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For the first time since Goeckerman suggested the therapeutic potential of tar photosensitization of psoriatic skin, this mechanism has been shown to the effective in treating generalized psoriasis vulgaris. Long treatment times, need for special high-intensity sources, the presence of skin pain, and absence of information about long-term effects makes this treatment impractical at present.
The hairless mouse was used to investigate the effects of a combination of glucocorticosteroid with either dithranol or tar on epidermal DNA synthesis, in order to determine whether such combinations reduce epidermal DNA synthesis more effectively than the single agents. Dithranol alone produced a significant local inhibition of DNA synthesis at concentrations of 0.1% and 0.05% but not at lower concentrations. Dose-response data for dilutions of clobetasol propionate and betamethasone 17-valerate showed progressive diminution of both local and systemic effects with decreasing concentrations. An additive effect was found from combining clobetasol propionate with dithranol and from combining betamethasone 17-valerate with liquor picis carbonis. These combined preparations were tested again after storage for 6 months and 2 months respectively and showed no loss of efficacy. These results lend justification to the use of these combined preparations in the treatment of psoriasis.
Arylhydrocarbon-hydroxylase (AHH) is a cytochrome P-450-dependent polysubstrate mono-oxygenase which plays an important role in converting some compounds (e.g. benzo[a]pyrene) to highly reactive carcinogenic species. A simple AHH assay is described, using [3H]benzo[a]-pyrene as substrate. 7,8-Benzoflavone (10(-4)M) inhibits 92% of the measured enzyme activity. Liquor carbonis detergens (which contains coal tar) induces AHH activity in human hair follicles in vivo. We suggest that using this simple assay, hair follicles would be a very suitable tissue to test whether the AHH-controlling gene is of significance in producing cancer.
Current concern over the carcinogenic potential of cytotoxic drugs and photochemotherapy used in the management of psoriasis increases the need for an accurate assessment of the 'background' incidence of carcinoma in psoriatics not receiving these modalities. This study compares the observed incidence of carcinoma in 719 tar-treated psoriatics with that expected, based on data from the West of Scotland Cancer Registry. No increase in malignancy was found in psoriasis over that expected in the general population.
The effect of UVB therapy after short contact dithranol therapy (SCDT) was examined in 53 patients with psoriasis. After dithranol application, patients were randomly allocated to receive either a tar bath and UVB therapy (27 patients) or an emulsifying ointment bath only (26 patients). Forty eight patients completed the study; 16 of the 21 dithranol only patients cleared in a mean of 19.5 days compared with 20 of the 27 dithranol + UVB patients who cleared in a mean of 20.3 days. These differences were not significant. Similarly there was no significant difference in response between the dithranol only and dithranol UVB group as measured by the change in plaque thickness measured using Harpenden calipers, and the severity of psoriasis assessed by the extent of the rash, the degree of scaling, redness and induration. Thirteen of the 16 dithranol only patients who cleared relapsed in a mean of 10.6 weeks compared with 14 of the 20 dithranol UVB patients who relapsed after a mean of 18.9 weeks (P less than 0.05). Comparison of pre- and post-treatment full blood count, biochemical screen and urinalysis showed no evidence of systemic toxicity due to SCDT. This study shows that UVB therapy does not improve the clearance of psoriasis in SCDT, but does significantly postpone relapse.
Baseline serum levels of interleukin-2 receptor (IL2R) were measured in 65 patients with active psoriasis. IL2R levels in psoriatic patients were significantly higher than in healthy controls (582.4 +/- 289.23 u/ml vs. 369.64 +/- 111.10 u/ml; P less than 0.05), but did not differ statistically from values found in an atopic dermatitis control group (619.88 +/- 254.27 u/ml). Sex, age and severity of the disease do not affect levels of IL2R. The same IL2R levels were measured in 26 psoriatic patients receiving UVB plus tar therapy. This therapy, continued until clinical remission, lowered IL2R levels to values comparable to controls. This decrease may be due to an immunosuppressive effect of therapy.
