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M Lebwohl

Publications and source records attributed to M Lebwohl.

At least 55 records · Page 3Linked to original sources
PubMed1999

PUVA (8-methoxy-psoralen plus ultraviolet A) induces the formation of 8-hydroxy-2'-deoxyguanosine and DNA fragmentation in calf thymus DNA and human epidermoid carcinoma cells.

The objective of this study is to investigate if 8-methoxy-psoralen (8-MOP) plus ultraviolet A (UVA) radiation (PUVA) induces oxidative DNA damage. When calf thymus DNA was incubated with 8-MOP and irradiated with UVA (335-400 nm), the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was substantially increased by approximately 6-fold. Formation of 8-OHdG proportionally correlated with both UVA fluence and 8-MOP concentrations. Human epidermoid carcinoma cells were incubated with 10 microg 8-MOP per milliliter, followed by irradiation of 25 kJ/m2 UVA. The level of 8-OHdG increased by nearly 3-fold in PUVA-treated cells compared to 8-MOP and UVA controls. The formation of 8-OHdG correlated with DNA fragmentation as determined by spectrofluorometry. To investigate the reactive oxygen species (ROS) involved in PUVA-induced oxidative DNA damage, less or more specific ROS quenchers were added to DNA solution prior to PUVA treatment. The results showed that only sodium azide and genistein significantly quenched PUVA-induced 8-OHdG, whereas catalase, superoxide dismutase, and mannitol exhibited no effect. The quencher study with cultured cells indicated that N-acetyl-cysteine and genistein protected oxidative DNA damage as well as DNA fragmentation by PUVA treatment. Our studies show that PUVA treatment is able to induce the formation of 8-OHdG in purified DNA and cultured cells and suggest that singlet oxygen is the principle reactive oxygen species involved in oxidative DNA damage by PUVA treatment.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Erythema nodosum.

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Erythema Nodosum↗
PubMed1998

Benzo[a]pyrene enhances the formation of 8-hydroxy-2'-deoxyguanosine by ultraviolet A radiation in calf thymus DNA and human epidermoid carcinoma cells.

The objective of this study is to investigate if benzo[a]pyrene (BaP) and ultraviolet (UV) radiation synergistically induce oxidative DNA damage. Calf thymus DNA was incubated with BaP and irradiated with UVB (280-320 nm) and UVA (335-400 nm). BaP substantially enhanced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) by UVA, but only moderately increased the level of 8-OHdG by UVB. Formation of 8-OHdG proportionally correlated with both UV dose and BaP concentration. Human epidermoid carcinoma cells were incubated with 10 microg of BaP/mL for 24 h and then exposed to 10 kJ/m2 UVB and 25 kJ/m2 UVA. UVB plus BaP did not affect the level of 8-OHdG in cultured cells, whereas UVA plus BaP substantially increased 8-OHdG by over 4-fold compared to BaP and UVA controls. To confirm what reactive oxygen species (ROS) are involved in BaP plus UVA-induced oxidative DNA damage, less or more specific ROS quenchers were added to DNA solution. The results showed that only superoxide dismutase and genistein significantly quenched BaP plus UVA-induced 8-OHdG, whereas catalase, sodium azide, and mannitol exhibited no effect. Our studies suggest that BaP enhances the formation of 8-OHdG in purified DNA and cultured cells by UVA, but not by UVB, and that superoxide anion plays an important role in the synergistic induction of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Atopic dermatitis.

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Dermatitis, Atopic↗
PubMed1998

DNA structural integrity and base composition affect ultraviolet light-induced oxidative DNA damage.

We previously demonstrated that ultraviolet (UV) light (254 nm) induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA via a singlet oxygen mechanism. In the present paper, we provide novel findings that DNA structure and base composition significantly affect the yield of 8-OHdG by UV radiation. Unlike ionizing radiation that induces 8-OHdG both in free 2'-deoxyguanosine (dG) and in DNA, UV light induced 8-OHdG formation in intact DNA and polydG.dC, but not in dG. When thermally denatured DNA was irradiated with UV light, the yield of 8-OHdG was reduced by more than 80% compared to intact DNA. Oxygenation of the denatured DNA solution did not restore the yield of UV-induced 8-OHdG. Irradiation of DNA with different AT/GC ratios showed that the yield of UV-induced 8-OHdG varied in proportion to the AT content, suggesting that AT base pairs in DNA enhance generation of the oxidizing species and subsequent oxidation of dG. The natural antioxidants genistein, estradiol, protocatechuic acid (PCA), and oleanolic acid (OA) were investigated for their inhibition of UV-induced 8-OHdG. Genistein and estradiol, that intercalate into DNA as shown by a computer modeling, significantly quenched UV-induced 8-OHdG, whereas PCA and OA did not fit into DNA and exhibited weak or no effect. These results suggest that the intercalation of genistein and estradiol into DNA may alter the DNA structural integrity, interrupt the production of oxidizing species, and subsequently reduce the formation of 8-OHdG by UV radiation.

