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PubMed2004

Characterization of mainstream cigarette smoke-induced biomarker responses in ICR and C57Bl/6 mice.

Pulmonary emphysema is a major component of the morbidity and mortality of chronic obstructive pulmonary disease (COPD). Currently there are no predictive biomarkers for COPD. Initial steps toward identifying potentially predictive biomarkers involve utilizing well-characterized mainstream smoke (MS) exposure conditions (dose-response) to identify changes in biomarkers of effect (inflammation, tissue injury, oxidative stress) in emphysema-susceptible and -resistant mouse strains. C57Bl/6 mice have been reported to develop emphysema when exposed chronically to cigarette smoke, while similarly exposed ICR mice do not. Male C57Bl/6 and ICR mice were exposed 2 h/day for 7 consecutive days to MS from a standard reference cigarette (2R4F) at 75, 250, and 600 microg total particulate matter (TPM)/L or filtered air. To confirm exposure, blood samples were collected toward the end of the last exposure and analyzed for carboxyhemoglobin, nicotine, and cotinine. Bronchoalveolar lavage (BAL) fluid samples were collected 2 or 12 h postexposure and analyzed for biomarkers of effect. MS dose differed slightly between strains. More necrosis was observed in nasal epithelium of exposed C57Bl/6 mice. Exposure concentration-dependent increases in apoptosis, chemokines, and neutrophil counts were greater in ICR mice. Similar increases in thymus and activated-regulated chemokine were only observed in C57Bl/6 mice. BAL fluid cells of C57Bl/6 mice appear to undergo necrosis, while the BAL fluid cells of ICR mice appear to undergo apoptosis following MS exposure. Utilizing two strains of mice we identified MS-responsive biomarkers of effect that may be predictive of COPD pathology. Chronic MS exposures are needed to link these biomarkers with emphysema.

Animals↗

PubMed2004

Comparative assessment of toxicities of mainstream smoke from commercial cigarettes.

Three cigarette types were compared using an experimental approach for quantifying selected toxicological effects of diluted fresh whole cigarette mainstream smoke in vitro. The test procedure involved automatic smoking of cigarettes according to the FTC/ISO standard, online monitoring of generated smoke aerosols with respect to particulate and gas-phase components, and direct exposure of a human type II-like lung cell line (A549) using exposure conditions relevant to human smoking. Test specimens were the K1R4F standard research cigarettes (9.2 mg tar/cigarette) and two commercial European light filter cigarettes (brand 1, brand 2) having the same tar content (7.0 mg/cigarette). As a representative of the toxicological effect of smoke, intracellular reduced glutathione was analyzed directly after exposure of cells. Results revealed statistically significant different quantitative effects with regard to glutathione depletion when comparing whole smoke and filtered smoke from all three cigarettes. ED50 values revealed a depletion of reduced glutathione by brand 1 cigarettes that was more than twice the depletion caused by brand 2 cigarettes on a per cigarette basis. Also, quantitatively different effects were found on a per particle and on a per CO concentration basis using whole or filtered smoke from the cigarettes. We conclude that the methods we employed provide sensitive and reproducible ways of detecting differences in the toxicological action of smoke from various types of cigarettes.

Cell Line, Tumor↗

PubMed2006

College binge drinking: deviant versus mainstream behavior.

College binge drinking is examined from the perspectives of two cultures. The traditional culture views binging as deviant; the second culture promotes it. In this context, logit regression is used to explore the effects of various factors, including student employment and parental education. Employed students are less likely to binge than are students who are not employed. Also, students whose mother is a college graduate, but whose father is not, are more likely to binge than other students. The prescriptions for reducing binge drinking are different when the behavior is perceived as mainstream rather than deviant. The research calls for the development of a process for promoting cultural change in an environment of continually changing student leadership.

Adolescent↗

PubMed2003

Rapid communication: effects of tobacco processing on the quantity of benzo[a]pyrene in mainstream smoke.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon produced during incomplete combustion of organic compounds and is one of the more carcinogenic PAHs detected in tobacco smoke. Addition of organic compounds during tobacco processing increases the likelihood of finding elevated concentrations of BaP in mainstream smoke when compared to smoke from unprocessed tobacco. To test this hypothesis, the tobacco from Marlboro "Red" (processed) cigarettes and nonprocessed Burley tobacco leaf cigarettes was combusted and the resulting combustion products were collected onto glass fiber filter pads. The quantity of BaP in the tobacco tar extracted from the pads was measured using reversed-phase liquid chromatography with fluorescence detection. The concentration of BaP in the processed tobacco smoke was significantly higher than in unprocessed tobacco smoke. These results suggest that compounds added during tobacco processing increase the concentrations of BaP and therefore the carcinogenic potential of cigarettes.

Air Pollutants↗

PubMed1997

Bringing mind-body medicine into the mainstream.

