Electrophysiological and contractile evidence of the ability of human mesenchymal stromal cells to correct vascular malfunction in rats after ionizing irradiation.

The effect of intravenous administration of human mesenchymal stromal stem cells (hMSC) has been evaluated by means of large-conductance calcium-dependent potassium channel (BK(Ca)) activity measurements in thoracic aorta smooth muscle cells (SMC) obtained from non-fatal whole-body irradiated rats, using the patch clamp technique in whole-cell modification, and the standard acetylcholine (ACh) test to evaluate functional endothelium integrity using SM contractile recordings. Myofilament calcium sensitivity was estimated using simultaneous contractile recordings versus [Ca(2+)](i). Arterial blood was measured in intact and irradiated rats before and after hMSC administration. Stimulation of isolated SMC from the control group of animals with depolarizing voltage steps showed that outward K(+) currents sensitive to the BK(Ca) inhibitor paxilline were expressed. Outward currents in SMC obtained from irradiated animals were significantly reduced on the 30th day of post-irradiation. Irradiation led to a significant elevation in arterial blood pressure and reduced ACh-induced relaxation responses in irradiated rats as compared with the control group. Simultaneous measurements of contractile force and [Ca(2+)](i) showed that myofilament Ca(2+) sensitivity had increased following irradiation. Intravenously injected hMSC effectively restored BK(Ca) current and the amplitude of ACh-induced endothelium-dependent vasodilatation in vascular tissues obtained from post-irradiated rats. SMC obtained from irradiated rats treated with hMSC demonstrated a significantly increased paxilline-sensitive component of outward potassium currents, indicating that BK(Ca) activity had been restored. hMSC administration normalized increased blood pressure and myofilament Ca(2+) sensitivity in irradiated animals. When administered to healthy rats, hMSC were without effects on either of these. This study does not provide any immunohistochemical proof of hMSC engraftment in the host rats. PCR analysis showed that hMSCs were negative for hematopoietic cell markers and positive for hMSC markers. There were no clinical signs of graft-versus-host disease throughout the experimental period of 30 days. The data obtained suggest that hMSC demonstrate a clearly expressed ability to normalize vascular function damaged following irradiation, i.e. to reduce an elevated arterial blood pressure and myofilament Ca(2+) sensitivity, and to repair BK(Ca) function and endothelium-dependent relaxation in vascular tissues obtained from irradiated animals. Thus, hMSC seem to be worthwhile therapeutic approach in cases of ionizing irradiation accident or radiation beam therapy.

Caution: a comment on Alena Erke's red light for red-light cameras? A meta-analysis of the effects of red-light cameras on crashes.

In Red Light for Red-Light Cameras?, Alena Erke concludes that "... on the whole, redlight cameras do not seem to be a successful safety measure." Although Erke's survey of the literature appears to have been comprehensive, her review of the studies was not critical. She appears to have accepted the authors' descriptions of their analyses rather than providing readers with her own considered opinion of how valid those analyses were and what their true implications might be. For the meta-analysis leading to her final conclusion, Erke combines data from two questionable studies with three other "well-controlled" studies. Non-peer-reviewed studies received substantial statistical weight in the meta-analysis. These problems likely produce misleading results. If the highway safety field is to succeed in identifying for policymakers those strategies that are most likely to reduce the human tragedy of motor vehicle crashes, we need first to focus on conducting valid research and analysis. Adding precision to the estimated benefits of those strategies through meta-analysis is important, but secondary, and cannot replace the function of a systematic and critical review.

Quercetin-filled phosphatidylcholine liposomes restore abnormalities in rat thoracic aorta BK(Ca) channel function following ionizing irradiation.

The goal of the present study was to investigate the effects of quercetin-filled phosphatidylcholine liposomes (PCL-Q) on the currents carried by large conductance Ca(2+)-dependent K(+) channels (BK(Ca)) in rat thoracic aorta following non-fatal whole-body ionizing irradiation. Using patch-clamp technique, it is found that the outward K(+) currents of isolated smooth muscle cells (SMCs) stimulated by depolarizing voltage steps were sensitive to BK(Ca) inhibitor, paxilline, and this kind of outward K(+) currents in SMCs from irradiated animals demonstrated a significant decrease in amplitude. Radiation-induced BK(Ca) suppression was evident 9 days post-irradiation and progressively increased over 30 days of experimental period. Thus, the vasorelaxing force of these SMCs may be diminished following irradiation. PCL-Q effectively restored BK(Ca) function in post-irradiated SMCs. It is noteworthy that the constituents of PCL-Q, i.e., free quercetin (Q) and "empty" liposomes (PCL), being taken separately, showed a decreased ability to recover BK(Ca) function as compared with combined composition. These results suggest that PCL-Q is able to regain normal function of BK(Ca) following irradiation. The protective effects of PCL-Q can be explained by its antioxidant and membrane repairing properties as well as its ability to inhibit protein kinase C activity. Thus, the lipid encapsulation of flavonoid, PCL-Q, appears to be a potential medication in the case of ionizing irradiation accident, and for the patients with neoplasm who have to receive external radiotherapy as well.

