Trends and subgroup differences in transportation-related injury risk and safety behaviors among high school students, 1991-1997.

PURPOSE: To examine national trends in transportation-related injury risk and safety behaviors among U.S. high school students. METHODS: To examine secular trends in riding with a driver who had been drinking, driving after drinking, and using seat belts, bicycle helmets, and motorcycle helmets, we used logistic regression to analyze data from national Youth Risk Behavior Surveys (YRBS) conducted in 1991, 1993, 1995, and 1997. The YRBS is a self-administered, anonymous survey that uses a national probability sample of U.S. students in public and private schools from grades 9-12 (N = 55,734 for all years combined). RESULTS: The percentages of students who rode with a driver who had been drinking (36.6% in 1997), drove after drinking alcohol (16.9% in 1997), always wore seat belts (33.2% in 1997), and always wore a motorcycle helmet when riding a motorcycle (45.0% in 1997) remained stable between 1991 and 1997. From 1991 to 1997, the percentage of bicycle riders who always wore a helmet when bicycling showed a small but statistically significant increase (1.1% in 1991 to 3.8% in 1997), but helmet use remained low. CONCLUSION: Many young people place themselves at unnecessary risk for motor vehicle- and bicycle-related crash injuries and fatalities. Improved motor vehicle- and bicycle-related injury prevention strategies are needed that specifically target adolescents.

Relationship between cigarette, smokeless tobacco, and cigar use, and other health risk behaviors among U.S. high school students.

This study examined relationships between tobacco use and use of other substances, intentional injury risk behaviors, and sexual risk behaviors among US high school students. Data about tobacco use and other health risk behaviors were analyzed from the 1997 national Youth Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. One-fourth of students (24%) reported current use of a single tobacco product (i.e., cigarettes, smokeless tobacco, or cigars during the 30 days preceding the survey), and 19.5% reported currently using more than one tobacco product. Generally, students who reported current tobacco use also reported engaging in other substance use, intentional injury risk behaviors, and sexual risk behaviors. For many risk behaviors, these results were especially pronounced among students who reported using two or all three tobacco products. Programs designed to prevent tobacco use should consider that such use often occurs concomitantly with other health risk behaviors.

Use of birth control pills, condoms, and withdrawal among U.S. high school students.

PURPOSE: To examine the use of contraception at last sexual intercourse among currently sexually active adolescents. METHODS: We analyzed data from national school-based Youth Risk Behavior Surveys (YRBS) conducted in 1991, 1993, 1995, and 1997. The YRBS is a self-administered, anonymous survey which uses a national probability sample of U.S. students in public and private schools from grades 9 through 12. RESULTS: From 1991 to 1997, condom use significantly increased (from 46% to 57%), birth control pill use decreased (from 21% to 17%), and use of withdrawal significantly decreased (from 18% to 13%). In 1997, although more students were using condoms, 13% reported using withdrawal and 15% reported using no method to prevent pregnancy at last sexual intercourse. In 1997, condom use among females was significantly lower in the 9th grade than in the 12th grade (p <.001), whereas birth control pill use was higher (p <.001) and use of withdrawal remained stable. Among males, condom use and withdrawal use remained stable from 9th to 12th grade, whereas birth control pill use by their partner increased (p <.001). CONCLUSIONS: Inadequate contraceptive use among sexually active adolescents continues to be a major public health problem in the United States. For young people who will not remain sexually abstinent, families, health care providers, schools, and other influential societal institutions should promote the correct and continued use of condoms as essential protection against sexually transmitted diseases and human immunodeficiency virus infection.

Suicide ideation among US college students. Associations with other injury risk behaviors.

Suicide, the endpoint of a continuum that begins with suicide ideation, is the third leading cause of death among the US college-aged population. The first and second leading causes of death among this age group, unintentional injury and homicide, may also be linked to suicide ideation. We used data from the National College Health Risk Behavior Survey to examine the association between suicide ideation and injury-related behaviors among 18- to 24-year-old college students. Students who reported suicide ideation were significantly more likely than students who did not report considering suicide to carry a weapon, engage in a physical fight, boat or swim after drinking alcohol, ride with a driver who had been drinking alcohol, drive after drinking alcohol, and rarely or never used seat belts. Given this clustering of injury-related risk behaviors, college prevention programs should aim to reduce risks for injuries comprehensively, rather than addressing each risk behavior separately.

Initiation of cigarette smoking and subsequent smoking behavior among U.S. high school students.

