[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

[Incidence of chronic obstructive pulmonary disease and risk factors in the Suzhou cohort].

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.

Evaluation of exposure risk for healthcare personnel performing the open technique HIPEC procedure using cisplatin.

OBJECTIVE: To perform an evaluation of the risk to healthcare personnel of exposure to cisplatin during a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure in an operating room environment. METHODS: Breathing zone air samples were taken from the operating room (OR) before, during and after the procedure of HIPEC filter membrane adsorption and the liquid impact method was applied to collect air samples. The samples of surface wipe from the floor of the OR were taken after the procedure. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of cisplatin in all the samples. RESULTS: Thirty-six air samples and three surface wipes were collected from three different locations of healthcare personnel breathing zones. All the breathing zone air samples were negative for cisplatin; however, cisplatin contamination was detected on three surface wipes from the floor, but in a lowconcentration(≤ 2.25 ng). CONCLUSION: The results suggest that the risk of inhalation of cisplatin was extremely low for the healthcare personnel during the procedure of HIPEC, but the contamination of the OR floor should be taken into consideration.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

[Magnetic resonance imaging characteristics of encephalopathy of prematurity].

Objective: To explore the MRI manifestation of encephalopathy of prematurity (EOP), so as to find an access to the early prevention, early diagnosis, effective treatment and prognosis. Methods: A total of 2 718 premature infants were collected, MRI and clinical data were analyzed who were admitted to NICU of Children's Hospital of Fudan University between January 1, 2009 and December 31, 2014. The manifestation and lesions distribution in MRI were analyzed. Results: All the 2 718 preterm infants underwent MRI. 58.8% (1 599/2 718) of which had normal MRI apperance, whereas 24.9% (678/2 718) showed manifestations of EOP.78.8% (534/678) EOP were non-cystic EOP. 21.2% (144/678) EOP were cystic EOP. Periventricular and cerebral lobe white matter were primary distributions of these lesions. Cystic lesions were primarily distributed in the body of periventricular whiter matter (49.3%). However, more non-cystic EOP were found in cerebral parietal lobe whiter matter (25.1%). Non-cystic EOP were also distributed in the body of periventricular whiter matter, frontal lobe and basal ganglia(20.8%, 20.2% and 18.9%, respectively ). Conclusions: The morbidity rate of EOP in preterm infants was 24.9%. 21.2% (144/678) EOP were cystic EOP. 78.8% (534/678) EOP were non-cystic EOP. Cystic lesions were primarily distributed in the body of periventricular whiter matter. Non-cystic EOP were also distributed in the body of periventricular whiter matter, frontal lobe and basal ganglia.

Effect of dual Bt-expression transformation vectors on transgene expression in tobacco.

This study aimed to determine the influence of vector structure on dual Bt gene expression and establish an efficient expression vector using Cry1Ac and Cry3A genes. Four vectors (N4, N5, N10, and S23) were developed and used for genetic transformation of tobacco to obtain insect-resistant transgenic lines. The vectors were constructed using the MAR structure, applying different promoter and enhancer sequences, and changing the transgene open-reading frame sequence. The average Cry1Ac toxalbumin expression quantity was 67 times higher in N5 than in N4 transgenic lines (8.77 and 0.13 µg/g, respectively). In contrast, the average Cry3A toxalbumin expression quantity was 1.5 times higher in N4 than in N5 lines (12.70 and 8.21 µg/g, respectively). The sequences of both Bt genes significantly influenced toxalbumin expression, although upstream Bt genes presented lower expression levels. The average Cry1Ac toxalbumin content was 13 times higher in the transgenic lines of AtADH 5'-non-translated sequence N5 (8.77 mg/g) than in the omega N10 lines (0.67 mg/g). Furthermore, the average Cry1Ac toxalbumin content was 5 times higher in MAR N5 than in non-MAR S23 lines (8.77 and 1.63 mg/g, respectively). The average Cry3A toxalbumin content was 1.3 times higher in N5 than in S23 lines (8.21 and 6.48 mg/g, respectively). Moreover, toxalbumin expression levels differed significantly among the S23-transformed lines. The MAR structure applied on both ends of the genes increased both the level and stability of exogenous gene expression. In conclusion, N5 was the most optimal of the four tested vectors.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

B7-H1 inhibits T cell proliferation through MHC class II in human mesenchymal stem cells.

