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Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or alpha 4 beta 2 receptors to nicotine.

Smokers are reported to have a higher density of central nicotinic acetylcholine receptors (nAChRs) that non-smokers at autopsy. Whether this increased receptor density is a response to smoking or a result of genetic variability is not known. While sub-chronic treatment of rats and mice with nicotine results in upregulation of central nAChRs, changes in receptor density in response to cigarette smoke have not been studied previously. In this study, male Sprague-Dawley rats were exposed nose-only for 13 weeks to mainstream cigarette smoke followed by assessment of [3H]nicotine binding in five brain regions of smoke- and sham-exposed animals. In smoke-exposed animals, there was a significant increase in nAChR density in the cortex, striatum, and cerebellum (35, 25, and 31% increases, respectively), while there was no significant change in receptor density in the thalamus and hippocampus. Smoke exposure did not alter markedly the affinity of the receptor for nicotine in these brain regions. Furthermore, up-regulation of nAChRs did not alter the biphasic binding properties by which nicotine binds to its receptor. There were no changes in the association (fast phase) or isomerization (slow phase) rate constants, and the percent contribution of slow and fast phase binding to nAChRs was not altered in the up-regulated receptor population compared with control. Similar results were observed following chronic nicotine exposure of cultured cortical cells from fetal rat brain or cells transfected with the alpha 4 beta 2 nAChR subtype. These results show that the up-regulation following smoke exposure in the rat is phenomenologically similar to that observed in vitro. These data provide preliminary evidence for a relationship between cigarette smoking and nAChR up-regulation in vivo and suggest that similar mechanisms of upregulation may underlie chronic smoke exposure of live animals and nicotine exposure of artificially expressed alpha 4 beta 2 receptors in vitro.

Animals↗

Free lung cell response of mice and rats to mainstream cigarette smoke exposure.

Male C57BL mice and F-344 rats were exposed through nose only to fresh mainstream smoke from one University of Kentucky Reference cigarette (2R1) daily under standardized conditions. At different exposure points, the lungs of room control (RM), sham control (SH), and smoke-exposed (SM) animals were lavaged and the number, composition, and properties of bronchoalveolar lavage (BAL) cells were studied. Significantly elevated levels of blood COHb and pulmonary aryl hydrocarbon hydroxylase activity indicated effective inhalation of smoke by animals. The BAL cell analysis showed that cigarette smoke induced a five- to sevenfold increase in the number of BAL cells in mice following 10- to 12-week exposure. The proportion of neutrophils (PMN) increased to about 18 +/- 3% in SM mice as compared to less than 1% in controls. Cessation of smoke treatments returned the PMN levels to those of controls within 5 weeks. Unlike mice, smoke exposure for up to 32 weeks failed to induce appreciable changes in the number and proportion of macrophages and neutrophils in rats. Large brown macrophages were observed in SM groups of both species. Functional analysis demonstrated that the BAL cells from SM mice but not rats released greater amounts of superoxides than controls under resting and phagocytically stimulated conditions. Enzymatic analysis of macrophages showed that the activity of N-acetylglucosaminidase was increased in SM groups of both species. The activity of 5'nucleotidase was significantly reduced in macrophages from SM mice but not rats. Activity of leucine aminopeptidase remained unaltered in both species. These results demonstrate distinct differences in the response of mice and rats to identically generated cigarette smoke.

5'-Nucleotidase↗

Making the alternative the mainstream. Maintaining a family-centered focus in a large freestanding birth center for low-income women.

The BirthPlace program in San Diego, California, is an example of a successfully "mainstreamed" alternative maternity care program. It was developed to address an access to prenatal care problem in the county, and it has successfully integrated four systems of care: 1) a private practice of nurse-midwives and obstetricians, 2) the public community clinic system, 3) the tertiary university hospital, and 4) a freestanding birth center. It provides a model of care that, if replicated, could be an answer for ensuring universal access to maternity care in the United States. The BirthPlace program primarily serves a public-funded, Hispanic population, with certified nurse-midwives as the primary providers. The program's greatest challenge has been to maintain a personalized, family-centered focus, which has been the hallmark of freestanding birth centers to date, in the face of large numbers of clients and low reimbursement for care. The program has addressed the challenge of increasing access and cost-effectiveness while ensuring family-centered care through decentralized clinic management, informed consent, culturally sensitive care, and appropriate use of technology. However, in the face of an ever-changing health care system, balancing these issues will remain a constant challenge as we reshape our maternity care services.

