Effect of alpha-tocopherol and N-acetylcysteine on benzoyl peroxide toxicity in human keratinocytes

Benzoyl peroxide is a free-radical generating compound widely used in the polymer industry and also in pharmaceuticals as antimicrobial agent to treat acne. However, benzoyl peroxide causes irritation and contact dermatitis in about 1% of patients. Concern over the use of this compound is motivated by the demonstration that it can also act as skin tumor promoter in mice. In addition, benzoyl peroxide induces DNA strand breaks in many cells, including keratinocytes. Benzoyl peroxide toxicity is presumably mediated by the formation of reactive free radicals and by the consumption of intracellular antioxidants.In this work we investigated the effect of both the lipophilic antioxidant alpha-tocopherol and the hydrophilic thiol donor N-acetylcysteine (NAC) in human keratinocyte line HaCaT exposed to benzoyl peroxide. A protective effect against benzoyl peroxide cytotoxicity was achieved when cells were grown on a alpha-tocopherol layer. On the contrary, the addition of alpha-tocopherol dissolved in ethanol had a pro-oxidant effect, leading to an enhancement of benzoyl peroxide toxicity. Cytotoxicity was also reduced adding NAC to the culture medium; the presence of both NAC and alpha-tocopherol exerts a synergistic cytoprotection.     

The role of suppressor cells in the induction of murine photoallergic contact dermatitis and in its suppression by prior UVB irradiation

Induction in mice of marked photoallergic contact dermatitis (PCD) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) with UVA (320 to 400 nm) radiation requires pretreatment with cyclophosphamide (CY). Attempts to induce photoallergic contact dermatitis without CY result in only a small degree of sensitivity, accompanied by significant net splenic suppressor cell activity. These suppressor cells are antigen specific, inhibit the induction but not the elicitation of photoallergic contact dermatitis to TCSA, and are T lymphocytes. Exposure of mice to UVB (280 to 320 nm) radiation at a site distant from that of sensitization, before CY administration and sensitization, inhibits the development of photoallergic contact dermatitis. This is analogous to the suppression of allergic contact dermatitis (ACD) observed in mice after exposure to UVB radiation; such suppression is accompanied by the formation of antigen-specific splenic suppressor cells. However, in contrast to the findings with allergic contact dermatitis, splenic suppressor cells are not detected in mice that are treated with UVB radiation before CY administration and sensitization to TCSA. This is presumably because CY prevents their formation. This provides evidence that UVB-irradiated mice have a second form of anergy that is not mediated by suppressor cells.     

Rearing Conditions and Foot-Pad Dermatitis in Swedish Turkey Poults

A method previously developed for classification of broiler foot health status was used in order to estimate the prevalence of foot-pad dermatitis in Swedish turkey poults. Data on foot health were collected from 53 commercial turkey flocks at slaughter. The producers were asked to fill in a questionnaire on rearing conditions and equipment for every flock. Lesions were very commonly observed, only 2% of the feet were classified as being without lesions, 78% had mild lesions (discoloration, erosions), and 20% had severe lesions (ulcers). There was a significant (p<0.01) effect of litter material on the presence of severe foot-pad dermatitis, flocks reared on straw showing higher prevalence than flocks reared on wood shavings. There was also a significant (p<0.001) effect of the type of water system, severe foot-pad dermatitis being more common in flocks reared in houses equipped with bell drinkers compared with flocks reared with small cups. The addition of extra litter during the rearing period resulted in significantly (p<0.01) lower prevalence of lesions compared with flocks where no extra litter had been added.     

Induction of in vivo hyporesponsiveness to contact allergens by hapten-modified Ia+ keratinocytes.

