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1.
Am J Physiol Heart Circ Physiol ; 320(4): H1510-H1525, 2021 04 01.
Article En | MEDLINE | ID: mdl-33543686

After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%), endothelium-dependent relaxation (-61.8 ± 4.2%), decreased WBC (-47 ± 7%), and, increased RBC (+6 ± 1%) and hemoglobin (+4 ± 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.NEW & NOTEWORTHY Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG-derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a "universal flaw" of E-cigs that use PG-VG.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/e-cigarettes-aldehydes-and-endothelial-dysfunction/.


Acetaldehyde/toxicity , Aorta, Thoracic/drug effects , E-Cigarette Vapor/toxicity , Endothelium, Vascular/drug effects , Formaldehyde/toxicity , Glycerol/toxicity , Lung/drug effects , Propylene Glycol/toxicity , Solvents/toxicity , Acetaldehyde/urine , Aerosols , Animals , Aorta, Thoracic/metabolism , Aorta, Thoracic/physiopathology , Biomarkers/blood , Biomarkers/urine , E-Cigarette Vapor/urine , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Formaldehyde/urine , Inhalation Exposure , Lung/metabolism , Lung/physiopathology , Male , Mice, Inbred C57BL , Respiration/drug effects , Risk Assessment , Vasoconstriction/drug effects , Vasodilation/drug effects
2.
Ann Clin Biochem ; 56(2): 210-218, 2019 03.
Article En | MEDLINE | ID: mdl-30373389

BACKGROUND: Morning urine formaldehyde concentrations could predict the severe degree of dementia in patients with post-stroke dementia and Alzheimer's disease. However, the routinely available technique of high-performance liquid chromatography (HPLC) for detecting urine formaldehyde requires expensive and sophisticated equipment. METHODS: We established a fluorescence spectrophotometric method by using a formaldehyde-specific fluorescent probe-NaFA (λex/em = 430/543 nm). As a standard reference method, the same batch of urine samples was analysed by HPLC with a fluorescence detector (λex/em = 346/422 nm). Then we compared the limits of detection and the limits of quantization detected by these two methods and addressed the relationship between urine formaldehyde and human cognitive ability. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating and Activities of Daily Living scale were used to evaluate cognition function in 30 Alzheimer's disease patients and 52 healthy age-matched controls. RESULTS: Limits of detection and limits of quantization (1.27 and 2.48 µM) of the NaFA probe method were more accurate than Fluo-HPLC (1.52 and 2.91 µM). There was no difference in the detected formaldehyde values within day and day-to-day. Notably, only 3/82 urine formaldehyde concentrations detected by NaFA probe were below zero, while 12/82 of the values analysed by Fluo-HPLC were abnormal. More importantly, there were negatively correlated between urine formaldehyde concentrations detected by NaFA probe and MMSE scores, but positively correlated with Clinical Dementia Rating scores in Alzheimer's disease patients. CONCLUSIONS: This detecting urine formaldehyde method by NaFA probe was more rapid, sensitive and accurate than Fluo-HPLC.


Alzheimer Disease/urine , Formaldehyde/urine , Limit of Detection , Spectrometry, Fluorescence/methods , Urinalysis/methods , Activities of Daily Living , Aged , Alzheimer Disease/physiopathology , Case-Control Studies , Cognition , Female , Humans , Male , Time Factors
3.
Iran J Kidney Dis ; 12(5): 253-260, 2018 10.
Article En | MEDLINE | ID: mdl-30367015

INTRODUCTION: Nowadays, creatine is one of the most common oral supplements used by professional athletes for boosting their strength and muscle mass. In this review, we collect available experimental and clinical data about renal safety of both short-term and long-term use of creatine. MATERIALS AND METHODS: Scientific literature was critically searched by keywords "creatine," "renal insufficiency," and "renal dysfunction" and their synonyms in medical databases (Scopus, MEDLINE, EMBase, and ISI Web of Knowledge). Overall, 19 relevant clinical and experimental articles were selected for this review. RESULTS: Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function. CONCLUSIONS: Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.