Birthing Centers↗

Comparative genotoxicity testing of mainstream whole smoke from cigarettes which burn or heat tobacco.

The genotoxic potential of mainstream whole smoke (MWS) from cigarettes which heat tobacco (TEST) was compared to the genotoxic potential of MWS from a cigarette which burns tobacco (REFERENCE). MWS was collected from a University of Kentucky 1R4F cigarette (REFERENCE) and two, TEST cigarettes, one with regular flavor and the other with menthol flavor. All cigarettes were smoked on a smoking machine and the particulate phase was collected on Cambridge filter pads. The vapor phase, which passed through the pad, was bubbled into a dimethyl sulfoxide (DMSO) trap. The filter pad was extracted with the DMSO in the trap and additional DMSO to obtain MWS. MWS representing an identical number of cigarettes was tested to make a per-cigarette comparison of their genotoxic potential. REFERENCE MWS was mutagenic and cytotoxic in the Ames assay in the presence of metabolic activation while it was cytotoxic but not mutagenic in the absence of metabolic activation. Statistically significant increases in frequency of both sister-chromatid exchanges and chromosomal aberrations were observed in Chinese hamster ovary cells exposed to REFERENCE MWS with and without metabolic activation. MWS from the TEST cigarettes, with either regular or menthol flavor, was neither cytotoxic nor mutagenic in any of these assays. In summary, MWS from the 2 TEST cigarettes was neither genotoxic nor cytotoxic under conditions where MWS from the REFERENCE cigarettes was genotoxic and/or cytotoxic in a concentration-dependent manner.

Biotransformation↗

The comparative clastogenic activity of mainstream tobacco smoke from cigarettes widely consumed in Armenia.

Whole-body exposure of male albino Swiss mice to the mainstream smoke produced by 10 types of cigarettes widely consumed in Armenia resulted in a significant increase (2.4-5.6-fold) of the number of micronucleated bone marrow polychromatic erythrocytes. The smoke produced by cigarettes manufactured in Armenia, Russia and Bulgaria was more clastogenic than the smoke produced by cigarettes manufactured in the USA. A high direct correlation was observed between the number of micronucleated polychromatic erythrocytes and the content of tar and nicotine.

Animals↗

Identification of social skill curriculum targets for severely handicapped children in mainstream preschools.

In order to identify potential social skills targets with severely handicapped preschool children, the social interactions of 80 children, 20 in each of the following groups were assessed; (a) nonhandicapped 3- to 5-year-olds who received high sociometric ratings from class peers, (b) severely handicapped 3- to 5-year-olds who received relatively higher sociometric ratings than their similarly handicapped class peers, (c) nonhandicapped 3- to 5-year-olds who received low sociometric ratings from class peers, and (d) severely handicapped 3- to 5-year-olds who received relatively lower sociometric ratings than their handicapped class peers. All children were recruited from 10 mainstream preschool programs. Continuous observations of specific social initiations and responses to those initiations (210 min total per child) indicated that: (a) nonhandicapped children seemed not to have been affected adversely by exposure to handicapped peers and, in fact, normal subjects regulated the complexity of their social initiations to match the developmental level of handicapped interactants; (b) negative social initiations emerged as a behavior pattern that powerfully influenced children's negative evaluations of others; (c) specific approach behaviors such as play organizers, shares, affection, and assistance were displayed more often by higher regard handicapped children; (d) responding to others' social initiations and having others respond to social bids were important requisites for social acceptability, and (e) the above-mentioned behavior patterns were not setting-specific.

Autistic Disorder↗

Mainstream and environmental tobacco smoke.

