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PubMed1976

An assessment of high and low temperature tars in Psoriasis.

Comparison of the efficacy of crude coal tar from high and low temperature sources in the treatment of patients suffering from chronic psoriasis showed the tars to be equally effective. High temperature tar was then compared with standard refined tar. Again, an equal therapeutic response was achieved. Crude coal tars obtained by the carbonization of coal in coke ovens and in smokeless fuel manufacture can be employed in dermatological therapy in place of the dwindling supplies of crude tar of gasworks origin.

Coal Tar↗
PubMed1983

The effect of low-, medium- and high-tar cigarette smoke on the fate of arachidonic acid in isolated hamster lungs.

Isolated hamster lungs were ventilated with smoke from low-, medium-and high-tar cigarettes when 45 nmol of 14C-arachidonic acid was infused into the pulmonary circulation. Most of the infused radioactivity was found in different phospholipid and neutral lipid fractions of the perfused lungs and a smaller amount was found in the nonrecirculating perfusion effluent mainly as metabolites. Cigarette smoke ventilation increased the amount of 14C-arachidonic acid in the triacylglycerols of the perfused lungs but had usually no effect on the amount of radioactivity in diacylglycerols or in different phospholipids. The increased amount of radiolabel in triacylglycerols was significantly greater in the lungs ventilated with smoke from medium-or high-tar cigarettes than in those ventilated with low-tar cigarette smoke. Cigarette smoke ventilation increased the amount of unmetabolized arachidonate in the perfusion effluent and decreased the amount of many metabolites. The present study indicates that low-, medium- and high-tar cigarettes have effects of the fate and metabolism of arachidonic acid in isolated hamster lungs and that the effects of medium- and high-tar cigarettes are more clear that those of low-tar cigarettes when the cigarettes are burned with a constant puff volume and rate.

Animals↗
PubMed1983

The radicals in cigarette tar: their nature and suggested physiological implications.

The paramagnetism of cigarette tar is found to be associated with at least four different types of species. One of the types is responsible for over 80 percent of the total paramagnetism and has a signal intensity that is independent of temperature from 60 to 250 K. This non-Curie-Weiss temperature dependence indicates that the principal paramagnetic species in tar is not an organic monoradical (doublet) species but instead is a donor-acceptor excimer with a paramagnetic excited state and a diamagnetic ground state. Modeling experiments suggest that the excimer consists of quinone (Q) and hydroquinone (QH2) molecules held in a tar matrix. Since such Q-QH2 species are catalysts for the oxidation of hydrocarbons and are very active redox systems, this paramagnetic species may be implicated in the cocarcinogenic properties of tar. Alternatively, since semiquinone radicals are known to bind to DNA, the tar paramagnetic species may be directly involved in the carcinogenic properties of tar.

Benzene↗
PubMed1995

Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts.

OBJECTIVE: To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN: Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING: Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS: Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES: Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS: Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION: About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.

Adult↗
PubMed1989

Risk of cancer from the use of tar bitumen in road works.

