; Ahrens N
[Ad] Endereço:Institute for Clinical Chemistry and Laboratory Medicine, Transfusion Medicine, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. norbert.ahrens@ukr.de.
[Ti] Título:A method for the quantification of 8-methoxypsoralen by mass spectrometry for offline extracorporeal photopheresis.
[So] Source:Photochem Photobiol Sci;16(2):193-200, 2017 02 15.
[Is] ISSN:1474-9092
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Extracorporeal photopheresis (ECP) is an efficient method to treat various autoimmune diseases, cutaneous T-cell lymphoma, and graft-versus-host disease. It is based on the ex vivo inactivation of lymphocytes by 8-methoxypsoralen (8-MOP)/UV light treatment. Despite the adhesive, lipophilic nature of 8-MOP, no quality control is established for the ECP procedure. METHODS: We developed a sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) assay to monitor residual 8-MOP concentration after UVA irradiation in the whole blood supernatant after acetonitrile precipitation. RESULTS: The preanalytical stability of 8-MOP exceeded 7 days, allowing batch mode analysis. Linearity was determined with R above 0.99. The 8-MOP concentrations decreased exponentially after UV exposure, with decay constants of 0.0259 in plasma and 0.0528 in saline. The recovery of 8-MOP in photopheresates was about 68%, indicating binding to DNA as well as to plastic structures. UVA induced no 8-MOP fragmentation, but caused self-adducts under extreme conditions (10-fold UV dosage). CONCLUSIONS: Detection of 8-MOP proved to be feasible and demonstrated that the doses were in the pharmaceutically active range.
[Mh] Termos MeSH primário: Análise Química do Sangue/métodos
Metoxaleno/análise
Fotoferese
Fármacos Fotossensibilizantes/análise
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Cromatografia Líquida de Alta Pressão
Feminino
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Linfócitos/efeitos da radiação
Masculino
Meia-Idade
Raios Ultravioleta
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Photosensitizing Agents); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1039/c6pp00327c


  10 / 2241 MEDLINE  
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[PMID]:27956194
[Au] Autor:Kassem AA; Abd El-Alim SH; Asfour MH
[Ad] Endereço:Pharmaceutical Technology Department, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address: aa.kassem@hotmail.com.
[Ti] Título:Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition.
[So] Source:Int J Pharm;517(1-2):256-268, 2017 Jan 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04-89.90%) with nanometric vesicle diameters (111.1-198.8nm) of monodisperse distribution (PDI=0.145-0.216), zeta potential values <-48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20-25°C) and refrigeration (4-8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37-7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP.
[Mh] Termos MeSH primário: Lipossomos/química
Metoxaleno/química
Metoxaleno/farmacocinética
Absorção Cutânea
[Mh] Termos MeSH secundário: Animais
Portadores de Fármacos/química
Sistemas de Liberação de Medicamentos
Liberação Controlada de Fármacos
Estabilidade de Medicamentos
Hidrogel de Polietilenoglicol-Dimetacrilato/química
Concentração de Íons de Hidrogênio
Lipossomos/administração & dosagem
Lipossomos/farmacocinética
Lipossomos/ultraestrutura
Masculino
Metoxaleno/administração & dosagem
Tamanho da Partícula
Ratos
Reologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Liposomes); 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate); U4VJ29L7BQ (Methoxsalen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE



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