Because our previous in vitro studies of hapten-modified Ia+ keratinocytes (KC) indicated that these cells induced anergy in Ag-specific Th1 cells, we assayed such cells for their ability to induce unresponsiveness in an in vivo animal model system of delayed type hypersensitivity (allergic contact dermatitis). Naive animals that were treated with i.p. injections of FITC-modified Ia+ cultured Langerhans cells (cLC) developed allergic contact dermatitis to subsequent hapten challenge; whereas, animals treated with similar doses of FITC-Ia+ KC failed to become sensitized to epicutaneous application of FITC, as evidenced by absent ear swelling responses to a FITC challenge. Those animals that were first treated with intraperitoneal injections of hapten modified Ia+ KC could not be sensitized when they were subsequently exposed to sensitizing doses of FITC; whereas a similar first exposure to FITC-cultured Langerhans cells did not interfere with epicutaneous sensitization. This hyporesponsiveness to sensitization was hapten specific, as FITC-Ia+ KC-treated animals were hyporesponsive only to FITC but not to the irrelevant hapten, TNCB. Additionally, Ia- KC failed to induce unresponsiveness. Additional studies indicate that the hyporesponsiveness was not passively transferrable with splenocytes and was not related to the I-J MHC locus. In contrast to our in vitro studies, the unresponsiveness induced by hapten-modified Ia+ KC in vivo was transient in nature. These data indicate that hapten-modified Ia+ KC function in vivo as nonstimulatory accessory cells, by generating down-regulatory signals that can interfere with the induction of contact hypersensitivity.     

Contact allergy to special and standard allergens in patients with venous ulcers

The aim of the study was to determine the prevalence of contact sensitivity in patients with leg ulcers, and possible difference in the rate of contact hypersensitivity to standard series of allergens used in patch testing, and to particular topical agents used in local therapy of leg ulcers in special series, patients with and without atopy. The study included 60 patients, 45 female and 15 male, aged 37-85 (mean 68.37 female and 51.13 male), 30 of them with and 30 without allergic contact dermatitis (ACD) of the leg (control group). The mean duration of leg ulceration was 5.62 years. The two groups of patients underwent testing to standard series allergens and target series allergens including mupirocin, bepanthene, silver sulfadiazine, chloramphenicol + clostridiopeptidase, betamethasone dipropionate, hydrocortisone + oxytetracycline, momethasone, alginate, hydrocolloid, lanolin, pyrogallol, Vaseline, permanganate, Rivanol, povidone-iodine, gentamicin, i.e. local agents most frequently used by the patients. Contact allergic hypersensitivity to standard series allergens was demonstrated in 25 patients with a total of 49 positive reactions and a mean of 1.6 reactions per patient. Positive reactions were most commonly recorded to balsam of Peru, fragrance mix and neomycin sulfate. There were 12 positive reactions to target series allergens, mean 0.4 reactions per patient. Forty-five positive reactions, mean 0.1 reactions per patient, were recorded in the control group. Positive reactions were most commonly demonstrated to corticosteroid ointments, lanolin and bepanthene. Study results did not confirm a statistically significantly higher rate of sensitization to particular topical agents frequently used in the treatment of patients with venous ulcers. Patch testing to standard and special series allergens should be performed in case of prolonged leg ulcer epithelization.     

Algerian ivy dermatitis; a California disease

A hitherto unrecognized cause of contact dermatitis in California is the widely cultivated plant known as Algerian ivy. This plant, which grows in California (and its close relative, English ivy) causes a dermatitis which is similar to although milder than that caused by poison oak. Dermatitis from this cause occurs most frequently when persons who have become sensitive to it by previous contact trim the plant back in the spring after its seasonal spurt of growth. For persons whose occupations require repeated contact with the plant, dermatitis from this cause is an occupational hazard. Dermatitis from this plant is easily diagnosed by means of a simple patch test. In a series of 12 cases the only effective treatment was with corticosteroid agents.     

ALGERIAN IVY DERMATITIS—A California Disease

A hitherto unrecognized cause of contact dermatitis in California is the widely cultivated plant known as Algerian ivy. This plant, which grows in California (and its close relative, English ivy) causes a dermatitis which is similar to although milder than that caused by poison oak. Dermatitis from this cause occurs most frequently when persons who have become sensitive to it by previous contact trim the plant back in the spring after its seasonal spurt of growth. For persons whose occupations require repeated contact with the plant, dermatitis from this cause is an occupational hazard. Dermatitis from this plant is easily diagnosed by means of a simple patch test.In a series of 12 cases the only effective treatment was with corticosteroid agents.     

Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats

Nonsteroidal anti-inflammatory drugs are the drugs of choice in the treatment of rheumatoid arthritis (RA) because of their rapid analgesic effect. However, they induce severe gastric damage in RA patients and animals by a process mediated by reactive oxygen species (ROS). Nitroxides (nitroxyl radicals) are widely used as imaging agents and antioxidants to explore the role of ROS generation in the pathogenesis of disease. In this study, the effectiveness of the newly synthesized nitroxides 8-aza-7,7,9,9-tetramethyl-1,4-dioxaspiro[4.5]undecan-8-oxyl (compound 1) and 4-oxo-2,2,6,6-tetraethylpiperidine-1-oxyl (compound 2) in the prevention of gastric ulcers in adjuvant arthritis rats treated with indomethacin was evaluated by monitoring the reaction of reactive oxygen species in gastric tissue with Overhauser-enhanced magnetic resonance imaging (OMRI). Pretreatment with all tested nitroxides suppressed the ulcers induced by indomethacin treatment in arthritic rats. OMRI using compounds 1 and 2 as well as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) demonstrated a redox imbalance in the stomach of these rats. Lipid peroxide and interleukin (IL)-1β levels in the gastric mucosa were significantly suppressed by compound 1 and TEMPOL, whereas CINC/gro, a member of the IL-8 family, was significantly suppressed by compound 1 only. These results suggest that the preventive effects of nitroxides on gastric ulcers may operate by different mechanisms.     

Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial.

Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia.     

Vagotomy for Gastric Ulcer

Out of a series of 75 patients who were treated by vagotomy and drainage for gastric ulcer 66 have been followed up for one to seven years (average three-and-a-half years). Four recurrent gastric ulcers occurred among the 33 cases of ulcer of the lesser curve or body with no antral or duodenal lesion (type I). Among the 42 patients with an antral ulcer or an associated active or healed pyloric or duodenal lesion (type II or III) there was only one recurrence. The recurrence rate for men was 5% and for women 12%. One patient died two years after operation from cancer which may have originated in the stomach. The clinical results in patients without recurrences were generally satisfactory.Vagotomy, preferably selective, with drainage is a satisfactory operation in gastric ulcers of types II and III. For ulcers of type I, gastrectomy is to be preferred except in selected cases.     

Protective Effects of a Culture Supernatant of Lactobacillus acidophilus and Antioxidants on Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug

Ileal ulcers and thiobarbituric acid (TBA)-reactive substances in the ileal mucosa were induced in rats treated with a nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene (BFMeT), at a dose of 1,000 mg/kg administered with tap water as drinking water. However, the formation of ileal ulcers and TBA-reactive substances in the ileal mucosa was repressed by giving the animals a culture supernatant of Lactobacillus acidophilus as drinking water. We measured the antioxidative activity of the culture supernatant and found that the supernatant inhibited the formation of t-butyl hydroperoxide-induced TBA-reactive substances in erythrocyte membrane ghosts. Therefore, the effects of various known antioxidative compounds on the ileal ulcer formation induced by BFMeT were investigated. While α-tocopherol, t-butyl-1,4-hydroxyanisole and allopurinol did not repress ulcer formation after BFMeT treatment, ascorbic acid, dimethyl sulfoxide, glutathione and β-carotene significantly inhibited formation. Among these compounds, ascorbic acid was the most effective. Accumulation of TBA-reactive substances in the ileal mucosa after BFMeT treatment also decreased significantly in rats treated with ascorbic acid. In addition, the percentage of Gram-negative rods in the ileal contents of rats treated with BFMeT and tap water was dramatically increased, but it was not increased in rats treated with BFMeT and these antioxidants. A positive correlation between the percentage of Gram-negative rods and the number of ileal ulcers was also observed. These results suggest that lipid peroxidation mediated by oxygen radicals plays an important role in the induction of ileal ulcers by BFMeT in rats, and that lipopolysaccharide-activated neutrophils probably produce highly reactive hypochlorous acid and hydrogen peroxide, which are inactivated by ascorbic acid and glutathione, respectively.     

