Toxicology and Applied PharmacologyVolume 235, Issue 2, 1 March 2009, Pages 208-215 Impaired mitochondrial respiration and protein nitration in the rat hippocampus after acute inhalation of combustion smoke
Heung M. Leea, Jason Reeda, George H. Greeley Jr.a and Ella W. Englandera, b, ,
aDepartment of Surgery, University of Texas Medical Branch, USA
bShriners Hospitals for Children, Galveston, TX, USA
Survivors of massive inhalation of combustion smoke endure critical injuries, including lasting neurological complications. We have previously reported that acute inhalation of combustion smoke disrupts the nitric oxide homeostasis in the rat brain. In this study, we extend our findings and report that a 30-minute exposure of awake rats to ambient wood combustion smoke induces protein nitration in the rat hippocampus and that mitochondrial proteins are a sensitive nitration target in this setting. Mitochondria are central to energy metabolism and cellular signaling and are critical to proper cell function. Here, analyses of the mitochondrial proteome showed elevated protein nitration in the course of a 24-hour recovery following exposure to smoke. Mass spectrometry identification of several significantly nitrated mitochondrial proteins revealed diverse functions and involvement in central aspects of mitochondrial physiology. The nitrated proteins include the ubiquitous mitochondrial creatine kinase, F1-ATP synthase α subunit, dihydrolipoamide dehydrogenase (E3), succinate dehydrogenase Fp subunit, and voltage-dependent anion channel (VDAC1) protein. Furthermore, acute exposure to combustion smoke significantly compromised the respiratory capacity of hippocampal mitochondria. Importantly, elevated protein nitration and reduced mitochondrial respiration in the hippocampus persisted beyond the time required for restoration of normal oxygen and carboxyhemoglobin blood levels after the cessation of exposure to smoke. Thus, the time frame for intensification of the various smoke-induced effects differs between blood and brain tissues. Taken together, our findings suggest that nitration of essential mitochondrial proteins may contribute to the reduction in mitochondrial respiratory capacity and underlie, in part, the brain pathophysiology after acute inhalation of combustion smoke.
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BrooklynDodger(s) comment: The Dodger(s) will have to search the full text to determine the exposure level. The Dodger(s) suspect that the nitration of proteins observed is triggered by nanoparticles in the smoke absorbed into the brain. The findings indicate that impaired energy metabolism attributed solely to carbon monoxide has other bases as well.
Monday, March 02, 2009
Sunday, March 01, 2009
Is Sex Change and Migration the Most Effective Way to Prevent Traffic Fatalities?
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5807a1.htm?s_cid=mm5807a1_e
MMWR February 27, 2009 / 58(07);161-165
Motor Vehicle--Related Death Rates --- United States, 1999--2005
"In 2005, the most recent year for which data are available, 45,520 deaths in the United States were related to motor vehicles (1). A Healthy People 2010 objective calls for reducing the rate of deaths related to motor vehicles to 9.2 per 100,000 population from a baseline of 15.6 in 1998 (2). ...during 1999--2005, although annual age-adjusted motor vehicle--related death rates overall were nearly unchanged (range: 15.2--15.7 per 100,000 population), substantial differences were observed by state, U.S. Census region,* sex, race, and age group. Among states, the average annual death rate ranged from 7.9 per 100,000 population in Massachusetts to 31.9 in Mississippi. Among regions, the rate ranged from 9.8 per 100,000 population in the Northeast to 19.5 in the South. The rate for men (21.7 per 100,000 population) was more than double the rate for women (9.4);
"...During an earlier period, from 1969 to 1992, the overall annual rate of motor vehicle--related deaths in the United States decreased 43%, from 27.7 per 100,000 population§ to 15.8 (1), a rate only slightly higher than the rate observed during 1999--2005."
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BrooklynDodger(s) Comment: Transportation injuries are important for occupational health, injury control needs greater recognition as part of public health, and traffic injuries become the frame through which practioners see many other injuries. So, the Dodger(s) will be making (snarky comments) about this important current report. The authors acknowledge that these data must be adjusted for vehicle miles driven, and for type of road. What would we think of an industry whose products, used as expected, kill over 45,000 Americans a year? That industry includes not just the vehicle makers, but the road makers, the transporation planners, the traffic cops, etc.
Intervention should be data based. From the numbers quoted here, whatever the intervention was between 1969 and 2002, it either stopped or stopped working having reached the limits of effectiveness. Sounding silly, the most obvious reductions could be achieved if men living in Missisippi (or the South in general) became women living in Massachusetts (or the Northeast.) Since the public health system can't achieve that transgender and geographic migration, what could be achieved?
MMWR February 27, 2009 / 58(07);161-165
Motor Vehicle--Related Death Rates --- United States, 1999--2005
"In 2005, the most recent year for which data are available, 45,520 deaths in the United States were related to motor vehicles (1). A Healthy People 2010 objective calls for reducing the rate of deaths related to motor vehicles to 9.2 per 100,000 population from a baseline of 15.6 in 1998 (2). ...during 1999--2005, although annual age-adjusted motor vehicle--related death rates overall were nearly unchanged (range: 15.2--15.7 per 100,000 population), substantial differences were observed by state, U.S. Census region,* sex, race, and age group. Among states, the average annual death rate ranged from 7.9 per 100,000 population in Massachusetts to 31.9 in Mississippi. Among regions, the rate ranged from 9.8 per 100,000 population in the Northeast to 19.5 in the South. The rate for men (21.7 per 100,000 population) was more than double the rate for women (9.4);
"...During an earlier period, from 1969 to 1992, the overall annual rate of motor vehicle--related deaths in the United States decreased 43%, from 27.7 per 100,000 population§ to 15.8 (1), a rate only slightly higher than the rate observed during 1999--2005."
>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: Transportation injuries are important for occupational health, injury control needs greater recognition as part of public health, and traffic injuries become the frame through which practioners see many other injuries. So, the Dodger(s) will be making (snarky comments) about this important current report. The authors acknowledge that these data must be adjusted for vehicle miles driven, and for type of road. What would we think of an industry whose products, used as expected, kill over 45,000 Americans a year? That industry includes not just the vehicle makers, but the road makers, the transporation planners, the traffic cops, etc.
Intervention should be data based. From the numbers quoted here, whatever the intervention was between 1969 and 2002, it either stopped or stopped working having reached the limits of effectiveness. Sounding silly, the most obvious reductions could be achieved if men living in Missisippi (or the South in general) became women living in Massachusetts (or the Northeast.) Since the public health system can't achieve that transgender and geographic migration, what could be achieved?
Saturday, February 28, 2009
Mechanisms of Formaldehyde Respiratory Effects Explored
Toxicology and Applied PharmacologyVolume 233, Issue 3, 15 December 2008, Pages 355-359
Mechanistic and dose considerations for supporting adverse pulmonary physiology in response to formaldehyde
Chad M. Thompsona, , , Ravi P. Subramaniama and Roland C. Grafströmb, c
aNational Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, 8623-P, Washington, DC, 20460, USA
bInstitute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
cVTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, FI-20521 Turku, Finland
Abstract
Induction of airway hyperresponsiveness and asthma from formaldehyde inhalation exposure remains a debated and controversial issue. Yet, recent evidences on pulmonary biology and the pharmacokinetics and toxicity of formaldehyde lend support for such adverse effects. Specifically, altered thiol biology from accelerated enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione and pulmonary inflammation from involvement of Th2-mediated immune responses might serve as key events and cooperate in airway pathophysiology.
Understanding what role these mechanisms play in various species and lifestages (e.g., child vs. adult) could be crucial for making more meaningful inter- and intra-species dosimetric extrapolations in human health risk assessment.
