Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma

Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics both large and small airways has not been investigated. Objective To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non-smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real-time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non-smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.

Intracellular mechanisms of hydroquinone toxicity on endotoxin-activated neutrophils

Circulating neutrophils promptly react to different substances in the blood and orchestrate the beginning of the innate inflammatory response. We have shown that in vivo exposure to hydroquinone (HQ), the most oxidative compound of cigarette smoke and a toxic benzene metabolite, affects circulating neutrophils, making them unresponsive to a subsequent bacterial infection. In order to understand the action of toxic molecular mechanisms on neutrophil functions, in vitro HQ actions on pro-inflammatory mediator secretions evoked by Escherichia coli lipopolysaccharide (LPS) were investigated. Neutrophils from male Wistar rats were cultured with vehicle or HQ (5 or 10 mu M; 2 h) and subsequently incubated with LPS (5 mu g/ml; 18 h). Hydroquinone treatment impaired LPS-induced nitric oxide (NO), tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 secretions by neutrophils. The toxic effect was not dependent on cell death, reduced expression of the LPS receptor or toll-like receptor-4 (TLR-4) or cell priming, as HQ did not induce reactive oxygen species generation or beta(2)integrin membrane expression. The action of toxic mechanisms on cytokine secretion was dependent on reduced gene synthesis, which may be due to decreased nuclear factor kappa B (NF-kappa B) nuclear translocation. Conversely, this intracellular pathway was not involved in impaired NO production because HQ treatments only affected inducible nitric oxide synthase protein expression and activity, suggesting posttranscriptional and/or posttranslational mechanisms of action. Altogether, our data show that HQ alters the action of different LPS-activated pathways on neutrophils, which may contribute to the impaired triggering of the host innate immune reaction detected during in vivo HQ exposure.

Prevalence of overweight and obesity in elderly people from Vitória-ES, Brazil

The scope of this study was to estimate the prevalence of overweight and obesity and its association with socio-economic status in a sample of non-institutionalized elderly people from Vitória-ES, Brazil. This was a cross-sectional survey with a sample of 882 elderly people aged 60 and over. Obesity and overweight were assessed using the body mass index (BMI) and waist circumference (WC). All subjects answered a personal and socio-demographic questionnaire in relation to age, gender, marital status, physical activity, number of children, chronic diseases and smoking. Associations between categorical variables were tested using chi-square analysis with a 5% significance level. The prevalence of overweight and obesity was high (41.8% and 23.4%, respectively) and 50.7% of the elderly had a substantially increased waist circumference. About 4.3% of the individuals had diabetes, 50.4% had hypertension and 14.9% were found to have both diseases. It was observed that both the BMI and WC were significant associated (p<0.05) with sex, marital status, the presence of diseases and with cigarette smoking.

Chemische und physikalische Charakterisierung von Aerosolpartikeln aus besonderen anthropogenen Emissionsquellen : ein integrativer Ansatz mittels online (HR-ToF-AMS)- und komplementärer offline (ATR-FTIR-Spektroskopie)-Analytik

