Differences in Caffeine 3-Demethylation Activity among Inbred Mouse Strains: A Comparison of Hepatic Cyp 1a2 Gene Expression between Two Inbred Strains

The 3-demethylation of caffeine can be used as an index of cytochromeP450 CYP1A2 activity in vivo. We compared the plasma levelsof caffeine and the 3-demethylated metabolite, 1,7-dimethylxanthine,in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J,and SWR/J) and one inbred strain (APN) derived in our laboratoryfrom outbred Swiss-Webster mice on the basis of its relativesusceptibility to acetaminophen-induced hepatotoxicity. We foundsignificant variations between a number of the common strains,all of which produced significantly higher caffeine 3-demethylationindices than our APN strain. In three of the six common strains,there was a significant difference between males and females,with the females having consistently lower 1,7-xanthine/caffeineratios. Hepatic Cyp1a2 expression was compared between APN andC3H/HeJ males. Microsomal methoxyresorufin O-demethylation,acetanilide 4-hydroxylation, and CYP1A2 immunoreactive proteinlevels were significantly higher in C3H/HeJ relative to APNmice, as were hepatic CYP1A2 mRNA levels. These results indicatethe importance of strain and gender to the outcome of pharmacologicalor toxicological studies involving CYP1A2-mediated metabolism,as well as the suitability of the plasma 1,7-dimethylxanthine/caffeineratio as a marker of CYP1A2 activity in the mouse. The strikingdifferences observed between the APN and C3H/HeJ mice suggestthat these strains may be suitable for a genetic analysis ofthe regulation of the basal expression of CYP1A2, a key enzymeIn procarcinogen activation.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

Effects of methanol on styrene metabolism among workers occupationally exposed at low concentrations

A survey was conducted in the second half of a work week on 39 male workers who were occupationally exposed to styrene in combination with methanol and methyl acetate during the production of plastic buttons. Time-weighted average exposure during an 8-h shift to styrene (Sty-A) and methyl acetate was monitored by carbon cloth-equipped personal samplers and to methanol by water-equipped ones. Urine samples were collected near the end of the shift and analyzed for mandelic (MA-U) and phenylglyoxylic acids (PhGA-U) by HPLC. Geometric mean styrene concentration was 12.4 ppm (g/g) with the maximum of 46 ppm, whereas the values for methanol and methyl acetate in combination were 23.5 ppm and 229 ppm, respectively. The relationship of MA-U and PhGA-U with Sty-A was examined by linear regression analysis. The equations for the regression lines were compared with the results from a previous survey (Ikeda et al. 1983) in which workers were exposed only to styrene, and the methods employed were identical with that in the present study. The comparison showed no evidence to suggest that styrene metabolism is suppressed by coexposure to methanol and methyl acetate at low concentrations below the current occupational exposure limit of 200 ppm.     

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.     

Posttraumatic stress disorder in injured adults: etiology by path analysis

OBJECTIVE: Posttraumatic Stress Disorder (PTSD) impairs outcome from injury. We present a path analysis of factors related to the development of PTSD in injured adults. METHODS: A prospective cohort of 250 patients without severe neurotrauma was evaluated by interview during admission and by mailed self-report 6 months later. Data were gathered from the trauma registry (age, injury mechanism, and Injury Severity Score), social history (gender, income, education, and social support), and survey instruments. Baseline assessment used the Michigan Critical Events Perception Scale (peritraumatic dissociation and subjective threat to life), the Life Experience Survey (stressful exposure history), and the SF36 (general and mental health). PTSD at 6 months was identified with the civilian Mississippi Scale for PTSD. Data are listed as mean +/- SEM or percent (%). Path analysis was conducted by linear regression and significant (p<0.05) variables are shown. Factors are listed with the standardized beta. A negative beta suggests a protective effect. RESULTS: The 176 patients (72%) who completed the 6-month follow-up were 37.7+/-0.88 years old; 75% were men; and blunt (70%), penetrating (13.5%), and burn (16.4%) mechanisms caused the injuries. Assault was involved in 14.5% of the cases. Average income was $44,300+/-2,700/yr, education was 13.0+/-0.15 years, and Injury Severity Score was 13.9+/-0.50. A total of 42.3% of the patients developed PTSD. The 39.7% of the variance in PTSD explained by the model was due to intentional injury (beta = 0.27), male gender (beta = -0.21), age (beta = -0.20), peritraumatic dissociation (beta = 0.174), baseline mental health (beta = -0.21), and prior life-threatening illness (beta = -0.29). Peritraumatic dissociation was due to the patient's sense of threat to life (beta = -0.47), and threat was related to Injury Severity Score (beta = 0.2), assault(beta = 0.14), education (beta = -0.15), and age (beta = -0.19). Baseline SF36 mental health was related to social support (beta = 0.27) and income (beta = 0.21). Income was contingent on education (beta = 0.21). CONCLUSION: PTSD occurred in 42.3% of injured adults 6 months after trauma and was related to assault, dissociation, female gender, youth, poor mental health, and prior illness. By modeling PTSD, we may learn more of the etiology, risk stratification, and potentials for the treatment of this common and important morbidity of injury.     

Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease

BACKGROUND: Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking. METHODS: Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10 remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians. RESULTS: Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated. CONCLUSIONS: This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD and DIP and their strong association with smoking, the term "smoking related interstitial lung disease" is suggested for those patients who are smokers.