Creatine/administration & dosage , Creatine/adverse effects , Dietary Supplements/adverse effects , Kidney/drug effects , Renal Insufficiency/chemically induced , Athletes , Formaldehyde/urine , Glomerular Filtration Rate/drug effects , Humans , Methylamines/urine , Randomized Controlled Trials as Topic , Weight Lifting
4.
Talanta ; 188: 630-636, 2018 Oct 01.
Article En | MEDLINE | ID: mdl-30029423

Most of efforts have been made to prepare high performance surface-enhanced Raman scattering (SERS) substrate for amplifying Raman signals. It still remains a grand challenging task in building a simple, conventional and low-cost SERS substrate with highly dense hotspots for improved sensitivity of the target analytes. Here, we report a very dexterous strategy to fabricate a distinctive SERS substrate with high density hotspots, using common adsorbent activated carbon (AC) as template to assemble silver nanoparticles (Ag NPs). It can be estimated that the enhancement effect of Ag NPs/AC composite is about 6.5-fold that of bare Ag NPs. Different from the resonant dyes, however, formaldehyde (FA) is a Raman-inactive molecule even though enhanced. Considering that, a novel method for quantitative analysis of FA using the Ag NPs/AC composite as SERS sensor has been developed, based on the catalytic effect of trace FA on the oxidation of malachite green (MG) through bromate under acidic condition. The change of MG from reduced form into oxidized leucomalachite green (LMG) results in the quench of Raman signals of MG, responding to 0.07 ppb FA that is about 2 orders of magnitude lower than the limit defined by the Nash's method as a standard procedure recommended in Europe, Japan and China. Moreover, SERS examinations of endogenous FA in human urine signify that the proposed method has high selectivity, reliability and accuracy. Thus, as-fabricated Ag NPs/AC composite is adequate as inexpensive and versatile SERS sensor utilized in the quantification of trace targets in various complicated matrices.


Carbon/chemistry , Formaldehyde/urine , Metal Nanoparticles/chemistry , Silver/chemistry , Spectrum Analysis, Raman/methods , Adsorption , Alzheimer Disease/diagnosis , Bromates/chemistry , Catalysis , Female , Humans , Limit of Detection , Male , Nanocomposites/chemistry , Oxidation-Reduction , Rosaniline Dyes/chemistry
5.
FASEB J ; 32(7): 3669-3679, 2018 07.
Article En | MEDLINE | ID: mdl-29401634

Patients with type 2 diabetes mellitus (T2DM) often develop cognitive impairments and have an increased risk of developing Alzheimer's disease. Hyperglycemia is a major characteristic of T2DM, but how elevated glucose levels lead to cognitive decline remains elusive. Here, we report that patients with T2DM and mutations in the formaldehyde (FA)-degrading enzyme aldehyde dehydrogenase 2 ( ALDH2) gene had higher levels of FA and more severe dementia. Injection of FA induced hyperglycemia and cognitive deficits in rats. Ablation of gene expression of ALDH2, the main enzyme to oxidize FA, resulted in abnormally high levels of hippocampal FA, leading to hyperglycemia and cognitive impairments as well as potentiating streptozotocin-induced diabetes development in ALDH2 knockout mice. We found that FA interacts with insulin to form FA-insulin adducts, and these FA-insulin adducts caused insulin deficiency, contributing to memory decline in diabetic rodent models. Reduction of FA by transgenic overexpression of human ALDH2 attenuates hyperglycemia and alleviates cognitive deficits in diabetic mouse models. These findings suggest that excess FA plays a critical role in mediating diabetes-related dementia. Targeting FA and its metabolizing enzyme ALDH2 may be a valid approach for preventing and treating dementia in diabetes mellitus.-Tan, T., Zhang, Y., Luo, W., Lv, J., Han, C., Hamlin, J. N. R., Luo, H., Li, H., Wan, Y., Yang, X., Song, W., Tong, Z. Formaldehyde induces diabetes-associated cognitive impairments.


Aldehyde Dehydrogenase, Mitochondrial/genetics , Cognitive Dysfunction/etiology , Diabetes Mellitus, Type 2/complications , Formaldehyde/toxicity , Aged , Aldehyde Dehydrogenase, Mitochondrial/metabolism , Animals , Female , Formaldehyde/blood , Formaldehyde/urine , Humans , Insulin/metabolism , Male , Mice , Mice, Inbred C57BL , Mutation , Rats , Rats, Sprague-Dawley
6.
Anal Chim Acta ; 970: 23-29, 2017 Jun 01.
Article En | MEDLINE | ID: mdl-28433055