Decontamination of dental unit water systems with hydrogen peroxide

AIMS: Transmission of microbial pathogens to patients from water in dental units is a concern. To reduce this risk, the decontaminating efficiency of hydrogen peroxide was evaluated. METHODS AND RESULTS: Three percent hydrogen peroxide diluted 1 : 4 in distilled water (contact time 15 min) was used daily to disinfect the waterlines of a pilot unit previously contaminated with Pseudomonas aeruginosa or Staphylococcus aureus. The behaviour of the test bacteria was seen to differ over time. Staph. aureus numbers slowly decreased until only low numbers were recovered, after which the levels remained stable. Ps. aeruginosa abatement was more rapid and the density of the bacteria reached a peak when the circuit was empty. CONCLUSIONS: Staph. aureus and Ps. aeruginosa treated with hydrogen peroxide fell from 6 to 4 log. SIGNIFICANCE AND IMPACT OF THE STUDY: Treatment of dental unit waterlines with hydrogen peroxide was seen to be able to keep the number of the bacteria under control, as long as the treatment was repeated daily.     

Community clinics for leg ulcers and impact on healing.

OBJECTIVE--To evaluate the effectiveness of community clinics for leg ulcers. DESIGN--All patients with leg ulceration were invited to community clinics that offered treatment developed in a hospital research clinic. Patients without serious arterial disease (Doppler ankle/brachial index > 0.8) were treated with a high compression bandage of four layers. SETTING--Six community clinics held in health centres in Riverside District Health Authority supported by the Charing Cross vascular surgical service. PATIENTS--All patients referred to the community services with leg ulceration, irrespective of cause and duration of ulceration. MAIN OUTCOME MEASURES--Time to complete healing by the life table method. RESULTS--550 ulcerated legs were seen in 475 patients of mean (SD) age 73.8 (11.9) years. There were 477 venous ulcers of median size 4.2 cm2 (range 0.1-117 cm2), 128 being larger than 10 cm2. These ulcers had been present for a median of three months (range one week to 63 years) with 150 present for over one year. Four layer bandaging in the community clinics achieved complete healing in 318 (69%) venous ulcers by 12 weeks and 375 (83%) by 24 weeks. There were 56 patients with an ankle/brachial arterial pressure index < 0.8, indicating arterial disease. The 50 patients with pressure index < 0.8 > 0.5 were treated with reduced compression, and 24 (56%) healed by 12 weeks and 31 (75%) by 24 weeks. The figures for overall healing for all leg ulcers were 351/550 (67%) at 12 weeks and 417/550 (81%) at 24 weeks, compared with only 11/51 (22%) at 12 weeks before the community clinics were set up. CONCLUSIONS--Community clinics for venous ulcers offer an effective means of achieving healing in most patients with leg ulcers.     

The brown-tail moth of Bombyx Euproctis chrysorrhoea L. (Lepidoptera) responsible for lepidopterism in France: biological interpretation

A scanning electron microscope study has enabled an explanation as to why the brown-tail moth provokes Lepidopterism. The brown-tail moth only provokes Lepidopterism via a transmission of the urticating hairs of its caterpillar. Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.     

Pilot study of IFN-gamma-induced specific hyposensitization for house dust mites in atopic dermatitis: IFN-gamma-induced immune deviation as a new therapeutic concept for atopic dermatitis

IFN-gamma/IL-4 imbalance is a central immunologic defect which is responsible for increased IgE antibody response in atopic dermatitis. Effects of hyposensitization were controversial in atopic dermatitis. Reversed IFN-gamma/IL-4 balance was induced using IFN-gamma in atopic dermatitis and specific hyposensitization with house dust mites (HDM) was tried in the status of IFN-gamma-induced immune deviation. A total of 58 atopic dermatitis patients who had obvious allergy to HDM were selected in this study. IFN-gamma-induced hyposensitization for HDM was tried in 10 patients. Twenty-two patients received IFN-gamma therapy and six were treated by simple hyposensitization. Twenty were enrolled as control subjects. The clinical severity scores decreased effectively only by IFN-gamma-induced hyposensitization for HDM. Specific hyposensitization for HDM in the status of IFN-gamma-induced immune deviation successfully improved atopic dermatitis. HDM might play a pathogenic role in subpopulation of atopic dermatitis.     