Environmental tobacco smoke (ETS) is derived from cigarette smoldering and active smoker exhalation. Its composition displays broad quantitative differences and redistributions between gas and respirable suspended particulate (RSP) phases when compared with the mainstream smoke (MSS) that smokers puff. This is because of different generation conditions and because ETS is diluted and ages vastly more than MSS. Such differences prevent a direct comparison of MSS and ETS and their biologic activities. However, even assuming similarities on an equal mass basis, ETS-RSP inhaled doses are estimated to be between 10,000- and 100,000-fold less than estimated average MSS-RSP doses for active smokers. Differences in effective gas phase doses are expected to be of similar magnitude. Thus the average person exposed to ETS would retain an annual dose analogous to the active MSS smoking of considerably less than one cigarette dispersed over a 1-year period. By contrast, consistent epidemiologic data indicate that active smoking of some 4-5 cigarettes per day may not be associated with a significantly increased risk of lung cancer. Similar indications also obtain for cardiovascular and respiratory diseases. Since average doses of ETS to nonsmoking subjects in epidemiologic studies are several thousand times less than this reported intake level, the marginal relative risks of lung cancer and other diseases attributed to ETS in some epidemiologic studies are likely to be statistical artifacts, derived from unaccounted confounders and unavoidable bias.

Animals↗

Simultaneous mainstream-sidestream smoke exposure systems I. Equipment and procedures.

Equipment and procedures for the simultaneous exposure of cell cultures and rodents to mainstream and sidestream smoke are described. Whole smoke or the gas phase of smoke can be generated and manipulated under a wide range of conditions. Identical smoke can be used for the exposure of cell cultures, perfused lungs, and for the exposure of experimental animals. The equipment is relatively inexpensive, and can be used by a small laboratory for efficient, controlled smoke exposure studies. Total particulate matter data are used to illustrate the flexibility of smoke generation, manipulation, and dose variables which can be obtained with the exposure systems.

Animals↗

Gaschromatographic determination of polycyclic aromatic hydrocarbons, aza-arenes, aromatic amines in the particle and vapor phase of mainstream and sidestream smoke of cigarettes.

The present arrangement collects particles and semivolatiles of main- and sidestream smoke and allows a recovery of the trapped substances nearly quantitatively and without impurities. The fractionation procedure allows to separate various groups of carcinogens such as PAH, aza-arenes and aromatic amines for analytical and biological studies. Sidestream smoke contains ten times more polycyclic aromatic hydrocarbons (PAH) compared with mainstream smoke. This holds also true for aza-arenes and amines. PAH of the gaseous phases include only 1% of the particle-bound PAH.

Aerosols↗

Discrimination training of phonemic contrasts enhances phonological processing in mainstream school children.

Auditory perceptual learning has been proposed as effective for remediating impaired language and for enhancing normal language development. We examined the effect of phonemic contrast discrimination training on the discrimination of whole words and on phonological awareness in 8- to 10-year-old mainstream school children. Eleven phonemic contrast continua were synthesised using linear interpolation coding from real speaker endpoints. Thirty children were pre-tested on the Word Discrimination Test (WDT) and the Phonological Assessment Battery (PhAB). Eighteen then trained for 12 x 30min sessions over 4 weeks using an adaptive three interval two alternative phonemic matching task. The remaining children participated in regular classroom activities. In Post-testing, trained children significantly increased their age-equivalent scores on both the WDT and PhAB by about 2 years. For the PhAB, no improvement was found in the controls. Enhanced performance in the trained children was maintained in a delayed test 5-6 weeks following training. Enhancements on the trained discriminations were weak and variable. The results indicate a dramatic improvement in phonological awareness following phonemic discrimination training without matching perceptual learning.

Child↗

Gas chromatography-mass spectrometry of carbonyl compounds in cigarette mainstream smoke after derivatization with 2,4-dinitrophenylhydrazine.

An improved gas chromatography-mass spectrometry (GC-MS) method was described for the analysis of carbonyl compounds in cigarette mainstream smoke (CMS) after 2,4-dinitrophenylhydrazine (DNPH) derivatization. Besides formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, methyl ethyl ketone, butyraldehyde, and crotonaldehyde that are routinely analyzed in cigarette smoke, this technique separates and allows the analysis of several C4, C5 and C6 isomeric carbonyl compounds. Differentiation could be made between the linear and branched carbon chain components. In cigarette smoke, the branched chain carbonyls are found at higher level than the linear chain carbonyls. Also, several trace carbonyl compounds such as methoxyacetaldehyde were found for the first time in cigarette smoke. For the analysis, cigarette smoke was collected using DNPH-treated pads, which is a simpler procedure compared to conventional impinger collection. Thermal decomposition of DNPH-carbonyl compounds was minimized by the optimization of the GC conditions. The linear range of the method was significantly improved by using a standard mixture of DNPH-carbonyl compounds instead of individual compounds for calibration. The minimum detectable quantity for the carbonyls ranged from 1.4 to 5.6 microg/cigarette.