Die Gesundheitseffekte von Aerosolpartikeln werden stark von ihren chemischen und physikalischen Eigenschaften und somit den jeweiligen Bildungsprozessen und Quellencharakteristika beeinflusst. Während die Hauptquellen der anthropogenen Partikelemissionen gut untersucht sind, stellen die spezifischen Emissionsmuster zahlreicher kleiner Aerosolquellen, welche lokal und temporär zu einer signifikanten Verschlechterung der Luftqualität beitragen können, ein Forschungsdesiderat dar.rnIn der vorliegenden Arbeit werden in kombinierten Labor- und Feldmessungen durch ein integratives Analysekonzept mittels online (HR-ToF-AMS ) und filterbasierter offline (ATR-FTIR-Spektroskopie ) Messverfahren die weitgehend unbekannten physikalischen und chemischen Eigenschaften der Emissionen besonderer anthropogener Aerosolquellen untersucht. Neben einem Fußballstadion als komplexe Mischung verschiedener Aerosolquellen wie Frittieren und Grillen, Zigarettenrauchen und Pyrotechnik werden die Emissionen durch Feuerwerkskörper, landwirtschaftliche Intensivtierhaltung (Legehennen), Tief- und Straßenbauarbeiten sowie abwasserbürtige Aerosolpartikel in die Studie mit eingebunden. Die primären Partikelemissionen der untersuchten Quellen sind vorrangig durch kleine Partikelgrößen (dp < 1 µm) und somit eine hohe Lungengängigkeit gekennzeichnet. Dagegen zeigen die Aerosolpartikel im Stall der landwirtschaftlichen Intensivtierhaltung sowie die Emissionen durch die Tiefbauarbeiten einen hohen Masseanteil von Partikeln dp > 1 µm. Der Fokus der Untersuchung liegt auf der chemischen Charakterisierung der organischen Partikelbestandteile, welche für viele Quellen die NR-PM1-Emissionen dominieren. Dabei zeigen sich wichtige quellenspezifische Unterschiede in der Zusammensetzung der organischen Aerosolfraktion. Die beim Abbrand von pyrotechnischen Gegenständen freigesetzten sowie die abwasserbürtigen Aerosolpartikel enthalten dagegen hohe relative Gehalte anorganischer Substanzen. Auch können in einigen spezifischen Emissionen Metallverbindungen in den AMS-Massenspektren nachgewiesen werden. Über die Charakterisierung der Emissionsmuster und -dynamiken hinaus werden für einige verschiedenfarbige Rauchpatronen sowie die Emissionen im Stall der Intensivtierhaltung Emissionsfaktoren bestimmt, die zur quantitativen Bilanzierung herangezogen werden können. In einem weiteren Schritt werden anhand der empirischen Daten die analytischen Limitierungen der Aerosolmassenspektrometrie wie die Interferenz organischer Fragmentionen durch (Hydrogen-)Carbonate und mögliche Auswertestrategien zur Überwindung dieser Grenzen vorgestellt und diskutiert.rnEine umfangreiche Methodenentwicklung zur Verbesserung der analytischen Aussagekraft von organischen AMS-Massenspektren zeigt, dass für bestimmte Partikeltypen einzelne Fragmentionen in den AMS-Massenspektren signifikant mit ausgewählten funktionellen Molekülgruppen der FTIR-Absorptionsspektren korrelieren. Bedingt durch ihre fehlende Spezifität ist eine allgemeingültige Interpretation von AMS-Fragmentionen als Marker für verschiedene funktionelle Gruppen nicht zulässig und häufig nur durch die Ergebnisse der komplementären FTIR-Spektroskopie möglich. Des Weiteren wurde die Verdampfung und Ionisation ausgewählter Metallverbindungen im AMS analysiert. Die Arbeit verdeutlicht, dass eine qualitative und quantitative Auswertung dieser Substanzen nicht ohne Weiteres möglich ist. Die Gründe hierfür liegen in einer fehlenden Reproduzierbarkeit des Verdampfungs- und Ionisationsprozesses aufgrund von Matrixeffekten sowie der in Abhängigkeit vorangegangener Analysen (Verdampferhistorie) in der Ionisationskammer und auf dem Verdampfer statt-findenden chemischen Reaktionen.rnDie Erkenntnisse der Arbeit erlauben eine Priorisierung der untersuchten anthropogenen Quellen nach bestimmten Messparametern und stellen für deren Partikelemissionen den Ausgangpunkt einer Risikobewertung von atmosphärischen Folgeprozessen sowie potentiell negativen Auswirkungen auf die menschliche Gesundheit dar. rn

Oral health risks of tobacco use and effects of cessation

The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages.

Oral leukoplakia in China: a review

BACKGROUND: Most prevalence studies on oral leukoplakia (OL) in China have been published in the Chinese language. The present review on the literature in Chinese aimed at making the data available to colleagues who are not familiar with the Chinese language. METHODS: The overall rate and 95% confidence interval of OL were calculated using Excel 2003. RESULTS: Overall prevalence of OL was 9.18% (95%CI = 9.06-9.30%). Gender ratio of prevalence was 8.03:1 (males/females). Prevalence was high in age groups over 40 years with the highest in the group aged 60-69 years (21.04%, 95%CI = 19.95-22.13%). The buccal mucosa was most commonly affected (47.08%, 95%CI = 46.52-47.64%), followed by lip (39.09%), palate (9.85%), gingiva (1.80%), and tongue (1.46%). The prevalence in smokers was 23.43% and in non-smokers 1.93%. Among three variants of smoking, the traditional Hanyan pipe smoking carried the highest risk for the development of OL followed by cigarette and Shuiyan water pipe smoking. The rate of alcohol drinkers with OL was 54.50% and 22.21% in individuals without OL. No case of oral cancer was found in six surveys. CONCLUSIONS: The present data on the prevalence of OL in China are comparable to those in other parts of the world. Some traditional smoking habits, however, are particular to certain regions of China.