Heavy metals in contact dermatitis: A review

Contact dermatitis is an inflammatory skin reaction caused by direct contact with chemical substances in the environment and can either be irritant or allergic in nature. The clinical symptoms of contact dermatitis, include local skin rash, itching, redness, swelling, and lesions. Nowadays, 15–20% of people have some degree of contact dermatitis, which can be more or less severe. Immune responses in allergic contact dermatitis (ACD) are due to the effects of cytokines and allergen-specific CD4⁺ and CD8⁺ T cells on the skin. Acids and alkalis such as drain cleaners, plants such as poinsettias, hair colors, and nail polish remover, are all prominent causes of irritant contact dermatitis (ICDs). Heavy metals are metallic elements with a high atomic weight that are hazardous in low quantities and are known to cause dermatitis after systemic or local exposure. Nickel (Ni), chromium (Cr), lead (Pb), and copper (Cu) are among the most common heavy metals used in various industries. Metal allergies may cause ACD and also systemic contact dermatitis (SCD). Contact dermatitis is detected by laboratory tests such as patch testing, lymphocyte stimulation test (LST), and evaluation of cytokine production by primary cultures of peripheral blood mononuclear cells. This article presents an update on the epidemiological and clinical characteristics of ACD and SCD caused by three heavy metals (Cr, Cu, and Pb). Ni is not discussed due to recent coverage. Furthermore, the effects of contact sensitivity to some other heavy metals, such as gold (Au), cobalt (Co), palladium (Pd), and mercury (Hg) are discussed.     

Follicular contact dermatitis due to coloured permanent-pressed sheets

A delayed hypersensitivity type of allergic contact dermatitis was observed following exposure to certain brands of 50% cotton, 50% polyester coloured permanent-pressed sheets produced by a particular manufacturer. The dermatitis presented as an extremely pruritic follicular eczema of the body and vesicular edema of the ears and face. Patch testing excluded formalin as the allergen but suggested permanent-pressing chemicals as a possibility. Several washings of the sheets did not prevent the development of the dermatitis. The removal of sheets did not immediately result in improvement: the condition could persist for up to eight weeks after their discontinuance.     

Contact allergy caused by fragrance mix and Myroxylon pereirae (balsam of Peru)--a retrospective study

Because of their widespread use, fragrances are among the most common causes of contact allergic dermatitis, second only to nickel. During a five-year period 3,065 patients with contact dermatitis were patch tested using a specific mix of fragrances. 509 (16.6%) patients were allergic to the fragrance mix, while 258 (8.4%) patients exhibited an allergic reaction to Myroxylon pereirae (balsam of Peru). Between those 509 patients, 157 were patch tested with eight individual substances contained in the fragrance mix: cinnamal, cinnamyl alcohol, eugenol, isoeugenol, geraniol, hydroxycitronellal, alpha-amyl cinnamal and Evernia prunastri (oak moss). The most frequent allergens were isoeugenol 57.9% (91/157), eugenol 55.4% (87/157), cinnamyl alcohol 34.4% (54/157) and Evernia prunastri (oak moss) 24.2% (38/157). There were 62 patients (39.5%) who exhibited an allergic reaction to both the fragrance mix and Myroxylon pereirae (balsam of Peru). The results prove the importance of avoiding allergens in daily life, especially in industrial and cosmetic products. In order to prevent ACD, better cooperation between industry and dermatologists is needed.     

RAPID HEALING OF PEPTIC ULCERS IN PATIENTS RECEIVING FRESH CABBAGE JUICE

Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs.The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days.The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy.The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man.     

A NEW CORTICOID FOR TOPICAL THERAPY—Fluocinolone Acetonide

Sixty-seven patients with chronic and subacute cutaneous lesions of varying long duration that had previously been resistant to topical use of corticosteroid compounds were treated with a cream containing fluocinolone acetonide. To avoid subjective bias, only two classifications were used in appraising results: “complete clearing of treated lesions” and “not effective.”Forty-eight patients had complete clearing of the treated area. Results were best in atopic dermatitis, chronic eczematous dermatitis and nummular dermatitis. Granuloma annulare, dyshidrotic dermatitis of the palms and psoriasis were not affected.In some cases in which there were multiple lesions some of the lesions were treated with fluocinolone acetonide cream and some were treated concurrently with other corticoid ointments or with noncorticoid compounds, either bland or with active ingredients. Fluocinolone was effective in more than twice as many cases as the other agents.In some of the patients with chronic disease it was possible to greatly reduce or discontinue systemic steroid therapy after fluocinolone acetonide became available.No untoward effects were observed.