Microsomal metabolism of 4-(N,N-diacetylamino)benzo[a]pyrene: a potent mutagenic arylamide derived from a carcinogenic polycyclic aromatic hydrocarbon

4-(N,N-Diacetylamino)benzo[a]pyrene, a potent mutagen, is derived from a carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene. Metabolism of this compound by rat liver microsomes was studied. Metabolites were separated by reversed-phase high-performance liquid chromatography and were identified by analysis of their UV-vis absorption, mass, and proton nuclear magnetic resonance spectral data. Seven metabolites were identified, namely, the 9-phenol, 1,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N,N-diacetylamino)benzo[a]pyrene, 4-(N-acetylamino)benzo[a]pyrene, and the 5-phenol, 5,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N-acetylamino)benzo[a]pyrene. Comparison of these results with those of metabolism of benzo[a]pyrene indicates that the N,N-diacetylamino substitutent at the 4-carbon of benzo[a]pyrene inhibits metabolism at the peri position (3-carbon) and positions (6-, 7-, and 8-carbons) remote from the substituent. The results also indicate that while 4-(N,N-diacetylamino)-benzo[a]pyrene is a substrate of the rat liver microsomal deacetylase, the formed 4-(N-acetylamino)benzo[a]pyrene apparently is not a substrate.     

Synthesis, spectral analysis, and mutagenicity of 1-, 3-, and 6-nitrobenzo[a]pyrene

The mutagenic environmental pollutants 1-, 3-, and 6-nitrobenzo[a]pyrene were synthesized. Nitration of 7,8,9,10-tetrahydrobenzo[a]pyrene with sodium nitrate in trifluoroacetic acid and acetic anhydride at ambient temperature gave a mixture of 1-, 3-, and 6-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, which was separated by chromatography. Dehydrogenation of the isolated nitrotetrahydrobenzo[a]pyrenes with 2,3-dichloro-4,5-dicyano-1,6-benzoquinone produced 1-, 3-, and 6-nitrobenzo[a]pyrene in high yield. Comparison of the spectral data of these compounds with those obtained from direct nitration of benzo[a]pyrene confirmed that 1- and 3-nitrobenzo[a]pyrenes are indeed the minor products of the latter reaction. This confirmation also verifies that 1- and 3-nitrobenzo[a]pyrene were the minor nitrated products of benzo[a]pyrene formed in model air atmospheres. The 1-, 3-, and 6-nitrobenzo[a]pyrene were mutagenic in Salmonella typhimurium tester strains TA98 and TA100 in the presence of a mammalian microsomal (S9) activating system. Both 1- and 3-nitrobenzo[a]pyrene, but not 6-nitrobenzo[a]pyrene, were also direct-acting mutagens in these strains. However, only 6-nitrobenzo[a]pyrene exhibited weak mutagenic activity when tested in Chinese hamster ovary cells, while only 3-nitrobenzo[a]pyrene produced a concentration-dependent decrease in cellular survival.     

Outbreak of acute hemorrhagic conjunctivitis due to coxsackie A24 variant--Taiwan

Outbreaks of acute hemorrhagic conjunctivitis caused by enterovirus 70 and several serotypes of adenovirus have occurred in Taiwan since 1971. In 1980-1981, there was a pandemic of acute hemorrhagic conjunctivitis in southeast Asia caused by coxsackie A24 variant (CA24v); however, this virus did not affect Taiwan. In October 1985, CA24v was isolated for the first time from patients with acute hemorrhagic conjunctivitis in southern Taiwan. The following summer, a large epidemic of acute hemorrhagic conjunctivitis due to CA24v occurred. An epidemiologic investigation of patients seen at one ophthalmology clinic in Taipei City revealed that school-age children were the most likely group to introduce illness into households (p less than 0.001) and that males were more often household index cases than were females (p less than 0.01). Multiple case households tended to be more crowded (3.0 vs. 2.5 persons per bathroom; p less than 0.05) and had illness introduced by younger family members (median age of index case = 10 vs. 17 years; p less than 0.01). It is unknown whether this outbreak is an isolated occurrence or represents another resurgence of CA24v in the area.     