B7-H1 on mesenchymal stem cells (MSCs) is known to modulate immune response. However, its expression pattern and exact immunomodulatory mechanism are unclear. In this study, we examined the immunomodulatory mechanism through the expression pattern of B7-H1 and major histocompatibility complex class II in various MSCs. Human bone marrow, adipose tissue, and cord blood MSCs were isolated and cultured. B7-H1, HLA-ABC, and HLA-DR expression on MSCs by interferon-γ (IFN-γ) was detected time-dependently by flow cytometry. The inhibitory effect of MSCs on T lymphocytes was observed in phytohemagglutinin antigen-induced T cell proliferation assay. The expression of B7-H1 was rapidly induced, but the expression of HLA-DR was induced at 48 hours after IFN-γ treatment. The inhibitory effect of MSCs on T cell proliferation could be restored when the anti-B7-H1 monoclonal antibody was used to block the B7-H1, or when the HLA-DRα small interfering RNA was used to interfere with its expression. These results show that MSCs could inhibit the T cell proliferation and activation by B7-H1 depending on the presence of HLA-DR. Therefore, MSCs would have a strong effect on immune diseases such as graft-versus-host disease and autoimmune diseases when MSCs are primed with IFN-γ 48 hours before transplantation.

iTRAQ-based proteomic profiling of the marine medaka (Oryzias melastigma) gonad exposed to BDE-47.

A recent study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) may have an adverse effect on the reproduction in marine medaka (Oryzias melastigma), but the molecular mechanisms remain largely unknown. In this study, we investigated the protein expression profiles of male and female gonads of O. melastigma exposed to dietary BDE-47 at two dosages (0.65 and 1.30 µg/g/day, respectively) for 21 days. Extracted proteins were labeled with iTRAQ and analyzed on a MALDI TOF/TOF analyzer, as results, 133 and 144 unique proteins were identified in testis and ovary, respective, and they exerted dose- and sex-dependent expression patterns. In testis, among the 42 differentially expressed proteins; down-regulation of histone variants and parvalbumins implicated BDE-47 may disrupt the spermatogenesis and induce sterility in fishes. In ovary, 38 proteins were differentially expressed; the elevation of vitellogenins and apolipoprotein A-I expression indicated BDE-47 acts as an estrogen-mimicking compound and led to reproductive impairment in O. melastigma.

Gender-specific transcriptional profiling of marine medaka (Oryzias melastigma) liver upon BDE-47 exposure.

Marine medaka (Oryzias melastigma) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) to investigate the gender-specific transcriptional profiles of liver tissue in response to this flame retardant. A cDNA library of O. melastigma was constructed, and 2304 clones were amplified from the library to fabricate a cDNA microarray. Sequences of these genes were assembled into 1800 sequences using Geneious, a bioinformatics software. Corresponding expressed sequence tags were blasted against the National Centre for Biotechnology Information non-redundant database and further classified into various biological categories according to the Gene Ontology project. Male and female three-month-old were fed a diet of BDE-47 contaminated Artemia at low dosage (290.3±172.3ng BDE-47/day) and high dosage (580.5±344.6ng BDE-47/day) for 5 and 21 days, respectively. The transcriptional profiles of O. melastigma liver were then generated by the species-specific cDNA microrarray. The results from microarray analysis suggested very different gene expression patterns between males and females for both BDE-47 exposure-dose and exposure-time, with male livers having stronger gene regulatory responses than female livers. Importantly, our results revealed that in male O. melastigma only, BDE-47 exposure may activate phosphoinositide-3-kinase and mitogen-activated protein kinase, proteins that play importance roles in cell growth, proliferation and survival.

In vitro evaluation of migratory capacity of human liver stem cells influenced by soluble factors.