Centuries-old concepts concerning the mind's influence on the body are being examined with renewed interest. As awareness of the health benefits of being able to voluntarily control vital aspects of the metabolic state increases, and as our understanding of the underlying molecular mechanisms of such control also increases, mind-body medicine may move further into the mainstream of Western medical practices.

Adult↗

PubMed2005

Toxicological effects of mainstream whole smoke solutions on embryonic movements of the developing embryo.

Cigarette smoking is unrivaled among developmental toxicants in terms of total adverse impact on the human population. Maternal tobacco use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of behavioral and developmental defects in children and adolescents. In the current study, the effects of different preparations of nicotine and mainstream whole smoke solutions (MSWSS) on embryonic movements during neonatal development were examined in vivo, using the chicken embryo model, recorded in real-time by a video camera. It was observed that low doses of nicotine induced hyperactivity and higher doses induced hypoactivity. Accordingly, a significant (p < 0.01) decrease in movements was observed by application of 10 microg of nicotine and different preparations of MSWSS. A dose-dependent decrease in embryonic movements was observed, which did not recover by the end of experiment. It was concluded that nicotine could alter embryonic movements, which are important during embryogenesis for differentiation and maturation of the body systems.

Animals↗

PubMed2002

A dozen years of drug treatment courts: uncovering our theoretical foundation and the construction of a mainstream paradigm.

The creation of the first drug treatment courts were in response to the revolving door of drug use and recidivism. There was no theoretical basis for these courts and no universal support for them. Twelve years have brought incredible changes. Therapeutic jurisprudence says, in essence, whether intended or not, that legal rules and procedures have therapeutic effects. Drug treatment courts have adopted principles of TJ to enhance their functioning. The Conference of Chief Justices recently issued a resolution supporting "problem-solving" courts. New trial court standards legitimize drug courts' procedures. Drug treatment courts are now mainstream and can no longer be seen as "boutique" courts staffed by renegade judges. Working therapeutically is an appropriate, effective, and productive way for the justice system to function.

Crime↗

PubMed2001

Publication of complementary and alternative medicine research in mainstream biomedical journals.

The growing interest in complementary and alternative medicine (CAM) among the public, patients, physicians, and academic medical centers has been accompanied by an increasing amount of research and publication of articles on unconventional medicine in mainstream biomedical journals. This presentation highlights recent trends in the publication of research articles on CAM therapies in major medical journals; delineates issues related to journal policies, scientific evaluation, and editorial decision-making regarding submitted manuscripts; and discusses the role of leading medical journals in providing reliable, evidence-based information on complementary and alternative medicine to the medical community and the public.

Complementary Therapies↗

PubMed2002

Blending the boundaries: steps toward an integration of complementary and alternative medicine into mainstream practice.

Complementary and alternative medicine (CAM) is growing in popularity among patients traditionally seen in an allopathic setting. A literature review and information search was conducted to determine the trend in demand for and the availability of CAM in the United States. The results of major surveys show that there is an increase in the use of CAM in the United States. The best predictor of CAM use is higher level of education. In addition, findings reveal that the field of CAM is poorly researched. Many studies in CAM therapies have flaws, such as insufficient statistical power, poor controls, inconsistent treatment, and lack of comparisons. The National Center for Complementary and Alternative Medicine of the National Institutes of Health, has declared their top strategic priority to be investing in research. Currently, more than 70 medical schools offer some type of training in alternative medicine, although there are few guidelines for curriculum and there is considerable heterogeneity in content, format, and requirements among CAM courses. As patients have greater access to information, their needs and values change. They become more involved in their overall health care and are taking a more natural and holistic approach to achieving well-being. Health care practitioners, both allopathic and alternative, must be well informed. There is an imperative to make CAM research a high priority. Valid and reliable empirical data must document the clinical efficacy and safety of CAM practices. In order to integrate CAM into the mainstream, there must be a coordinated effort among all the entities involved. Physicians need to be familiar with proven CAM therapies in order to advise patients about these modalities and the potential benefits and limitations. CAM practitioners should be licensed and regulated in scope of practice to provide a high standard of care, and be sufficiently educated in conventional medical science(s) in order to recognize how, where, and why their respective complementary practice is most effective for integration.

Attitude of Health Personnel↗

PubMed2004

Bringing holism into mainstream biomedical education.