Horizontal transfer of genes responsible for pollutant biodegradation may play a key role in the evolution of bacterial populations and the adaptation of microbial communities to environmental contaminants. However, field evidence for horizontal gene transfer between microorganisms has traditionally been very difficult to obtain. In this study, the sequences of the 16S rRNA and naphthalene dioxygenase iron-sulfur protein (nahAc) genes of nine naphthalene-degrading bacteria isolated from a coal tar waste-contaminated site, as well as a naphthalene-degrading bacterium from a contaminated site in Washington state and two archetypal naphthalene-degrading strains, were compared. Seven strains from the study site had a single nahAc allele, whereas the 16S rRNA gene sequences of the strains differed by as much as 7.9%. No nahAc alleles from the site were identical to those of the archetypal strains, although the predominant allele was closely related to that of Pseudomonas putida NCIB 9816-4, isolated in the British Isles. However, one site-derived nahAc allele was identical to that of the Washington state strain. Lack of phylogenetic congruence of the nahAc and 16S rRNA genes indicates that relatively recent in situ horizontal transfer of the nahAc gene has occurred, possibly as a direct or indirect consequence of pollutant contamination. Alkaline lysis plasmid preparations and pulsed-field gel electrophoresis have revealed the presence of plasmids ranging in size from 70 to 88 kb in all site isolates. Southern hybridizations with a 407-bp nahAc probe have suggested that the nahAc gene is plasmid borne in all the site isolates but one, a strain isolated from subsurface sediment 400 m upstream from the source of the other site isolates. In this strain and in the naphthalene-degrading strain from Washington state, nahAc appears to be chromosomally located. In addition, one site isolate may carry nahAc on both chromosome and plasmid. Within the group of bacteria with identical nahAc sequences the Southern hybridizations showed that the gene was distributed between plasmids of different sizes and a chromosome. This suggests that plasmid modification after transfer may have been effected by transposons. Horizontal transfer of catabolic genes may play a significant role in the acclimation of microbial communities to pollutants.
Anaerobic cometabolic conversion of benzothiophene was studied with a sulfate-reducing enrichment culture growing with naphthalene as the sole source of carbon and energy. The sulfate-reducing bacteria were not able to grow with benzothiophene as the primary substrate. Metabolite analysis was performed with culture supernatants obtained by cometabolization experiments and revealed the formation of three isomeric carboxybenzothiophenes. Two isomers were identified as 2-carboxybenzothiophene and 5-carboxybenzothiophene. In some experiments, further reduced dihydrocarboxybenzothiophene was identified. No other products of benzothiophene degradation could be determined. In isotope-labeling experiments with a [(13)C]bicarbonate-buffered culture medium, carboxybenzothiophenes which were significantly enriched in the (13)C content of the carboxyl group were formed, indicating the addition of a C(1) unit from bicarbonate to benzothiophene as the initial activation reaction. This finding was consistent with the results of earlier studies on anaerobic naphthalene degradation with the same culture, and we therefore propose that benzothiophene was cometabolically converted by the same enzyme system. Groundwater analyses of the tar-oil-contaminated aquifer from which the naphthalene-degrading enrichment culture was isolated exhibited the same carboxybenzothiophene isomers as the culture supernatants. In addition, the benzothiophene degradation products, in particular, dihydrocarboxybenzothiophene, were significantly enriched in the contaminated groundwater to concentrations almost the same as those of the parent compound, benzothiophene. The identification of identical metabolites of benzothiophene conversion in the sulfate-reducing enrichment culture and in the contaminated aquifer indicated that the same enzymatic reactions were responsible for the conversion of benzothiophene in situ.
We designed a real-time PCR assay able to recognize dioxygenase large-subunit gene sequences with more than 90% similarity to the Ralstonia sp. strain U2 nagAc gene (nagAc-like gene sequences) in order to study the importance of organisms carrying these genes in the biodegradation of naphthalene. Sequencing of PCR products indicated that this real-time PCR assay was specific and able to detect a variety of nagAc-like gene sequences. One to 100 ng of contaminated-sediment total DNA in 25-microl reaction mixtures produced an amplification efficiency of 0.97 without evident PCR inhibition. The assay was applied to surficial freshwater sediment samples obtained in or in close proximity to a coal tar-contaminated Superfund site. Naphthalene concentrations in the analyzed samples varied between 0.18 and 106 mg/kg of dry weight sediment. The assay for nagAc-like sequences indicated the presence of (4.1 +/- 0.7) x 10(3) to (2.9 +/- 0.3) x 10(5) copies of nagAc-like dioxygenase genes per microg of DNA extracted from sediment samples. These values corresponded to (1.2 +/- 0.6) x 10(5) to (5.4 +/- 0.4) x 10(7) copies of this target per g of dry weight sediment when losses of DNA during extraction were taken into account. There was a positive correlation between naphthalene concentrations and nagAc-like gene copies per microgram of DNA (r = 0.89) and per gram of dry weight sediment (r = 0.77). These results provide evidence of the ecological significance of organisms carrying nagAc-like genes in the biodegradation of naphthalene.
Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for "non-inhalers", particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease.
Phenol (87.3 mg/l), p-cresol (58.6 mg/l), o-cresol (76.9 mg/l), and 2,5-xylenol (36.7 mg/l) were detected in the urine of workers employed in the distillation of the high temperature phenolic fraction of tar (carbolic oil). The concentrations of these compounds in the urine of non-exposed male workers was 11.7 mg/l, 25.7 mg/l, 68.1 micrograms/l, and 69 micrograms/l respectively. The excretion rates were 4.20 mg/h for phenol, 2.4 mg/h for p-cresol, 3.3 mg/h for o-cresol; and 1.5 mg/h for 2,5-xylenol. The highest concentrations of the mentioned compounds were detected in urine collected between eight and 10 hours from the beginning of exposure. The kinetics of excretion are considered.
BACKGROUND: In atopic eczema (AE), skin colonization with Staphylococcus aureus plays a possible role in the pathophysiology of the disease. METHODS: Thirty-eight patients with AE were screened for their cutaneous colonization with S. aureus. The antibacterial and clinical efficacy of topical therapy with the antiseptic dye gentian violet, a potent glucocorticosteroid or a tar solution (liquor carbonis detergens) was evaluated in vivo in 21 patients with a density of >10(4) CFU/cm(2) and in vitro. Skin sites were treated twice daily for 4 days with the active drug or a corresponding control. Quantification of S. aureus was done daily during therapy as well as 3 days thereafter. The severity of the lesions was rated by a regional SCORAD. RESULTS: In gentian-violet-treated skin, bacterial density decreased significantly in lesional (p < 0.001) and unaffected skin (p < 0. 001). Bacterial densities did not decrease during therapy with glucocorticosteroid or liquor carbonis detergens but dropped afterwards. All therapeutics reduced the severity score, reduction being greatest for the glucocorticosteroid and lowest for liquor carbonis detergens. In vitro, a high antibactericidal efficacy was demonstrated only for gentian violet. CONCLUSIONS: Antibacterial therapy with gentian violet not only reduces S. aureus dramatically, but also reduces the severity of the eczema. Reduction of S. aureus after therapy with glucocorticosteroids and LCD seems to be secondary to improvement of the skin condition.
Thirty-two subjects were tested in five double-blind sessions-16 subjects in the morning (a.m.) following overnight smoking abstention, and 16 in the afternoon (p.m.) following ad lib smoking. In each session, subjects smoked 1 of 5 cigarettes having the following FTC nicotine/'tar' yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. On a pre- to postsmoking basis, blood nicotine and heart rate increased with nicotine yield. The effect of nicotine yield on changes in self-rated anxiety was an inverted-U function, but this effect was possibly confounded by baseline differences. The following effects on EEG spectral-band magnitude were also obtained: (1) nicotine yields > or = 0.17 mg decreased delta; (2) nicotine yields of 0.37 and 0.48 mg decreased theta in a.m. subjects; (3) nicotine yields > or = 0.37 mg decreased alpha, the effect being greater in a.m. subjects; (4) no effect of yield on beta 1 was obtained; (5) nicotine yields of 0.48 and 0.74 mg increased the Cz-minus-T5 differential in beta 2. Pre- to postsmoking changes in this measure of beta 2 were not correlated with either blood nicotine or anxiety.
A clinical therapy for psoriasis, a hyperproliferative disease of the skin, utilizes topical application of crude coal tar sometimes followed by UV irradiation (Goeckerman therapy). To investigate the formation of covalent DNA adducts resulting from this therapy, skin biopsies were obtained from treated patients and controls. Indirect immunofluorescence staining with antisera generated against benzo(a)pyrene diol epoxide-modified DNA was used to investigate cell-specific localization of adduct formation. Specific nuclear staining was detected in the epidermal cells of all biopsies from treated patients but not from control biopsies obtained from untreated individuals. 32P postlabeling of DNA isolated from the biopsies was used to determine the spectrum of hydrophobic adducts present. A pattern of multiple adducts was detected in the samples obtained from the treated patients but not from controls.
In 20 guinea pigs 4 test areas were treated with a standard surfactant vehicle twice weekly for 3 weeks. In another 20 animals the same treatment was carried out with the addition of 1% cadmium sulfide on one area, of 10% coal tar distillate on another, 2% ichthyol sodium on the 3rd and 1% Omadine MDS on the 4th. At the end of the test in both animal collectives the number of mitoses in the basal cells of the epidermis (Colcemid method) and the thickness of the epidermis (microscopically) were determined in each of the 4 test areals. All 4 agents lead to a significant inhibition of mitoses compared with the surfactant vehicle. Coal rat also produces an acanthosis. The mitosis inhibition supports the opinion that these agents are suitable for the treatment of dandruff.
