Changes in biomarkers of endothelial function, oxidative stress, inflammation and lipids after smoking cessation: A cohort study.

BACKGROUND: Tobacco use is known to be involved in the development of cardiovascular diseases, which leads to premature mortality. Endothelial dysfunction, the first step in this process, was shown induced by smoking. It is reported that quitting smoking could reduce the risk of diseases, but the implied mechanisms are still unclear. This study aimed to evaluate the biological markers of endothelial function in smokers when actively smoking and after cessation. METHODS: Quantification of several biomarkers reflecting inflammation, endothelium activation, oxidative stress, and lipids was performed in 65 smokers when actively smoking and after cessation (median abstinence duration of 70 days). RESULTS: A possible decrease of inflammation was observed through the concentration reduction of a proinflammatory cytokine (interleukine-6) on quitting. A decrease of endothelium activation was visible by the reduced level of the soluble intercellular adhesion molecule. Two antioxidants, uric acid and vitamin C, were found at higher concentration than before the cessation, potentially reflecting the decrease of oxidative stress on quitting. Lipid profile was improved post-quit since HDL level was increased and LDL level was decreased. All these effects were visible at short term with abstinence duration less than 70 days. No sex-specific difference was observed and no additional changes were observed for longer abstinence duration. CONCLUSION: These observations suggest that some adverse effects of smoking on endothelial function could be reversible on quitting smoking. It could encourage smokers to enter a cessation program to reduce the risk for cardiovascular diseases development.

Effect of the Nicotine Replacement Therapy on Biomarkers of Inflammation, Endothelial Dysfunction, Oxidative Stress, and Lipids in Smokers Who Quit Smoking.

INTRODUCTION: Our previous study showed major changes in biomarkers on quitting compared to the smoking state. They reflected a decrease in inflammation, endothelial activation, and oxidative stress, as well as an improved lipid profile. Nicotine replacement therapy (NRT) is effective to increase the rate of successful quitting, but healthcare professionals may have concerns to prescribe this first-line smoking cessation treatment because its effect on inflammation and related processes is controversial. AIMS AND METHODS: The present study assessed the influence of NRT on biomarkers of inflammation, endothelial function, oxidative stress, and lipids, in people who quit smoking. Sixty-five subjects who daily smoke cigarettes were recruited and followed on quitting. Thirty-five quit using NRT and thirty quit without NRT. Biomarkers of inflammation, endothelial function, oxidative stress, and lipids were quantified at baseline when actively smoking and after cessation in the presence of NRT or not. RESULTS: Changes in biomarkers on quitting did not differ according to the treatment used. No difference was found when comparing participants who were exposed to NRT and those who were not. CONCLUSIONS: These results may indicate that NRT has no effect on inflammation, endothelial function, oxidative stress, and lipids, when used as a medication aid for quitting smoking. IMPLICATIONS: This study provides new evidence to support the safety profile of NRT products regarding the biomarkers of endothelial function, oxidative stress, inflammation, and lipids.

Long-term physicochemical stability of 5-fluorouracil at selected standardised rounded doses in polyolefin bags.

BACKGROUND: Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. AIM OF THE STUDY: To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. MATERIALS AND METHODS: Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. RESULTS: No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. CONCLUSION: Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation.

Novel proposed cutoff values for anatabine and anabasine in differentiating smokers from non-smokers.

OBJECTIVES: Anatabine and anabasine are two tobacco alkaloids used to differentiate between tobacco users and abstainers, including users of nicotine replacement therapy. Cutoff values (>2 ng/mL for both alkaloids) have not been revised since their implementation in 2002. These values may be too high, leading to increased likelihood of misclassification between smokers and abstainers. This results in major consequences, especially adverse outcomes of transplantation when smokers were incorrectly identified as being abstinent. This study proposes that a lower threshold for anatabine and anabasine will better distinguish tobacco users from non-users and thereby improve patients' care. DESIGN AND METHODS: A new and more sensitive analytical method by liquid chromatography-mass detection was developed to allow the quantification of low concentrations. Anatabine and anabasine were measured in urine samples of 116 self-reported daily smokers and 47 long-term non-smokers (confirmed by the analysis of nicotine and its metabolites). The best compromise between sensitivity and specificity allowed us to determine new cutoff values. RESULTS: The thresholds >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine were associated with a sensitivity of 97% (anatabine) and 89% (anabasine) and a specificity of 98% for both alkaloids. These cutoff values greatly increased the sensitivity given that it dropped to 75% (anatabine) and 47% (anabasine) when using the reference value (>2 ng/mL). CONCLUSIONS: The cutoff values >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine appear to better differentiate tobacco users from abstainers than the current reference threshold (>2 ng/mL for both alkaloids). It may considerably impact patients' care, especially in transplantation settings in which smoking abstinence is essential to avoid adverse outcomes of transplantation.

An ultra-high-performance chromatography method to study the long term stability of gemcitabine in dose banding conditions.

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation.

Long-term physico-chemical stability of 5-fluorouracile at standardised rounded doses (SRD) in MyFuser® portable infusion pump.

Management of chemotherapies is a strategic issue for european healthcare. Dose-banding enables to reduce waiting time of patients in day care units and drug wastage. The aim of this study was to assess the stability of 5-Fluorouracile (5-FU) at standardised rounded doses of 4 and 5 g in MyFuser® portable infusion pump for in-advance preparation. Ten MyFuser® (4 and 5 gr 5-FU added to NaCl 0.9%) were prepared under aseptic conditions and stored at room temperature (23 ± 2 °C) for 28 days then at 30 °C for three days. Physical stability tests were periodically performed: visual and microscopic inspection, pH measurements and optical densities. The concentration of solutions was measured by High Performance Liquid Chromatography/UV detector. Results confirm the stability of 5-FU at selected SRD of 4 g and 5 g with NaCl 0.9% in MyFuser® for at least 28 days at room temperature and three days at 30 °C, allowing in-advance preparation.