Biomarkers of exposure and potential harm in adult smokers of 3–7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers

Abstract

The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0–6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F_2α (8-epi-PGF_2α) and 11-dehydro-thromboxane B₂ (11-dehydro-TxB₂) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus??1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl^?1 (p=0.05), fibrinogen 292 versus 248 mg dl^?1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl^?1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl^?1 (p=0.18), urine 8-epi-PGF_2α 1935 versus 1034 pg mg^?1 creatinine (p<0.001) and urine 11-dehydro-TxB₂ 973 versus 710 pg mg^?1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.     

Effects of smoking,schizotypy, and eyes open/closed conditions on the γ1 rhythm phase synchrony of the electroencephalogram

This study aims at discrimination between various subject conditions and states on the basis of their electroencephalogram (EEG). For the purpose of such discrimination, phase synchrony (PS) coefficients were evaluated for two groups of participants. Statistical tests – such as two-factor ANOVA and Kruskal–Wallis – were used to select sets of EEG electrodes producing statistically different PS coefficients between two groups. The coefficients selected were used by Euclidean, weighted Euclidean, and Mahalanobis distance-based classifiers, as well as by the classifier using a quadratic discriminant function, to test their suitability for reliable discrimination. The method above has been tested on the EEG of smokers and non-smokers, of high and low schizotypy individuals, and for the experimental conditions of eyes open and eyes closed.We have observed that the average γ₁ rhythm PS is higher for high schizotypy non-smokers than for high schizotypy smokers and also higher for high schizotypy non-smokers than for low schizotypy non-smokers. Statistical tests showed that the differences between high schizotypy smokers and high schizotypy non-smokers are significant – at the 99% significance level – for a number of electrode pairs. The differences between the average γ₁ rhythm PS of high schizotypy non-smokers and all other participants are also significant for a number of electrode pairs. On the other hand, the differences between the average phase synchrony of high schizotypy smokers and low schizotypy individuals do not exceed within-group variations. These observations may support the hypothesis of nicotine self-medication in schizophrenia patients.For the eyes closed condition, γ₁ rhythm PS was also observed to be higher than for the eyes open condition. The Euclidean distance-based classifier showed, on average, better than 80% correct classification between the eyes open and eyes closed subject conditions while using a subset of the available electrode pairs (i.e., electrode masking). This discrimination could be useful, for instance, for automated vigilance monitoring.     

High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction

Abstract

Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H₂O₂ to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN^?) ions, respectively. SCN^? is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN^? levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN^? levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN^? levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN^? results in increased survival, compared to below-median SCN^?. Cox proportional hazard analysis showed a significant decrease in mortality for each 1 μM increase in SCN^? (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN^? have better long-term survival, and that elevated plasma levels of SCN^? might be protective in at least some populations.     

Products of 5-lipoxygenase and myeloperoxidase activities are increased in young male cigarette smokers

Abstract

The significance of 5-lipoxygenase and myeloperoxidase activities has not been extensively studied among young male smokers. Leukotriene B₄, 20-hydroxy-leukotriene B₄, 20-carboxy-leukotriene B₄ and 3-chlorotyrosine were measured in plasma and urinary samples of young male smokers at 8 hours following cigarette abstinence and an hour after cigarette smoking. Leukotriene B₄ and 3-chlorotyrosine were determined in neutrophils isolated from these individuals. The levels of these markers were compared with those of age-matched controls. In vitro studies were performed to evaluate the production of leukotriene B₄ and 3-chlorotyrosine from human neutrophils following exposure to nicotine and cotinine. Thirty male smokers (mean age, 27.4 years) and 28 male non-smokers (mean age, 28.7 years) were studied. Plasma levels of leukotriene B₄, 20-carboxy-leukotriene B₄ and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B₄ and 20-carboxy-leukotriene B₄ levels increased further an hour after cigarette smoking. Peripheral neutrophils isolated from smokers showed greater expressions of myeloperoxidase and 5-lipoxygenase activities compared with non-smokers, while plasma leukotriene B₄ and 3-chlorotyrosine were correlated significantly with high-sensitivity C-reactive protein and plasma nicotine concentrations. Exposure of human neutrophils to nicotine and cotinine resulted in a higher production of leukotriene B₄ and 3-chlorotyrosine. To conclude, leukotriene B₄ and 3-chlorotyrosine levels are increased in young male cigarette smokers. These results suggest that cigarette smoking aggravates neutrophil-mediated inflammation by modulating the activities of myeloperoxidase and 5-lipoxygenase pathways.     