Measurement of ultra-low (e.g., parts-per-billion) levels of small-molecule markers in body fluids (e.g., serum, urine, saliva) involves a considerable challenge in view of designing assay strategies with sensitivity and selectivity. Herein we report for the first time an amperometric nano-bioelectrode design that uniquely combines 1-pyrenebutyric acid units pi-pi stacked with carboxylated multiwalled carbon nanotubes on the surface of gold screen printed electrodes for covalent attachment of NAD+ dependent formaldehyde dehydrogenase (FDH). The designed enzyme bioelectrode offered 6 ppb formaldehyde detection in 10-times diluted urine with a wide dynamic range of 10 ppb to 10 ppm. Fourier transform infrared, Raman, and electrochemical impedance spectroscopic characterizations confirmed the successful design of the FDH bioelectrode. Flow injection analysis provided lower detection limit and greater affinity for formaldehyde (apparent KM 9.6 ± 1.2 ppm) when compared with stirred solution method (apparent KM 19.9 ± 4.6 ppm). Selectivity assays revealed that the bioelectrode was selective toward formaldehyde with a moderate cross-reactivity for acetaldehyde (∼25%) and negligible cross-reactivity toward propanaldehyde, acetone, methanol, and ethanol. Formaldehyde is an indoor pollutant, and studies have indicated neurotoxic characteristics and systemic toxic effects of this compound upon chronic and high doses of exposure. Moreover, reported chromatography and mass spectrometry methods identified elevated urine formaldehyde levels in patients with bladder cancer, dementia, and early stages of cognitive impairments compared to healthy people. Results demonstrate that pyrenyl carbon nanostructures-based FDH bioelectrode design represents novelty and simplicity for enzyme-selective electrochemical quantitation of small 30 Da formaldehyde. Broader applicability of the presented approach for other small-molecule markers is feasible that requires only the design of appropriate marker-specific enzyme systems or receptor molecules.


Formaldehyde/urine , Nanotubes, Carbon , Acetaldehyde , Aldehyde Oxidoreductases/chemistry , Electrodes , Enzymes, Immobilized/chemistry , Humans
7.
J Alzheimers Dis ; 55(3): 1031-1038, 2017.
Article En | MEDLINE | ID: mdl-27802225

Although Alzheimer's disease (AD) was first described over 100 years ago, there is still no suitable biomarker for diagnosing AD in easily collectable samples (e.g., blood plasma, saliva, and urine). Here, we investigated the relationship between morning urine formaldehyde concentration and cognitive impairment in patients with post-stroke dementia (PSD) or AD in this cross-sectional survey for 7 years. Cognitive abilities of the study participants (n = 577, four groups: 231 controls, 61 stroke, 65 PSD, and 220 AD) were assessed by Mini-Mental State Examination (MMSE). Morning urine formaldehyde concentrations were measured by high performance liquid chromatography (HPLC). Gender- and age-matched participants were selected from the four groups (n = 42 in each group). Both semicarbazide-sensitive amine oxidase (SSAO, a formaldehyde-generating enzyme) and formaldehyde levels in the blood and urine were analyzed by using an enzyme-linked immunosorbent assay (ELISA) and HPLC, respectively. We found that morning urine formaldehyde levels were inversely correlated with MMSE scores. The threshold value (the best Cut-Off value) of formaldehyde concentration for predicting cognitive impairment was 0.0418 mM in patients with PSD (Sensitivity: 92.3%; Specificity: 77.1%), and 0.0449 mM in patients with AD (Sensitivity: 94.1%; Specificity: 81.8%), respectively. The results of biochemical analysis revealed that the observed increase in urine formaldehyde resulted from an overexpression of SSAO in the blood. The findings suggest that measuring the concentration of formaldehyde in overnight fasting urine could be used as a potentially noninvasive method for evaluating the likelihood of ensuing cognitive impairment or dementia.


Alzheimer Disease/complications , Cognition Disorders/etiology , Cognition Disorders/urine , Dementia/complications , Formaldehyde/urine , Aged , Chromatography, High Pressure Liquid , Cognition Disorders/pathology , Cross-Sectional Studies , Dementia/etiology , Enzyme-Linked Immunosorbent Assay , Female , Hippocampus/metabolism , Humans , Longitudinal Studies , Male , Mental Status and Dementia Tests , Neuropsychological Tests , Predictive Value of Tests , ROC Curve , Stroke/complications
8.
J Sports Med Phys Fitness ; 56(4): 458-64, 2016 Apr.
Article En | MEDLINE | ID: mdl-25286897