Gas Chromatography-Mass Spectrometry↗

Actions speak louder than words: mainstream health providers' definitions and behaviour regarding complementary and alternative medicine.

The purpose of this paper is to explore how mainstream practitioners define and categorize complementary and alternative medicine (CAM) as one component of assessing their views. The following themes emerged from interviews with Canadian physicians, midwives and nurses: epistemological, evidence-based, medical domain, political-regulatory, funding-based, and role-based definitions of CAM. We also assess any possible links to their behaviour vis-à-vis CAM. We found that classifying something as CAM does not appear to inhibit most providers from recommending, referring for, or supporting their patients' use of these treatments. In conclusion, we highlight that despite their clear definitional boundaries around CAM, providers tend to evaluate each individual therapy on its own merits, taking other situational factors into consideration.

Attitude of Health Personnel↗

Communication between CAM and mainstream medicine: Delphi panel perspectives.

Healthcare practitioners' models of health affect their patient interactions and services. We surveyed mainstream (MM), integrative (IM) and CAM providers to investigate their models of health. This study generated ideas for actions to improve MM/CAM communication based on survey findings. Through the Delphi technique, a panel of 14 MM, IM and CAM experts participated in two rounds of questioning regarding survey findings. MM panel members were less supportive of almost all suggestions for actions than IM and CAM members. Suggestions most likely to be implemented were enabling the patient to take an active role in care, establishing understanding between patient and practitioner of treatment and its goals, fostering patients' taking responsibility for their health and communicating about patient assessment in ways understandable to others. Actions to foster better MM/CAM communication promote focus by a team of providers on the patient's goals, functioning and involvement in their care.

Complementary Therapies↗

Cadmium, lead, and thallium in mainstream tobacco smoke particulate.

The deliveries of cadmium, thallium, and lead in mainstream smoke particulate from cigarettes with different smoke delivery designs were determined by inductively coupled plasma-mass spectrometry in order to investigate their impact on the delivery of these known toxic compounds. Analyses showed that the levels of all three metals in smoke particulate were associated with their tar delivery category. After normalizing the metal concentrations to tar, there were no longer any statistically significant delivery differences between full-flavor, light or ultra-light cigarettes. When the concentrations were normalized to nicotine, the mean levels from the three delivery groups were much smaller than before normalization. But unlike the case using tar to normalize, in some of the cases, there were still some statistically significant differences in the nicotine-normalized results. These findings suggest that if smokers compensate for differences in nicotine intake, they receive exposures to toxic heavy metals from ultra-light, light and full-flavor cigarettes that are more similar than results would suggest from using the Federal Trade Commission method alone.

Cadmium↗

Gas/particle partitioning and yield levels of polycyclic aromatic hydrocarbons and n-alkanes in the mainstream cigarette smoke of commercial cigarette brands.

The gas/particle partitioning of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes was investigated in the mainstream smoke (MSS) from 59 commercial cigarette brands classified according to the existence of filter tip, the tar yield indicated on the packet, and the cigarette length and diameter, into 15 cigarette classes: non filter (NF), high (H), medium (M), light (L), super light (SL), ultra light (UL), one-tar yield (O), 100-mm long (H-100, L-100, SL-100, UL-100, O-100), and slim (SL-SLIM, UL-SLIM, O-SLIM). The gas/particle partitioning constant, Kp, was determined and its relationship with the subcooled liquid vapour pressure pL degrees of individual compounds was investigated. A good linear relationship was obtained for both chemical classes following the equation log Kp=mr log pL degrees+br. In all cigarette classes, PAHs were found to sorb more strongly on MSS particles than n-alkanes. Carcinogenic PAHs were detectable only in the total particulate matter (TPM) of MSS and their yields increased linearly with the TPM yield. However, when normalized against TPM, the yields of carcinogenic PAHs were quite similar in all cigarette classes with a slight drop from low tar- to high tar-yield brands suggesting probably lower biological activity per mg TPM for the latter. The nicotine-normalized PAH yields were also similar among the different cigarette classes suggesting that, if smokers adjust their smoking behavior to achieve a consistent nicotine intake, they will be exposed to an equivalent amount of carcinogenic PAHs regardless of whether they smoke full-flavored, light, or ultralight varieties.

