Reductive activation of potential antitumor bis(aziridinyl)benzoquinones by xanthine oxidase: Competition between oxygen reduction and quinone reduction

The reduction of a series of 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives with various 3,6 substituents by the enzyme xanthine oxidase has been studied. The reduction rate has been assayed by measuring the rate of reduction of cytochrome c, which is very efficiently reduced by reduced BABQ species. Under nitrogen, the reduction rate correlated with the quinone reduction potential and steric parameters. Comparing reduction rates under nitrogen and air demonstrates that at BABQ concentrations > 25 μm the competition for electrons from xanthine oxidase between oxygen and the BABQ derivative is dominated by the latter. This is also confirmed by the effect of superoxide dismutase (SOD): in the presence of a BABQ derivative, cytochrome c reduction can be totally inhibited by SOD, although the required amount of SOD depends on the redox potential of the quinones. This indicates that SOD causes the equilibrium between semiquinone and superoxide to shift, resulting in a decrease of the semiquinone concentration. It is concluded that reduction by xanthine oxidase is a simple and effective method for reducing aziridinylbenzoquinones

The relationship between blood benzodiazepine concentration and vehicle crash culpability

© International Association for Accident and Traffic MedicineOBJECTIVE: The purpose of this study was to determine the relationship between blood benzodiazepine concentration and crash risk. METHODS: Blood samples from 2500 injured drivers were analyzed for benzodiazepines and the relationship between concentration and crash risk was assessed using culpability analysis. Benzodiazepine concentrations were expressed as a proportion of the peak concentration of the drug in blood or plasma for a standard therapeutic dose of the drug. RESULTS: There were 68 drivers (2.7%) who tested positive for at least one benzodiazepine. Of these, 16 (23.5%) also tested positive for alcohol. Drivers who tested positive for benzodiazepines, either alone or in combination with alcohol, had a higher culpability rate than drug-free drivers. There was a significant linear relationship between benzodiazepine concentration and culpability for drivers who tested positive for benzodiazepines alone. CONCLUSION: The results here provide clear evidence of increased culpability associated with benzodiazepine use, which was marked at higher concentrations.Marie C. Longo, Robert J. Lokan and Jason M. Whit

The relation between the use of psychoactive substances and the severity of the injury in a group of crash-involved drivers admitted to a regional trauma center

OBJECTIVE: There is much evidence that driving under the influence of alcohol and/or drugs of abuse is related to an increased accident risk. A remaining question is whether the use of psychoactive substances is also related to clinically more severe accidents. The aim of this study is to explore the relationship between the use of psychoactive substances and the injury severity in a group of crash-involved drivers. METHODS: The study group included all injured car drivers, admitted to the regional trauma center, in the period from May 2000 until August 2001. The outcome of interest was the severity of injury, measured by using the Injury Severity Score (ISS). The determinant was the presence of psychoactive substances in blood and urine samples. Psychoactive substances tested for were alcohol, amphetamines, barbiturates, benzodiazepines, cannabis, methadone, opiates, and tricyclic antidepressants in blood and urine. RESULTS: The number of injured car drivers included in this study was 106. Overall, 43% (46/106) of the drivers tested positive for at least one psychoactive substance. Comparison of the means of the log ISS suggests that there is no significant difference between drivers who tested positive for alcohol and/or drugs, compared to drivers tested negative. CONCLUSION: The results of this study support the hypothesis that there is no clear association between use of psychoactive substances and the severity of crash-related injury

Comparison of urine and oral fluid as matrices for screening of thirty-three benzodiazepines and benzodiazepine-like substances using immunoassay and LC-MS(-MS)

Benzodiazepines are the most frequently detected medicinal drugs in drivers. The use of benzodiazepines is associated with an increased road accident risk. In this study, the presence of benzodiazepines detected by liquid chromatography-(tandem) mass spectrometry [LC-MS(-MS)] in oral fluid and urine samples obtained from drivers stopped during a roadside survey was compared. In addition, the sensitivity and selectivity of enzyme multiplied immunoassay technique (EMIT | II Plus) relative to LC-MS(-MS) was determined for both matrices. A total number of 1011 urine samples were collected and screened for benzodiazepines using immunoassay (IA) (EMIT II Plus; cutoff 300 ng/mL). In the IA-positive (n = 25) and a group of randomly selected negative urine samples (n = 79), the presence or absence of benzodiazepines was confirme