>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: This publication co-authored by EPA again suggests that EPA is laying on ammunition for an upcoming battle over a risk assessment for formaldehyde. Apparently some investigators have generated a controversy over formaldehyde as a risk factor for asthma, so EPA has sought to explore the other side of the argument. Apparently, the mechanistic extrapolation market has been cornered by the other guys in the US, so EPA went to Scandinavia for collaborators.
Mechanistic and dose considerations for supporting adverse pulmonary physiology in response to formaldehyde
Chad M. Thompsona, , , Ravi P. Subramaniama and Roland C. Grafströmb, c
aNational Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, 8623-P, Washington, DC, 20460, USA
bInstitute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
cVTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, FI-20521 Turku, Finland
Abstract
Induction of airway hyperresponsiveness and asthma from formaldehyde inhalation exposure remains a debated and controversial issue. Yet, recent evidences on pulmonary biology and the pharmacokinetics and toxicity of formaldehyde lend support for such adverse effects. Specifically, altered thiol biology from accelerated enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione and pulmonary inflammation from involvement of Th2-mediated immune responses might serve as key events and cooperate in airway pathophysiology.
Understanding what role these mechanisms play in various species and lifestages (e.g., child vs. adult) could be crucial for making more meaningful inter- and intra-species dosimetric extrapolations in human health risk assessment.
>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: This publication co-authored by EPA again suggests that EPA is laying on ammunition for an upcoming battle over a risk assessment for formaldehyde. Apparently some investigators have generated a controversy over formaldehyde as a risk factor for asthma, so EPA has sought to explore the other side of the argument. Apparently, the mechanistic extrapolation market has been cornered by the other guys in the US, so EPA went to Scandinavia for collaborators.
Friday, February 27, 2009
Some Evidence That Ultrafine Carbon Particles Cause autonomic modulation of the heart and repolarization of the ventricular myocardium.
ECG Parameters and Exposure to Carbon Ultrafine Particles in Young Healthy Subjects.
Zareba, Wojciech1Couderc, Jean Philippe1Oberdörster, Gunter2Chalupa, David1Cox, Christopher3Li-Shan Huang4Peters, Annette5Utell, Mark J.1Frampton, Mark W.1 mark•frampton@urmc.rochester.edu
Inhalation Toxicology; Mar2009, Vol. 21 Issue 3, p223-233, 11p
Abstract:
The mechanisms underlying the association between air pollution and cardiovascular morbidity and mortality are unknown. This study aimed to determine whether controlled exposure to elemental carbon ultrafine particles (UFP) affects electrocardiogram (ECG) parameters describing heart rate variability; repolarization duration, morphology, and variability; and changes in the ST segment. Two separate controlled studies (12 subjects each) were performed using a crossover design, in which each subject was exposed to filtered air and carbon UFP for 2 hours. The first protocol involved 2 exposures to air and 10 μg/m3 (∼ 2× 106 particles/cm3, count median diameter ∼25 nm, geometric standard deviation ∼1.6), at rest. The second protocol included 3 exposures to air, 10, and 25 μg/m3 UFP (∼ 7× 106 particles/cm3), with repeated exercise. Each subject underwent a continuous digital 12-lead ECG Holter recording to analyze the above ECG parameters. Repeated measures analysis of variance (ANOVA) was used to compare tested parameters between exposures. The observed responses to UFP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFP in comparison to air exposure. In conclusion, transient exposure to 10-25 μ g/m3 ultrafine carbon particles does not cause marked changes in ECG-derived parameters in young healthy subjects. However, trends are observed indicating that some subjects might be susceptible to air pollution, with a response involving autonomic modulation of the heart and repolarization of the ventricular myocardium.
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BrooklynDodger(s) Comment: Oberdorster is a leading authority on health effects of inhalation of small particles. Remember that carbon used to be considered inert, but now is a 2B carcinogen, among other respiratory effects. The text of the abstract gives indication of negotiation with the reviewers; whether the conclusion was bargained down or bargained up can't be told. So maybe this is equivocal evidence rather than some evidence for an effect on the heart after 2 hours at 25 ug/M3 in a small sample size of healthy volunteers. ?graduate students?
Zareba, Wojciech1Couderc, Jean Philippe1Oberdörster, Gunter2Chalupa, David1Cox, Christopher3Li-Shan Huang4Peters, Annette5Utell, Mark J.1Frampton, Mark W.1 mark•frampton@urmc.rochester.edu
Inhalation Toxicology; Mar2009, Vol. 21 Issue 3, p223-233, 11p
Abstract:
The mechanisms underlying the association between air pollution and cardiovascular morbidity and mortality are unknown. This study aimed to determine whether controlled exposure to elemental carbon ultrafine particles (UFP) affects electrocardiogram (ECG) parameters describing heart rate variability; repolarization duration, morphology, and variability; and changes in the ST segment. Two separate controlled studies (12 subjects each) were performed using a crossover design, in which each subject was exposed to filtered air and carbon UFP for 2 hours. The first protocol involved 2 exposures to air and 10 μg/m3 (∼ 2× 106 particles/cm3, count median diameter ∼25 nm, geometric standard deviation ∼1.6), at rest. The second protocol included 3 exposures to air, 10, and 25 μg/m3 UFP (∼ 7× 106 particles/cm3), with repeated exercise. Each subject underwent a continuous digital 12-lead ECG Holter recording to analyze the above ECG parameters. Repeated measures analysis of variance (ANOVA) was used to compare tested parameters between exposures. The observed responses to UFP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFP in comparison to air exposure. In conclusion, transient exposure to 10-25 μ g/m3 ultrafine carbon particles does not cause marked changes in ECG-derived parameters in young healthy subjects. However, trends are observed indicating that some subjects might be susceptible to air pollution, with a response involving autonomic modulation of the heart and repolarization of the ventricular myocardium.
>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: Oberdorster is a leading authority on health effects of inhalation of small particles. Remember that carbon used to be considered inert, but now is a 2B carcinogen, among other respiratory effects. The text of the abstract gives indication of negotiation with the reviewers; whether the conclusion was bargained down or bargained up can't be told. So maybe this is equivocal evidence rather than some evidence for an effect on the heart after 2 hours at 25 ug/M3 in a small sample size of healthy volunteers. ?graduate students?
Thursday, February 26, 2009
Rating Posture: The Bigger the Better
Applied ErgonomicsVolume 40, Issue 3, May 2009, Pages 371-378
Reliability of assessing upper limb postures among workers performing manufacturing tasks
Angela Dartta, , , John Rosecrancea, Fred Gerrb, Peter Chenc, Dan Antond and Linda Merlinob
aColorado State University, Occupational and Environmental Health Section, ERHS, Environmental Health Building, Fort Collins, CO 80523, USA
bUniversity of Iowa, Occupational and Environmental Health, IREH, Iowa City, IA 52245, USA
cColorado State University, Industrial Organizational Psychology, Clark Building, Fort Collins, CO 80523, USA
dEastern Washington University, Department of Physical Therapy, Spokane, WA 99202 USA
Abstract
The purpose of this study was to determine the inter- and intra-rater reliability of assessing upper limb postures of workers performing manufacturing tasks. Assessment of neck, shoulder, and wrist postures of 20 manufacturing employees was conducted by two raters observing digital video files using Multimedia Video Task Analysis (MVTA). Generalizability theory was used to estimate the inter- and intra-rater reliability. The results demonstrated good to excellent inter-rater reliability for neck and shoulder postures and fair to excellent inter-rater reliability for wrist postures. Intra-rater posture assessment demonstrated good to excellent reliability for both raters in all postures of the neck, shoulder, and wrist. This study demonstrated that posture assessment of manufacturing workers using MVTA is a reliable method.
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BrooklynDodger(s) comment: Was this a doctoral project, or a master's essay? Posture assessment for hand work is a challenge in ergonomic studies. Not surprisingly, ratings were more consistent for the big stuff - head and neck - than the wrist. Although these raters did pretty well with the wrist. This provides important support for an ergonomic standard. The Dodger(s) wonder how trained hourly workers would have done.