Functional and molecular consequences of ionizing irradiation on large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells.

AIMS: The goal of this study was to evaluate the influence of gamma-irradiation on Ca(2+)-activated K(+) channel (BK(Ca)) function and expression in rat thoracic aorta. MAIN METHODS: Aortic cells or tissues were studied by the measurement of force versus [Ca(2+)](i), patch-clamp technique, and RT-PCR. KEY FINDINGS: Stimulation of smooth muscle cells with depolarizing voltage steps showed expression of outward K(+) currents. Paxilline, an inhibitor of BK(Ca) channels, decreased outward K(+) current density. Outward currents in smooth muscle cells obtained from irradiated animals 9 and 30 days following radiation exposure demonstrated a significant decrease in K(+) current density. Paxilline decreased K(+) current in cells obtained 9 days, but was without effect 30 days after irradiation suggesting the absence of BK(Ca) channels. Aortic tissue from irradiated animals showed progressively enhanced contractile responses to phenylephrine in the post-irradiation period of 9 and 30 days. The concomitant Ca(2+) transients were significantly smaller, as compared to tissues from control animals, 9 days following irradiation but were increased above control levels 30 days following irradiation. Irradiation produced a decrease in BK(Ca) alpha- and beta(1)-subunit mRNA levels in aortic smooth muscle cells suggesting that the vasorelaxant effect of these channels may be diminished. SIGNIFICANCE: These results suggest that the enhanced contractility of vascular tissue from animals exposed to radiation may result from an increase in myofilament Ca(2+) sensitivity in the early post-irradiation period and a decrease in BK(Ca) channel expression in the late post-irradiation period.

Evaluation of automated speed enforcement on Loop 101 freeway in Scottsdale, Arizona.

Speed cameras can reduce speeding and injury crashes, but in many communities they are confined to low-speed settings such as residential streets and school zones. In 2006 the city of Scottsdale, Arizona, implemented a 9-month pilot program to evaluate the feasibility and effects of highly visible speed camera enforcement on a busy urban freeway. This was the first use of fixed speed cameras on a major US highway. Deployment of six cameras along an 8-mile corridor was associated with large declines in mean speeds and an 88% decrease in the odds of vehicles traveling 11 mph or more above the 65 mph limit. Traffic speeds increased soon after the pilot program was suspended. In addition to reducing speeding along the enforcement corridor, speed cameras were associated with large reductions in speeding on the same highway but 25 miles away from the camera installations. However, traffic speeds were fairly stable on urban freeways in Scottsdale that were not part of the study road. Public opinion surveys found widespread concerns about speeding on the Loop 101 freeway and high levels of support for speed camera enforcement on this road.

Efficacy of side airbags in reducing driver deaths in driver-side car and SUV collisions.

OBJECTIVE: To estimate the efficacy of side airbags in preventing driver deaths in passenger vehicles struck on the driver side. METHODS: Risk ratios for driver deaths per driver-side collision were computed for side airbag-equipped cars and SUVs, relative to vehicles without side airbags. Driver fatality ratios also were calculated for the same vehicles in front and rear impacts, and these were used to adjust the side crash risk ratios for differences in fatality risk unrelated to side airbags. Risk ratios were calculated separately for side airbags providing torso-only protection and side airbags with head protection; almost all head protecting airbags also had airbags protecting the torso. RESULTS: Car driver death risk in driver-side crashes was reduced by 37 percent for head protecting airbags and 26 percent for torso-only side airbags. Car driver death risk was reduced for older and younger drivers, males and females, and drivers of small and midsize cars, and when the striking vehicle was an SUV/pickup or a car/minivan. Death risk for drivers of SUVs was reduced by 52 percent with head protecting side airbags and by 30 percent with torso-only airbags. The effectiveness of side airbags could not be assessed for pickups and minivans due to the small number of these vehicles with airbags involved in crashes. CONCLUSION: Side airbags substantially reduce the risk of car and SUV driver death in driver-side collisions. Making side airbags with head protection available to drivers and right front passengers in all passenger vehicles could reduce the number of fatalities in motor vehicle crashes in the United States by about 2,000 each year.

Use and misuse of motor-vehicle crash death rates in assessing highway-safety performance.

