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Drug-induced Photosensitivity

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3321. Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers. (Full text)

Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers. DNA modifications induced either by photosensitization (illumination in the presence of methylene blue) or by chemically generated singlet oxygen (thermal decomposition of an 1,4-etheno-2,3-benzodioxin) are recognized and incised by repair endonucleases present in crude bacterial cell extracts. Only a small fraction of the incised modifications are sites of base loss (AP-sites) sensitive to exonuclease (...) III, endonuclease IV from E. coli or to the UV-endonuclease from M. luteus. Cell extracts from E. coli strains overproducing or defective in endonuclease III recognize the modifications induced by illumination in the presence of methylene blue just as well as do those from wild-type E. coli strains. This indicates that dihydropyrimidine derivatives, which are characteristic of hydroxyl radical-induced DNA modifications, are absent. In contrast, most of the modifications induced are not recognized

1990 Nucleic acids research PubMed

3322. Endonuclease-sensitive DNA modifications induced by acetone and acetophenone as photosensitizers. (Full text)

Endonuclease-sensitive DNA modifications induced by acetone and acetophenone as photosensitizers. Repair endonucleases, viz. endonuclease III, formamidopyrimidine-DNA glycosylase (FPG protein), endonuclease IV, exonuclease III and UV endonuclease, were used to analyse the modifications induced in bacteriophage PM2 DNA by 333 nm laser irradiation in the presence of acetone or acetophenone. In addition to pyrimidine dimers sensitive to UV endonuclease, 5,6-dihydropyrimidines (sensitive (...) to endonuclease III) and base modifications sensitive to FPG protein were generated. The level of the last in the case of acetone was 50% and in the case of acetophenone 9% of the level of pyrimidine dimers. HPLC analysis of the bases excised by FPG protein revealed that least some of them were 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). In the damage induced by direct excitation of DNA at 254 nm, which was analysed for comparison, the number of FPG protein-sensitive base modifications was only 0.6

1993 Nucleic acids research PubMed

3323. Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy (Full text)

Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided (...) , and higher light doses produced nearly total cell killing. Comparing the PPIX production and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-esters equally sensitize the cells to photoinactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer employed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient

2001 British journal of cancer PubMed

3324. Effect of N-acetylcysteïne on Photofrin-induced skin photosensitivity in patients. (PubMed)

Effect of N-acetylcysteïne on Photofrin-induced skin photosensitivity in patients. One of the major side effects of photodynamic therapy (PDT) employing Photofrin as the sensitizer is enhanced photosensitivity of the skin. The basic mechanism in PDT damage is believed to be the formation of singlet oxygen and radical species. N-acetylcysteïne (NAC) increases glutathione levels and is known to prevent pathology elicited by radicals and reactive species.NAC was tested in a randomized, open label (...) study for its protective effect on skin photosensitivity. Twenty-seven patients treated with PDT for central obstructive lung cancer or esophageal cancer received either "early" or "delayed" NAC, starting 5 or 10 days after Photofrin, in a dose of 3 x 600 mg per day for 5 days. Light, obtained from a halogen lamp (fluence rate 200 mW.cm-2) was used to illuminate skin patches of 2.5 cm2 on the back (10, 25, and 50 J.cm-2). Skin response was measured by using a visual scoring system and by measuring

1995 Lasers in surgery and medicine

3325. Prolonged skin photosensitization induced by methoxsalen and subphototoxic UVA irradiation. (PubMed)

Prolonged skin photosensitization induced by methoxsalen and subphototoxic UVA irradiation. Topical 8-methoxypsoralen (8-MOP) was used to briefly provide free psoralen sufficient for marked cutaneous photosensitization, but only a small dose of UVA was delivered initially, in an effort to produce many monoadducts but few crosslinks. After ample time for clearance of the remaining free psoralen a second UVA exposure was delivered. The second exposure should not have generated any additional (...) monoadducts in the absence of free psoralen, but the remaining monoadducts could be converted to crosslinks. The observation of a prolonged persistent UVA-photosensitive state caused by prior, very small doses of UVA given while free 8-MOP was present strongly suggests that psoralen-DNA crosslinks per se initiate much of the phototoxic effect of 8-MOP on skin, and that monoadducts induce much less acute inflammatory response. Because erythema was studied as the end point, the data say nothing about

1984 The Journal of investigative dermatology

3326. Thiazide-induced lichenoid photosensitivity. (PubMed)

Thiazide-induced lichenoid photosensitivity. We report the case of a 77-year-old male who developed a florid photosensitive eruption while taking thiazide diuretics for heart failure. The lesions were lichenoid in appearance and this was confirmed histologically. The eruption cleared on withdrawal of the drug. Although thiazide-induced photosensitivity is a well-documented phenomenon, there have been no histologically proven cases of a lichenoid eruption in light exposed areas in the recent

2002 Clinical & Experimental Dermatology

3327. Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjögren's syndrome associated with photosensitivity. (PubMed)

Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjögren's syndrome associated with photosensitivity. Annular erythema (AE) in Sjögren's syndrome (SS) usually develops on areas of sun-exposed skin and is exacerbated during summer.To evaluate photosensitivity in SS and to investigate the involvement of ultraviolet (UV) radiation in the development of AE in SS.Phototesting with UVA and UVB was performed on 14 SS patients (...) , including 10 with primary SS. Clinical and histological features as well as expression of inducible nitric oxide synthase (iNOS) in the evoked skin lesions were compared with those of lupus erythematosus (LE). Eleven SS patients had a history of photosensitive AE (n = 4), papules (n = 3) or other types (n = 4) of lesions on their sun-exposed skin that were induced or aggravated by sunlight exposure.Phototesting induced a prolonged erythematous response (n = 8), infiltrated erythema (IE) (n = 4

2002 British Journal of Dermatology

3328. Serum levels of 8-methoxypsoralen in two different drug preparations: correlation with photosensitivity and UV-A dose requirements for photochemotherapy. (PubMed)

Serum levels of 8-methoxypsoralen in two different drug preparations: correlation with photosensitivity and UV-A dose requirements for photochemotherapy. In a quantitative study we have compared the serum levels, the time course and the photosensitizing capacity of a conventional crystalline 8-methoxypsoralen brand and an investigational liquid formula. Evidence is presented showing that the liquid preparation is superior to the crystalline form: it peaks earlier after ingestion, it produces (...) higher and more constant degree of photosensitization, it is eliminated more rapidly from the blood, and it requires a lower UV-A dose for eliciting photosensitivity reactions aiming at a reduction of the total cumulative UV-A dose required for clearing psoriasis.

1982 The Journal of investigative dermatology

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