Reliability of assessing upper limb postures among workers performing manufacturing tasks
Angela Dartta, , , John Rosecrancea, Fred Gerrb, Peter Chenc, Dan Antond and Linda Merlinob
aColorado State University, Occupational and Environmental Health Section, ERHS, Environmental Health Building, Fort Collins, CO 80523, USA
bUniversity of Iowa, Occupational and Environmental Health, IREH, Iowa City, IA 52245, USA
cColorado State University, Industrial Organizational Psychology, Clark Building, Fort Collins, CO 80523, USA
dEastern Washington University, Department of Physical Therapy, Spokane, WA 99202 USA
Abstract
The purpose of this study was to determine the inter- and intra-rater reliability of assessing upper limb postures of workers performing manufacturing tasks. Assessment of neck, shoulder, and wrist postures of 20 manufacturing employees was conducted by two raters observing digital video files using Multimedia Video Task Analysis (MVTA). Generalizability theory was used to estimate the inter- and intra-rater reliability. The results demonstrated good to excellent inter-rater reliability for neck and shoulder postures and fair to excellent inter-rater reliability for wrist postures. Intra-rater posture assessment demonstrated good to excellent reliability for both raters in all postures of the neck, shoulder, and wrist. This study demonstrated that posture assessment of manufacturing workers using MVTA is a reliable method.
>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: Was this a doctoral project, or a master's essay? Posture assessment for hand work is a challenge in ergonomic studies. Not surprisingly, ratings were more consistent for the big stuff - head and neck - than the wrist. Although these raters did pretty well with the wrist. This provides important support for an ergonomic standard. The Dodger(s) wonder how trained hourly workers would have done.
Wednesday, February 25, 2009
No New Information about Artificial Soccer Fields
Applied ErgonomicsVolume 40, Issue 3, May 2009, Pages 485-490
Amateur football game on artificial turf: Players’ perceptions
Elisabetta M. Zanetti, a,
aDepartment of Industrial and Mechanical Engineering (DIIM), University of Catania, V.le Andrea Doria 6, 95125 Catania, Ct, Italy
Abstract
The purpose of this study was to establish whether players’ perceptions in football competitions played on artificial turf can be influenced by the pitch under examination, the kind of infill material used, the weather conditions and by player's role in the team.
A multifactorial statistical analysis was made of the results obtained from over 1600 U.E.F.A. questionnaires completed by amateur footballers.
Pitch and weather factors were demonstrated to be relevant to the aspects investigated. Conversely, the players’ role and the infill material were significant for only a few aspects; for each variable, the analysis indicated the most favourable conditions. Overall, the analysis provided insight into amateur players’ favourable feelings about artificial turf, compared with its natural alternative (actually made of earth, without grass in the case of amateur players).
>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: The Dodger(s) click up this abstract because there's a concern - maybe a moral panic - about artificial turf on playgrounds in NYC. The Dodger(s) believe(s) some of this concern is the ideal comparison of turf with grass, rather than the actual comparison of turf with packed earth with a few clumps of grass. The chemical exposure comparison in real life is the offgassing of crumb rubber infill with dust maybe containing silica, although the main contaminant is PM2.5 in NYC air. On the other hand, infill turf is a polymeric mat sprinkled with rubber crumbs layered over a bed of sand. Which is a carcinogen, but not one which outgasses.
The Dodger(s) was (were) chagrined [had to look this up. "Chagrinned" is not allowed. Is it really legitimate to make a noun into a verb like this? Intermet dictionary said it was a transitive verb, but the Dodger(s) can't see that. Did the Steelers chagrin the Cardinals in the Superbowl?] to find no more than a hint of the results in the abstract. Where were the reviewers?
It seems like the players prefer turf to dirt. Better living through chemistry.
Amateur football game on artificial turf: Players’ perceptions
Elisabetta M. Zanetti, a,
aDepartment of Industrial and Mechanical Engineering (DIIM), University of Catania, V.le Andrea Doria 6, 95125 Catania, Ct, Italy
Abstract
The purpose of this study was to establish whether players’ perceptions in football competitions played on artificial turf can be influenced by the pitch under examination, the kind of infill material used, the weather conditions and by player's role in the team.
A multifactorial statistical analysis was made of the results obtained from over 1600 U.E.F.A. questionnaires completed by amateur footballers.
Pitch and weather factors were demonstrated to be relevant to the aspects investigated. Conversely, the players’ role and the infill material were significant for only a few aspects; for each variable, the analysis indicated the most favourable conditions. Overall, the analysis provided insight into amateur players’ favourable feelings about artificial turf, compared with its natural alternative (actually made of earth, without grass in the case of amateur players).
>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: The Dodger(s) click up this abstract because there's a concern - maybe a moral panic - about artificial turf on playgrounds in NYC. The Dodger(s) believe(s) some of this concern is the ideal comparison of turf with grass, rather than the actual comparison of turf with packed earth with a few clumps of grass. The chemical exposure comparison in real life is the offgassing of crumb rubber infill with dust maybe containing silica, although the main contaminant is PM2.5 in NYC air. On the other hand, infill turf is a polymeric mat sprinkled with rubber crumbs layered over a bed of sand. Which is a carcinogen, but not one which outgasses.
The Dodger(s) was (were) chagrined [had to look this up. "Chagrinned" is not allowed. Is it really legitimate to make a noun into a verb like this? Intermet dictionary said it was a transitive verb, but the Dodger(s) can't see that. Did the Steelers chagrin the Cardinals in the Superbowl?] to find no more than a hint of the results in the abstract. Where were the reviewers?
It seems like the players prefer turf to dirt. Better living through chemistry.
Monday, February 23, 2009
Workplace Violence Prevention in Health Care Settings Works
Annals of Epidemiology Volume 19, Issue 2, February 2009, Pages 125-133
Hospital Employee Assault Rates Before and After Enactment of the California Hospital Safety and Security Act
Carri Casteel PhDa, b, , , Corinne Peek-Asa PhDc, d, Maryalice NoceraMSNb, Jamie B. Smith MAb, James Blando PhDe, Suzi Goldmacher MSN, Emily O'Hagan MPHe, David Valiante PhDe and Robert Harrison PhDf
aDepartment of Epidemiology, University of North Carolina at Chapel Hill
bUniversity of North Carolina Injury Prevention Research Center, Chapel Hill
cDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, IA
dUniversity of Iowa Injury Prevention Research Center, Iowa City, IA
eNew Jersey Department of Health and Senior Services, Trenton, NJ
fUniversity of California, San Francisco
Purpose
This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995.
Methods
We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993–1995) and a 6-year post-enactment period (1996–2001) using New Jersey hospitals as a temporal control.
Results
Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment.
Conclusion
Policy may be an effective method to increase safety to health care workers.
>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The Dodger(s) couldn't get the full text to find the most interesting findings, which would have been the actual rates rather than the ratios, were New Jersey and California different, were emergency rooms and psychiatric facilities different? (The Dodger(s) suspect higher rates of assault in custodial facilities.) The reviewers get a demerit for not making the authors put that in the abstract. Injury control research is difficult, but this is a meager data base
Hospital Employee Assault Rates Before and After Enactment of the California Hospital Safety and Security Act
Carri Casteel PhDa, b, , , Corinne Peek-Asa PhDc, d, Maryalice NoceraMSNb, Jamie B. Smith MAb, James Blando PhDe, Suzi Goldmacher MSN, Emily O'Hagan MPHe, David Valiante PhDe and Robert Harrison PhDf
aDepartment of Epidemiology, University of North Carolina at Chapel Hill
bUniversity of North Carolina Injury Prevention Research Center, Chapel Hill
cDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, IA
dUniversity of Iowa Injury Prevention Research Center, Iowa City, IA
eNew Jersey Department of Health and Senior Services, Trenton, NJ
fUniversity of California, San Francisco
Purpose
This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995.