BACKGROUND: Formaldehyde is a cytotoxic agent produced from creatine through a metabolic pathway, and in this regard, it has been claimed that creatine supplementation could be cytotoxic. Even though the cytotoxic effects of creatine supplementation have been widely studied, yet little is known about how resistance training can alter these toxic effects. This study aimed to determine the effects of short-term creatine supplementation plus resistance training on the level of urinary formaldehyde and concentrations of serum enzymes in young male wrestlers. METHODS: In a double-blind design twenty-one subjects were randomized into creatine supplementation (Cr), creatine supplementation plus resistance training (Cr + T) and placebo plus resistance training (Pl + T) groups. Participants ingested creatine (0.3 g/kg/day) or placebo for 7 days. The training protocol consisted of 3 sessions in one week, each session including three sets of 6-9 repetitions at 80-85% of one-repetition maximum for whole-body exercise. Urine and blood samples were collected at baseline and at the end of the supplementation. RESULTS: Creatine supplementation significantly increased the excretion rate of urinary formaldehyde in the Cr and Cr + T groups by 63.4% and 30.4%, respectively (P<0.05), indicating that resistance training could partially lower this rate by 17.7%. No significant differences were detected in the levels of serum enzymes across time and groups (P>0.05). CONCLUSIONS: These findings indicate that resistance training may lower the increase of urinary formaldehyde excretion induced by creatine supplementation, suggesting that creatine consumption could be relatively less toxic when combined with resistance training.


Creatine/adverse effects , Dietary Supplements/adverse effects , Formaldehyde/urine , Resistance Training/methods , Wrestling , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Creatine/metabolism , Creatine Kinase/blood , Double-Blind Method , Humans , L-Lactate Dehydrogenase/blood , Male , Random Allocation , Young Adult
9.
Przegl Lek ; 72(3): 140-3, 2015.
Article Pl | MEDLINE | ID: mdl-26731871

Environmental Tobacco Smoke (ETS) is ranked as one of the factors of confirmed carcinogenicity to human. It consists of the mixture of smoke exhaled by the smoker as well as the sidestream smoke and contains many times higher concentrations of some toxic substances in comparison to the amount of toxic compounds inhaled by a smoker. From many years the issue of passive smoking has been the subject of many research and still not all of its aspects of affecting human health have been explored. Apart from the tobacco varieties, also diverse additives added during the process of tobacco manufacturing, including particularly carbohydrates, influence the composition of the environmental tobacco smoke. During smoking they can undergo many complex transformations, as a result of which toxic components of the environmental tobacco smoke are formed, carbonyl compounds in particular, like aldehydes. They are marked by a significant chemical reactivity which enables them to modify amino groups of proteins leading to the changes in their structure, biological functions and often antigenicity. Therefore their influence to the human body is the cause of numerous adverse health effects caused by the increase in free radical processes which can constitute to the source of these compounds. Well known representative of this group of xenobiotics is formaldehyde as a compound that reflects well the environmental exposure to carbonyl compounds. The considerable source of this compound is tobacco smoke. Therefore analysis of formaldehyde in body fluids is a valuable biomonitoring tool of exposure to it. The aim of this study was the evaluation of formaldehyde concentration in urine samples of medicine students exposed to ETS. The study material consisted of 149 urine samples of students from School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia. The concentration of formaldehyde in urine samples was determined by a spectrophotometric method using the Purpald reagent. To verify the collected questionnaire data regarding exposure to constituents of tobacco smoke, the immuno-enzymatic method was used to determine main nicotine metabolites in tested urine samples. This enabled dividing the investigated students' group into active smokers, passively exposed to tobacco smoke and not exposed. Analysis of obtained results showed that mean concentration of formaldehyde in urine of active smokers (68.45 ± 58.67 µmol/l) and passive smokers (79.23 ± 53.64 µmol/l) were significantly higher in comparison to not exposed students (42.99 ± 30.29 µmol/l). Mean concentrations of formaldehyde in urine samples of active and passive smokers are comparable. The results of our study allow to conclude that passive exposure to tobacco smoke is an equivalent source of exposure to active smoking regarding formaldehyde adverse influence to human. Applied method enables to quick evaluation of formaldehyde concentration in biological samples.


Environmental Exposure/analysis , Environmental Monitoring/methods , Formaldehyde/urine , Tobacco Smoke Pollution/analysis , Adult , Female , Humans , Male , Students, Medical/statistics & numerical data , Young Adult
10.
PLoS One ; 9(8): e104069, 2014.
Article En | MEDLINE | ID: mdl-25157974

Formaldehyde (FA) is a well-known irritant, and it is suggested to increase the risk of immune diseases and cancer. The present study aimed to evaluate the distribution of major lymphocyte subsets and cytokine expression profiles in the peripheral blood of FA-exposed workers. A total of 118 FA-exposed workers and 79 controls were enrolled in the study. High performance liquid chromatography, flow cytometry, and cytometric bead array were used to analyze FA in air sample and formic acid in urine, blood lymphocyte subpopulations, and serum cytokines, respectively. The FA-exposed workers were divided into low and high exposure groups according to their exposure levels. The results showed that both the low and high FA-exposed groups had a significant increase of formic acid in urine when compared to the controls. Both the low and high exposure groups had a significant increase in the percentage of B cells (CD19+) compared to the control group (p<0.01). A significant increase in the percentage of the natural killer (NK) cells (CD56+) was observed in the low exposure group compared to the control (p = 0.013). Moreover, the FA-exposed workers in both exposure groups showed a significant higher level of IL-10 but lower level of IL-8 than the control (p<0.01). Subjects in the high exposure group had a higher level of IL-4 but a lower level of IFN-γ than the control (p<0.05). Finally, there is a significant correlation between the levels of IL-10, IL-4, and IL-8 and formic acid (p<0.05). The findings from the present study may explain, at least in part, the association between FA exposure and immune diseases and cancer.


