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Sandrine F. Chebekoue 《Journal of occupational and environmental hygiene》2019,16(4):308-319
This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10?2 and 9?×?10?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10?1 and 8.5?×?10?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r2 = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework. 相似文献
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Sandrine Souverain Chin Eap Jean-Luc Veuthey Serge Rudaz 《Clinical chemistry and laboratory medicine》2003,41(12):1615-1621
Methadone (MTD) is a chiral drug widely used for the treatment of opioid dependence for which a rapid analytical method for the determination of each enantiomer would be advantageous. In order to improve method sensitivity and to automate the entire analytical process, a column-switching configuration has been developed. An online extraction system coupled to a cellulose-based chiral stationary phase (CSP), namely Chiralcel OJ-R, was used and detection was performed by mass spectrometry. Fifty microl of plasma were injected into the liquid chromatography-mass spectrometry (LC-MS) system after addition of acetonitrile (ACN) containing methadone deuterated D9 (MTD-D9) (internal standard) and centrifugation. For the rapid extraction step, a large particle size support was selected. A baseline separation of MTD enantiomers was obtained in less than 12 min. Trueness and precision were evaluated with control samples at 500 ng/ml of (R,S)-methadone. Trueness values were 106.6% and 103.0% for (R)-MTD and (S)-MTD, respectively, with a coefficient of variation inferior to 2.5% for both compounds. Finally, a good concordance was found using this method for analysis of plasma samples from patients in maintenance treatment as compared to a previously described HPLC-UV method after liquid-liquid extraction. 相似文献
5.
R. Volpi P. Caffarra A. Marcato A. Scaglioni D. Maestri R. Delsignore P. Chiodera V. Coiro 《Journal of neural transmission (Vienna, Austria : 1996)》1991,3(2):127-132
Summary In order to establish whether the inhibitory control exerted by endogenous opioid peptides on ACTH/cortisol secretion changes in patients affected by Parkinson's disease, ten parkinsonian male subjects and eight age matched normal controls were tested with naloxone (4 mg an i.v. bolus plus 10 mg infused in two hours). In a different occasion all subjects were tested with normal saline. Experiments started at 09.00 h. Plasma ACTH and cortisol concentrations showed a slight physiological decline during saline test in both groups. In the normal controls and in the parkinsonian patients both ACTH and cortisol levels were significantly higher after naloxone administration than during saline test. However, both naloxone induced ACTH and cortisol responses were significantly higher in normal than in parkinsonian subjects. In agreement with the well-known opioid deficiency characterizing the parkinsonian brain, these data show a reduced opioid inhibitory control of ACTH/cortisol secretion in patients with Parkinson's disease. 相似文献
6.
Sandrine Péroche Ghania Degobert Jean-Luc Putaux Marie-Geneviève Blanchin Hatem Fessi Hélène Parrot-Lopez 《European journal of pharmaceutics and biopharmaceutics》2005,60(1):123-131
This work describes the synthesis of new amphiphilic perfluorohexyl- and perfluorooctyl-propanethio-beta-cyclodextrins and the comparison of the ability of these molecules and alkyl analogue, nonanethio-beta-cyclodextrin to form nanospheres. Nanospheres were prepared using nanoprecipitation method (perfluoroalkylthio-beta-cyclodextrin in THF [0.11 x 10(-3)M], stirring rate 700rpm, addition of aqueous phase at 64 degrees C into organic phase at 50 degrees C). They were characterised by Photon Correlation Spectroscopy (PCS) and by electron microscopy (SEM and cryo-TEM). The nanospheres prepared from these new beta-cyclodextrin derivatives have an average size of 260nm, and appear to be spherical in cryo-TEM images. Whereas alkyl analogue forms polydisperse aggregates with sizes in the range 60-350nm. 相似文献
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Sandrine Cappellesso Jean-Fran?ois Valentin Bruno Giraudeau Marie-Denise Boulanger Azmi Al-Najjar Mathias Büchler Jean-Michel Halimi Hubert Nivet Pierre Bardos Yvon Lebranchu Hervé Watier 《Nephrology, dialysis, transplantation》2004,19(2):439-443
BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes. 相似文献
9.
Teresa Coccini Luciano Maestri Francesco S. Robustelli della Cuna L. Bin Lucio G. Costa Luigi Manzo 《Archives of toxicology》1996,70(11):736-741
Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers
of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic
acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene
oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine
of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were
given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also
exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers
of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in
urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the
animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease.
Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased
M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary
mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism
in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators
of styrene-induced disorders of GSH homeostasis in nonaccessible organs.
Received: 19 December 1995/Accepted: 10 May 1996 相似文献
10.
Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma 总被引:5,自引:0,他引:5
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Lehours P Ménard A Dupouy S Bergey B Richy F Zerbib F Ruskoné-Fourmestraux A Delchier JC Mégraud F 《Infection and immunity》2004,72(2):880-888
Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ "off" status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified. 相似文献