OBJECTIVES: The objectives of the article are to assess the extent to which comparisons of motor-vehicle crash death rates can be used to determine the effectiveness of highway-safety policies over time in a country or to compare policy effectiveness across countries. METHODS: Motor-vehicle crash death rates per mile traveled in the 50 U.S. states from 1980 to 2003 are used to show the influence on these rates of factors independent of highway-safety interventions. Multiple regression models relating state death rates to various measures related to urbanization and demographics are used. RESULTS: The analyses demonstrate strong relationships between state death rates and urbanization and demographics. Almost 60% of the variability among the state death rates can be explained by the independent variables in the multiple regression models. When the death rates for passenger vehicle occupants (i.e., excluding motorcycle, pedestrian, and other deaths) are used in the regression models, almost 70% of the variability in the rates can be explained by urbanization and demographics. CONCLUSIONS: The analyses presented in the article demonstrate that motor-vehicle crash death rates are strongly influenced by factors unrelated to highway-safety countermeasures. Overall death rates should not be used as a basis for judging the effectiveness (or ineffectiveness) of specific highway-safety countermeasures or to assess overall highway-safety policies, especially across jurisdictions. There can be no substitute for the use of carefully designed scientific evaluations of highway-safety interventions that use outcome measures directly related to the intervention; e.g., motorcyclist deaths should be used to assess the effectiveness of motorcycle helmet laws. While this may seem obvious, there are numerous examples in the literature of death rates from all crashes being used to assess the effectiveness of interventions aimed at specific subsets of crashes.

Characteristics of speeders.

OBJECTIVE: To determine the characteristics of speeders, defined as drivers of vehicles traveling at least 15 mph above the posted speed limit and relatively faster than surrounding vehicles. METHODS: Vehicle speeds were recorded on 13 roads in Virginia with speed limits ranging from 40 to 55 mph. Speeders were compared with slower drivers, defined as drivers of adjacent vehicles traveling no more than 5 mph above the speed limit. License plates were used to identify vehicle owners; owners were inferred to have been driving if observed gender and estimated age matched those of the registered owner. For these drivers, information on exact driver age and gender, vehicle make and model, and driving record was obtained from the Virginia Department of Motor Vehicles. RESULTS: Five percent of the vehicles observed were traveling at least 15 mph above the limit, and 3% qualified as speeders, as defined in this study. Speeders were younger than drivers in the comparison group, drove newer vehicles, and had more speeding violations and other moving violations on their records. They also had 60% more crashes. DISCUSSION: Speeders are a high-risk group. Their speeding behavior is not likely to be controlled without vigorous, consistent enforcement, including the use of automated technology.

Florida's weakened motorcycle helmet law: effects on death rates in motorcycle crashes.

OBJECTIVES: Effective July 1, 2000, Florida's universal helmet law was amended to exclude riders ages 21 and older with insurance coverage providing at least 10,000 US dollars in medical benefits for injuries sustained in a motorcycle crash. Observed helmet use in Florida was reported to have declined from nearly 100% in 1998, before the law change, to 53% after. This study examined the effects of the law change on the likelihood of death, given involvement in a motorcycle crash. METHODS: Rates of motorcyclist deaths per crash involvement in Florida for 2001-2002 (after the law change) were compared with those for 1998-1999 (before the law change). Before/after death rate ratios (95% CIs) were examined, and logistic regression models estimated the effect of the helmet law change on the odds of death in a crash, while controlling for rider gender, age, and seating position, and number of vehicles. RESULTS: The motorcyclist death rate increased significantly after the law change, from 30.8 to 38.8 deaths per 1,000 crash involvements. Motorcyclist death rates increased for single- and multiple-vehicle crashes, for male and female operators, and for riders of all ages including those younger than 21. After controlling for gender and age, the likelihood of death given involvement in a motorcycle crash was 25% higher than expected after the law change. It is estimated that 117 motorcyclist deaths could have been avoided during 2001-2002 if Florida's universal helmet law had remained in place. CONCLUSIONS: This study provides evidence of the life-saving benefits of universal helmet laws. The results also suggest that age-specific helmet laws are not effective in protecting the youngest drivers. This is not surprising, as these laws are largely unenforceable.

Driver mortality in frontal crashes: comparison of newer and older airbag designs.