Tar bitumens are increasingly being used as a binder in road works. They consist of a standard product of about 70% bitumen and 25-30% tar. Tar bitumens are classifiable as the pyrolysis products of organic materials and are applied hot. Depending on the temperature used there are emissions of various intensities of polycyclic aromatic hydrocarbons (PAH), some of which are carcinogenic. A total of 250 one hour air samples was taken at breathing height on 20 days at 11 road works sites. The region of road paving operations in the immediate neighbourhood of the finishing machine operator and the screedmen were the chosen sampling points. A total of 19 unsubstituted chromatography/mass spectrometry. These included benzo[b]fluoranthene, benzo[a]pyrene, chrysene, dibenzo[a,h]anthracene, and indeno[1,2,3-cd]pyrene, all of which are carcinogenic. The median concentrations of chrysene and of benzo[b,j + k] fluoranthenes (determined en masse) were 9.3 and 2.8 micrograms/m3 respectively. The median concentrations of benzo[a]pyrene (BaP) and indeno[1,2,3,-cd]pyrene were 0.7 and 0.2 micrograms/m3 respectively. Dibenzo[a,h]anthracene had the lowest median concentration with about 0.03 micrograms/m3. Of the resulting shift means, the BaP concentration was over 1 microgram/m3 in about 50% of the cases, over 2 micrograms/m3 in 35%, and over 5 micrograms/m3 in about 15%. Even when the temperature of the paving mix was only between 120 degrees and 135 degrees C. 4.8% of the concentrations (identical to 3 samples) were greater than 2 micrograms BaP/m3, this value was exceeded in 34.9% of the determinations (identical to 30 samples) when the temperature of the tar bitumen was between 135 degrees and 150 degrees C. The highest concentration measured here was 17.8 micrograms BaP/m3. The recommended maximum paving temperature of the paving mix of 150 degrees C was exceeded in about 23% of all cases. The maximum concentration determined under any condition was 22 microgram/m(3). Thus the employment of tar bitumen as a binding material during road paving operations must be regarded as causing a considerable risk to health. The primary task is to ascertain whether tar bitumen can be replaced as a binder in paving for roads and what safety measures are practicable.

Air Pollutants, Occupational↗
PubMed1984

Relative intakes of tar, nicotine, and carbon monoxide from cigarettes of different yields.

The relative intakes of tar, nicotine, and carbon monoxide were estimated in 2455 cigarette smokers, who freely smoked their usual brands of cigarette. The estimates were derived by using an objective index of inhaling based on the measurement of carboxyhaemoglobin divided by the carbon monoxide yield of the cigarettes smoked, after background and carry over carboxyhaemoglobin effects had been allowed for. Separate analyses were performed according to the yield and type (plain, filter, etc) of cigarette smoked. The analyses based on yield indicated that the extent of inhaling was adjusted sufficiently to achieve similar intakes of nicotine/carbon monoxide regardless of the nicotine/carbon monoxide yield. It was not, however, sufficiently increased to achieve a similar intake of tar as the tar yield of the cigarette decreased. The analyses based on type of cigarette indicated that the extent of inhaling was adjusted to achieve similar intakes of tar and nicotine regardless of the type of cigarette smoked, but that this led to a greater intake of carbon monoxide among filter cigarette smokers than that among smokers of plain cigarettes--more so than would have been expected from their relative carbon monoxide yields. Two conclusions arise from these results. Firstly, any harmful effects of nicotine/carbon monoxide are unlikely to be materially reduced by smoking cigarettes with lower yields of nicotine/carbon monoxide, but the harmful effects of tar are likely to be reduced by smoking cigarettes with lower tar yields. These predictions appear to be borne out by epidemiological observations. Secondly, any harmful effects of carbon monoxide on the cardiovascular system will be greater in smokers of modern filter cigarettes than in smokers of modern plain cigarettes, provided that these two groups of smokers are otherwise similar with respect to risk of cardiovascular disease.

Adult↗
PubMed1982

Effect of cigarette tar content and smoking habits on respiratory symptoms in women.

Standardized respiratory disease questionnaires (ATS-DLD-78) were administered to 5,686 adult women. Risk factors were evaluated by logistic analysis that adjusted for multiple potential confounding factors. Among current smokers, the number of cigarettes smoked per day was consistently the strongest risk factor for chronic cough, chronic phlegm, wheeze, and dyspnea. The odds ratios for these symptoms in a smoker of 25 or more cigarettes per day relative to a smoker of 1--14 cigarettes per day were 4.74, 4.21, 2.05, and 3.71, respectively. Ex-smokers showed risks between those of current and never smokers. Cigarette tar content was a significant independent risk factor for chronic cough (p = 0.005) and of borderline significance for chronic phlegm (p = 0.077). High tar cigarette smokers in this population (average, 22 mg) had an odds ratio of 2.01 for chronic cough and 1.59 for chronic phlegm relative to low tar cigarette smokers (average, 7 mg). The effect of cigarette tar was linear and independent of cigarettes smoked per day. Smoke inhalation was a significant risk factor for chronic cough (p = 0.029) and for chronic phlegm (p = 0.038). Tar content and smoke inhalation were not significant risk factors for wheeze or dyspnea. Cigarette particulate content (tar) appears to be causally linked to cough and phlegm production., but the association of cigarette smoking and symptoms of wheeze and dyspnea may be more strongly related to the vapor phase of cigarette smoke.