Animals↗
PubMed1998

Consensus workshop on the toxic effects of long-term PUVA therapy.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Humans↗
PubMed1998

Effect of UV-B phototherapy on plasma HIV type 1 RNA viral level: a self-controlled prospective study.

OBJECTIVE: To study the plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 12 patients seropositive for HIV who were undergoing UV-B phototherapy to determine if UV-B phototherapy upregulates HIV activity in humans. DESIGN: A self-controlled prospective cohort of HIV-infected patients seen for the treatment of a skin disorder responsive to UV-B phototherapy. Viral levels were measured weekly for 8 weeks of phototherapy. Follow-up viral levels were measured for patients who continued phototherapy beyond 8 weeks, those who had a significant change in their viral level, or both. SETTING: Outpatient clinic of an academic hospital. PATIENTS: Patients with HIV disease and a skin disorder responsive to UV-B phototherapy. Inclusion criteria for patients in this study were those receiving a stable antiviral regimen for at least 6 weeks and who had no major illness or immunization in the 2 months before starting phototherapy. Of 72 patient volunteers screened, 15 met the criteria, 2 declined to participate, and 13 entered the study. One patient was dropped from the study because an accurate baseline measurement could not be obtained. Twelve patients were analyzed, 2 of whom left the study early, 1 at 6 weeks and 1 at 7 weeks. INTERVENTIONS: Ultraviolet-B phototherapy. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA viral level. RESULTS: Plasma HIV-1 RNA levels showed no significant increase or decrease in most of the patients, defined as a 3-fold change from baseline (mean fold change from baseline after 8 weeks of phototherapy, -1.1; 95% confidence interval, 2.9 to -5.0). Trend analysis indicated no significant pattern of change in viral levels (slope, -0.013 log; P > .25). The CD4+ cell counts also remained unchanged (mean before therapy, 277 x 10(9)/L; mean after therapy, 285 x 10(9)/L; P = .67). CONCLUSION: No significant effect of UV-B exposure was seen on plasma HIV-1 levels.

Adult↗
PubMed1998

Tazarotene in combination with topical corticosteroids.

The use of a topical corticosteroid in combination with tazarotene has theoretic appeal because each drug has a different mechanism of action, and it is therefore likely that combination therapy will offer additive or synergistic effects. For example, the steroid may promote a rapid initial response together with minimization of erythema during the treatment period, and tazarotene may prolong the duration of the therapeutic effect and lower the probability of relapse. The results of a large, controlled clinical trial in which corticosteroids of various potencies were added to tazarotene therapy showed that tazarotene plus a medium- or high potency corticosteroid produced greater and more rapid efficacy, and superior tolerability, than tazarotene plus placebo cream.

Administration, Cutaneous↗
PubMed1998

Calcipotriene ointment and halobetasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement.

BACKGROUND: Weekend therapy with superpotent topical corticosteroids has been used for the long-term treatment of psoriasis. Recently, calcipotriene ointment has been added to this regimen for use on weekdays, but there are no long-term studies of that combination. OBJECTIVE: The purpose of this study was to determine whether the addition of weekday calcipotriene to a pulse therapy regimen of weekend superpotent corticosteroids results in a longer duration of remission of plaque psoriasis. SUBJECTS: This was a double-blind, placebo-controlled, parallel-group study. Forty-four patients with mild to moderate psoriasis were treated with calcipotriene ointment in the morning and halobetasol ointment in the evening for 2 weeks. Thereafter, 40 patients who were at least moderately (50% or greater) improved were randomized to 2 treatment groups. After 2 weeks of treatment with calcipotriene ointment in the morning and halobetasol ointment in the evening, 20 patients were randomized to receive halobetasol ointment twice daily on weekends and calcipotriene ointment twice daily on weekdays, and 20 patients were randomized to receive halobetasol ointment twice daily on weekends and placebo ointment twice daily on weekdays. RESULTS: Seventy-six percent of patients applying halobetasol ointments on weekends and calcipotriene ointment on weekdays were able to maintain remission for 6 months compared with 40% of patients applying halobetasol ointment on weekends only with the vehicle on weekdays. CONCLUSION: The addition of calcipotriene ointment applied on weekdays to a weekend pulse therapy regimen of superpotent corticosteroids can increase the duration of remission of psoriasis.

Administration, Topical↗
PubMed1998

Cyclosporine consensus conference: with emphasis on the treatment of psoriasis.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy.

Contraindications↗