Although several studies have addressed the engraftment of stem cells into the liver, the exact mechanisms in vivo remain unclear. In this study, we investigated the effects of soluble factors on cell migration using purified, expanded human liver stem cells (HLSCs) obtained from a pediatric liver resection. Using a in vitro transwell migration assay, we evaluated the migratory capacity of HLSCs under the influence of the cytokines tumor necross factor- [TNF]-α, interleukin [IL]-6, and interferon (IFN)-γ or the growth factors vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and hepatocyte growth factor [HGF], which are known to be highly secreted during liver injury. We also evaluated the migratory capacity indirectly influenced by cryopreserved human hepatocytes. The migration across the transwell membrane was promoted by VEGF, bFGF, TNF-α, IFN-γ, or hepatocytes. The cryopreserved human hepatocytes especially induced significant migration. These results suggested the presence of unidentified soluble factors from hepatocytes. This experiment described a reliable system for quantitative migration studies to broaden our understanding of the directional nature of cell migration.

Analysis of adenosine phosphates in HepG-2 cell by a HPLC-ESI-MS system with porous graphitic carbon as stationary phase.

A high performance liquid chromatography coupled with electrospray ionization/mass spectrometry method was developed for the determination of adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), and adenosine 5'-triphosphate (ATP) in the extract of HepG-2 cells. The chromatographic conditions were optimized by using porous graphitic carbon as the stationary phase for the retention and separation of the AMP, ADP and ATP. Negative-ion mode ESI-MS in basic mobile phase was applied to improve the method sensitivity. An external calibration method with linear ranges from 0.22 to 57.80 microM for AMP, from 0.59 to 117.37 microM for ADP, and from 0.49 to 98.81 microM for ATP was used for quantitative analysis. The levels of ATP, ADP, and AMP in HepG-2 cells treated with benzo[a]pyrene with different time periods were determined. Total adenine nucleotides and the energy charge potential were calculated for the investigation of the effect of benzo[a]pyrene on cell energy metabolism.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response.

BACKGROUND: Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium. CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

MAPK regulate p53-dependent cell death induced by benzo[a]pyrene: involvement of p53 phosphorylation and acetylation.

Benzo[a]pyrene (BaP) is a potentially genotoxic and cytotoxic environmental pollutant. Previous studies showed that exposure of HepG(2) cells to BaP causes necrotic cell death [Lin, T., Yang, M.S., 2007b. Cell death induced by benzo[a]pyrene in the HepG(2) cells is dependent on PARP-1 activation and NAD depletion. Toxicology 245, 147-153]. In the present study, the signaling pathways associated with this response was studied. BaP induced accumulation and activation of p53 in HepG(2) cells, which occurred as early as 12h after exposure. Activation of p53 was evidenced by its phosphorylation at serine 15 (Ser15) and acetylation at lysine 382 (Lys382). Chemical inhibition and siRNA-mediated knockdown of p53 expression suppressed its phosphorylation as well as cell death. BaP also activated p38 MAPK and ERK, but not JNK, at 6h after exposure. SB203580 and PD98059, specific inhibitors of p38 MAPK and ERK, respectively, suppressed phosphorylation of p53 at Ser15, but the accumulation of p53 was only moderately reduced. Acetylation of p53 at Lys 382 was not affected by these inhibitors, suggesting that acetylation stabilizes p53 in response to DNA damage. SB203580 and PD98059 prevented downstream energy failure and BaP-induced cell death. Similar results were obtained with siRNA against two isoforms of p38 MAPK, p38alpha and p38beta. Wortmannin, selective inhibitor of DNA-PK and ATM/ATR, abolished p53 phosphorylation, indicating an involvement of multiple pathways of p53 phosphorylation upon exposure to BaP. In summary, the current study demonstrated that both MAPK and p53 activation are required for BaP-induced necrotic cell death. The results also provide a novel model for studying the regulation between p53 and p38 MAPK in the progression of cellular necrosis.

Increase in intracellular free/bound NAD[P]H as a cause of Cd-induced oxidative stress in the HepG(2) cells.