BACKGROUND: Most adult smokers report trying their first cigarette before age 18 years. Understanding the impact of smoking initiation at young ages may help public health policy makers and practitioners improve strategies to prevent or delay adolescent cigarette smoking. METHODS: This paper examined age of initiation of cigarette smoking and subsequent patterns of smoking among U.S. high school students 16 years of age and older (N = 13,858). We used data from the 1991-1997 national Youth Risk Behavior Surveys, conducted by the Centers for Disease Control and Prevention. RESULTS: The majority of students 16 years of age and older (60.4%) reported ever having smoked a whole cigarette, and 11.1% initiated smoking at age 10 years or younger. Age of smoking initiation was significantly related to current frequent smoking, daily smoking, and whether students had ever smoked daily. A younger age of smoking initiation was associated with smoking more cigarettes per day than was initiating at an older age. CONCLUSIONS: Delaying the onset of smoking may affect the likelihood of becoming addicted to nicotine and smoking heavily. For students who are already addicted to nicotine, smoking cessation programs are needed.

Bioreductive activation of a series of indolequinones by human DT-diaphorase: structure-activity relationships.

A series of indolequinones including derivatives of EO9 bearing various functional groups and related indole-2-carboxamides have been studied with a view to identifying molecular features which confer substrate specificity for purified human NAD(P)H:quinone oxidoreductase (DT-diaphorase), bioreductive activation to DNA-damaging species, and selectivity for DT-diaphorase-rich cells in vitro. A broad spectrum of substrate specificity exists, but minor changes to the indolequinone nucleus have a significant effect upon substrate specificity. Modifications at the 2-position are favorable in terms of substrate specificity as these positions are located at the binding site entrance as determined by molecular modeling studies. In contrast, substitutions at the (indol-3-yl)methyl position with bulky leaving groups or a group containing a chlorine atom result in compounds which are poor substrates, some of which inactivate DT-diaphorase. Modeling studies demonstrate that these groups sit close to the mechanistically important amino acids Tyr 156 and His 162 possibly resulting in either alkylation within the active site or disruption of charge-relay mechanisms. An aziridinyl group at the 5-position is essential for potency and selectivity to DT-diaphorase-rich cells under aerobic conditions. The most efficient substrates induced qualitatively greater single-strand DNA breaks in cell-free assays via a redox mechanism involving the production of hydrogen peroxide (catalase inhibitable). This damage is unlikely to form a major part of their mechanism of action in cells since potency does not correlate with extent of DNA damage. In terms of hypoxia selectivity, modifications at the 3-position generate compounds which are poor substrates for DT-diaphorase but have high hypoxic cytotoxicity ratios.

Smoking initiation and smoking patterns among US college students.

The ages at which 18- to 24-year-old college students started smoking and its relationship to subsequent smoking were explored, using data from the 1995 National College Health Risk Behavior Survey. Most students (70%) had tried smoking; among those who had tried, 42% were current smokers, 19% were current frequent smokers, and 13% were current daily smokers. The majority (81%) who had ever smoked daily began doing so at age 18 years or younger, and 19% began smoking daily at age 19 years or older. Women were as likely as men to report ever having smoked a whole cigarette or ever having smoked daily. Most students (82%) who had ever smoked daily had tried to quit, but 3 in 4 were still smokers. Policies and programs designed to prevent the initiation of smoking and to help smokers quit are needed at both the high school and the college levels to reduce the proportion of young adults who smoke cigarettes.

Unsafe motor vehicle practices among substance-using college students.

This study examines the relationship between substance use and behaviors that increase the risk for motor vehicle crashes and crash-related injuries. The investigation uses National College Health Risk Behavior Survey data collected in 1995 by the Centers for Disease Control and Prevention. These data are representative of 2- and 4-year undergraduate college students in private and public colleges and universities in the United States. Smokers, episodic heavy drinkers, marijuana users and users of illegal drugs in combination with alcohol were significantly more likely to drive after drinking alcohol and ride with a driver who had been drinking alcohol and significantly less likely to wear safety belts while driving or while riding in a car as a passenger. This study indicates that college students who are substance users are more likely to behave in a manner which increases their risk for motor vehicle crashes and motor vehicle crash injuries.

Bioreductively-activated prodrugs for targeting hypoxic tissues: elimination of aspirin from 2-nitroimidazole derivatives.

2-Nitroimidazoles were synthesised substituted with aspirin or salicylic acid, as leaving groups linked through the (imidazol-5-yl)methyl position. Activation of aqueous solutions by CO2*- (a model one-electron reductant) resulted in release of aspirin or salicylate, probably via the 2-hydroxyaminoimidazole. The analogous 2-nitroimidazole with bromide as leaving group eliminated bromide in < 1 ms via the radical-anion.

Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones.

A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug.

Other substance use among high school students who use tobacco.

PURPOSE: To examine relationships between tobacco use and use of other substances among U.S. high school students, by gender and racial/ethnic subgroups. METHODS: Data about tobacco and other substance use were analyzed from the 1995 national Youth Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. RESULTS: Compared to nonsmokers, current smokers were significantly more likely to report use of all other substances we examined, including lifetime use of cocaine, inhalants, other illegal substances, and multiple substances and current alcohol use, episodic heavy drinking, marijuana use, and cocaine use. A strong dose-dependent relationship between current cigarette smoking and other substance use was identified. Among smokeless tobacco users, a strong dose-dependent relationship was found for all examined substances with the exception of lifetime and current cocaine use. Finally, a pattern of risk emerged suggesting that the likelihood of other substance use increases as students move from no tobacco use to smokeless tobacco use only, to cigarette smoking only, and to use of both smokeless tobacco and cigarettes. CONCLUSIONS: Programs designed to prevent tobacco or other substance use should consider that such use often occurs concomitantly.

Indolequinone bioreductive drugs: kinetic factors which influence selectivity for hypoxia.

The factors influencing the kinetics of the oxygen-sensitive reduction of indolequinones, including those bearing leaving groups in the (indol-3-yl)methyl position, have been studied. The hydroquinones derived from some representative indolequinones were found to autoxidize slowly in oxygenated solution at rates (effective rate constant with O2 approximately 40-300 M-1 s-1) that cannot compete with the reductive elimination of leaving groups. The rates of reaction between hydroquinone and O2 were even slower in the presence of approximately 4 microM superoxide dismutase (effective rate constant approximately 2-7 M-1 s-1), indicating the role of superoxide radicals in hydroquinone autoxidation. Since the release of the leaving groups from the hydroquinones is not significantly oxygen-sensitive, tumour selectivity requires specific reduction by enzymes that are overexpressed in some tumours. Conversely, the release of leaving groups from semiquinone radicals is inhibited by oxygen too efficiently unless the semiquinone reacts with targets on a timescale of milliseconds. Modification of redox properties has been explored with the aim of changing this oxygen sensitivity. The new 2-phenylindolequinones are approximately 60-100 mV higher in reduction potential than 2-alkyl derivatives but this is insufficient to decrease the rate of electron transfer from semiquinone to oxygen to a degree which might confer hypoxia-selective cytotoxicity. These results are discussed in the context of toxicity of EO9 and related compounds towards hypoxic rather than anoxic cells.

Sexual behavior among U.S. high school students, 1990-1995.

CONTEXT: High rates of unintended pregnancy and sexually transmitted diseases (STDs), including HIV infection, among adolescents are major public health concerns that have created interest in trends in teenage sexual activity. METHODS: Nationally representative data from Youth Risk Behavior Surveys conducted in 1990, 1991, 1993 and 1995 are used to examine levels of sexual experience, age at first intercourse, current sexual activity and condom use at last intercourse among students in grades 9-12. RESULTS: The proportion of students who reported being sexually experienced remained at 53-54% from 1990 through 1995, while the percentage of sexually active students who used condoms at last intercourse rose from 46% to 54% between 1991 and 1995. Black students were more likely than white students to report being sexually experienced, being currently sexually active and having had four or more lifetime sexual partners; black students also reported a significantly younger age at first intercourse. Gender differences in sexual behavior were found more frequently among black students than among white or Hispanic students. CONCLUSIONS: Although levels of sexual experience for high school students in the United States have not risen during the 1990s, a very high percentage of students continue to be at risk for unintended pregnancy and STDs, including HIV infection.

PIP: Nationally representative self-reported data from Youth Risk Behavior Surveys conducted in the US in 1990, 1991, 1993, and 1995 were used to examine levels of sexual experience, age at first intercourse, current sexual activity, and condom use at last intercourse among students in grades 9-12. The surveys sampled students at public and private schools in the 50 states and the District of Columbia; 11,631 in 1990, 12,272 in 1991, 16,296 in 1993, and 10,904 in 1995. Schools with high percentages of Black and Hispanic students were sampled at a higher rate. The proportion of students who reported being sexually experienced remained at 53-54% during 1990-95, while the percentage of sexually active students who used condoms at last intercourse increased from 46% in 1991 to 54% in 1995. Black students were more likely than White students to report being sexually experienced, being currently sexually active, and having had 4 or more lifetime sex partners. The median age reported for first intercourse was 16.5 years in all years. In 1995, the median age at first intercourse was 15.0 years among Blacks, 16.2 years among Hispanics, and 16.7 years among Whites. Gender differences in sexual behavior were found more often among Black students than among White and Hispanic students.