Association between circulating microRNA-126 expression level and tumour necrosis factor alpha in healthy smokers

Introduction: Smoking contributes to the death of a million people worldwide each year. Smokers experience an alteration in tumour necrosis factor-alpha (TNF-α), and the risk of expected lung cancer. The study aimed at investigating the expression levels of mir-126 and mir-124, as well as TNF-α as possible biomarkers of expected smoking-related diseases.

Methods: Twenty-five male smokers’ age and sex-matched with 25 non-smokers were recruited for the present study. Plasma expression levels of mir-126 and mir-124 were evaluated using quantitative real-time PCR. Lipid profile, TNF-α, interleukin-6 and C-reactive protein were assessed in plasma of each participant.

Results: Plasma miR-126 was statistically down-regulated in smokers relative to non-smokers; however, mir-124 did not show any significant changes between groups. Among the measured parameters, mir-126 and tumour necrosis factor alpha (TNF-α) displayed a good discrimination and sensitivity between smokers and non-smokers (AUC = 0.809 (95% CI: 0.668–0.95; p?<?0.001) and 0.742(95% CI: 0.584–0.9; p?<?0.01), respectively. Also, the combined evaluation of miR-126 and TNF-α levels showed high discrimination (AUC= 0.889 (95% CI: 0.779–1.00; p?<?0.0001), sensitivity = 85%, and specificity = 80% in the diagnosis of smokers with non-smokers.

Conclusions: MiR-126 and TNF-α are potential biomarkers of smoking-related diseases and are important in assessing the expected tobacco-related harm.     

Smoking Is Associated with More Abdominal Fat in Morbidly Obese Patients

IntroductionWhile the association between cigarette smoking and abdominal fat has been well studied in normal and overweight patients, data regarding the influence of tobacco use in patients with morbid obesity remain scarce. The aim of this study is to evaluate body fat distribution in morbidly obese smokers.MethodsWe employed a cross-sectional study and grouped severely obese patients (body mass index [BMI] >40 kg/m² or >35 kg/m² with comorbidities) according to their smoking habits (smokers or non-smokers). We next compared the anthropometrical measurements and body composition data (measured by electric bioimpedance) of both groups. We analyzed the effect of smoking on body composition variables using univariate and multiple linear regression (MLR); differences are presented as regression coefficients (b) and their respective 95% confidence intervals.ResultsWe included 536 morbidly obese individuals, 453 (84.5%) non-smokers and 83 (15.5%) smokers. Male smokers had a higher BMI (b=3.28 kg/m², p=0.036), larger waist circumference (b=6.07 cm, p=0.041) and higher percentage of body fat (b=2.33%, p=0.050) than non-smokers. These differences remained significant even after controlling for confounding factors. For females, the only significant finding in MLR was a greater muscle mass among smokers (b=1.34kg, p=0.028). No associations were found between tobacco load measured in pack-years and anthropometric measures or body composition.DiscussionPositive associations between smoking and BMI, and waist circumference and percentage of body fat, were found among male morbidly obese patients, but not among females. To the best of our knowledge, this study is the first investigation of these aspects in morbidly obese subjects. We speculate that our findings may indicate that the coexistence of morbid obesity and smoking helps to explain the more serious medical conditions, particularly cardiovascular diseases and neoplasms, seen in these patients.     

Smoking-related DNA adducts in anal epithelium

Several studies have identified tobacco smoking as a risk factor for anal cancer in both women and men. Samples of anal epithelium from haemorrhoidectomy specimens from current smokers (n=20) and age-matched life-long non-smokers (n=16) were analysed for DNA adducts by the nuclease P₁ digestion enhancement procedure of ³²P-postlabelling analysis. The study included 14 men and 22 women. Both qualitative and quantitative differences in the adduct profiles were observed between the smokers and non-smokers. The mean adduct level was significantly higher in the smokers than in the non-smokers (1.88±0.71 (S.D.) versus 1.36±0.60 adducts per 10⁸ nucleotides, P=0.02, two-tailed unpaired t-test with Welch’s correction); furthermore, the adduct pattern seen in two-dimensional chromatograms revealed the smoking-related diagonal radioactive zone in 17/20 smokers, but not in any of the non-smokers (P<0.00001, Fisher’s exact test). These results indicate that components of tobacco smoke inflict genotoxic damage in the anal epithelium of smokers and provide a plausible mechanism for a causal association between smoking and anal cancer.     

Comparison of temporal changes in established cardiovascular biomarkers after acute coronary syndrome between Caucasian and Chinese patients with diabetes mellitus

Abstract

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS).

Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30?days to 1?year after the index ACS.

Results: In the >30?day post ACS period, mean serum levels of LDL (2.16 vs. 1.47?mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11?mmol/L; p-value <0.001), TnT (11.0 vs. 7.76?ng/L; p-value 0.010) and CRP (2.0 vs. 0.78?mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar.

Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.     

Revised and extended serum cotinine cut-offs to classify smokers and non-smokers

Purpose: To revise and extend the previously published serum cotinine cut offs to classify smokers and non-smokers for US adolescents and adults.

Materials and methods: Cross-sectional data (N?=?10171) from National Health and Nutrition Examination Survey for 2011–2014 were used to compute serum cotinine cut-offs to classify smokers and non-smokers for US adults aged ≥20?years and 2007–2014 (N?=?4583) data were used to compute serum cotinine cut-offs for US adolescents aged 12–19?years.

Results: Specificities and sensitivities for the cut-offs among adults were ≥95% and ≥75% among adolescents. For adults, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 3.3 for the total population, 4.13 for males, 2.99 for females, 4.03 for non-Hispanic whites, 8.85 for non-Hispanic blacks, 0.377 for Mexican Americans, 1.72 for other Hispanics and 1.41 for non-Hispanic Asians. For adolescents, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 0.765 for the total population, 1.1 for males, 0.408 for females, 1.2 for non-Hispanic whites, 1.98 for non-Hispanic blacks, 0.215 for Mexican Americans and 0.321 for other Hispanics.

Conclusions: Serum cotinine cut-offs to distinguish smokers from non-smokers for US adults and adolescents were developed.     

A cross-sectional analysis of candidate biomarkers of biological effect in smokers,never-smokers and ex-smokers

Abstract

Context: Biomarkers of biological effect (BOBE) have been proposed as potential tools to assess tobacco product use, toxicity and disease risk.

Objective: To determine if candidate BOBE can distinguish between smokers, never-smokers and former smokers.

Methods: Biomarker levels were compared from 143 smokers, 61 never-smokers and 61 ex-smokers.

Results: In total, 27 candidate biomarkers were assessed, 14 were significantly different between smokers and never-smokers (p?<?0.01) and of these 14 biomarkers, 12 were able to distinguish between smokers and former smokers (p?<?0.05), which indicates the potential for reversibility.

Conclusions: A total of 12 of 27 BOBE are potentially useful tools for future product assessment.     

α-Tocopherol supplementation reduces 5-nitro-γ-tocopherol accumulation by decreasing γ-tocopherol in young adult smokers

Abstract

γ-Tocopherol (γ-T) scavenges reactive nitrogen species (RNS) to form 5-NO₂-γ-T (NGT). However, α-T supplementation decreases circulating γ-T, which could limit its RNS scavenging activities. We hypothesized that α-T supplementation would mitigate NGT accumulation by impairing γ-T status. Healthy smokers (21 ± 1 y, n = 11) and non-smokers (21 ± 2 y, n = 10) ingested 75 mg/d each of RRR- and all-rac-α-tocopheryl acetate for 6 d. Plasma α-T, γ-T, γ-carboxyethyl hydroxychromanol (CEHC), NGT, and nitrate/nitrite were measured prior to supplementation (Pre), the morning after 6 consecutive evenings of supplementation (Post 1), and on the mornings of d 6 (Post 6) and d 14 (Post 14) during the post-supplementation period. α-T supplementation increased plasma α-T, and decreased γ-T, in both groups and these returned to Pre concentrations on Post 6 regardless of smoking status. Plasma γ-CEHC increased after the first dose of supplementation in both groups, suggesting that α-T supplementation decreased plasma γ-T in part by increasing its metabolism. Plasma NGT and nitrate/nitrite concentrations at Pre were greater in smokers, indicating greater nitrative stress due to cigarette smoking. Plasma NGT concentration was lowered only in smokers on Post 1 and Post 6 and was restored to Pre levels on Post 14. Plasma nitrate/nitrite tended (P = 0.07) to increase post-supplementation only in smokers, supporting decreases in RNS scavenging by γ-T. Plasma NGT concentration was more strongly correlated (P < 0.05) with γ-T in smokers (R = 0.83) compared with non-smokers (R = 0.50), supporting that α-T-mediated decreases in γ-T reduces NGT formation. These data indicate that α-T supplementation limits γ-T scavenging of RNS in smokers by decreasing γ-T availability.     