Methods
We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993–1995) and a 6-year post-enactment period (1996–2001) using New Jersey hospitals as a temporal control.
Results
Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment.
Conclusion
Policy may be an effective method to increase safety to health care workers.
>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The Dodger(s) couldn't get the full text to find the most interesting findings, which would have been the actual rates rather than the ratios, were New Jersey and California different, were emergency rooms and psychiatric facilities different? (The Dodger(s) suspect higher rates of assault in custodial facilities.) The reviewers get a demerit for not making the authors put that in the abstract. Injury control research is difficult, but this is a meager data base
Sunday, February 22, 2009
Exposure Response Variation among Differing Diesel Particulate Types
Toxicological Sciences 2009 107(2):522-534;
Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples
Tina Stevens*, Seung-Hyun Cho,, William P. Linak and M. Ian Gilmour,1
* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 Air Pollution and Prevention Control Division, National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831 Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-0026. E-mail: gilmour.ian@epa.gov
Abstract
Numerous studies have demonstrated that diesel exhaust particles (DEP) potentiate allergic immune responses, however the chemical components associated with this effect, and the underlying mechanisms are not well understood. This study characterized the composition of three chemically distinct DEP samples (N, C, and A-DEP), and compared post-sensitization and post-challenge inflammatory allergic phenotypes in BALB/c mice. Mice were instilled intranasally with saline or 150 µg of N-DEP, A-DEP, or C-DEP with or without 20 µg of ovalbumin (OVA) on days 0 and 13, and were subsequently challenged with 20 µg of OVA on days 23, 26, and 29. Mice were necropsied 18 h post-sensitization and 18 and 48 h post-challenge. N-DEP, A-DEP, and C-DEP contained 1.5, 68.6, and 18.9% extractable organic material (EOM) and 47, 431, and 522 µg of polycyclic aromatic hydrocarbons (PAHs), respectively. The post-challenge results showed that DEP given with OVA induced a gradation of adjuvancy as follows: C-DEP A-DEP > N-DEP. The C- and A-DEP/OVA exposure groups had significant increases in eosinophils, OVA-specific IgG1, and airway hyperresponsiveness. In addition, the C-DEP/OVA exposure increased the T helper 2 (TH2) chemoattractant chemokine, thymus and activation-regulated chemokine and exhibited the most severe perivascular inflammation in the lung, whereas A-DEP/OVA increased interleukin (IL)-5 and IL-10. In contrast, N-DEP/OVA exposure only increased OVA-specific IgG1 post-challenge. Analysis of early signaling showed that C-DEP induced a greater number of TH2 cytokines compared with A-DEP and N-DEP. The results suggest that potentiation of allergic immune responses by DEP is associated with PAH content rather than the total amount of EOM.
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The Dodger(s) need(s) to figure out the provenance of these different diesel exhaust types. The article was not available in full text, at least yet. Since extractable organic matter and PAH were confounded, it's not clear why the authors conclude it's PAH.
Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples
Tina Stevens*, Seung-Hyun Cho,, William P. Linak and M. Ian Gilmour,1
* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 Air Pollution and Prevention Control Division, National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831 Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-0026. E-mail: gilmour.ian@epa.gov
Abstract
Numerous studies have demonstrated that diesel exhaust particles (DEP) potentiate allergic immune responses, however the chemical components associated with this effect, and the underlying mechanisms are not well understood. This study characterized the composition of three chemically distinct DEP samples (N, C, and A-DEP), and compared post-sensitization and post-challenge inflammatory allergic phenotypes in BALB/c mice. Mice were instilled intranasally with saline or 150 µg of N-DEP, A-DEP, or C-DEP with or without 20 µg of ovalbumin (OVA) on days 0 and 13, and were subsequently challenged with 20 µg of OVA on days 23, 26, and 29. Mice were necropsied 18 h post-sensitization and 18 and 48 h post-challenge. N-DEP, A-DEP, and C-DEP contained 1.5, 68.6, and 18.9% extractable organic material (EOM) and 47, 431, and 522 µg of polycyclic aromatic hydrocarbons (PAHs), respectively. The post-challenge results showed that DEP given with OVA induced a gradation of adjuvancy as follows: C-DEP A-DEP > N-DEP. The C- and A-DEP/OVA exposure groups had significant increases in eosinophils, OVA-specific IgG1, and airway hyperresponsiveness. In addition, the C-DEP/OVA exposure increased the T helper 2 (TH2) chemoattractant chemokine, thymus and activation-regulated chemokine and exhibited the most severe perivascular inflammation in the lung, whereas A-DEP/OVA increased interleukin (IL)-5 and IL-10. In contrast, N-DEP/OVA exposure only increased OVA-specific IgG1 post-challenge. Analysis of early signaling showed that C-DEP induced a greater number of TH2 cytokines compared with A-DEP and N-DEP. The results suggest that potentiation of allergic immune responses by DEP is associated with PAH content rather than the total amount of EOM.
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BrooklynDodger(s) comment: The Dodger(s) need(s) to figure out the provenance of these different diesel exhaust types. The article was not available in full text, at least yet. Since extractable organic matter and PAH were confounded, it's not clear why the authors conclude it's PAH.
Saturday, February 21, 2009
2 Weeks of Modest Levels of Nanoparticles Cause Systemic Immune System Changes
Toxicological Sciences 2007 100(1):203-214;
Pulmonary and Systemic Immune Response to Inhaled Multiwalled Carbon Nanotubes
Leah A. Mitchell*,, Jun Gao*, Randy Vander Wal, Andrew Gigliotti, Scott W. Burchiel* and Jacob D. McDonald,1
* College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131–0001 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 The National Center for Microgravity Research, c/o The NASA-Glenn Research Center, Cleveland, Ohio 44135
1 To whom correspondence should be addressed at Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108. Fax: (505) 348-4980. E-mail: jmcdonal@lrri.org
Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell–dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m3 had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.
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BrooklynDodger(s) comment: Investigators demonstrated subtantial effects on immune system from modest, short term exposure to nanoparticles. Hazard identification accomplished- toxic potency established What will be done for potency estimates?
Pulmonary and Systemic Immune Response to Inhaled Multiwalled Carbon Nanotubes
Leah A. Mitchell*,, Jun Gao*, Randy Vander Wal, Andrew Gigliotti, Scott W. Burchiel* and Jacob D. McDonald,1
* College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131–0001 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 The National Center for Microgravity Research, c/o The NASA-Glenn Research Center, Cleveland, Ohio 44135
1 To whom correspondence should be addressed at Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108. Fax: (505) 348-4980. E-mail: jmcdonal@lrri.org
Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3 to 5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10- to 12-week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused nonmonotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell–dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A. Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m3 had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin-10 (IL-10) and NAD(P)H oxidoreductase 1 mRNA levels were increased in spleen.
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BrooklynDodger(s) comment: Investigators demonstrated subtantial effects on immune system from modest, short term exposure to nanoparticles. Hazard identification accomplished- toxic potency established What will be done for potency estimates?
Friday, February 20, 2009
Another Pathway to Non-cancer Nanoparticle Toxicity
American Journal of Respiratory Cell and Molecular Biology. Vol. 40, pp. 349-358, 2009© 2009 American Thoracic Society
Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma
Jessica P. Ryman-Rasmussen1,2, Earl W. Tewksbury2, Owen R. Moss2, Mark F. Cesta1,2,3, Brian A. Wong2 and James C. Bonner1,2
1 Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina; 2 The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina; and 3 Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Correspondence and requests for reprints should be addressed to James C. Bonner, Ph.D., North Carolina State University, Box 7633, Raleigh, NC 27695. E-mail: james_bonner@ncsu.edu
'//-->
Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
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BrooklynDodger(s) Comment: This study provides another view of the toxic potential of carbon nanotubes. The small numbers of mice and short exposure time means these data don't support inference of a threshold or no risk without allergic inflammation. The data do support an inference that persons with allergic inflammation might be less resistent to nano particles.
Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma
Jessica P. Ryman-Rasmussen1,2, Earl W. Tewksbury2, Owen R. Moss2, Mark F. Cesta1,2,3, Brian A. Wong2 and James C. Bonner1,2
1 Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina; 2 The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina; and 3 Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Correspondence and requests for reprints should be addressed to James C. Bonner, Ph.D., North Carolina State University, Box 7633, Raleigh, NC 27695. E-mail: james_bonner@ncsu.edu
'//-->
Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: This study provides another view of the toxic potential of carbon nanotubes. The small numbers of mice and short exposure time means these data don't support inference of a threshold or no risk without allergic inflammation. The data do support an inference that persons with allergic inflammation might be less resistent to nano particles.
Thursday, February 19, 2009
Injury Control Implications of Surgery Safety Study
http://content.nejm.org/cgi/content/full/360/5/491?query=TOC
A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population
Alex B. Haynes, M.D., M.P.H., Thomas G. Weiser, M.D., M.P.H., William R. Berry, M.D., M.P.H., Stuart R. Lipsitz, Sc.D., Abdel-Hadi S. Breizat, M.D., Ph.D., E. Patchen Dellinger, M.D., Teodoro Herbosa, M.D., Sudhir Joseph, M.S., Pascience L. Kibatala, M.D., Marie Carmela M. Lapitan, M.D., Alan F. Merry, M.B., Ch.B., F.A.N.Z.C.A., F.R.C.A., Krishna Moorthy, M.D., F.R.C.S., Richard K. Reznick, M.D., M.Ed., Bryce Taylor, M.D., Atul A. Gawande, M.D., M.P.H., for the Safe Surgery Saves Lives Study Group
Background Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery.
Methods Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation.
Results The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001).>Conclusions Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals.
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BrooklynDodger(s) comment: Once again, a simple industrial quality control or safety protocol is applied to a health care setting, and proves to drastically improve patient safety and also outcomes, thereby also saving further procedures and money. Likely, compliance with the checklist varied across hospitals and times, thereby reducing effectiveness. That said, the nearly 1% fatality rate after intervention gives the Dodger(s) pause about undergoing surgery.
A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population
Alex B. Haynes, M.D., M.P.H., Thomas G. Weiser, M.D., M.P.H., William R. Berry, M.D., M.P.H., Stuart R. Lipsitz, Sc.D., Abdel-Hadi S. Breizat, M.D., Ph.D., E. Patchen Dellinger, M.D., Teodoro Herbosa, M.D., Sudhir Joseph, M.S., Pascience L. Kibatala, M.D., Marie Carmela M. Lapitan, M.D., Alan F. Merry, M.B., Ch.B., F.A.N.Z.C.A., F.R.C.A., Krishna Moorthy, M.D., F.R.C.S., Richard K. Reznick, M.D., M.Ed., Bryce Taylor, M.D., Atul A. Gawande, M.D., M.P.H., for the Safe Surgery Saves Lives Study Group
Background Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery.
Methods Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation.
Results The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001).>Conclusions Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals.
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BrooklynDodger(s) comment: Once again, a simple industrial quality control or safety protocol is applied to a health care setting, and proves to drastically improve patient safety and also outcomes, thereby also saving further procedures and money. Likely, compliance with the checklist varied across hospitals and times, thereby reducing effectiveness. That said, the nearly 1% fatality rate after intervention gives the Dodger(s) pause about undergoing surgery.
Wednesday, February 18, 2009
Chemoprevention Fails Again - Selenium and Vitamin E Fail to Prevent Prostate Cancer
JAMA. 2009;301(1):39-51
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologicand preclinical data indicated the potential of selenium and vitamin E forpreventing prostate cancer.
Objective To determine whether selenium, vitamin E, or both could prevent prostatecancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo-controlled trial (Seleniumand Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium vitamin E, and placebo) in a double-blindfashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serumprostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination notsuspicious for prostate cancer.
Interventions Oral selenium (200 $B&L(Bg/d from L-selenomethionine) and matched vitaminE placebo, vitamin E (400 IU/d of all rac- -tocopheryl acetate) and matchedselenium placebo, selenium vitamin E, or placebo placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.Main Outcome Measures Prostate cancer and prespecified secondary outcomes,including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow-up was 5.46 years (range,4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancerwere 1.13 (99% CI, 0.95-1.35; n=473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n=432)for selenium, and 1.05 (99% CI, 0.88-1.25; n=437) for selenium vitamin E vs 1.00(n=416) for placebo. There were no significant differences (all P .15) in any otherprespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P=.06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P=.16) but not in the selenium vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
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BrooklynDodger(s) Comments: Seems like the bloom will never be off the funding rose for chemoprevention. Imagine what a 35000 person study cost!!! And, starting in 2001 against a backdrop of mostly failed clinical trials of anti oxidant chemoprevention. The trail did not run long enough to evaluate the hazard of these treatments, although it suggests Selenium may increase risks of prostate cancer and type II diabetes. Schadenfreud aside, the anti-oxidant model posits that initiation by oxidant mechanisms is reduced by the treatment. By 55, most men are initiated. So the trial doesn't really test the model. Vitamins are likely good for cancer cells as well as regular cells, so increased cancer is a likely outcome of late stage treatment. The Dodger(s) confess not to know the street doses which gullibles take to prevent cancer, to compare with those in this study.
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologicand preclinical data indicated the potential of selenium and vitamin E forpreventing prostate cancer.
Objective To determine whether selenium, vitamin E, or both could prevent prostatecancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo-controlled trial (Seleniumand Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium vitamin E, and placebo) in a double-blindfashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serumprostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination notsuspicious for prostate cancer.
Interventions Oral selenium (200 $B&L(Bg/d from L-selenomethionine) and matched vitaminE placebo, vitamin E (400 IU/d of all rac- -tocopheryl acetate) and matchedselenium placebo, selenium vitamin E, or placebo placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.Main Outcome Measures Prostate cancer and prespecified secondary outcomes,including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow-up was 5.46 years (range,4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancerwere 1.13 (99% CI, 0.95-1.35; n=473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n=432)for selenium, and 1.05 (99% CI, 0.88-1.25; n=437) for selenium vitamin E vs 1.00(n=416) for placebo. There were no significant differences (all P .15) in any otherprespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P=.06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P=.16) but not in the selenium vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
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BrooklynDodger(s) Comments: Seems like the bloom will never be off the funding rose for chemoprevention. Imagine what a 35000 person study cost!!! And, starting in 2001 against a backdrop of mostly failed clinical trials of anti oxidant chemoprevention. The trail did not run long enough to evaluate the hazard of these treatments, although it suggests Selenium may increase risks of prostate cancer and type II diabetes. Schadenfreud aside, the anti-oxidant model posits that initiation by oxidant mechanisms is reduced by the treatment. By 55, most men are initiated. So the trial doesn't really test the model. Vitamins are likely good for cancer cells as well as regular cells, so increased cancer is a likely outcome of late stage treatment. The Dodger(s) confess not to know the street doses which gullibles take to prevent cancer, to compare with those in this study.