In 1997, the National Highway Traffic Safety Administration amended its requirements for frontal crash performance under Federal Motor Vehicle Safety Standard 208 to temporarily allow 30 mi/h (48 km/h) sled tests with unbelted dummies as an alternative to 30 mi/h head-on rigid-barrier vehicle tests. This change permitted automakers to reduce airbag inflation forces so that they would be less likely to injure occupants who are close to airbags when they first deploy. Most vehicle models were sled-certified starting in model year 1998. Airbag-related deaths have decreased since 1997; however, controversy persists about whether reduced inflation forces might be decreasing protection for some occupants in high-severity frontal crashes. To examine the effects of the regulatory changes, this study computed rate ratios (RR) and 95% confidence intervals (95% CI) for passenger vehicle driver deaths per vehicle registration during 2000-2002 at principal impact points of 12 o'clock for 1998-99 model year vehicles relative to 1997 models. Passenger vehicles included in the study had both driver and passenger front airbags, had the same essential designs during the 1997-1999 model years, and had been sled-certified for drivers throughout model years 1998 and 1999. An adjustment was made for the higher annual mileage of newer vehicles. Findings were that the effect of the regulatory change varied by vehicle type. For cars, sport utility vehicles, and minivans combined, there was an 11 percent decrease in fatality risk in frontal crashes after changing to sled certification (RR = 0.89; 95% CI = 0.82-0.96). Among pickups, however, estimated frontal fatality risk increased 35 percent (RR = 1.35; 95% CI = 1.12-1.62). For a broad range of frontal crashes (11, 12, and 1 o'clock combined), the results indicated a modest net benefit of the regulatory change across all vehicle types and driver characteristics. However, the contrary finding for pickups needs to be researched further.

Comparing driver frontal mortality in vehicles with redesigned and older-design front airbags.

In 1997, the National Highway Traffic Safety Administration amended its requirements for frontal crash performance under Federal Motor Vehicle Safety Standard 208 to temporarily allow 30 mph (48 kph) sled tests with unbelted dummies as an alternative to 30 mph head-on rigid-barrier vehicle tests. This change permitted automakers to reduce airbag inflation forces so that they would be less likely to injure occupants who are close to airbags when they first deploy. Most vehicle models were sled-certified starting in model year 1998. Airbag-related deaths have decreased since 1997; however, controversy persists about whether reduced inflation forces might be decreasing protection for some occupants in high-severity frontal crashes. To examine the effects of the regulatory changes, this study computed rate ratios (RR) and 95 percent confidence intervals (95% CI) for passenger vehicle driver deaths per vehicle registration during 2000-02 at principal impact points of 12 o'clock for 1998-99 model year vehicles relative to 1997 models. Passenger vehicles included in the study had both driver and passenger front airbags, had the same essential designs during the 1997-99 model years, and had been sled-certified for drivers throughout model years 1998 and 1999. An adjustment was made for the higher annual mileage of newer vehicles. Findings were that the effect of the regulatory change varied by vehicle type. For cars, sport utility vehicles, and minivans combined, there was an 11 percent decrease in fatality risk in frontal crashes after changing to sled certification (RR=0.89; 95% CI=0.82-0.96). Among pickups, however, estimated frontal fatality risk increased 35 percent (RR=1.35; 95% CI=1.12-1.62). For a broad range of frontal crashes (11, 12, and 1 o'clock combined), the results indicated a modest net benefit of the regulatory change across all vehicle types and driver characteristics. However, the contrary finding for pickups needs to be researched further.

Efficacy of side air bags in reducing driver deaths in driver-side collisions.

Side air bags, a relatively new technology designed to protect the head and/or torso in side-impact collisions, are becoming increasingly common in automobiles. Their efficacy in preventing US driver deaths among cars struck on the near (driver's) side was examined using data from the Fatality Analysis Reporting System and the General Estimates System. Risk ratios for driver death per nearside collision during 1999-2001 were computed for head/torso and torso-only side air bags in cars from model years 1997-2002, relative to cars without side air bags. Confounding was addressed by adjusting nearside risk ratios for front- and rear-impact mortality, which is unaffected by side air bags. Risk ratios were 0.55 (95% confidence interval: 0.43, 0.71) for head/torso air bags and 0.89 (95% confidence interval: 0.79, 1.01) for torso-only air bags. Risk was reduced when cars with head/torso air bags were struck by cars/minivans (significant) or pickup trucks/sport utility vehicles (nonsignificant). Risk was reduced in two-vehicle collisions and among male drivers and drivers aged 16-64 years. Protective effects associated with torso-only air bags were observed in single-vehicle crashes and among male and 16- to 64-year-old drivers. Head/torso side air bags appear to be very effective in reducing nearside driver deaths, whereas torso-only air bags appear less protective.

Reductions in injury crashes associated with red light camera enforcement in oxnard, california.

OBJECTIVES: This study estimated the impact of red light camera enforcement on motor vehicle crashes in one of the first US communities to employ such cameras-Oxnard, California. METHODS: Crash data were analyzed for Oxnard and for 3 comparison cities. Changes in crash frequencies were compared for Oxnard and control cities and for signalized and nonsignalized intersections by means of a generalized linear regression model. RESULTS: Overall, crashes at signalized intersections throughout Oxnard were reduced by 7% and injury crashes were reduced by 29%. Right-angle crashes, those most associated with red light violations, were reduced by 32%; right-angle crashes involving injuries were reduced by 68%. CONCLUSIONS: Because red light cameras can be a permanent component of the transportation infrastructure, crash reductions attributed to camera enforcement should be sustainable.