Evaluation of Serum Cotinine Cut-Off to Distinguish Smokers From Nonsmokers in the Korean Population

BACKGROUND: Cotinine has been widely used as an objective marker to identify current smokers. We conducted this study to address the absence of Korean studies investigating the efficacy of immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the detection of serum cotinine and to determine the optimal serum cotinine cut-off level for differentiating current smokers from nonsmokers. METHODS: Serum specimens were obtained from 120 subjects. They were randomly chosen to represent a broad distribution of urine cotinine levels based on a retrospective review of questionnaires and results of urine cotinine levels. We determined serum cotinine levels using the IMMULITE 2000 XPi Immunoassay System (Siemens Healthcare Diagnostics Inc., USA) and LC-MS/MS (API-4000, Applied Biosystems, USA). Correlation was analyzed between IMMULITE serum cotinine, urine cotinine, and LC-MS/MS serum cotinine levels. ROC curve was analyzed to identify the optimal IMMULITE serum cotinine cut-off level for differentiating current smokers from nonsmokers. RESULTS: IMMULITE serum cotinine levels correlated with both urine cotinine and LC-MS/MS serum cotinine levels, with correlation coefficients of 0.958 and 0.986, respectively. The optimal serum cotinine cut-off level for distinguishing current smokers from nonsmokers was 13.2 ng/mL (95.7% sensitivity, 94.1% specificity) using IMMULITE. CONCLUSIONS: This is the first study to investigate the use of LC-MS/MS for the measurement of serum cotinine and to determine the optimal serum cotinine cut-off level for the IMMULITE immunoassay. Our results could provide guidelines for differentiating current smokers from nonsmokers in the Korean population.

Relationship between Malondialdehyde in Renal Cortex and Urinary NAG Activity of Rats exposed to Cadmium

BACKGROUND: To investigate the relationship between malondialdehyde in renal cortex and Urinary NAG activity of rats exposed to cadmium. METHODS: Rats were treated with a single intraperitoneal injection of cadmium (as CdCl2, 1 mg/kg) for cadmium-treated group and 24-hour urine were obtained prior to sacrifice on days 1, 2, 4, 8 and 16 (N=10 per each group), respectively. The concentration of malondialdehyde by thiobarbituric acid reaction and cadmium were measured in the homogenates of renal cortex. Nephrotoxocity indices such as N-acetyl--D-glucosaminidase (NAG) activity, total protein, and 24 hours urine volume, and cadmium concentration were measured in the urine. RESULT: The cadmium injection caused significant increase of cadmium concentration in the renal cortex on days 1 and 2, and in urine on days 1, 2 and 4. NAG activity and total protein concentration in urine were significantly increased on days 1, 2 and 4, and on days 1, 4 and 8, respectively. The peak values of NAG activity and total protein in urine were observed on days 1 and 4, respectively. Significant decrease of 24 hours urinary volume was induced on day 1. These results indicated that cadmium induced acute nephrotoxicity in the rats. Urinary NAG activity was changed earlier and at a higher rate than urinary total protein, which suggest that NAG activity is a more sensitive biological index in terms of early diagnosis of cadmium-induced nephrotoxicity. Renal MDA concentration was significantly increased on day 2 and on day 4, and on day 8, MDA concentration and nephrotoxicity indices except urinary total protein were returned to control level. CONCLUSION: Based on the results obtained as above, it was concluded that the malondialdehyde in renal cortex, product of lipid peroxidation was related with the changes of urinary NAG activity indicating nephrotoxic injury.

Effects of Manganese on Lipid Peroxidation and Compositional Changes of Fatty Acids in Hippocampus of Rat Brain

BACKGROUND: To investigate the effect of manganese on lipid peroxidation and compositional changes of fatty acids in hippocampus of rat brain. METHODS: Seven rats in experimental group were given with MnCl2 intraperitoneally for 4 weeks (4 mg/kg once daily, 5 days per week). Twenty four hours after the last injection, rats were decapitated and, hippocampus were separated from the rat brain. RESULT: In Mn-treated group, manganese concentrations increased significantly in the hippocampus by 222% compared with control group (P<0.01). MDA concentrations increased significantly by 149% compared with control group (P<0.05). Among fatty acids, total n-6 polyunsaturated fatty acids (PUFAs) increased significantly by 237% compared with control group (P<0.05). Linoleic acid (LA) and arachidonic acids (AA) increased by 213%, 238% (P<0.05, P<0.01, respectively). Among n-3 PUFAs except linolenic acids, eicosapentanoic acid(EPA) and docosahexanoic acids (DHA) decreased significantly by 70%, 50% respectively compared with control group (both P<0.01). CONCLUSION: Our results suggest that manganese may cause compositional changes of fatty acids in hippocampus of rat brain. Characteristics of fatty acids compositional changes by manganese were the decrease of EPAs and DHAs (n-3 PUFAs), and increase of AA and LA (n-6 PUFAs). These changes with the increase of MDA, suggest that manganese neurotoxicity is caused by lipid peroxidation.

A Study of Relationship between Exposure to Manganese Chloride and Malondialdehyde in Rat Tissues / 대한산업의학회지

OBJECTIVES: This research was intended to investigate the relationship between manganese and malodndialdehyde concentration in tissues of rats exposed to maganese chloride. METHODS: The study groups were 12 manganese treated rats and 9 control rats. Manganese treated rats were given intraperitoneally manganese chloride (Mn, 4 mg/kg) daily for a period of 30 days except Sunday. Control rats were injected 1ml of saline. The plasma manganese concentrations of rats were determined by graphite furnace atomic absorption spectrometry. The tissue manganese concentration was determined by flame atomic absorption spectrometry. Malondialdehyde, the product of lipid peroxidation was determined by ultraviolet-visible spectrophotometry. The plasma malondialdehyde was determined by gas chromatography with mass-detector. Protein concentration was quantified by ultraviolet-visible spectrometry and was used for the compensation of tissue malondialdehyde and manganese concentration. RESULTS: Manganese concentrations of plasma, brain, liver, and pancreas were very significantly higher in the manganese-treated rats than in the control rats. Malondialdehyde concentration of plasma, brain, and pacrease were significantly higher in the manganese-treated rats than in the control rats. The concentration of malondialdehyde was correlated with manganese levels in plasma, brain and pancreas. Conclusion: Based on the results obtained as above, it was concluded that the malondialdehyde, product of lipid peroxidation was related to the cell death due to dosing excess manganese.