Alkanes↗

Utility of the mouse dermal promotion assay in comparing the tumorigenic potential of cigarette mainstream smoke.

The International Agency for Research on Cancer (IARC) has classified a number of the chemical constituents reported in cigarette mainstream smoke (MS) as carcinogens. In the international literature, 81 IARC classified carcinogens have been reported historically in MS. Cigarette smoke is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The gases and semi-volatiles are termed the vapor phase. Due to early difficulties in inducing carcinomas in laboratory animals following inhalation exposure to MS, the mouse dermal promotion assay became the standard method of comparing the tumorigenic potential of cigarette smoke condensates (the particulate phase of MS nearly devoid of MS gases and having a significant reduction of the semi-volatile components of the vapor phase). Of the 81 IARC carcinogens reported in MS, 48 are found exclusively in the particulate phase, 29 in the vapor phase only, and four IARC carcinogens in both phases. A general comparison of the quantity and potency of the individual carcinogenic constituents of the MS vapor and particulate phases illustrates that the potential carcinogenic contribution from the vapor phase might be significant. Therefore, the mouse dermal promotion assay may not be a sensitive comparator of the tumorigenic potential of different MSs displaying a diversity of vapor phase components. However, when used in a weight-of-the-evidence approach that includes smoke chemistry, in vitro studies using whole smoke and human exposure studies evaluating both vapor and particulate phase smoke constituents, the mouse dermal promotion assay remains an important risk assessment tool as the only test that reproducibly measures the tumorigenic potential of cigarette smoke condensate.

Animals↗

Sugars as tobacco ingredient: Effects on mainstream smoke composition.

Sugars are natural tobacco components, and are also frequently added to tobacco during the manufacturing process. This review describes the fate of sugars during tobacco smoking, in particular the effect of tobacco sugars on mainstream smoke composition. In natural tobacco, sugars can be present in levels up to 20 wt%. In addition, various sugars are added in tobacco manufacturing in amounts up to 4 wt% per sugar. The added sugars are usually reported to serve as flavour/casing and humectant. However, sugars also promote tobacco smoking, because they generate acids that neutralize the harsh taste and throat impact of tobacco smoke. Moreover, the sweet taste and the agreeable smell of caramelized sugar flavors are appreciated in particular by starting adolescent smokers. Finally, sugars generate acetaldehyde, which has addictive properties and acts synergistically with nicotine in rodents. Apart from these consumption-enhancing pyrolysis products, many toxic (including carcinogenic) smoke compounds are generated from sugars. In particular, sugars increase the level of formaldehyde, acetaldehyde, acetone, acrolein, and 2-furfural in tobacco smoke. It is concluded that sugars in tobacco significantly contribute to the adverse health effects of tobacco smoking.

Acetaldehyde↗

FTIR analysis of gaseous compounds in the mainstream smoke of regular and light cigarettes.

Fourier-transform infrared (FTIR) spectroscopy has been applied to the study of mainstream cigarette smoke from cigarettes of different stated strengths (regular and various light cigarettes with different reported nicotine, tar and CO contents). This technique has allowed for the measurement of a variety of gaseous components including hydrocarbons and both nitrogen and carbon oxides. The results demonstrate that the strength of the cigarette does not have a significant bearing on the quantity of the observed components produced. Additionally, open-path FTIR studies of diluted sidestream and exhaled smoke have been conducted. These measurements revealed that the majority of gaseous pollutants originated from the sidestream smoke, while the primary smoke was 'purified' or diluted upon exhalation by the smoker.

Carbon Monoxide↗