Effect of Vegetarianism and Smoking on Vitamin B12, Thiocyanate,and Folate Levels in the Blood of Normal Subjects

Vitamin B₁₂, thiocyanate, and folate levels in the blood were estimated in 69 apparently normal subjects, of whom 26 were non-vegetarian non-smokers, 19 non-vegetarian smokers, 15 vegetarian non-smokers, and nine vegetarian smokers. The serum total (cyanide-extracted) B₁₂ level (value A) ranged from 105 to 728 pg/ml, with a mean of 292 pg/ml. The highest values were found in non-vegetarian non-smokers and the lowest in vegetarian smokers. There was no significant difference in value A between smokers as a group and non-smokers as a group. On the other hand, in vegetarians value A was very significantly lower than in non-vegetarians regardless of their smoking habits.It is suggested that A may represent both the protein-bound and free forms of vitamin B₁₂ in the blood, and B mainly the free B₁₂, which may be the physiologically active form. The plasma thiocyanate level varied from 1·0 to 15 μmol/100 ml, being, as expected, much higher in smokers (mean 8·20 μmol/100 ml) than in non-smokers (mean 2·02 μmol/100 ml). There was a rough correlation between falling B₁₂ levels and rising thiocyanate levels. The serum folate level ranged from 2·75 to 15·75 ng/ml, and was slightly but significantly higher in vegetarians (mean 6·60 ng/ml) than in non-vegetarians (mean 4·79 ng/ml), reflecting the greater content of folate in a vegetarian diet.     

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p?p?p?p?Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.     

Association between Self-Reported Smoking and Hemoglobin A1c in a Korean Population without Diabetes: The 2011–2012 Korean National Health and Nutrition Examination Survey

BackgroundSeveral Western studies have revealed that among non-diabetics, glycosylated hemoglobin A1c (HbA1c) levels are higher in smokers than non-smokers. While studies conducted in Western populations consistently support this association, a recent meta-analysis reported that studies carried out in non-Western populations, including studies of Chinese, Egyptian, and Japanese-Americans, did not detect any significant differences in HbA1c levels between smokers and non-smokers.ObjectivesWe assessed the association between smoking habits and HbA1c levels in the general Korean adult population using data from the Korean National Health and Nutrition Examination Survey (KNHANES) performed in 2011–2012.MethodsA total of 10,241 participants (weighted n=33,946,561 including 16,769,320 men and 17,177,241 women) without diabetes were divided into four categories according to their smoking habits: never smokers (unweighted n/ weighted n= 6,349/19,105,564), ex-smokers (unweighted n/ weighted n= 1,912/6,207,144), current light smokers (<15 cigarettes per day, unweighted n/ weighted n=1,205/5,130,073), and current heavy smokers (≥15 cigarettes per day, unweighted n/ weighted n=775/3,503,781).ResultsIn age- and gender-adjusted comparisons, the HbA1c levels of each group were 5.52 ± 0.01% in non-smokers, 5.49 ± 0.01% in ex-smokers, 5.53 ± 0.01% in light smokers, and 5.61 ± 0.02% in heavy smokers. HbA1c levels were significantly higher in light smokers than in ex-smokers (p = 0.033), and in heavy smokers compared with light smokers (p < 0.001). The significant differences remained after adjusting for age, gender, fasting plasma glucose, heavy alcohol drinking, hematocrit, college graduation, and waist circumference. Linear regression analyses for HbA1c using the above-mentioned variables as covariates revealed that a significant association between current smoking and HbA1c (coefficient 0.021, 95% CI 0.003–0.039, p = 0.019).ConclusionsCurrent smoking was independently associated with higher HbA1c levels in a cigarette exposure-dependent manner in a representative population of Korean non-diabetic adults. In this study, we have observed an association between smoking status and HbA1c levels in non-diabetics drawn from a non-Western population, consistent with previous findings in Western populations.     

Estimation of urinary cotinine cut-off points distinguishing non-smokers,passive and active smokers

Abstract

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 µg l^?1 (differentiation of non-smokers from passive smokers), 170 µg l^?1 (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 µg l^?1 (differentiation of passive smokers from active smokers), and 2100 µg l^?1 (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.     

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction

AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking.BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed.Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis.ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis.ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.     

