Topical therapies for psoriasis: evidence-based review.
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OBJECTIVE: To review current understandings of and approaches to topical psoriasis therapies and to assess their efficacies and adverse effects. QUALITY OF EVIDENCE: Literature from 1987 to 2003, inclusive, was reviewed via MEDLINE using the search term "psoriasis" combined with "topical treatment." Articles were prioritized based on their level of evidence, favouring double-blind, randomized controlled trials over other comparison studies. Other studies were included where level I research was unavailable. No level III research was included. MAIN MESSAGE: Psoriasis is very common and causes substantial morbidity. Because most psoriasis is mild to moderate, patients are well suited to outpatient topical therapy. Advances in topical treatments for psoriasis have kept pace with a rapidly evolving comprehension of its pathogenesis, making a review of current therapies useful for those who treat psoriasis. While research supports continued reliance on corticosteroids as first-line therapy, comparable efficacy has been shown for vitamin D analogues and topical retinoids, albeit with a slight increase in adverse effects. CONCLUSION: The combination of steroids and vitamin D analogues or topical retinoids is perhaps the most promising current treatment. It seems to have increased efficacy and fewer side effects. (+info)
Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle.
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BACKGROUND: Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD) an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8). Human airway smooth muscle cells (HASMC) are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC. METHODS: HASMC in primary culture were exposed to cigarette smoke extract (CSE) with or without TNFalpha. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA) and gene expression by real time polymerase chain reaction (PCR). Data were analysed using one-way analysis of variance (ANOVA) followed by Bonferroni's t test RESULTS: CSE (5, 10 and 15%) induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFalpha enhanced CSE-induced IL-8 release and expression. However, CSE (5-30%) inhibited TNFalpha-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH) and associated with the induction of the oxidant sensing protein, heme oxygenase-1. CONCLUSION: Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-alpha which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD. (+info)
Carcinogens in tobacco smoke: benzo[a]pyrene from Canadian cigarettes and cigarette tobacco.
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We evaluated the benzo[a]pyrene (BaP) content in the smoke from 35 brands of Canadian cigarettes and 5 brands of Canadian tobaccos for roll-your-own cigarettes. For the cigarettes, mean values of BaP ranged from 3.36 ng to 28.39 ng per cigarette, roughly in proportion with declared tar values. The relationship between declared tar and yields of BaP, however, does not allow accurate prediction of one from the other. For the tobaccos, mean BaP values ranged from 22.92 ng to 26.27 ng (average, 24.7 ng) per cigarette. The implications of these findings are discussed with respect to overall exposure. (+info)
Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.
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Exhaled nitric oxide (eNO) is decreased by cigarette smoking. The hypothesis that oxides of nitrogen (NOX) in cigarette smoke solution (CSS) may exert a negative feedback mechanism upon NO release from epithelial (AEC, A549, and NHTBE) and basophilic cells (RBL-2H3) was tested in vitro. CSS inhibited both NO production and degranulation (measured as release of beta-hexosaminidase) in a dose-dependent manner from RBL-2H3 cells. Inhibition of NO production by CSS in AEC, A549, and NHTBE cells was also dose-dependent. In addition, CSS decreased expression of NOS mRNA and protein expression. The addition of NO inhibitors and scavengers did not, however, reverse the effects of CSS, nor did a NO donor (SNP) or nicotine mimic CSS. N-acetyl-cysteine, partially reversed the inhibition of beta-hexosaminidase release suggesting CSS may act via oxidative free radicals. Thus, some of the inhibitory effects of CSS appear to be via oxidative free radicals rather than a NOX-related negative feedback. (+info)
Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione.