Tobacco and alcohol use in top-grossing American films.

This study assessed the prevalence of tobacco and alcohol use in top-grossing American films from 1985 to 1995. The top ten money-making films for 1985 to 1995 were viewed to identify the prevalence of alcohol and tobacco use overall and by lead characters. While the use of tobacco and alcohol was stable across the study period, use of these substances was common. Most films (98%) had references that supported tobacco use and 96% had references that supported alcohol use. Discouraging the use of these substances was uncommon. Only one third of films had any references that discouraged the use of tobacco or alcohol (38% and 37%, respectively). At least one lead character used tobacco or alcohol in 46% and 79% of the films, respectively. The hazards of smoking and drinking are not reflected in the behaviors of film characters who are potential role models for youth facing the decision to smoke or drink.

Indolequinone antitumor agents: reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro.

A series of indolequinones bearing a variety of leaving groups at the (indol-3-yl)methyl position was synthesized by functionalization of the corresponding 3-(hydroxymethyl)indolequinone, and the resulting compounds were evaluated in vitro as bioreductively activated cytotoxins. The elimination of a range of functional groups-carboxylate, phenol, and thiol-was demonstrated upon reductive activation under both chemical and quantitative radiolytic conditions. Only those compounds which eliminated such groups under both sets of conditions exhibited significant hypoxia selectivity, with anoxic:oxic toxicity ratios in the range 10-200. With the exception of the 3-hydroxymethyl derivative, radiolytic generation of semiquinone radicals and HPLC analysis indicated that efficient elimination of the leaving group occurred following one-electron reduction of the parent compound. The active species in leaving group elimination was predominantly the hydroquinone rather than the semiquinone radical. The resulting iminium derivative acted as an alkylating agent and was efficiently trapped by added thiol following chemical reduction and by either water or 2-propanol following radiolytic reduction. A chain reaction in the radical-initiated reduction of these indolequinones (not seen in a simpler benzoquinone) in the presence of a hydrogen donor (2-propanol) was observed. Compounds that were unsubstituted at C-2 were found to be up to 300 times more potent as cytotoxins than their 2-alkyl-substituted analogues in V79-379A cells, but with lower hypoxic cytotoxicity ratios.

Trends in tobacco use among high school students in the United States, 1991-1995.

This study examined demographic characteristics of tobacco-using high school students in the United States from 1991 through 1995. Data about cigarette smoking and smokeless tobacco use among adolescent were collected in 1991, 1993, and 1995 using the Youth Risk Behavior Survey, part of the Youth Risk Behavior Surveillance System implemented by the Centers for Disease Control and Prevention. Data indicated current smoking increased 26.5% from 1991 to 1995 with one-third [31.2% (+/- 1.7)] of ninth grade students and 38.2% (+/- 3.5) of 12th grade students reporting current smoking in 1995. Smokeless tobacco use remained stable with 11.4% (+/- 1.7) of all students and one-fourth [25.1% (+/- 3.0)] of White male students reporting smokeless tobacco use in 1995. Many students already have begun using tobacco before reaching high school. Thus, interventions should begin well before high school to prevent adolescents from using and becoming addicted to tobacco.

5-substituted analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7-dione]prop-2-en- 1-ol (EO9, NSC 382459) and their regioisomers as hypoxia-selective agents: structure-cytotoxicity in vitro.

A series of regioisomeric analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7-dione]prop-2-en-1 -ol (EO9, NSC 382459) with the hydroxymethyl and hydroxypropenyl substituents situated at either the 2- or the 3-position of the indole ring were synthesized. The compound lacking the 2-hydroxypropenyl substituent (31) had similar properties to EO9 under both aerobic and hypoxic conditions against V79 cells and was more potent against a human tumour cell line (A549) than EO9. It was reduced by human DT-diaphorase (DTD) at more than double the rate of EO9, thus implicating the importance of the enzyme activation step. Compound 16 (lacking the 3-hydroxymethyl substituent) was a better substrate for human DTD than EO9, yet exhibited lesser toxicity under both aerobic and hypoxic conditions. The toxicity generated by 16 was attributed to the 5-aziridinyl moiety and suggests a greater contribution from the 3-substituent over the 2-substituent. The toxicity of EO9 was attributed to a combination of the aziridinyl group and the leaving group properties of the 3-hydroxymethyl substituent. In general, compounds with a 5-methylaziridinyl moiety, such as EO8, exhibited substantially better hypoxia-selectivity due to much slower reduction by DTD (20-fold), thus reducing aerobic potency. All compounds had similar electron affinities, as indicated by their one-electron reduction potentials.