Introducing holism and complementary medicine into mainstream medical education provides many scientific, philosophical, and personal challenges. The growth of new knowledge always necessitates venturing into areas, which are, by definition, unknown, hence arise potential clashes of ideology, knowledge, evidence, interpretation, language, and personality. This paper outlines some of the experience and progress made at Monash University Victoria, Australia, in teaching this material in undergraduate medical education. The Monash medical course has always been known for its commitment to an integrated curriculum, a holistic perspective, and the personal development of its students. Some of the points of integration in the core curriculum already achieved include health enhancement and mindfulness-based stress management programs right from first year, lectures and forums on complementary medicine, integration of this material into weekly case-based teaching, and health promotion and mind-body medicine. For very interested students, electives provide an opportunity to explore subjects in more depth. Experience has taught us that it is as important to learn how to deliver the message as it is to refine its content. This presents challenges that are as much personal as they are intellectual. Areas of particular importance are the academic environment, language, diplomacy, style, relevance, and evidence. In this process, building relationships, collegiality, patience, objectivity, impartiality, and humor are helpful.

Academic Medical Centers↗

PubMed2006

A closed-loop control "playback" smoking machine for generating mainstream smoke aerosols.

A first generation smoking machine capable of reading and replicating detailed puffing behavior from recorded smoking topography data is presented. Unlike standard smoking machines, which model human puffing behavior as a steady periodic waveform with a fixed puff frequency, volume, and duration, this novel machine generates a mainstream smoke aerosol by automatically "playing-back" puff topography recordings. Because combustion chemistry is highly non-linear, representing real smoking behavior with a smoothed periodic waveform may result in a tobacco smoke aerosol with a significantly different chemical composition and physical properties than that generated by a smoker. The machine presented here utilizes a rapid closed-loop control algorithm coded in Labview to generate smoke aerosols for toxicological assessment and inhalation studies. To illustrate its use, dry particulate matter and carbon monoxide yields generated using the playback and equivalent periodic puffing regimens are compared for a single smoking session by a 26-year-old male narghile water-pipe smoker. It was found that the periodic puffing regimen yielded 20% less carbon monoxide (CO) than the played-back smoking session, indicating that steady periodic smoking regimens, which are widely used in tobacco smoke research, may not produce realistic smoke aerosols.

Aerosols↗

PubMed2003

Gene expression profiling in respiratory tissues from rats exposed to mainstream cigarette smoke.

Cigarette smoke (CS) is known to cause cancer and other diseases, but little is known about the global molecular and cellular changes that occur prior to the appearance of clinically detectable symptoms. Using DNA microarrays covering 2031 cDNA probes, we investigated differential gene expression in tissues of the rat respiratory tract, i.e. respiratory nasal epithelium (RNE) and lungs of rats exposed either acutely (3 h) or subchronically (3 h/day, 5 days/week, 3 weeks) to mainstream CS with death either immediately or at 20 h after exposure. Differential gene expression was most evident in RNE of rats exposed once and was characterized by strong up-regulation of genes encoding oxidative stress-responsive and Phase II drug-metabolizing enzymes, such as haem oxygenase-1 and NAD(P)H:quinone oxidoreductase, which are all, at least in part, transcriptionally regulated by NF-E2-related factor 2 (Nrf2). After 3 weeks of exposure, the strength of expression of this class of genes was markedly reduced, pointing to an adaptive response. The generally lower response in the lungs of exposed rats is indicative of a deposition gradient of active smoke constituents from the upper to the lower respiratory tract. In sharp contrast to the CS-induced expression of oxidative stress and Phase II-responsive genes, induction of the genes encoding the Phase I drug-metabolizing enzymes cytochrome P450 (CYP)1A1 and aldehyde dehydrogenase-3 was not reduced after 3 weeks of exposure and was similarly high in lungs and RNE. Gene expression patterns in rats allowed to recover for 20 h showed that the CS-induced transcriptional changes observed immediately after exposure returned almost completely to normal, even after 3 weeks of repeated CS exposure. In general, these results demonstrate that CS induces a specific differential gene expression pattern in vivo, which may be instrumental in identifying the molecular mechanisms leading to the onset of inflammatory and/or morphological changes.

Animals↗

PubMed2005

Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer in B6C3F1 mice through genetic and epigenetic pathways.

Although cigarette smoke has been epidemiologically associated with lung cancer in humans for many years, animal models of cigarette smoke-induced lung cancer have been lacking. This study demonstrated that life time whole body exposures of female B6C3F1 mice to mainstream cigarette smoke at 250 mg total particulate matter/m(3) for 6 h per day, 5 days a week induces marked increases in the incidence of focal alveolar hyperplasias, pulmonary adenomas, papillomas and adenocarcinomas. Cigarette smoke-exposed mice (n = 330) had a 10-fold increase in the incidence of hyperplastic lesions, and a 4.6-fold (adenomas and papillomas), 7.25-fold (adenocarcinomas) and 5-fold (metastatic pulmonary adenocarcinomas) increase in primary lung neoplasms compared with sham-exposed mice (n = 326). Activating point mutations in codon 12 of the K-ras gene were identified at a similar rate in tumors from sham-exposed mice (47%) and cigarette smoke-exposed mice (60%). The percentages of transversion and transition mutations were similar in both the groups. Hypermethylation of the death associated protein (DAP)-kinase and retinoic acid receptor (RAR)-beta gene promoters was detected in tumors from both sham- and cigarette smoke-exposed mice, with a tendency towards increased frequency of RAR-beta methylation in the tumors from the cigarette smoke-exposed mice. These results emphasize the importance of the activation of K-ras and silencing of DAP-kinase and RAR-beta in lung cancer development, and confirm the relevance of this mouse model for studying lung tumorigenesis.