应用低场磁共振成像诊断高血压脑出血的探讨

讨论了２６３例高血压脑出血超急性期及急性期血肿在低磁场磁共振成像中的信号特征，在Ｔ１加权像表现为高信号，Ｔ２加权像为混杂信号，与中、高磁场ＭＲＩ图像有所不同。低磁场ＭＲＩ对显示超急性期及急性期脑出血有较高的诊断敏感性和准确性。     

Difference in urinary stone components between obese and non-obese patients

The prevalence and incidence of urinary stone disease have been reported to be associated with body weight and body mass index (BMI). The aim of the study was to determine the difference in stone components among different BMI groups in patients with urolithiasis. Between Dec 2005 and Jan 2008, 907 urinary calculi were collected and analyzed by infrared spectroscopy. Most of the stones had been passed spontaneously, and some were collected during surgical manipulations. The data on patients’ gender, age, BMI at diagnosis, and stone composition were collected. The patients were classified as normal weight (18.5≤ BMI <24), overweight (24≤ BMI <27), or obese (BMI ≥27). Of the 907 patients with urinary stone disease, 27.7% had normal weight, 33.5% were overweight, and 38.8% were obese. The prevalence of calcium oxalate stones in the normal weight, overweight, and obese groups were 23.1, 30.6, and 34.9%, respectively (P = 0.002), and the prevalence of uric acid stones in the different groups was 2.8, 7.2, and 7.7%, respectively (P = 0.002). The prevalence of calcium oxalate and uric acid stones, but not that of calcium phosphate stones, increased with body size. There was a significant correlation between BMI and uric acid stones in the overweight and obesity groups, with odds ratios of 3.28 and 4.35, respectively. The prevalence and incidence of urinary stone disease were found to be associated with BMI. The percentage of uric acid and calcium oxalate stones was higher in obese than in non-obese patients. There was no apparent difference in the prevalence of calcium phosphate stones between obese and non-obese patients.     

Use of SternaLock plating system in acute treatment of unstable traumatic sternal fractures

Optimal surgical treatment of unstable sternal fractures is controversial. Wiring provides suboptimal fixation and adaptations of existing non-sternum specific plating systems may be dangerous when rapid sternal reentry is required. We present our experience with the sternal specific fixation system, SternaLock (Biomet Microfixation Inc, Jacksonville, FL), in the acute treatment of transverse sternal body fractures in 2 patients who sustained significant blunt anterior chest wall trauma. SternaLock provides the rigid sternal fixation necessary for reliable fracture healing while offering advantages over other systems with regards to ease of use and safety.     

Norepinephrine and hospital mortality in critically ill patients undergoing continuous renal replacement therapy

High-dose vasopressor use is associated with increasing mortality in patients with septic shock. We conducted this study to determine if the high-dose of vasopressor used before the initiation of continuous renal replacement therapy (CRRT) is associated with increasing mortality in critically ill patients. We retrospectively reviewed all patients who underwent CRRT in the medical intensive care unit of China Medical University Hospital between 2003 and 2007. The association between mortality and highest vasopressors (dopamine and norepinephrine [NE]) dose used were analyzed using Kaplan-Meier analysis and multivariate Cox regression. A total of 279 patients (170 men and 109 women) treated with CRRT in medical intensive care were reviewed and 237 (84.9%) died. In Kaplan-Meier analysis with log-rank test, dopamine dose of ≥20 μg/kg/min and NE dose of ≥0.3 μg/kg/min were significantly linked to mortality (P = 0.007 and <0.001). In multivariate Cox proportional hazards regression, NE dose of ≥0.3 μg/kg/min, Acute Physiology and Chronic Health Evaluation II score, and low platelet count were independently linked to mortality. The hazard ratios and 95% confidence interval (CI) were 1.771 (95% CI: 1.247-2.516, P = 0.001), 1.035 (95% CI: 1.012-1.058, P = 0.003), and 0.997 (95% CI: 0.996-0.999, P = 0.003), respectively. Critically ill patients treated with very high dose of NE before the initiation of CRRT have a very high mortality rate regardless of the acute kidney injury stage.