The anti-inflammatory activity of the dry distillation tar of delipidated soybean (GL, 0.1 approximately 10%) was investigated by its topical application to mice, rats and guinea pigs; and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), ibuprofen (IP, 5%), phenylbutazone (PB, 5%) and flufenamic acid (FA, 5%), which were all prepared with the same ointment base. GL (1 approximately 10%) showed a concentration-dependent inhibition of the increased vascular permeability induced by histamine and bradykinin in guinea pigs. GL significantly inhibited rat paw edema induced by carrageenin, but in serotonin-induced paw edema, GL showed only a weak effect. GL also inhibited the erythema formation induced by ultra-violet rays, and the activity was equal to that of PB. The inhibitory potency of GL against the erythema formation induced by arachidonic acid in guinea pigs was equal to that of IP. It is suggested from these results that the mode of action of GL is similar to that of other acidic non-steroidal anti-inflammatory drugs. However, GL did not inhibit paper disk granuloma in rats. Furthermore, GL markedly inhibited the delayed-type hypersensitivity induced by picryl chloride, and the activity was stronger than that of IB, PB and FA. Here GL showed the mode of action seen with steroidal anti-inflammatory drugs. The present data provide evidence that GL applied externally possesses a potent effect as an anti-inflammatory drug.
The anti-inflammatory effects of Glyteer (GL) were investigated by its local administration using the CMC-pouch method in rats, and the effects were compared with those of betamethasone 17-valerate (BV, 1 mg), phenylbutazone (PB, 10 mg), flufenamic acid (FA, 10 mg), bufexamac (BM, 10 and 20 mg), bendazac (BZ, 10 and 20 mg), icthammol (IT, 10 mg) and pine tar (PT, 10 mg). At three hours after CMC-treatment, GL (10 mg) significantly inhibited not only the protein exudation, but also the leucocyte migration. The inhibitory activity of GL on the leucocyte migration had the same potency as that of FA, but was stronger than those of PB, BV, BM, BZ, IT and PT. Furthermore, in relation to the leucocyte migration, GL markedly inhibited not only the neutrophil, but also the macrophage migration. At three hours after CMC-treatment, the inhibitory activity of GL on the neutrophil migration had the same potency as those of PB and FA, but was stronger than those of BV, BM, BZ, IT and PT. On the other hand, GL, BM, BZ, FA, IT and PT had an inhibitory activity on the macrophage migration, and the activity was more potent in GL, FA and IT. From these results, it is suggested that the inhibition of GL on increased vascular permeability and leucocyte migration is one of the mechanisms of its anti-inflammatory action.
Assessment of cancer risk from exposure to polycyclic aromatic hydrocarbons (PAHs) has been traditionally conducted by applying the conservative linearized multistage (LMS) model to animal tumor data for benzo(a)pyrene (BaP), considered the most potent carcinogen in PAH mixtures. Because it has been argued that LMS use of 95% lower confidence limits on dose is unnecessarily conservative, that assumptions of low-dose linearity to zero in the dose response imply clear mechanistic understanding, and that "acceptable" cancer risk rests on a policy decision, an alternative cancer risk assessment approach has been developed. Based in part on the emerging benchmark dose (BMD) method, the modified BMD method we used involves applying a suite of conventional mathematical models to tumor dose-response data. This permits derivation of the average dose corresponding to 5% extra tumor incidence (BMD0.05) to which a number of modifying factors are applied to achieve a guideline dose, that is, a daily dose considered safe for human lifetime exposure. Application of the modified BMD method to recent forestomach tumor data from BaP ingestion studies in mice suggests a guideline dose of 0.08 microg/kg/day. Based on this and an understanding of dietary BaP, and considering that BaP is a common contaminant in soil and therefore poses human health risk via soil ingestion, we propose a BaP soil guideline value of 5 ppm (milligrams per kilogram). Mouse tumor data from ingestion of coal tar mixtures containing PAHs and BaP show that lung and not forestomach tumors are most prevalent and that BaP content cannot explain the lung tumors. This calls into question the common use of toxicity equivalence factors based on BaP for assessing risk from complex PAH mixtures. Emerging data point to another PAH compound--H-benzo(c)fluorene--as the possible lung tumorigen.