Cytokines/immunology , Formaldehyde/adverse effects , Formaldehyde/toxicity , Lymphocyte Subsets/drug effects , Occupational Exposure/adverse effects , Respiratory Hypersensitivity/immunology , Adult , Cytokines/blood , Female , Formaldehyde/blood , Formaldehyde/immunology , Formaldehyde/urine , Formates/urine , Humans , Lymphocyte Subsets/immunology , Male , Occupational Exposure/analysis , Respiratory Hypersensitivity/blood , Respiratory Hypersensitivity/chemically induced , Respiratory Hypersensitivity/urine
11.
Neurosci Bull ; 30(2): 172-84, 2014 Apr.
Article En | MEDLINE | ID: mdl-24733650

Recent studies have shown that the abnormal accumulation of endogenous formaldehyde could be a critical factor in age-related cognitive decline. The aim of this study was to estimate the correlation between uric formaldehyde and general cognitive abilities in a community-based elderly population, and to measure the extent and direction in which the correlation varied with demographic characteristics. Using a double-blind design, formaldehyde in human urine was analyzed by high-performance liquid chromatography (n = 604), and general cognitive abilities were measured using the Montreal Cognitive Assessment (MoCA). Demographic characteristics, in terms of age, gender, residential region, and education were taken into consideration. We found that uric formaldehyde levels were inversely correlated with the MoCA score, and the concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated and those living in old urban or rural areas. In cytological experiments, the level of cellular formaldehyde released into the medium increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in excess impaired the processes of N2a cells and neurites of primary cultured rat hippocampal cells. However, removal of formaldehyde markedly rescued and regenerated the processes of N2a cells. These results demonstrated a negative correlation between the endogenous formaldehyde and general cognitive abilities. High formaldehyde levels could be a risk factor for cognitive impairment in older adults, and could be developed as a non-invasive marker for detection and monitoring of age-related cognitive impairment.


Cognition , Formaldehyde/urine , Aged , Aged, 80 and over , Animals , Chromatography, High Pressure Liquid , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Rats , Rats, Sprague-Dawley , Sus scrofa
12.
Neurochem Res ; 37(10): 2125-34, 2012 Oct.
Article En | MEDLINE | ID: mdl-22869018

Post-operative cognitive dysfunction (POCD), especially in elderly patients, has been reported in many studies. Although increasing age, duration of anesthesia, postoperative infections, and respiratory complications were regarded as the risk factors for POCD, no extracerebral diagnostic biomarkers have been identified as indicators of POCD. Ninety-five patients, ages 65-80 years, scheduled for major orthopedic or abdominal surgery were enrolled. Twenty-two patients aged between 20 and 40 years undergoing the same procedures served as controls. Subjects received neuropsychological tests one-day prior and one week post procedure. To determine the presence of POCD, the criteria were used as described in most previous studies. Morning urine samples were obtained one day before surgery and on day 1, day 2 and day 7 post operatively. Urine formaldehyde was determined with high-performance liquid chromatography. The urine formaldehyde level of all patients with and without POCD increased on the first 2 days after surgery. But the formaldehyde concentration (on day 7) in patients with POCD was significantly higher than that in patients without POCD (p < 0.01). In the young control group, no patient was diagnosed with POCD. Although the changes in urine formaldehyde of young patients during perioperative period were similar to those in elderly patients without POCD, the formaldehyde concentrations measured at four time points were all significantly lower than those in elderly patients (p < 0.05). Levels of urine formaldehyde were elevated in the perioperative period, with the highest levels at day 7 in patients with POCD. This suggests that the increase on day 7 may provide a new physiologic marker along with neuropsychological assessments to assist in the diagnosis of POCD.