Monday, February 16, 2009
Biomarkers of Effect Found Associated with Chemical Exposure in a Community Population
Toxicology Letters Volume 184, Issue 2, 30 January 2009, Pages 139-144
Community level exposure to chemicals and oxidative stress in adult population
Yun-Chul Honga, b, Eun-Young Parka, Min-Seon Parkc, Jeong Ah Koc, Se-Young Ohd, Ho Kime, Kwan-Hee Leef, Jong-Han Leemf and Eun-Hee Hag, ,
aDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
bInstitute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
cDepartment of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
dDepartment of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea
eDepartment of Epidemiology and Biostatistics, Seoul National University School of Public Health, Seoul, Republic of Korea
fDepartment of Occupational and Environmental Medicine, Inha University Hospital, Incheon, Republic of Korea
gDepartment of Preventive Medicine, Ewha Womans University Medical School, Seoul, Republic of Korea
Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P <>). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P <> The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.
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BrookkynDodger(s) comment: The Dodger(s) generally fear that community survey projects like this will generate spurious null results. So finding an association should be considered of special weight. The investigators identify a pathway from oxidative stress to diabetes. Oxidative stress is relatively easily measured in live people as an intermediate outcome. This broadens the range of conditions which may be caused by occupational or environmental chemical exposures.
Community level exposure to chemicals and oxidative stress in adult population
Yun-Chul Honga, b, Eun-Young Parka, Min-Seon Parkc, Jeong Ah Koc, Se-Young Ohd, Ho Kime, Kwan-Hee Leef, Jong-Han Leemf and Eun-Hee Hag, ,
aDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
bInstitute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
cDepartment of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
dDepartment of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea
eDepartment of Epidemiology and Biostatistics, Seoul National University School of Public Health, Seoul, Republic of Korea
fDepartment of Occupational and Environmental Medicine, Inha University Hospital, Incheon, Republic of Korea
gDepartment of Preventive Medicine, Ewha Womans University Medical School, Seoul, Republic of Korea
Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P <>). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P <> The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.
>>>>>>>>>>>>>>>>
BrookkynDodger(s) comment: The Dodger(s) generally fear that community survey projects like this will generate spurious null results. So finding an association should be considered of special weight. The investigators identify a pathway from oxidative stress to diabetes. Oxidative stress is relatively easily measured in live people as an intermediate outcome. This broadens the range of conditions which may be caused by occupational or environmental chemical exposures.
Sunday, February 15, 2009
National Health Insurance Coverage Improves Breast Cancer Survival
Annals of EpidemiologyVolume 19, Issue 2, February 2009, Pages 121-124
Breast Cancer Survival in Ontario and California, 1998–2006: Socioeconomic Inequity Remains Much Greater in the United States
Kevin M. Gorey PhD, MSWa, , , Isaac N. Luginaah PhDb, Eric J. Holowaty MDc, Karen Y. Fung PhDd and Caroline Hamm MDe
aSchool of Social Work, University of Windsor, Ontario
bDepartment of Geography, University of Western Ontario, London
cDivision of Preventive Oncology, Cancer Care Ontario, Toronto
dDepartment of Mathematics and Statistics, University of Windsor, Ontario
eWindsor Regional Cancer Center, Ontario
Abstract
This study re-examined the differential effect of socioeconomic status on the survival of women with breast cancer in Canada and the United States. Ontario and California cancer registries provided 1,913 cases from urban and rural places. Stage-adjusted cohorts (1998–2000) were followed until 2006. Socioeconomic data were taken from population censuses. SES-survival associations were observed in California, but not in Ontario, and Canadian survival advantages in low-income areas were replicated. A better controlled and updated comparison reaffirmed the equity advantage of Canadian health care.
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BrooklynDodger(s) Comment: Chemicals are part of the environment, psychosocial stress and class bias are part of the environment, but we EOHS folks forget that social insurance is also part of the environment which determines health outcomes.
Breast Cancer Survival in Ontario and California, 1998–2006: Socioeconomic Inequity Remains Much Greater in the United States
Kevin M. Gorey PhD, MSWa, , , Isaac N. Luginaah PhDb, Eric J. Holowaty MDc, Karen Y. Fung PhDd and Caroline Hamm MDe
aSchool of Social Work, University of Windsor, Ontario
bDepartment of Geography, University of Western Ontario, London
cDivision of Preventive Oncology, Cancer Care Ontario, Toronto
dDepartment of Mathematics and Statistics, University of Windsor, Ontario
eWindsor Regional Cancer Center, Ontario
Abstract
This study re-examined the differential effect of socioeconomic status on the survival of women with breast cancer in Canada and the United States. Ontario and California cancer registries provided 1,913 cases from urban and rural places. Stage-adjusted cohorts (1998–2000) were followed until 2006. Socioeconomic data were taken from population censuses. SES-survival associations were observed in California, but not in Ontario, and Canadian survival advantages in low-income areas were replicated. A better controlled and updated comparison reaffirmed the equity advantage of Canadian health care.
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BrooklynDodger(s) Comment: Chemicals are part of the environment, psychosocial stress and class bias are part of the environment, but we EOHS folks forget that social insurance is also part of the environment which determines health outcomes.
Saturday, February 14, 2009
Review of Nanoparticle Toxicity Concludes That Application and Hazard are Tied Together in Physicochemical Properties
Pulmonary applications and toxicity of engineered nanoparticles
J. W. Card, D. C. Zeldin, J. C. Bonner, and E. R. Nestmann
Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L400 - L411.
Because of their unique physicochemical properties, engineered nanoparticles have the potential to significantly impact respiratory research and medicine by means of improving imaging capability and drug delivery, among other applications. These same properties, however, present potential safety concerns, and there is accumulating evidence to suggest that nanoparticles may exert adverse effects on pulmonary structure and function. The respiratory system is susceptible to injury resulting from inhalation of gases, aerosols, and particles, and also from systemic delivery of drugs, chemicals, and other compounds to the lungs via direct cardiac output to the pulmonary arteries. As such, it is a prime target for the possible toxic effects of engineered nanoparticles. The purpose of this article is to provide an overview of the potential usefulness of nanoparticles and nanotechnology in respiratory research and medicine and to highlight important issues and recent data pertaining to nanoparticle-related pulmonary toxicity.
>>>>>>>>>>>>>
BrooklynDodger(s) comment: This abstract conveys no information, but having saved it, the Dodger(s) need to fill a day's post. The toxic potential of nanoparticles is well established, the equivalent of hazard identification in the NAS Red Book paradigm. No uncertainty left. Potency estimates - exposure response assessment - are grounded in short term exposure studies in laboratories, but can be grounded in potency estimates for diesel particulate matter and carbon black.
J. W. Card, D. C. Zeldin, J. C. Bonner, and E. R. Nestmann
Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L400 - L411.
Because of their unique physicochemical properties, engineered nanoparticles have the potential to significantly impact respiratory research and medicine by means of improving imaging capability and drug delivery, among other applications. These same properties, however, present potential safety concerns, and there is accumulating evidence to suggest that nanoparticles may exert adverse effects on pulmonary structure and function. The respiratory system is susceptible to injury resulting from inhalation of gases, aerosols, and particles, and also from systemic delivery of drugs, chemicals, and other compounds to the lungs via direct cardiac output to the pulmonary arteries. As such, it is a prime target for the possible toxic effects of engineered nanoparticles. The purpose of this article is to provide an overview of the potential usefulness of nanoparticles and nanotechnology in respiratory research and medicine and to highlight important issues and recent data pertaining to nanoparticle-related pulmonary toxicity.
>>>>>>>>>>>>>
BrooklynDodger(s) comment: This abstract conveys no information, but having saved it, the Dodger(s) need to fill a day's post. The toxic potential of nanoparticles is well established, the equivalent of hazard identification in the NAS Red Book paradigm. No uncertainty left. Potency estimates - exposure response assessment - are grounded in short term exposure studies in laboratories, but can be grounded in potency estimates for diesel particulate matter and carbon black.
