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1.
Environ Toxicol Pharmacol ; 105: 104343, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38122861

ABSTRACT

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days. Exposure to α-HBCDD did not affect the pharmacokinetics of VPA in pregnant or non-pregnant rats. Surprisingly, VPA administration altered the pharmacokinetics of α-HBCDD. VPA also triggered higher foetal toxicity and lethality with the PO than IP route. α-HBCDD did not aggravate the embryotoxicity observed with VPA, regardless of the route of exposure. Based on this evidence, a single administration of 500 mg/kg IP is the most suitable VPA model to investigate α-HBCDD co-exposure.


Subject(s)
Autism Spectrum Disorder , Hydrocarbons, Brominated , Prenatal Exposure Delayed Effects , Pregnancy , Humans , Female , Rats , Animals , Valproic Acid/toxicity , Autism Spectrum Disorder/chemically induced , Prenatal Exposure Delayed Effects/chemically induced , Hydrocarbons, Brominated/toxicity , Disease Models, Animal
2.
Sci Total Environ ; 747: 141185, 2020 Dec 10.
Article in English | MEDLINE | ID: mdl-32771784

ABSTRACT

In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.


Subject(s)
Endocrine Disruptors , Pesticides , Phthalic Acids , Biomarkers , Environmental Exposure/analysis , Humans , Reproducibility of Results
3.
J Chromatogr A ; 1612: 460648, 2020 Feb 08.
Article in English | MEDLINE | ID: mdl-31679711

ABSTRACT

Hair is increasingly used as a biological matrix of interest for the assessment of hormone secretion over extended periods of time. This study described the development and the validation of a sensitive UPLC-MS/MS method for simultaneous analysis of steroid and thyroid hormones in human hair. The gradient designed in this method enables to obtain a satisfactory separation of 9 hormones of interest: cortisol, cortisone, THE, THF, α-THF, triiodothyronine (T3) and thyroxine (T4), estradiol, and testosterone. Several methodological parameters of extraction (such as the used of "cut hair" versus "pulverized hair", the extraction time, the incubation solvent purification on SPE column and hydrolysis) that may influence the determination of hormones levels in human hair, have thus been tested here. Therefore, the results obtained highlighted the necessity of using a C18 SPE purification method for the determination of both steroid and thyroid hormones in hair. This method allows reaching suitable levels of sensitivity for cortisol and cortisone since the results obtained pointed out concentration levels of cortisol in hair of volunteers similar to those observed in the literature. This method could also offer an important impact in the field of hormone analysis since it allows, for the first time, the quantification of both T3 and T4 in human hair.


Subject(s)
Chromatography, Liquid/methods , Hair/chemistry , Tandem Mass Spectrometry/methods , Thyroid Hormones/analysis , Cortisone/analysis , Estradiol/analysis , Female , Humans , Hydrocortisone/analysis , Male , Steroids/analysis , Testosterone/analysis , Thyroxine/analysis , Triiodothyronine/analysis
4.
Environ Pollut ; 230: 163-177, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28651088

ABSTRACT

Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM2.5.


Subject(s)
Air Pollutants/toxicity , Particulate Matter/toxicity , Pulmonary Disease, Chronic Obstructive/genetics , Air Pollutants/analysis , Air Pollution/analysis , Cell Line , Epigenesis, Genetic , Epithelial Cells/drug effects , Humans , Hypersensitivity , Particulate Matter/analysis , Toxicity Tests
5.
Environ Pollut ; 228: 484-495, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28575812

ABSTRACT

A gas chromatography tandem mass-spectrometry method dedicated to the analysis of 50 metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) was applied to urine specimens collected from female Long Evans rats under controlled exposure to a mixture of PAHs (at 7 doses ranging from 0.01 to 0.8 mg/kg, by gavage, 3 times per week for 90 days). On four occasions (day 1, 28, 60 and 90), urine samples were collected over a 24 h period. Among these 50 OH-PAHs, 41 were detected in urine samples. Seven additional OH-PAHs were identified for the first time: 1 corresponding to metabolite of pyrene and 3 of anthracene. Strong linear dose versus urinary concentration relationships were observed for 25 of the 41 OH-PAHs detected in rat urine, confirming their suitability for assessing exposure to their respective parent compound. In addition, some isomers (e.g. 1-OH-pyrene, 3-OH-/4-OH-chrysene, 10-OH-benz[a]anthracene, 8-OH-benzo[k]fluoranthene, 11-OH-benzo[b]fluoranthene and 3-OH-benzo[a]pyrene) that were detected starting from the lowest levels of exposure or even in controls were considered particularly relevant biomarkers compared to metabolites only detected at higher levels of exposure. Finally, on the basis of the excretion profiles (on days 1, 28, 60 and 90) and urinary elimination kinetics of each OH-PAH detected at days 1 and 60, this study highlighted the fact that sampling time may influence the measurement of metabolites in urine. Taken together, these results provide interesting information on the suitability of the analysis of OH-PAHs in urine for the assessment of PAH exposure, which could be taken into consideration for the design of epidemiological studies in the future.