Cognition Disorders/physiopathology , Formaldehyde/urine , Postoperative Complications , Surgical Procedures, Operative , Aged , Aged, 80 and over , Cognition Disorders/urine , Female , Humans , Male
13.
Drug Metab Dispos ; 40(8): 1478-86, 2012 Aug.
Article En | MEDLINE | ID: mdl-22550270

Drug reactivity and bioactivation are of major concern to the development of potential drug candidates in the pharmaceutical industry (Chem Res Toxicol 17:3-16, 2004; Chem Res Toxicol 19:889-893, 2006). Identifying potentially problematic compounds as soon as possible in the discovery process is of great importance, so often early in vitro screening is used to speed up attrition. Identification of reactive moieties is relatively straightforward with appropriate in vitro trapping experiments; however, on occasion unexpected reactive intermediates can be found later during more detailed in vivo studies. Here, we present one such example involving a series of compounds from an early drug discovery campaign. These compounds were found to react with endogenous formaldehyde from a rat in vivo study, resulting in the formation of novel +13-Da bridged homopiperazine products (equivalent to the addition of one carbon and one hydrogen atom), which were detected in urine and blood. The identification of these +13-Da products and their origin and mechanism of formation are described in detail through analyses of a representative homopiperazine compound [N-(3-(3-fluorophenyl)-1,2,4-thiadiazol-5-yl)-4-(4-isopropyl-1,4-diaze-pane-2-carbonyl)piperazine-1-carboxamide (AZX)] by liquid chromatography-UV-mass spectrometry, (1)H NMR, and chemical tests.


Formaldehyde/metabolism , Piperazines/pharmacology , Animals , Formaldehyde/blood , Formaldehyde/urine , Magnetic Resonance Spectroscopy , Piperazine , Piperazines/metabolism , Rats
14.
J Occup Environ Med ; 53(4): 346-51, 2011 Apr.
Article En | MEDLINE | ID: mdl-21436733

OBJECTIVE: This study quantified casino dealers' occupational exposure to environmental tobacco smoke (ETS). METHODS: We measured casino dealers' exposure to ETS components by analyzing full-shift air and preshift and postshift urine samples. RESULTS: Casino dealers were exposed to nicotine, 4-vinyl pyridine, benzene, toluene, naphthalene, formaldehyde, acetaldehyde, solanesol, and respirable suspended particulates. Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine increased significantly during an 8-hour work shift both with and without adjustment for creatinine clearance. Creatinine-unadjusted cotinine significantly increased during the 8-hour shift, but creatinine-adjusted cotinine did not increase significantly. CONCLUSIONS: Casino dealers at the three casinos were exposed to airborne ETS components and absorbed an ETS-specific component into their bodies, as demonstrated by detectable levels of urinary NNAL. The casinos should ban smoking on their premises and offer employee smoking cessation programs.


Gambling , Occupational Exposure , Tobacco Smoke Pollution , Acetaldehyde/urine , Cotinine/urine , Creatinine/urine , Formaldehyde/urine , Humans , Hydrocarbons, Aromatic/urine , Nevada , Nicotine/urine , Nitrosamines/urine , Particulate Matter/urine , Pyridines/urine , Terpenes/urine
15.
Neurobiol Aging ; 32(1): 31-41, 2011 Jan.
Article En | MEDLINE | ID: mdl-19879019

It is widely known that exogenous formaldehyde exposure induces human cognitive impairment and animal memory loss; and recent studies show that formaldehyde at pathological levels induces Aß deposition and misfolding of tau protein to form globular amyloid-like aggregates. Endogenous formaldehyde may be a marker for progressive senile dementia. The aim of this study was to investigate the correlation of endogenous formaldehyde in urine of senile dementia and mini mental state examination (MMSE) scores. Formaldehyde level was analyzed by high-performance liquid chromatography (with fluorescence detection) in human urine from dementia patients (n=141), patients with hypertension (n=33) or diabetes (n=16) and healthy individuals (n=38), autopsy hippocampus samples from Alzheimer's disease (AD) patients and brains of three types of AD animal model: namely, senescence accelerated mice (SAMP8), APP-transgenic mice and APP/PS1-transgenic mice. In a double-blind study, there was marked elevation of urine formaldehyde levels in patients (n=91) with dementia, and a slight increase in patients (n=50) with mild cognitive impairment. Urine formaldehyde level was inversely correlated with mini mental state examination scores (Rs=-0.441, p<0.0001). Furthermore, formaldehyde levels were significantly increased in the autopsy hippocampus from Alzheimer's patients (n=4). In SAMP8 brains the formaldehyde level was significantly increased, suggesting that the endogenous formaldehyde is related to aging in mice. The brain formaldehyde level in APP/PS1-transgenic (n=8) mice at age of 3 months and APP-transgenic (n=8) mice at age of 6 months was increased (0.56 ± 0.02 mM), respectively, as compared with their respective age-matched controls, when these two types of AD-like animals, respectively, started to form Aß deposits and memory loss obviously. According to the level of formaldehyde in the brain of the transgenic mice, we treated normal mice with formaldehyde (0.5mM, intraperitoneal administration) and observed the memory loss of the animal in Morris water maze trial. Cognitive impairments for the senile dementia are probably related to endogenous formaldehyde levels; and the mini mental state examination scores referred to the evaluation of urine formaldehyde level in dementia patients may be used as a non-invasive method for the investigation and diagnosis of senile dementia.