Friday, February 13, 2009
p53 - Maybe Genetics Doesn't Load the Gun After All
NATURe RevIewS CanCer voLUMe 9 FeBRUARy 2009 95
p53 polymorphisms: cancer implications
Catherine Whibley*, Paul D. P. Pharoah‡ and Monica Hollstein*
Abstract The normal functioning of p53 is a potent barrier to cancer. Tumour-associated mutations in TP53, typically single nucleotide substitutions in the coding sequence, are a hallmark of most human cancers and cause dramatic defects in p53 function. By contrast,
only a small fraction, if any, of the >200 naturally occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Polymorphisms in the TP53 locus that might have cancer-related phenotypical manifestations are the subject of this Review. Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are also discussed.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: No highlights here, because the full text doesn't have much fat, although little information. The expression of the p53 gene leads to cell suicide, apoptosis. Something you want in a tumor cell. Defective p53 lets the tumor cell grow in the face of other triggers for apoptosis, so it's logical that p53 mutations are found in tumor cells. The review suggests that few defective p53 genotypes are found in the human population, meaning that it's not a place for specially sensitive populations.
p53 polymorphisms: cancer implications
Catherine Whibley*, Paul D. P. Pharoah‡ and Monica Hollstein*
Abstract The normal functioning of p53 is a potent barrier to cancer. Tumour-associated mutations in TP53, typically single nucleotide substitutions in the coding sequence, are a hallmark of most human cancers and cause dramatic defects in p53 function. By contrast,
only a small fraction, if any, of the >200 naturally occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Polymorphisms in the TP53 locus that might have cancer-related phenotypical manifestations are the subject of this Review. Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are also discussed.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: No highlights here, because the full text doesn't have much fat, although little information. The expression of the p53 gene leads to cell suicide, apoptosis. Something you want in a tumor cell. Defective p53 lets the tumor cell grow in the face of other triggers for apoptosis, so it's logical that p53 mutations are found in tumor cells. The review suggests that few defective p53 genotypes are found in the human population, meaning that it's not a place for specially sensitive populations.
Thursday, February 12, 2009
Reference Values for Indoor Air Problems Orders of Magnitude Less Than PEL's
Airborne Concentrations of Volatile Organic Compounds, Formaldehyde and Ammonia in Finnish Office Buildings with Suspected Indoor Air Problems
Authors: Heidi J. Salonen a; Anna-Liisa Pasanen b; Sanna K. Lappalainen a; Henri M. Riuttala a; Tapani M. Tuomi a; Pertti O. Pasanen c; Beatrice C. Bck a; Kari E. Reijula a
Affiliations: a Finnish Institute of Occupational Health, Helsinki, Finland
b Finnish Institute of Occupational Health, Kuopio, Finland
c Department of Environmental Science, University of Kuopio, Kuopio, Finland
Journal of Occupational and Environmental Hygiene, Volume 6, Issue 3 March 2009 , pages 200 - 209
Abstract
A database of indoor air concentrations of volatile organic compounds (VOCs) (n = 528), formaldehyde (n = 76), and ammonia (n = 47) in office environments was analyzed to suggest interpretation guidelines for chemical measurements in office buildings with suspected indoor air problems. Indoor air samples were collected for VOCs from 176 office buildings, 23 offices for formaldehyde, and 14 office buildings for ammonia in 2001-2006. Although the buildings had reported indoor air complaints, a walk-through inspection by indoor air specialists showed no exceptional sources of indoor air pollutants. The measurements of chemical pollutants did not indicate any clear reason for the complaints. The geometric mean concentration of total volatile organic compounds (TVOC) was 88 μg m-3 in office rooms and 75 μg m-3 in the open plan offices. The mechanical supply and exhaust ventilation significantly (p <>The highest mean concentration and frequency distributions were determined for the individual VOCs. The most common VOCs found in ≥ 84% of the indoor samples include toluene, xylene (p,m), 1-butanol, nonanal, and benzene. According to concentrations, the most abundant VOCs were 2-(2-ethoxyethoxy)ethanol, acetic acid, 1,2-propanediol, and toluene. The geometric mean concentration of formaldehyde and ammonia in the office buildings was 11 μg m-3 (3-44 μg m-3 and 14 μg m-3 (1-49 μg m-3, respectively. On the basis of statistical analyses, the guideline value indicating a usual concentration of the pollutant in office buildings is 70 μg m-3 for TVOC, 7 μg m-3 for most individual VOCs, 10 μg m-3 for formaldehyde, and 12 μg m-3 for ammonia… The guidance value suggested for TVOC is 250 μg m-3, for formaldehyde 15 μg m-3, and for ammonia 25 μg m-3. If the guidance value is exceeded, this may indicate the existence of an exceptional source and the need for additional environmental investigations. The levels should not be used for the evaluation of health risks. The guideline values are applicable in a subarctic climate for modern, urban office buildings.
>>>>>>>>>>>>>>>>
BrooklynDodger(s) comments: The Dodger(s) appreciate(s) that these investigators are willing to put an index value on exposure levels associated with indoor air complaints, although the Dodger(s) see no clear rational for these values. Formaldehyde at .010 mg/m^3 is equivalent to 0.008 ppm, well below the ATSDR MRL for intermediate duration exposure of 0.03 ppm. An interesting account of an indoor air investigation at the National Center for Health Statistics can be found at
http://www.atsdr.cdc.gov/hac/PHA/nationalcenter/nch_p1.html
Authors: Heidi J. Salonen a; Anna-Liisa Pasanen b; Sanna K. Lappalainen a; Henri M. Riuttala a; Tapani M. Tuomi a; Pertti O. Pasanen c; Beatrice C. Bck a; Kari E. Reijula a
Affiliations: a Finnish Institute of Occupational Health, Helsinki, Finland
b Finnish Institute of Occupational Health, Kuopio, Finland
c Department of Environmental Science, University of Kuopio, Kuopio, Finland
Journal of Occupational and Environmental Hygiene, Volume 6, Issue 3 March 2009 , pages 200 - 209
Abstract
A database of indoor air concentrations of volatile organic compounds (VOCs) (n = 528), formaldehyde (n = 76), and ammonia (n = 47) in office environments was analyzed to suggest interpretation guidelines for chemical measurements in office buildings with suspected indoor air problems. Indoor air samples were collected for VOCs from 176 office buildings, 23 offices for formaldehyde, and 14 office buildings for ammonia in 2001-2006. Although the buildings had reported indoor air complaints, a walk-through inspection by indoor air specialists showed no exceptional sources of indoor air pollutants. The measurements of chemical pollutants did not indicate any clear reason for the complaints. The geometric mean concentration of total volatile organic compounds (TVOC) was 88 μg m-3 in office rooms and 75 μg m-3 in the open plan offices. The mechanical supply and exhaust ventilation significantly (p <>The highest mean concentration and frequency distributions were determined for the individual VOCs. The most common VOCs found in ≥ 84% of the indoor samples include toluene, xylene (p,m), 1-butanol, nonanal, and benzene. According to concentrations, the most abundant VOCs were 2-(2-ethoxyethoxy)ethanol, acetic acid, 1,2-propanediol, and toluene. The geometric mean concentration of formaldehyde and ammonia in the office buildings was 11 μg m-3 (3-44 μg m-3 and 14 μg m-3 (1-49 μg m-3, respectively. On the basis of statistical analyses, the guideline value indicating a usual concentration of the pollutant in office buildings is 70 μg m-3 for TVOC, 7 μg m-3 for most individual VOCs, 10 μg m-3 for formaldehyde, and 12 μg m-3 for ammonia… The guidance value suggested for TVOC is 250 μg m-3, for formaldehyde 15 μg m-3, and for ammonia 25 μg m-3. If the guidance value is exceeded, this may indicate the existence of an exceptional source and the need for additional environmental investigations. The levels should not be used for the evaluation of health risks. The guideline values are applicable in a subarctic climate for modern, urban office buildings.