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BACKGROUND: Increased airway epithelial proliferation is frequently observed in smokers. To elucidate the molecular mechanisms leading to these epithelial changes, we studied the effect of cigarette smoke condensate (CSC) on cell proliferation, wound closure and mitogen activated protein kinase (MAPK) activation. We also studied whether modulation of intracellular glutathione/thiol levels could attenuate CSC-induced cell proliferation. METHODS: Cells of the bronchial epithelial cell line NCI-H292 and subcultures of primary bronchial epithelial cells were used for the present study. The effect of CSC on epithelial proliferation was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. Modulation of epithelial wound repair was studied by analysis of closure of 3 mm circular scrape wounds during 72 hours of culture. Wound closure was calculated from digital images obtained at 24 h intervals. Activation of mitogen-activated protein kinases was assessed by Western blotting using phospho-specific antibodies. RESULTS: At low concentrations CSC increased proliferation of NCI-H292 cells, whereas high concentrations were inhibitory as a result of cytotoxicity. Low concentrations of CSC also increased epithelial wound closure of both NCI-H292 and PBEC, whereas at high concentrations closure was inhibited. At low, mitogenic concentrations, CSC caused persistent activation of ERK1/2, a MAPK involved in cell proliferation. Inhibition of cell proliferation by high concentrations of CSC was associated with activation of the pro-apoptotic MAP kinases p38 and JNK. Modulation of intracellular glutathione (GSH)/thiol levels using N-acetyl-L-cysteine, GSH or buthionine sulphoximine (BSO), demonstrated that both the stimulatory and the inhibitory effects of CSC were regulated in part by intracellular GSH levels. CONCLUSION: These results indicate that CSC may increase cell proliferation and wound closure dependent on the local concentration of cigarette smoke and the anti-oxidant status. These findings are consistent with increased epithelial proliferation in smokers, and may provide further insight in the development of lung cancer. (+info)
Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. I. Design of a randomised controlled trial.
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STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Postal questionnaires were sent to 265,016 individuals selected from the electoral registers of 21 local authority districts of England; 64% of questionnaires were returned revealing 7736 men aged 18-44 years who smoked only middle tar cigarettes. Of these, 7029 (90%) were sent a health warning and 707 (10%) were not; the latter acted as a control group to assess the effect of the health warning. Of the 7029 men who had received a health warning and were visited at the recruitment stage, 2666 agreed and were eligible to participate in the trial although only 1541 (58% of those who agreed and were eligible) actually started smoking the study cigarettes; 643 men (24% of those willing to participate at the beginning of the trial and 42% of those who actually started smoking the study cigarettes) completed the trial smoking the study cigarettes. Of these, 213 were in the low tar middle nicotine group, 220 were in the middle tar middle nicotine group, and 210 were in the low tar low nicotine group. CONCLUSIONS: This study shows the feasibility of identifying and recruiting sufficient numbers of male middle tar smokers, with adequate numbers completing the trial, to detect any changes in respiratory health over a six month period. (+info)
Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. II. Results of a randomised controlled trial.
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STUDY OBJECTIVE: The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN: This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING: 21 local authority districts of England. SUBJECTS: Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS: Changes in the measures of respiratory health showed little difference over the trial period between the three cigarette groups. Analyses of the urinary nicotine metabolites showed that smokers allocated to each of the three study cigarettes adjusted their smoking so that throughout the trial their nicotine inhalation differed little from their pretrial intakes when they were smoking their own cigarettes. As a result of the altered patterns of smoking to compensate for the reduced nicotine yields of the three study cigarettes, the tar intake of those allocated to smoke the middle tar, middle nicotine cigarettes remained essentially unchanged, while those allocated to smoke the low tar, low nicotine and low tar, middle nicotine cigarettes had calculated reductions in tar intakes of about 14% and 18%, respectively. CONCLUSIONS: Due to the phenomenon of compensation, tar intake can only be reduced substantially by using a cigarette with a markedly lower tar/nicotine ratio. Nevertheless reductions of up to about 18% in tar intake failed to result in any detectable effect on respiratory symptoms or peak expiratory flow rates over a six month period. (+info)
Multifactorial etiology of cervical cancer: a hypothesis.
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Cancer of the cervix is the second most common life-threatening cancer among women worldwide, with incidence rates ranging from 4.8 per 100,000 women per year in the Middle East to 44.3 per 100,000 in East Africa. Epidemiologic and clinical data demonstrate that human papillomaviruses (HPV), especially HPV-16 and HPV-18, play at least a major if not a necessary role in the etiology of cervical cancer. However, many investigators acknowledge that HPV is not sufficient to induce cervical cancer and that a multifactorial etiology is likely. HPV can be found in a growing proportion of patients with cervical cancer, approaching 100%, but is not yet found in every patient with disease. Other factors, such as herpes simplex virus type 2 infections, cigarette smoking, vaginal douching, nutrition, and use of oral contraceptives, have been proposed as contributing factors. In the first half of the 20th century, Peyton Rous and colleagues demonstrated the joint action of tars and Shope papillomavirus to consistently induce squamous cell carcinomas in rabbits. Using the Rous model as a prototype, one might hypothesize that some cases of cervical cancer arise from an interaction between oncogenic viruses and cervical tar exposures. Cervical tar exposures include cigarette smoking, use of tar-based vaginal douches, and long years of inhaling smoke from wood- and coal-burning stoves in poorly ventilated kitchens. (+info)