Subject(s)
Environmental Pollutants/urine , Polycyclic Aromatic Hydrocarbons/urine , Animals , Anthracenes , Benzo(a)pyrene/analysis , Biomarkers/urine , Body Fluids , Chrysenes , Female , Kinetics , Pyrenes , Rats , Rats, Long-Evans
6.
Environ Pollut ; 218: 1074-1088, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27593349

ABSTRACT

While the knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects is still incomplete, detailed in vitro studies are highly needed. With the aim of getting closer to the human in vivo conditions and better integrating a number of factors related to pre-existing chronic pulmonary inflammatory, we sought to develop primary cultures of normal human bronchial epithelial (NHBE) cells and chronic obstructive pulmonary disease (COPD)-diseased human bronchial epithelial (DHBE) cells, grown at the air-liquid interface. Pan-cytokeratin and MUC5AC immunostaining confirmed the specific cell-types of both these healthy and diseased cell models and showed they are closed to human bronchial epithelia. Thereafter, healthy and diseased cells were repeatedly exposed to air pollution-derived PM4 at the non-cytotoxic concentration of 5 µg/cm2. The differences between the oxidative and inflammatory states in non-exposed NHBE and COPD-DHBE cells indicated that diseased cells conserved their specific physiopathological characteristics. Increases in both oxidative damage and cytokine secretion were reported in repeatedly exposed NHBE cells and particularly in COPD-DHBE cells. Diseased cells repeatedly exposed had lower capacities to metabolize the organic chemicals-coated onto the air-pollution-derived PM4, such as benzo[a]pyrene (B[a]P), but showed higher sensibility to the formation of OH-B[a]P DNA adducts, because their diseased state possibly affected their defenses. Differential profiles of epigenetic hallmarks (i.e., global DNA hypomethylation, P16 promoter hypermethylation, telomere length shortening, telomerase activation, and histone H3 modifications) occurred in repeatedly exposed NHBE and particularly in COPD-DHBE cells. Taken together, these results closely supported the highest responsiveness of COPD-DHBE cells to a repeated exposure to air pollution-derived PM4. The use of these innovative in vitro exposure systems such as NHBE and COPD-DHBE cells could therefore be consider as a very useful and powerful promising tool in the field of the respiratory toxicology, taking into account sensitive individuals.


Subject(s)
Air Pollutants/toxicity , Epithelial Cells/drug effects , Particulate Matter/toxicity , Air Pollution , Cell Line , Epithelial Cells/metabolism , Humans , Lung/cytology , Lung/drug effects , Lung/metabolism , Oxidative Stress/drug effects , Pulmonary Disease, Chronic Obstructive/metabolism
7.
Orthop Nurs ; 13(6): 37-42, 1994.
Article in English | MEDLINE | ID: mdl-7870479

ABSTRACT

Myasthenia gravis is a chronic autoimmune disease that results in progressive weakness of the striated muscles. Autoantibodies destroy acetylcholine receptor sites, preventing adequate nerve impulse conduction to the muscles. Medical treatment is directed at increasing the amount of available acetylcholine or at reducing the levels of circulating antibodies. Nursing care is complex and involves patient education about drug therapy and treatment options as well as caring for the numerous problems that arise from varying degrees of muscle weakness. Skilled nursing assessment and intervention can help protect the myasthenic patient from the life-threatening complications of respiratory compromise.


Subject(s)
Myasthenia Gravis , Humans , Myasthenia Gravis/diagnosis , Myasthenia Gravis/physiopathology , Myasthenia Gravis/therapy , Nursing Assessment , Patient Education as Topic
8.
Orthop Nurs ; 11(6): 27-30, 1992.
Article in English | MEDLINE | ID: mdl-1491877

ABSTRACT

Corticosteroids are encountered on a regular basis in the treatment of orthopaedic problems. Foreseeing potential dangers and complications and taking appropriate actions, the nurse helps to minimize the negative effects steroids may produce. This article discusses the physiologic production of corticosteroids and their effects. Potential risks associated with larger doses are described along with nursing interventions directed at assessing, avoiding, and managing steroid-related problems.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Orthopedic Nursing/methods , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/pharmacology , Humans
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