>>>>>>>>>>>>>>>>
BrooklynDodger(s) comments: The Dodger(s) appreciate(s) that these investigators are willing to put an index value on exposure levels associated with indoor air complaints, although the Dodger(s) see no clear rational for these values. Formaldehyde at .010 mg/m^3 is equivalent to 0.008 ppm, well below the ATSDR MRL for intermediate duration exposure of 0.03 ppm. An interesting account of an indoor air investigation at the National Center for Health Statistics can be found at
http://www.atsdr.cdc.gov/hac/PHA/nationalcenter/nch_p1.html
Wednesday, February 11, 2009
Putting a Carcinogen on Your Hair - Diethanolamine in Shampoo
Journal of AOAC INTERNATIONAL Volume: 88 Issue: 2 Page(s): 592-594 March 2005
Determination of Diethanolamine in Shampoo Products Containing Fatty Acid Diethanolamides by Liquid Chromatography with a Thermal Energy Analyzer
Author(s): Hardy J. Chou 1
A liquid chromatography (LC) method using a thermal energy analyzer (TEA) is described for the determination of diethanolamine (DEA) in shampoo products containing fatty acid diethanolamides. DEA was converted to N-nitrosodiethanolamine (NDELA) by dissolving a portion of the product in 6M acetic acid and mixing with sodium nitrite for 1 h at room temperature. The reaction mixture was dried, dissolved in acetone, and analyzed for NDELA by LC-TEA. The recovery of DEA from 2 shampoo products at fortification levels of 25, 250, and 1000 ppm ranged from 70 to 105%. Twenty shampoo products were analyzed by this method, and 19 were found to contain DEA at levels ranging from 140 to 15 200 ppm.
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: NTP bioassays of diethanolamine and diethanolamine fatty acid condensates by skin exposure provided clear evidence of carcinogenicity in male and female mice, but not the rat. Some years ago, IARC relegated DEA to group 3, not classifiable. The working group considered the male and female mouse experiments to be a single study - not so under current rules - and declined to consider the fatty acid condensate studies to be DEA studies. Years later, DEA exposure to much of the population continues.
Determination of Diethanolamine in Shampoo Products Containing Fatty Acid Diethanolamides by Liquid Chromatography with a Thermal Energy Analyzer
Author(s): Hardy J. Chou 1
A liquid chromatography (LC) method using a thermal energy analyzer (TEA) is described for the determination of diethanolamine (DEA) in shampoo products containing fatty acid diethanolamides. DEA was converted to N-nitrosodiethanolamine (NDELA) by dissolving a portion of the product in 6M acetic acid and mixing with sodium nitrite for 1 h at room temperature. The reaction mixture was dried, dissolved in acetone, and analyzed for NDELA by LC-TEA. The recovery of DEA from 2 shampoo products at fortification levels of 25, 250, and 1000 ppm ranged from 70 to 105%. Twenty shampoo products were analyzed by this method, and 19 were found to contain DEA at levels ranging from 140 to 15 200 ppm.
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: NTP bioassays of diethanolamine and diethanolamine fatty acid condensates by skin exposure provided clear evidence of carcinogenicity in male and female mice, but not the rat. Some years ago, IARC relegated DEA to group 3, not classifiable. The working group considered the male and female mouse experiments to be a single study - not so under current rules - and declined to consider the fatty acid condensate studies to be DEA studies. Years later, DEA exposure to much of the population continues.
Tuesday, February 10, 2009
Mechanistic Explanation of Chrome Carcinogenicity - What about other agents?
Toxicology and Applied PharmacologyVolume 235, Issue 1, 15 February 2009, Pages 47-56
Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium
Laura M. Beavera, b, Erik J. Stemmyb, c, Stephanie L. Constantb, c, Arnold Schwartzd, Laura G. Littleg, Jason P. Gigleyc, Gina Chuna, b, Kent D. Sugdeng, Susan M. Ceryaka, b, e, f and Steven R. Patiernoa, b, f, ,
aDepartment of Pharmacology and Physiology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
bInstitute of Biomedical Sciences, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
cDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
dDepartment of Pathology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
eDepartment of Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
fGW Cancer Institute, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
gThe University of Montana, Department of Chemistry, 32 Campus Drive, Missoula, MT 59812, USA
Abstract
Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: This study provides some single dose results for a known human carcinogen in the target organ. Chromate ion appears the active agent. Should all agents which impact survival signaling, apoptosis, be considered carcinogens? At least, would this biological response trigger further study? The Dodger(s) wonder about ferric oxide, which is also an oxidizer.
Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium
Laura M. Beavera, b, Erik J. Stemmyb, c, Stephanie L. Constantb, c, Arnold Schwartzd, Laura G. Littleg, Jason P. Gigleyc, Gina Chuna, b, Kent D. Sugdeng, Susan M. Ceryaka, b, e, f and Steven R. Patiernoa, b, f, ,
aDepartment of Pharmacology and Physiology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
bInstitute of Biomedical Sciences, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
cDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
dDepartment of Pathology, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
eDepartment of Medicine, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
fGW Cancer Institute, The George Washington University Medical Center, 2300 I Street NW, Washington, DC 20037, USA
gThe University of Montana, Department of Chemistry, 32 Campus Drive, Missoula, MT 59812, USA
Abstract
Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comment: This study provides some single dose results for a known human carcinogen in the target organ. Chromate ion appears the active agent. Should all agents which impact survival signaling, apoptosis, be considered carcinogens? At least, would this biological response trigger further study? The Dodger(s) wonder about ferric oxide, which is also an oxidizer.
Monday, February 09, 2009
Low Levels of Arsenic in Drinking Water Causes Irreversible Damage to Lungs to Newborns
Toxicology and Applied PharmacologyVolume 235, Issue 1, 15 February 2009, Pages 105-113
In utero and postnatal exposure to arsenic alters pulmonary structure and function
R. Clark Lantza, b, c, , , Binh Chaua, Priyanka Sarihana, Mark L. Wittenb, d, Vadim I. Pivniouka, e and Guan Jie Chena
aDepartment of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
bSouthwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721, USA
cBIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
dDepartment of Pediatrics, University of Arizona, Tucson, AZ 85724, USA
eArizona Respiratory Center, University of Arizona, Tucson, AZ 85724, USA
Abstract
In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comments: Risk assessors debate whether cancer causing properties discovered by one route apply (are relevent) to another - inhalation v. ingestion usually. Houdinists default to no relevence. Arsenic became known to be a human carcinogen as a result of inhalation exposure in the workplace causing lung cancer. Then as a result of ingestion of water in the developing world. Now comes laboratory support for human epidemiology. Also, this study shows the potential importance of looking at all stages of life. The Dodger(s) need to search for drinking water bioassays of arsenic. And, it would be nice if the investigators repeated the study with in utero only and perinatal only exposure.
In utero and postnatal exposure to arsenic alters pulmonary structure and function
R. Clark Lantza, b, c, , , Binh Chaua, Priyanka Sarihana, Mark L. Wittenb, d, Vadim I. Pivniouka, e and Guan Jie Chena
aDepartment of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
bSouthwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721, USA
cBIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
dDepartment of Pediatrics, University of Arizona, Tucson, AZ 85724, USA
eArizona Respiratory Center, University of Arizona, Tucson, AZ 85724, USA
Abstract
In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.
>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comments: Risk assessors debate whether cancer causing properties discovered by one route apply (are relevent) to another - inhalation v. ingestion usually. Houdinists default to no relevence. Arsenic became known to be a human carcinogen as a result of inhalation exposure in the workplace causing lung cancer. Then as a result of ingestion of water in the developing world. Now comes laboratory support for human epidemiology. Also, this study shows the potential importance of looking at all stages of life. The Dodger(s) need to search for drinking water bioassays of arsenic. And, it would be nice if the investigators repeated the study with in utero only and perinatal only exposure.
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