Re-appraisal of the tocopheroxyl radical reaction with beta-carotene: evidence for oxidation of vitamin E by the beta-carotene radical cation.

Photobleached beta-carotene (Car) is regenerated in hexane on a microsecond timescale in the presence of alpha-tocopherol (TOH) but not when alpha-tocopherol is absent, as studied by laser flash photolysis. Beta-carotene radical cations (Car.+) likewise react with (excess) alpha-tocopherol: Car.+ + TOH-->Car + TO. + H+ (second-order rate constant of k = 1.7 +/- 0.1 x 10(7) M(-1) s(-1) in homogeneous di-tert-butylperoxide/benzene at 20 degrees C) rather than alpha-tocopheroxyl radicals (TO.) reacting with beta-carotene. In hexane, hexane radicals formed by pulse radiolysis react considerably faster with beta-carotene (k = 2.1 +/- 0.1 x 10(9) M(-1) s(-1)) than with alpha-tocopherol (k = 4.9 +/- 0.1 x 10(6) M(-1) s(-1)). No evidence was obtained for a slower rate of beta-carotene radical cation formation in beta-carotene/alpha-tocopherol mixtures resulting from alpha-tocopheroxyl radical oxidation of beta-carotene. Steady-state radiolysis experiments confirmed that alpha-tocopherol protects beta-carotene from oxidation by hexane radicals. In both solvent systems, beta-carotene is regenerated from the radical cation by alpha-tocopherol rather than alpha-tocopherol being regenerated by beta-carotene from the alpha-tocopheroxyl radical.

Oxidative denitrification of the antitumour drug hydroxyguanidine.

The oxidative denitrification of the antitumour agent hydroxyguanidine (HOG) has been investigated by radiolysis methods and EPR spectroscopy. The azide radical (N3.), a model one-electron oxidant, reacts with HOG with the rate constant 5.1 x 10(9) dm3 mol(-1) s(-1) to yield the guanidino carbon-centred radical (HOG.) which rapidly eliminates nitric oxide (k = 3.1 x 10[3] s[-1]) with the concomitant formation of urea. The HOG. undergoes conjugation with molecular oxygen to form a peroxyl radical (HOGOO.) with a rate constant 8.8 x 10(8) dm3 mol(-1) s(-1). The HOGOO. radical also eliminates nitric oxide but may act as a precursor to the peroxynitrite (ONOO-) ion. The oxidation of HOG by the dibromide radical (Br2.-) was found to release nitric oxide with a yield of 95% relative to Br2.- as determined from the combined yields of inorganic nitrite, nitrate and a HOG/nitric oxide-adduct. This study provides a possible mechanistic basis for the oxidative denitrification of HOG which may contribute to the observed toxicity of the drug both in vitro and in vivo and for the oxidation of nonphysiological hydroxyguanidines to NO. via nitric oxide synthase-independent pathways.

Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants.

The comparative mechanisms and relative rates of nitrogen dioxide (NO2.), thiyl (RS.) and sulphonyl (RSO2.) radical scavenging by the carotenoid antioxidants lycopene, lutein, zeaxanthin, astaxanthin and canthaxanthin have been determined by pulse radiolysis. All the carotenoids under study react with the NO2. radical via electron transfer to generate the carotenoid radical cation (Car.+). In marked contrast the glutathione and 2-mercaptoethanol thiyl radicals react via a radical addition process to generate carotenoid-thiyl radical adducts [RS-Car].. The RSO2. radical undergoes both radical addition, [RSO2-Car]. and electron abstraction, Car.+. Both carotenoid adduct radicals and radical cations decay bimolecularly. Absolute rate constants for radical scavenging were in the order of approximately 10(7)-10(9) M(-1) s(-1) and follow the sequence HO(CH2)2S. > RSO2. > GS. > NO2.. Although there were some discernible trends in carotenoid reactivity for individual radicals, rate constants varied by no greater than a factor of 2.5. The mechanism and rate of scavenging is strongly dependent on the nature of the oxidising radical species but much less dependent on the carotenoid structure.