Adenocarcinoma↗

PubMed1990

Separation and quantitation of monovalent anionic and cationic species in mainstream cigarette smoke aerosols by high-performance ion chromatography.

A simple method has been developed to separate and quantitate monovalent ionic species in mainstream cigarette smoke aerosols based on ion chromatography (IC) with conductivity detection. The method entails collecting the smoke aerosol particulate phase by electrostatic precipitation, dissolving the smoke condensate in methanol (MeOH), and separating the ionic species on either a cation- or anion-exchange column. The method has been applied to the analysis of smoke aerosols from two cigarettes, 1R4F Kentucky Reference cigarettes and a new cigarette that heats but does not burn tobacco. The predominant cations in smoke aerosols from 1R4F Kentucky Reference and the new cigarettes are sodium (Na+), ammonium (NH4+), and potassium (K+) ions; the predominant anions are acetate (AcO-) and formate (HCOO-). Trace amounts of chloride (Cl-), nitrite (NO2-), and nitrate (NO3-) ions are also present.

1-Propanol↗

PubMed2006

Rapid and sensitive method for the determination of propylene oxide in cigarette mainstream smoke by gas chromatography-mass spectrometry.

A rapid method using gas chromatography-mass spectrometry for the analysis of propylene oxide in cigarette mainstream smoke is reported. Validation data show the method, which requires a minimum of sample preparation, to be selective, sensitive, reliable, and robust. Propylene oxide is found in the University of Kentucky Reference Cigarettes 1R4F and 2R4F at concentrations of 0.93 and 0.65 microg/cigarette, respectively, with a quantitation limit of 0.135 microg/cigarette.

Epoxy Compounds↗

PubMed2003

Influences of student and family factors on academic outcomes of mainstream secondary school deaf students.

This article considers some of the student and family factors influencing the educational achievements of deaf children. It is based on a study of 16-year-old deaf students in mainstream schools in England. Findings indicate the complexity of interpreting statistical results, especially on the effect of degree of hearing loss. The discussion addresses the specific question of why this factor is often reported as not significant in academic achievement. It also considers the surprisingly low effect of family socioeconomic status, speculates on the size of the "school effect" in deaf education, and considers the coding of data.

Journal Article↗

PubMed1994

Mainstreaming gerontology in the policy arena.

Aging has come of age and is now one of the important domestic issues facing the United States. What we do or don't do in the 1990s will determine what type of aging society we will have in the next century. The challenge we face as gerontologists is to think about new ways to help broaden the debate about preparing for an aging society in a comprehensive manner that takes into account the diverse disciplines and interest groups that will increasingly shape aging-related issues. Those who have labored in the field of aging when it was a relatively cloistered profession should delight in the new-found respect and recognition of their work by the larger society. On the other hand, this mainstreaming of aging will create new challenges and opportunities, as we look ahead to the new aging.

Aged↗

PubMed2005

Sidestream smoking is equally as damaging as mainstream smoking on IVF outcomes.

BACKGROUND: Cigarette smoking (CS) is a widely recognized health hazard, yet it remains prevalent in society and the effects of environmental tobacco smoke exposure on fertility are unknown. Our objective was to measure the effects of CS on the fertility of mainstream (MS) or sidestream (SS) smoke-exposed women compared to their non-smoking (NS) counterparts. METHODS: This retrospective study investigated 225 female patients undergoing IVF (n = 97) or ICSI (n = 128). Patients were grouped based on their smoking status for comparison. This included: 39 MS (18 IVF and 21 ICSI); 40 SS (16 IVF and 24 ICSI); and 146 NS (63 IVF and 83 ICSI) women. Fertility treatment outcomes including embryo quality, implantation and pregnancy rate were measured. RESULTS: No difference in embryo quality between the three groups was observed. However, there was a significant difference in implantation rate (MS = 12.0%, SS = 12.6%, and NS = 25.0%) and pregnancy rate (MS = 19.4%, SS = 20.0%, and NS = 48.3%) per embryo transfer. CONCLUSIONS: Despite similar embryo quality there was a striking difference in implantation and pregnancy rates of MS and SS smokers when compared with NS. Our data demonstrate that the effects of SS smoking are equally as damaging as MS smoke on fertility.

Embryo Implantation↗