Alzheimer Disease/urine , Formaldehyde/urine , Mental Status Schedule , Statistics as Topic , Age Factors , Aging/pathology , Aging/urine , Alzheimer Disease/complications , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Angiotensin Amide/urine , Animals , Chromatography, High Pressure Liquid/methods , Disease Models, Animal , Female , Hippocampus/pathology , Humans , Male , Maze Learning/physiology , Memory Disorders/etiology , Mice , Mice, Transgenic , Neuropsychological Tests , Presenilin-1/genetics
16.
Toxicol Lett ; 192(1): 61-5, 2010 Jan 15.
Article En | MEDLINE | ID: mdl-19576276

It is well known that fire fighters are potentially exposed to various carcinogenic agents at a fire scene. An almost unheeded issue, however, is fire fighters' exposure to carcinogenic agents in smoke diving simulators. Biomonitoring (urinary muconic acid, 1-naphthol and 1-pyrenol), dermal (polycyclic aromatic hydrocarbons) and occupational hygiene measurements (cyanides, hydrogen cyanide, polycyclic aromatic hydrocarbons, volatile organic compounds and formaldehyde) were used to determine how the burning material, the type of simulator and protective clothing used affect fire fighting trainers' exposure. The highest excretion of 1-pyrenol (sampled 6h after end of exposure, in average 4.3-9.2nmol/L) and emissions of benzene (1.0-2.5mg/m(3)) and hydrogen cyanide (0.2-0.9mg/m(3)) were measured during the burning of conifer plywood and chipboard, and the lowest when pure pine and spruce wood (1.5nmol/L, 0.6mg/m(3), and 0.05mg/m(3)) was burned. However the safest burning material seemed to be propane (1.0nmol/L, 0.2mg/m(3), and not measured). The type of simulator used affected trainers' exposure very clearly. The highest dermal whole body exposures to polycyclic aromatic hydrocarbons were measured in the fire house simulator (in average 1200ng/cm(2)). Clearly lower exposure levels were measured in container training sessions (760ng/cm(2)), where the average dermal exposure level was 35% lower than in the fire house. The exposure levels (30ng/cm(2)) in the gas simulator in turn, were only 4% of the levels in container training sessions. The amount of polycyclic aromatic hydrocarbons decreased by 80% on trainers' hands when they used under gloves (in average 8.7ng/cm(2)) compared to those (48.4ng/cm(2)) who did not. There was not difference in protection efficiency against polycyclic aromatic hydrocarbons between tested fire suits (Brage and Bristol).


Air Pollutants, Occupational/analysis , Biomarkers/urine , Carcinogens/analysis , Equipment Safety , Occupational Exposure/analysis , Cyanides/urine , Fires , Formaldehyde/urine , Humans , Naphthols/urine , Polycyclic Aromatic Hydrocarbons/urine , Pyrenes/analysis , Sorbic Acid/analogs & derivatives , Sorbic Acid/analysis
17.
Med Sci Sports Exerc ; 40(9): 1645-52, 2008 Sep.
Article En | MEDLINE | ID: mdl-18685526

PURPOSE: To determine whether low-dose creatine and protein supplementation during resistance training (RT; 3 d x wk(-1); 10 wk) in older men (59-77 yr) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites (formaldehyde). METHODS: Older men were randomized (double-blind) to receive 0.1 g x kg(-1) creatine + 0.3 g x kg(-1) protein (CP; n = 10), creatine (C; n = 13), or placebo (PLA; n = 12) on training days. Measurements before and after RT included lean tissue mass (air-displacement plethysmography), muscle thickness (ultrasound) of elbow, knee, and ankle flexors and extensors, leg and bench press strength, and urinary indicators of cytotoxicity (formaldehyde), myofibrillar protein degradation [3-methylhistidine (3-MH)],and bone resorption [cross-linked N-telopeptides of type I collagen (NTx)]. RESULTS: Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA (P < 0.05). Subjects who received CP increased lean tissue mass (+5.6%) more than C (+2.2%) or PLA (+1.0%; P < 0.05) and increased bench press strength (+25%) to a greater extent than C and PLA combined (+12.5%; P < 0.05). CP and C did not differ from PLA for changes in formaldehyde production (+24% each). Subjects receiving creatine (C and CP) experienced a decrease in 3-MH by 40% compared with an increase of 29% for PLA (P < 0.05) and a reduction in NTx (-27%) versus PLA (+13%; P = 0.05). CONCLUSIONS: Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength. Low-dose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production.