Chromosomal Aberrations (CA), Sister Chromatid Exchanges (SCE), and High-Frequency Cells (HFC) Frequencies in Peripheral Blood Lymphocytes of Tunisian Gasoline Truck Loaders

Gasoline constitutes a mixture of chemicals that contain well-known genotoxicants. Thus, chronic occupational exposure to gasoline may be considered to possess genotoxic risk. In this study, the frequencies of total chromosomal aberrations (TCA), aberrant cells (Ab.c.), sister chromatid exchanges (SCE), high-frequency cells (HFC), and high-frequency cell individual (HFI) were investigated in peripheral blood lymphocytes from 17 gasoline-exposed workers (10 smokers and 7 non-smokers) and 22 unexposed reference subjects (12 smokers and 10 non-smokers). The exposed subjects were gasoline truck loaders at a gasoline company from Tunis City, north of Tunisia. The results indicate multiple CA, such as dicentrics (DIC), chromatid breaks (SB), and chromosome breaks (DB). A significant difference was observed in TCA and Ab.c. frequencies between exposed and unexposed groups (p < 0.01). A significant difference was found in frequencies of SCE (p < 0.01) and HFI (p < 0.05) between exposed and unexposed groups. SCE and TCA frequencies of smokers were found to be significantly higher than those of non-smokers in both groups. There was an interaction between gasoline exposure and smoking habit for TCA (p = 0.020), but not for SCE. Our findings indicate that gasoline truck loaders were under risk of significant cytogenetic damage that was enhanced by their smoking habit.     

Gas chromatographic method using photoionization detection for the determination of breath pentane

Lipid peroxidation is thought to be an important event in the pathogenesis of atherosclerosis. It has been suggested that pentane, which can be formed during the oxidation of ω-6 fatty acids, is a marker of lipid peroxidation. Previous studies have reported elevated breath pentane and serum markers of lipid peroxidation in smokers. However, chromatographic separation of pentane from isoprene in virtually all of these studies was incomplete and the methods used did not resolve pentane into its isomers, n-pentane and isopentane. Additionally, most current methods are complicated, requiring trapping and concentrating steps to obtain adequate sensitivity prior to hydrocarbon analysis. The purpose of the current study was to develop a gas chromatographic system to analyze breath pentane, that addressses the above technical problems and that would provide a simple in vivo method for measuring lipid. n-Pentane and isopentane standards were easily separated from isoprene with a Al₂O₃/KCl capillary column contained in a portable gas chromatograph equipped with a photoionization detector. The analysis of repeated measures showed a low coefficient of variation for measurements of n-pentane (10%) and isopentane (9%). We measured breath pentane in 27 subjects (15 smokers, 12 non-smokers). There were no significant difference between the baseline and 4 week interval measurements of n-pentane for smokers both before and after cigarette smoking. The within-subject variability data showed that the assay is highly reproducible for both low and high pentane levels in smokers. Smokers were found to have higher levels of both n-pentane and isopentane than non-smokers (P<0.001). In addition, smokers had further significant elevation of pentane levels 10 min after smoking (P<0.001), which returned to baseline by 1 h. These studies demonstrate that measurement of breath pentane, using a gas chromatograph with a photoionization detector, is simple and reproducible. Additionally, these results suggest that pentane elevation associated with smoking is secondary to the oxidant effects of cigarette smoke and an important temporal relationship exists between cigarette smoking and breath sample analysis.     

Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases

Introduction: Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 – an indicator of microglial activation ? has recently been identified by proteomic studies as a candidate biomarker for Alzheimer’s disease (AD).

Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia. Moreover, a positive association between CSF YKL-40 and other biomarkers of neurodegeneration – particularly total tau protein ? has been reported during the asymptomatic preclinical stage of AD and other neurodegenerative diseases. Albeit preliminary, current data do not support an association between APOE-ε4 status and CSF YKL-40 concentrations. When interpreting the diagnostic/prognostic significance of CSF YKL-40 concentrations in neurodegenerative diseases, potential confounders – including age, metabolic and cardiovascular risk factors, diagnostic criteria for selecting cases/controls – need to be considered.

Expert opinion/commentary: CSF YKL-40 represents a pathophysiological biomarker reflecting immune/inflammatory mechanisms in neurodegenerative diseases, associated with tau protein pathology. Besides being associated with tau pathology, CSF YKL-40 adds to the growing array of biomarkers reflecting distinct molecular brain mechanisms potentially useful for stratifying individuals for biomarker-guided, targeted anti-inflammatory therapies emerging from precision medicine.     

Biomarkers of exposure and potential harm in adult smokers of 3-7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers.

The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0-6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TxB2) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus < 0.034 nmol mg-1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl-1 (p=0.05), fibrinogen 292 versus 248 mg dl-1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl-1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl-1 (p=0.18), urine 8-epi-PGF2alpha 1935 versus 1034 pg mg-1 creatinine (p<0.001) and urine 11-dehydro-TxB2 973 versus 710 pg mg-1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.