Adolescent↗
PubMed2000

Periorbital comedones and their relationship to pitch tar: a cross-sectional analysis and a review of the literature.

BACKGROUND: Comedones, often in a periorbital distribution, have been claimed to be associated with pitch tar. OBJECTIVE: This cross-sectional study compares the incidence of periorbital comedones between a group of individuals exposed to pitch tar and a control group. METHODS: The incidence of periorbital comedones was determined in workers (n = 55) at a tar distillation plant. A comparison group (n = 55) not exposed to pitch tar was also examined for the presence of facial comedones. The respective incidence rates were compared by using the Fisher exact test. RESULTS: Eighteen percent (10/55) of the study group and 4% (2/55) of the control group had periorbital comedones. The study group had a significantly greater incidence of periorbital comedones (P =.01). CONCLUSION: The incidence of periorbital comedones is significantly greater in individuals exposed to pitch tar. Further studies are needed to elucidate the potential relationship between pitch tar and periorbital comedones.

Acne Vulgaris↗
PubMed1977

Clinical and histological study of coal tar phototoxicity in humans.

Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar.

Adrenal Cortex Hormones↗
PubMed2006

[Influence of smoke tar on mRNA expression of aromatic hydrocarbon receptor and cytochrome P4501A1 gene of mice lungs].

OBJECTIVE: To investigate the influence of the smoke tar on the expression of aromatic hydrocarbon receptor (AHR) and the cytochrome P4501Al (CYP1A1) gene of mice lungs. METHODS: The smoke tar of 5.29, 10.58 and 15.87 mg/kg was administered intraperitoneally in mice respectively. RNA of mice lungs was got with RNA kit. RT-PCR technique was used for determining AHR and CYP1A1 gene expression with beta-actin as control. RESULTS: The AHR gene expression level was (0.554 +/- 0.023) for the mice intraperitoneally administered with 5.29 mg/kg smoke tar for 72 hours with the significant difference in gene expression level compared with the Tween-80 group (0.484 +/- 0.045) (P < 0.05). The AHR gene expression levels were (0.555 +/- 0.014), (0.606 +/- 0.051), and (0.566 +/- 0.014), (0.684 +/- 0.069) for the mice intraperitoneally administered with 10.58 and 15.87 mg/kg smoke tar for 48 hours and 72 hours respectively with the significant difference in gene expression level compared with the Tween-80 group (0.486 +/- 0.060, 0.484 +/- 0.045) (P < 0.05, P < 0.01). The CYP1Al gene expression levels were (1.535 +/- 0.021), (1.643 +/- 0.046) and (1.624 +/- 0.056), (1.739 +/- 0.038) respectively with the significant difference compared with the Tween-80 group (l.436 +/- 0.016, 1.404 +/- 0.036) (P < 0.01). CONCLUSION: The smoke tar can regulate up the expression of AHR and CYP1A1 gene at a certain dosage and time. The regulation of the smoke tar for the expression of AHR was earlier than for that of CYP1A1.

Animals↗
PubMed1986

A double-blind randomized controlled trial of the effect of a low- versus a middle-tar cigarette on respiratory symptoms--a feasibility study.