The present study shows the use of confocal autofluorescence spectroscopy coupled with the time-resolved fluorescence decay analysis to measure changes in FAD/NAD[P]H and free/bound NAD[P]H in HepG(2) cells at 0.5, 1.5, 3 and 4.5h after exposure to cadmium chloride (Cd). These changes were compared to changes in GSSG/GSH and production of reactive oxygen radicals (ROS) production. The results demonstrated that both FAD/NAD[P]H and GSSG/GSH increased significantly upon exposure to Cd. The change in GSSG/GSH occurred as early as 1.5h after treatment while the change in FAD/NAD[P]H did not occur until 3h after exposure. Production of ROS was also increased at 1.5h. The ratio of free/bound NAD[P]H was studied. It was demonstrated that free/bound NAD[P]H increased significantly as early as 0.5h and remained elevated until 4.5h after treatment with Cd. The present study provides novel data to show that changes in NAD[P]H metabolism precedes the increase in ROS production and cellular oxidative stress (increase GSSG/GSH, FAD/NAD[P]H). It is suggested that Cd causes a release of NAD[P]H, an important cofactor for electron transfer, from its normal protein binding sites. This may result in a disruption of the activity of the enzyme and proteins, and may lead to the subsequent toxic events.

Benzo[a]pyrene-induced necrosis in the HepG(2) cells via PARP-1 activation and NAD(+) depletion.

Benzo[a]pyrene (BaP), a member of polycyclic aromatic hydrocarbons (PAH), has been reported to induce cell death in various cell types. However, the underlying mechanisms are controversial. In the present study, we report that BaP induces necrotic cell death in human hepatoma (HepG(2)) cells. The process is dependent on the activation of poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme responsible for repairing DNA damage. Once activated, PARP-1 catalyzes the formation of ADP-ribose polymers on acceptor proteins at the expense of NAD(+). Incubation of cells with high extracellular concentration of NAD(+) (5mM) after BaP treatment caused an elevation in intracellular NAD(+) level and blocked cell death. Inhibitor of PARP-1 suppressed both overactivation of PARP-1 activity and NAD(+) depletion. Moreover, addition of pyruvate (5mM), but not glutamate (5mM) or glutamine (5mM), could restore ATP production and prevent cell death. These results elucidated a sequence of events linking cellular metabolism to the progression of cell death induced by this organic toxicant.

Manipulation of energy and redox states in the C6 glioma cells by buthionine sulfoxamine and N-acetylcysteine and the effect on cell survival to cadmium toxicity.

Changes in cellular energy and redox states were studied in the C6 glioma cells following exposure to chemicals that affect glutathione metabolism. It was demonstrated that treatment with sublethal concentrations (25, 50 and 100 microM) of buthionine sulfoxamine (BSO) did not affect cellular energy state as measured by total adenosine nucleotides (TAN=ATP+ADP+ AMP), ATP:ADP:AMP and energy charge potential (ECP=[ATP + 0.5 (ADP)]/TAN). However, there was a significantly decrease in cellular GSH/GSSG and total glutathione (TG=[GSH+GSSG]/ TAN). The change was due to a significant decrease in intracellular GSH level without significant change in [GSSG]. Cells exposed to BSO for 24 hr were much more sensitive to subsequent injuries caused by Cd (0.6 mM for 3 hr). The results indicated that while a significant reduction of intracellular redox state did not affect cell viability, it could increase the susceptibility of cells to subsequent chemical stress. N-acetylcysteine (NAC), on the other hand, caused a dose (1, 5 and 10 mM)-dependent increase in GSH/GSSG without significant changes in intracellular energy state. Improvement of intracellular GSH/GSSG offered no protection against subsequent Cd induced cell death unless NAC was present at the time Cd was added. The pattern of cell death also correlated with the increase in intracellular free radial generation as measured by the fluorescence labeling with 27- dichlorofluorescin. Results of the present study demonstrated that intracellular redox states could be manipulated by addition of chemicals that affect glutathione metabolism. While the redox state may not be the sufficient condition to cause cell death, it could modulate the response of cells to subsequent Cd treatment. Furthermore, the action of NAC against Cd cytotoxicity may not be related to intracellular redox status.