Tuesday, December 29, 2009

NostrumDamus

BrooklynDodger(s) comment: Gingko extract contains flavenoids and terpenoids, thought to be anti oxidant. 3000+ subjects followed over a median of 6 years because of some people think it's a folk remedy. Think of what that cost. The anti-oxidant mechanism hasn't hardly worked.

JAMA 2009;302 2663-2670
Ginkgo biloba for Preventing Cognitive Decline in Older Adults

A Randomized Trial

Beth E. Snitz, PhD; Ellen S. O’Meara, PhD; Michelle C. Carlson, PhD; Alice M. Arnold, PhD; Diane G. Ives, MPH; Stephen R. Rapp, PhD; Judith Saxton, PhD; Oscar L. Lopez, MD; Leslie O. Dunn, MPH; Kaycee M. Sink, MD; Steven T. DeKosky, MD; for the Ginkgo Evaluation of Memory (GEM) Study Investigators

JAMA. 2009;302(24):2663-2670.

Context The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.

Objective To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults.

Design, Setting, and Participants The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.

Intervention Twice-daily dose of 120-mg extract of G biloba (n = 1545) or identical-appearing placebo (n = 1524).

Main Outcome Measures Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.

Results Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P > .05).

Conclusion Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.

Wednesday, December 02, 2009

Hairdressers: Another Non-Industrial Population at Increased Risk Due to Chemical Exposure

BrooklynDodger(s) comment: IARC lists occupation of hairdresser as Group 2A. Volume 57.

>>>>>>>>>>>>>>>>>>
International Journal of Epidemiology 2009 38(6):1512-1531; doi:10.1093/ije/dyp283















































Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2009; all rights reserved.

Risk of cancer among hairdressers and related workers: a meta-analysis

Bahi Takkouche1,2,*, Carlos Regueira-Méndez1,2 and Agustín Montes-Martínez1,2

1 Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
2 CIBER en Epidemiología y Salud Pública (CIBER-ESP), Spain.

* Corresponding author. Department of Preventive Medicine, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. E-mail: bahi.takkouche@usc.es


 Abstract

Background Hairdressers and allied occupations represent a large and fast growing group of professionals. The fact that these professionals are chronically exposed to a large number of chemicals present in their work environment, including potential carcinogens contained in hair dyes, makes it necessary to carry out a systematic evaluation of the risk of cancer in this group.

Methods We retrieved studies by systematically searching Medline and other computerized databases, and by manually examining the references of the original articles and monographs retrieved. We also contacted international researchers working on this or similar topics to complete our search. We included 247 studies reporting relative risk (RR) estimates of hairdresser occupation and cancer of different sites.

Results Study-specific RRs were weighted by the inverse of their variance to obtain fixed and random effects pooled estimates. The pooled RR of occupational exposure as a hairdresser was 1.27 (95% CI 1.15–1.41) for lung cancer, 1.52 [95% confidence interval (CI) 1.11–2.08] for larynx cancer, 1.30 (95% CI 1.20–1.42) for bladder cancer and 1.62 (95% CI 1.22–2.14) for multiple myeloma. Data for other anatomic sites showed increases of smaller magnitude. The results restricted to those studies carried out before the ban of two major carcinogens from hair dyes in the mid-1970s were similar to the general results.

Conclusions Hairdressers have a higher risk of cancer than the general population. Improvement of the ventilation system in the hairdresser salons and implementation of hygiene measures aimed at mitigating exposure to potential carcinogens at work may reduce the risk.

Tuesday, December 01, 2009

Thursday, October 29, 2009

Markers of nitrosamine carcinogenesis?

BrooklynDodger(s) comment: These novel assay experiments should be related to exposure levels in which toxicity or carcinogenicity is expressed in an intact animal.


Toxicology and Applied Pharmacology
Volume 241, Issue 2, 1 December 2009, Pages 230-245


Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: Comparison of genomic and proteomic responses and anchoring to histopathological parameters

A. Oberemma, Corresponding Author Contact Information, E-mail The Corresponding Author, H.-J. Ahrb, P. Bannaschc, H. Ellinger-Ziegelbauerb, M. Glückmanne, J. Hellmannd, C. Ittrichc, 1, A. Kopp-Schneiderc, P.-J. Kramerd, E. Krausef, M. Krögerd, E. Kissc, H.-B. Richter-Reichhelma, G. Scholzb, 2, K. Seemannd, M. Weimerc and U. Gundert-Remya

aFederal Institute for Risk Assessment (BfR), 14195 Berlin, Germany

bBayer Schering Pharma AG, Special Toxicology, 42096 Wuppertal, Germany

cGerman Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

dMerck KGaA, Institute for Toxicology, 64293 Darmstadt, Germany

eApplied Biosystems Deutschland GmbH, 64293 Darmstadt, Germany

fLeibniz Institute for Molecular Pharmacology (FMP), 13125 Berlin, Germany


Received 29 July 2009;
accepted 18 August 2009.
Available online 28 August 2009.

Abstract

A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplastic and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.