Assessment of smoking behaviour in the dental setting. A study comparing self-reported questionnaire data and exhaled carbon monoxide levels

The present study validated the accuracy of data from a self-reported questionnaire on smoking behaviour with the use of exhaled carbon monoxide (CO) level measurements in two groups of patients. Group 1 included patients referred to an oral medicine unit, whereas group 2 was recruited from the daily outpatient service. All patients filled in a standardized questionnaire regarding their current and former smoking habits. Additionally, exhaled CO levels were measured using a monitor. A total of 121 patients were included in group 1, and 116 patients were included in group 2. The mean value of exhaled CO was 7.6 ppm in the first group and 9.2 ppm in the second group. The mean CO values did not statistically significantly differ between the two groups. The two exhaled CO level measurements taken for each patient exhibited very good correlation (Spearman's coefficient of 0.9857). Smokers had a mean difference of exhaled CO values of 13.95 ppm (p < 0.001) compared to non-smokers adjusted for the first or second group. The consumption of one additional pack year resulted in an increase in CO values of 0.16 ppm (p = 0.003). The consumption of one additional cigarette per day elevated the CO measurements by 0.88 ppm (p < 0.001). Based on these results, the correlations between the self-reported smoking habits and exhaled CO values are robust and highly reproducible. CO monitors may offer a non-invasive method to objectively assess current smoking behaviour and to monitor tobacco use cessation attempts in the dental setting.

Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population

OBJECTIVE: The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs). METHOD: Thorough physical investigations, biological measures and standardized interview techniques were used to assess 3716 subjects of an urban area, aged 35-66 years. RESULTS: Atypical depression was associated with increased prevalence of overweight, diabetes and the metabolic syndrome (OR = 1.5, 95% C.I. 1.1-2.0; OR = 2.0, 95% C.I. 1.1-3.5, OR = 1.6, 95% C.I. 1.0-2.4 respectively), whereas decreased prevalence of overweight was found in melancholic (OR = 0.7, 95% C.I. 0.6-0.9) and unspecified depression (OR = 0.8, 95% C.I. 0.7-1.0). Alcohol abuse was associated with diabetes (OR = 1.8, 95% C.I. 1.1-2.9) and dyslipidemia (OR = 1.3, 95% C.I. 1.0-1.8), alcohol dependence with dyslipidemia only (OR = 1.4, 95% C.I. 1.0-2.0). Almost all mental disorders were associated with a lifetime history of regular cigarette smoking, and atypical depression, alcohol misuse and drug dependence were associated with inactivity. CONCLUSION: To conclude results emphasize the need to subtype depression and to pay particular attention to the atypical subtype. Comorbid alcohol misuse may further increase the cardiovascular risk. Efforts to diminish smoking in subjects with mental disorders could be crucial measures to reduce their high incidence of cardiovascular disease.

Mouse lung CYP1A1 catalyzes the metabolic activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

PhIP carcinogenesis is initiated by N(2)-hydroxylation, mediated by several cytochromes P450, including CYP1A1. However, the role of CYP1A1 in PhIP metabolic activation in vivo is unclear. In this study, Cyp1a1-null and wild-type (WT) mice were used to investigate the potential role of CYP1A1 in PhIP metabolic activation in vivo. PhIP N(2)-hydroxylation was actively catalyzed by lung homogenates of WT mice, at a rate of 14.9 +/- 5.0 pmol/min/g tissue, but < 1 pmol/min/g tissue in stomach and small intestine, and almost undetectable in mammary gland and colon. PhIP N(2)-hydroxylation catalyzed by lung homogenates of Cyp1a1-null mice was approximately 10-fold lower than that of WT mice. In contrast, PhIP N(2)-hydroxylation activity in lung homogenates of Cyp1a2-null versus WT mice was not decreased. Pretreatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased lung Cyp1a1 mRNA and lung homogenate PhIP N(2)-hydroxylase activity approximately 50-fold in WT mice, where the activity was substantially inhibited (70%) by monoclonal antibodies against CYP1A1. In vivo, 30 min after oral treatment with PhIP, PhIP levels in lung were similar to those in liver. After a single dose of 0.1 mg/kg [(14)C]PhIP, lung PhIP-DNA adduct levels in Cyp1a1-null mice, but not in Cyp1a2-null mice, were significantly lower (P=0.0028) than in WT mice. These results reveal that mouse lung has basal and inducible PhIP N(2)-hydroxylase activity predominantly catalyzed by CYP1A1. Because of the high inducibility of human CYP1A1, especially in cigarette smokers, the role of lung CYP1A1 in PhIP carcinogenesis should be considered.

Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty

OBJECTIVES: Aim of this study is to correlate distribution pattern of lower limb atherosclerosis with cardiovascular risk factor profile of patients with peripheral arterial occlusive disease (PAD). PATIENTS AND METHODS: Analysis is based on a consecutive series of 2659 patients (1583 men, 1076 women, 70+/-11 years) with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower extremity arteries. Pattern of atherosclerosis was grouped into iliac (n=1166), femoropopliteal (n=2151) and infrageniculate (n=888) disease defined according to target lesions treated. A multivariable multinomial logistic regression analysis was performed to assess relation with age, gender and classical cardiovascular risk factors (diabetes mellitus, arterial hypertension, hypercholesterolemia, cigarette smoking) using femoropopliteal disease as reference. RESULTS: Iliac disease was associated with younger age (RRR 0.95 per year of age, 95%-CI 0.94-0.96, p<0.001), male gender (RRR 1.32, 95%-CI 1.09-1.59, p=0.004) and cigarette smoking (RRR 2.02, 95%-CI 1.68-2.42, p<0.001). Infrageniculate disease was associated with higher age (RRR 1.02, 95%-CI 1.01-1.02, p<0.001), male gender (RRR 1.23, 95%-CI 1.06-1.41, p=0.005) and diabetes mellitus (RRR 1.68, 95%-CI 1.47-1.92, p<0.001). Hypercholesterolemia was less prevalent in patients with lesions below the knee (RRR 0.82, 95%-CI 0.71-0.94, p=0.006), whereas no distinct pattern was apparent related to arterial hypertension. CONCLUSION: Clinical phenotype of peripheral atherosclerosis varies with prevalence of cardiovascular risk factors suggesting differences in mechanisms involved in iliac as compared with infrageniculate lesions. Identification of molecular mechanism might have influence on future therapeutic strategies in PAD patients.

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.

Application of headspace solid phase microextraction to qualitative and quantitative analysis of tobacco additives in cigarettes

Cigarettes may contain up to 10% by weight additives which are intended to make them more attractive. A fast and rugged method for a cigarette-screening for additives with medium volatility was developed using automatic headspace solid phase microextraction (HS-SPME) with a 65 microm carbowax-divinylbenzene fiber and gas chromatography-mass spectrometry (GC-MS) with standard electron impact ionisation. In three runs, each cigarette sample was extracted in closed headspace vials using basic, acidic and neutral medium containing 0.5 g NaCl or Na2SO4. Furthermore, the method was optimized for quantitative determination of 17 frequently occurring additives. The practical applicability of the method was demonstrated for cigarettes from 32 brands.

Female patients with atherosclerotic lesions of the lower limbs. Not all are alike

BACKGROUND: Data on female patients with atherosclerotic peripheral arterial disease (PAD) are scarce, and limited primarily to the elderly population with multilevel disease. In this longitudinal observational study we compare female patients below 60 years of age with isolated lesions at the aortic bifurcation or focal superficial femoral artery disease. PATIENTS AND METHODS: Analysis is based on consecutive series of 43 female patients with PAD limited to the aortoiliac bifurcation (n = 28, group I) or an isolated femoral segment at the adductor channel (n = 15, group II) seen in a tertiary referral center between 1998 and 2000. The first assessment provided baseline data, with follow up data obtained at this study. Traditional risk factors, carotid artery disease and clinical outcome (mortality, cardiovascular events, vascular re-intervention rate, PAD progression) were evaluated over an interval of 5 (2 to 8) years. RESULTS: Female patients with aortic disease [group I] were younger (51.8 +/- 7.7 vs. 56.7 +/- 7.6 years in group II; p = 0.048), presented a more masculine phenotype, and smoked significantly more often (82% vs. 40%; p = 0.007). Arterial hypertension and diabetes mellitus were more common in group II, though it missed statistical significance (p = 0.068 and p = 0.085). Cardiovascular and limb outcome were comparable in both groups of female patients, while carotid artery disease was more severe in group I (i.e., carotid plaques in 71 vs. 53%). CONCLUSION: Our data support previous findings that cigarette smoking is a stronger risk factor for aortic disease as compared to femoral disease in younger female patients, with the strongest effect of smoking on a localized region of the aortic bifurcation.

Pain and swelling after periapical surgery related to oral hygiene and smoking

OBJECTIVES: To evaluate pain and swelling during the first week after periapical surgery and its relation to patient age, gender, oral hygiene, and smoking. STUDY DESIGN: One hundred two patients (31 men and 71 women) with a mean age of 40.2 years underwent periapical surgery. Age, gender, and oral hygiene and cigarette smoking before and during the postoperative course were noted. Pain and swelling scores were recorded on a descriptive 4-point scale at 2, 6, and 12 hours after surgery, and each day thereafter for 1 week. The data were statistically evaluated for significant differences. RESULTS: The highest intensity of pain occurred during the first 48 hours, and swelling peaked on the second postoperative day. Patient age and gender had no significant effect on postoperative symptoms (P > .05). Patients with poor oral hygiene before surgery presented greater pain and swelling during the first postsurgical hours, and smokers before surgery also suffered more pain. The number of cigarettes smoked in the postoperative period and oral hygiene after surgery had no effect on pain or inflammation (P > .05). CONCLUSIONS: Periapical surgery caused little pain and moderate swelling during the first 2 days after the intervention; these findings were more distinct in patients with poor oral hygiene before surgery and in smokers.