A feasibility study of a double-blind, randomized controlled trial of the effect of a low-versus a middle-tar cigarette on respiratory symptoms is described. A smoking questionnaire was sent to 19,366 households. Returned questionnaires (64%) yielded 604 middle-tar cigarette smokers aged 20-44 years; 342 replied to a health warning stating that they did not want to or had failed to stop smoking and of these 183 volunteered for the trial. Thus about every 100 households originally mailed yielded one volunteer. Of the volunteers, 95 men were randomly allocated to be sold a middle-tar cigarette and 88 to be sold a low-tar cigarette of identical appearance. The cigarettes were sold at three different reduced prices and the men were asked to smoke them for five weeks. There was a 22% drop-out and this was unrelated to type of cigarette smoked. A reduction in price of 20% was sufficient incentive for volunteers to participate. Cigarette butts were collected weekly or fortnightly and urine samples were collected initially and after three and five weeks. Compliance with the trial cigarettes was good. The excretion of nicotine metabolites, number of cigarettes smoked and average butt weight for men allocated the low-tar cigarette was not significantly different from that of those allocated the middle-tar cigarette. This suggested that the former compensated for the 37% reduction in the nicotine yield of their cigarette by taking more frequent or deeper puffs from their cigarette. The implications of these results for a large-scale, randomized controlled trial are discussed.

Adult↗
PubMed1987

Inhaled smoke volume and puff indices with cigarettes of different tar and nicotine levels.

Ten asymptomatic smokers each smoked a low, low-to-middle and a middle tar cigarette with approximately the same tar-to-nicotine ratio, in a randomised order. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded using an electronic smoking analyser and flowhead/cigarette holder. Throughout the study neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette changed significantly; however, the mean and total puff volumes were largest with the low tar cigarette and decreased with the higher tar brands. Puff volume was related to puff work (rs = 0.83, P less than 0.001) but was not related to puff resistance (rs = 0.10, P greater than 0.1). It is concluded that when switched between brands with the same tar-to-nicotine ratio, smokers increase their puff volumes with a lower tar cigarette but do not change the volume of smoke inhaled. Puff work and puff resistance were significantly correlated (rs = 0.45, P less than 0.02).

Adolescent↗
PubMed1986

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes.

An unresolved public health issue is whether some modern cigarettes are less hazardous than others and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. We studied "tar" (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smoking ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite cotinine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. Our data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposures are considerably less than for other cigarettes.

Adult↗
PubMed1993

Similarity of the 5' and 3'-TAR secondary structures in HIV-1.

The structure of the TAR RNA element transcribed at the 5' end of the R region of the human immunodeficiency virus is compared to the structure of its duplicate sequence in the 3' R region of the viral genome. Based on the 5'-TAR secondary structure already described, we assessed by RNase T1 primer extension assay the degree of similarity between the 5'-TAR and the 3'-TAR RNA secondary structures. We also analysed the influence of modifications in the flanking sequences. We show that the secondary structures of the 5'-TAR and the 3'-TAR are very similar and are not influenced by the flanking sequences.

Base Composition↗
PubMed2005

The N-terminus of HIV-1 Tat protein is essential for Tat-TAR RNA interaction.

The human HIV transactivator protein Tat is essential for efficient viral transcription that occurs by a complex mechanism involving interaction of Tat with the TAR RNA element. This interaction appears to require the mediation of a cellular protein, cyclin T1. However, the possibility that Tat and TAR associate in a binary Tat-TAR complex has been little investigated. Using a chemically synthesized active Tat protein, the kinetic and equilibrium parameters of its interaction with TAR were determined by surface plasmon resonance technology. Independently of partner and method of immobilization onto the sensor chip, the association (k(a) = 5-9 x 10(5) M(-1) s(-1)) and dissociation rate constants (k(d) = 1.7-4.3 x 10(-3) s(-1)) yielded similar equilibrium dissociation constants (K(d) = 2-8 nM). A truncated peptide encompassing residues 30-86 of Tat did not bind to TAR at all. We conclude that Tat can form a high-affinity complex with TAR in the absence of cyclin T1 and that the N-terminal domain of Tat is essential for this interaction, suggesting a conformational link between this domain and the basic domain of Tat. These results are important in our quest for developing therapeutic compounds that impair viral replication.

Gene Products, tat↗
PubMed2003

The influence of changing nicotine to tar ratios on human puffing behaviour and perceived sensory response.