Wednesday, October 28, 2009

Another endpoint for nano titanium dioxide

BrooklynDodger(s) comment: Continuing to run nano particles through novel test systems. Historically, titanium dioxide is the negative control for lung damage. What's needed is a systematic testing of a spectrum of particles in the same system - full size titanium dioxide, silica (a known human carcinogen), diesel, carbon materials. So that relative potency can be measured.


Toxicology and Applied Pharmacology
Volume 241, Issue 2, 1 December 2009, Pages 182-194

Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure

Shing Huanga, Pin Ju Chueha, Yun-Wei Linb, Tung-Sheng Shihc and Show-Mei Chuanga, Corresponding Author Contact Information, E-mail The Corresponding Author

aInstitute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan

bMolecular Oncology Laboratory, Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan

cInstitute of Occupational Safety and Healthy Council of Labor Affairs, Executive Yuan, Taipei 221, Taiwan


Received 9 March 2009;
revised 10 August 2009;
accepted 11 August 2009.
Available online 18 August 2009.

Abstract

Titanium dioxide (TiO2) nano-particles (< 100 nm in diameter) have been of interest in a wide range of applications, such as in cosmetics and pharmaceuticals because of their low toxicity. However, recent studies have shown that TiO2 nano-particles (nano-TiO2) induce cytotoxicity and genotoxicity in various lines of cultured cells as well as tumorigenesis in animal models. The biological roles of nano-TiO2 are shown to be controversial and no comprehensive study paradigm has been developed to investigate their molecular mechanisms. In this study, we showed that short-term exposure to nano-TiO2 enhanced cell proliferation, survival, ERK signaling activation and ROS production in cultured fibroblast cells. Moreover, long-term exposure to nano-TiO2 not only increased cell survival and growth on soft agar but also the numbers of multinucleated cells and micronucleus (MN) as suggested in confocal microscopy analysis. Cell cycle phase analysis showed G2/M delay and slower cell division in long-term exposed cells. Most importantly, long-term TiO2 exposure remarkably affected mitotic progression at anaphase and telophase leading to aberrant multipolar spindles and chromatin alignment/segregation. Moreover, PLK1 was demonstrated as the target for nano-TiO2 in the regulation of mitotic progression and exit. Notably, a higher fraction of sub-G1 phase population appeared in TiO2-exposed cells after releasing from G2/M synchronization. Our results demonstrate that long-term exposure to nano-TiO2 disturbs cell cycle progression and duplicated genome segregation, leading to chromosomal instability and cell transformation

Sunday, October 25, 2009

IRIS Summary for 1,2,3-trichloropropane

BrooklynDodger(s) comment: The Dodger(s) figure this is a drinking water contaminant. As with most IRIS chemicals, the chronic RfC is essentially zero. This came to attention because other bloggers noted OMB meddling. OMB was selling site specificity, animal to man, which is an old Houdini chestnut.


http://www.epa.gov/iris/subst/0200.htm

Critical Effect
Point of Departure*
UF
Chronic RfC
peribronchial lymphoid hyperplasia in male rats




13-week inhalation Study

Johannsen et al., 1988
BMC10: 1.6 ppm
BMCL10: 0.84 ppm
BMCLADJ: 0.90 mg/m3
BMCLHEC: 0.90 mg/m3
3000
0.0003 mg/m3

Saturday, October 24, 2009

Gene Environmental Interactions for Bladder Cancer

BrooklynDodger(s) comment: First, urothelial carcinoma is the most common type of bladder cancer - the Dodger(s) had to google it. Learn something every day. The trouble with most genetic studies of cancer is they end with blaming the victim - or the victims' ancestors - and yield no new ideas for intervention. Controlling for less resistant genetic types would enable better human studies of associations with exposures. Glutathione continues to get more play, compared to cytochrome. CYP can be thought of as activating and dotoxicating, while GST is mostly detox unless there's an ad hoc Houdini hypothesis, as for methylene chloride.


Toxicology and Applied Pharmacology
Volume 241, Issue 1, 15 November 2009, Pages 111-118


A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma

Yuan-Hung Wanga, b, Shauh-Der Yehb, Kun-Hung Shenc, Cheng-Huang Shend, Guang-Dar Juange, Ling-I Hsuf, Hung-Yi Chioua, Corresponding Author Contact Information, E-mail The Corresponding Author and Chien-Jen Chenf, g

aSchool of Public Health, Taipei Medical University, Taipei 110, Taiwan

bDepartment of Urology, Taipei Medical University Hospital, Taipei 110, Taiwan

cDepartment of Urology, Chi-Mei Medical Center, Tainan 710, Taiwan

dDepartment of Urology, Chiayi Christian Hospital, Chia-Yi 600, Taiwan

eDivision of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan

fThe Genomics Research Center, Academia Sinica, Taipei 115, Taiwan

gGraduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 100, Taiwan


Received 17 April 2009;
revised 3 August 2009;
accepted 7 August 2009.
Available online 15 August 2009.

Abstract

Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case–control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.9–4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2–H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.