Creatine/administration & dosage , Dietary Proteins/administration & dosage , Resistance Training , Aged , Bone Resorption/metabolism , Dietary Supplements , Dose-Response Relationship, Drug , Double-Blind Method , Formaldehyde/analysis , Formaldehyde/urine , Humans , Male , Middle Aged , Muscle Strength , Myofibrils/metabolism , Placebos
18.
Gig Sanit ; (4): 73-5, 2007.
Article Ru | MEDLINE | ID: mdl-17726955

Formaldehyde is one of the major pollutants of both ambient and indoors air. Thus, by comparing the concentrations of formaldehyde in ambient air (on study days) and in the air of classes and living rooms, the study has demonstrated that they may be 13.5 and 10.5 times greater than the normal values in the classes and living rooms, respectively. Biomonitoring of formaldehyde in the urinary samples from the pediatric population of the Irkutsk Region as an indicator of its chemical action has revealed the higher average group concentration of the substance in the urinary samples from urban children than that in rural ones (235 children from 6 inhabited localities). A significant correlation has been also found between the levels of formaldehyde in the urine of children (aged 5-10 years) and its concentration in the air of living rooms in the town of Shelekhov.


Environmental Illness/epidemiology , Environmental Illness/urine , Environmental Monitoring/methods , Formaldehyde/urine , Catchment Area, Health , Child , Child, Preschool , Epidemiological Monitoring , Female , Humans , Industry , Male , Russia/epidemiology
19.
Bull Environ Contam Toxicol ; 79(1): 1-4, 2007 Jul.
Article En | MEDLINE | ID: mdl-17618393

Formaldehyde is a carcinogen to which humans are exposed daily, but few methods are available to quantify formaldehyde in biological samples. We developed a simple, sensitive and rapid technique for the quantification of formaldehyde in urine by derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, using a headspace sampler coupled to a gas chromatograph equipped with an electron capture detector. The detection limit was 1.08 microg/L. The overall recovery of formaldehyde spiked in urine was 99%. The concentration of formaldehyde in urine obtained from healthy volunteers ranged from 56.85 to 144.57 microg/L. This method can be used successfully to measure formaldehyde in urine.


Formaldehyde/urine , Adult , Carcinogens/metabolism , Chromatography, Gas , Environmental Pollutants/urine , Female , Humans , Male , Middle Aged
20.
Toxicol Lett ; 161(1): 10-7, 2006 Feb 08.
Article En | MEDLINE | ID: mdl-16153790

Aim of this pilot study was to correlate the human exposure to formaldehyde (F) with N-methylenvaline, a molecular adduct formed by addiction of F to the N-terminal valine in hemoglobin. A group of 21 subjects employed in a plywood factory and a laminate factory, and occupationally exposed to F, together with a group of 30 controls, were recruited as volunteers to test this biomarker. Each subject received a questionnaire and a passive personal F sampler. Exposure to F vapors and occurrence of N-methylenvaline in blood were measured. Integrated F concentrations always proved lower than threshold limit value as a ceiling (TLV-TWA) (0.37 mg/m(3), 0.3 ppm). N-Methylenvaline distribution in blood, as measured by GC/MS upon derivatization, showed direct positive relationship to F exposure, with r=0.465. Prevalence of the molecular adduct expressed in nmol/g of globin was significantly higher in the exposed group (p<0.04) than in the control group. However, the N-methylenvaline marker was unable to provide significant distinction between the subjects exposed to F through tobacco smoke habit and the non smokers. Despite this interference, in this pilot study the usefulness of N-methylenvaline as a biomarker for testing occupational exposure to F was demonstrated.


Air Pollutants, Occupational/poisoning , Formaldehyde/poisoning , Hemoglobins , Valine/blood , Adult , Air Pollutants, Occupational/blood , Air Pollutants, Occupational/urine , Cotinine/urine , Environmental Monitoring/instrumentation , Environmental Monitoring/methods , Female , Formaldehyde/blood , Formaldehyde/urine , Gas Chromatography-Mass Spectrometry , Humans , Inhalation Exposure , Male , Multivariate Analysis , Pilot Projects , Surveys and Questionnaires , Threshold Limit Values , Tobacco Smoke Pollution , Valine/analogs & derivatives , Workplace
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