RATIONALE: Smokers modify their smoking behaviour when switching from their usual product to higher or lower tar and nicotine-yield cigarettes. OBJECTIVE: The aims of the current study were to assess the influence of varying nicotine yields at constant tar yield on human puffing measures, nicotine deliveries under human smoking conditions and the sensory response to mainstream cigarette smoke. These assessments would allow an evaluation of the degree of compensation and the various possible causes of changes, if any. METHODS: The participants were 13 regular smokers of commercial or hand-rolled cigarettes. They were tested with four cigarettes, which exhibited a wide range of nicotine to "tar" ratios at a relatively constant "tar" yield. Their smoking behaviour was monitored by placing the test cigarettes into an orifice-type holder/flowmeter attached to a custom-built smoker behaviour analyser. In addition, a comprehensive sensory evaluation of the products was carried out. RESULTS: The differences in the nicotine to tar ratios of the samples did not significantly influence the puffing behaviour patterns, i.e. puff number and interval, total and average puff volume, integrated pressure and puff duration. Additionally the pre- to post-exhaled CO boosts were not significantly influenced by the experimental samples used in the study. However, the nicotine yields obtained by the smokers were significantly influenced by the machine-smoked nicotine yields or the nicotine to tar ratios of the samples. The machine-smoked nicotine yields were highly correlated with the nicotine yields obtained under human smoking conditions. For the sensory evaluation, there was only a significant difference between the samples in the intensity of the impact. CONCLUSION: These observations imply that these puffing variables are not controlled by the nicotine yield of the cigarette.

Breath Tests↗
PubMed1996

Structural rearrangements on HIV-1 Tat (32-72) TAR complex formation.

Expression of the early genes of the human immunodeficiency virus type-I (HIV-1) genome is under the control of a trans-activator (Tat) protein. HIV-1 Tat action requires binding to TAR (trans-activation responsive element), an RNA sequence located at the 5'-end of all lentiviral mRNAs. We used various spectroscopic methods to investigate conformational changes on HIV-1 TAR binding to the HIV-1 (32-72) Tat peptide BP1. It comprises the RNA binding region and binds specifically to TAR. We conclude from our experiments that the regular A-form of the TAR RNA is slightly distorted towards the B-form when bound to BP1. Thus, the major groove is widened and the binding of BP1 facilitated. BP1 presumably adopts an extended conformation when binding to TAR and may fit well into the TAR major groove.

Amino Acid Sequence↗
PubMed1995

Molecular recognition in the bovine immunodeficiency virus Tat peptide-TAR RNA complex.

BACKGROUND: In lentiviruses such as human immunodeficiency virus (HIV) and bovine immunodeficiency virus (BIV), the Tat (trans-activating) protein enhances transcription of the viral RNA by complexing to the 5'-end of the transcribed mRNA, at a region known as TAR (the trans-activation response element). Identification of the determinants that account for specific molecular recognition requires a high resolution structure of the Tat peptide-TAR RNA complex. RESULTS: We report here on the structural characterization of a complex of the recognition domains of BIV Tat and TAR in aqueous solution using a combination of NMR and molecular dynamics. The 17-mer Tat peptide recognition domain folds into a beta-hairpin and penetrates in an edge-on orientation deep into a widened major groove of the 28-mer TAR RNA recognition domain in the complex. The RNA fold is defined, in part, by two uracil bulged bases; U12 has a looped-out conformation that widens the major groove and U10 forms a U.AU base triple that buttresses the RNA helix. Together, these bulged bases induce a approximately 40 degree bend between the two helical stems of the TAR RNA in the complex. A set of specific intermolecular hydrogen bonds between arginine side chains and the major-groove edge of guanine residues contributes to sequence specificity. These peptide-RNA contacts are complemented by other intermolecular hydrogen bonds and intermolecular hydrophobic packing contacts involving glycine and isoleucine side chains. CONCLUSIONS: We have identified a new structural motif for protein-RNA recognition, a beta-hairpin peptide that interacts with the RNA major groove. Specificity is associated with formation of a novel RNA structural motif, a U.AU base triple, which facilitates hydrogen bonding of an arginine residue to a guanine and to a backbone phosphate. These results should facilitate the design of inhibitors that can disrupt HIV Tat-TAR association.

Animals↗