Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage in Qidong, China

ABSTRACT Background Airborne pollutants have collectively been classified as a known human carcinogen and, more broadly, affect the health of hundreds of millions of people worldwide. Benzene is a frequent component of air pollution, and strategies to protect individuals against unavoidable exposure to this and other airborne carcinogens could improve the public's health. Earlier clinical trials in Qidong, China, demonstrated efficacy in enhancing the detoxication of benzene using a broccoli sprout beverage. Objectives A randomized, placebo-controlled, multidose trial of a broccoli sprout beverage was designed to determine the lowest effective concentration that enhances benzene detoxication adjudged by enhanced excretion of the urinary biomarker, S-phenylmercapturic acid (SPMA). Methods Following informed consent, 170 subjects were randomly assigned in 5 blocks of 34 each to drink either a placebo beverage (n = 55) or 1 of 3 graded concentrations of a broccoli sprout beverage [full (n = 25), one-half (n = 35), and one-fifth (n = 55)] for 10 consecutive days. Concentrations of SPMA arising through induced benzene conjugation with glutathione were quantified by MS in sequential 12-h overnight urine collections during the intervention. Results MS was also used to quantify urinary sulforaphane metabolites in each dosing regimen that resulted in a median 24-h urinary output of 24.6, 10.3, and 4.3 µmol, respectively, confirming a dose-dependent de-escalation of the inducing principle within the beverage. A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period. The one-half dose (+11.3%) and one-fifth dose groups (−6.4%) were not significantly different from placebo controls. Conclusions An intervention with a broccoli sprout beverage enhanced the detoxication of benzene, an important airborne pollutant, when dosed at a concentration evoking a urinary elimination of ∼25 µmol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution. This trial was registered at clinicaltrials.gov as NCT02656420.

Download Full-text

Incident cardiovascular disease and particulate matter air pollution in South Korea using a population-based and nationwide cohort of 0.2 million adults

Environmental Health ◽

10.1186/s12940-020-00671-1 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Ok-Jin Kim ◽

Soo Hyun Lee ◽

Si-Hyuck Kang ◽

Sun-Young Kim

Keyword(s):

Cardiovascular Disease ◽

Air Pollution ◽

Particulate Matter ◽

South Korea ◽

Proportional Hazards ◽

Population Based ◽

Average Concentration ◽

Cox Proportional Hazards ◽

High Dose

Abstract Background While many studies reported the association between long-term exposure to particulate matter air pollution (PM) and cardiovascular disease (CVD), few studies focused on incidence with relatively high-dose exposure using a nationwide cohort. This study aimed to investigate the association between long-term exposure to PM10 and PM2.5 and incidence of CVD in a nationwide and population-based cohort in South Korea where the annual average concentration of PM2.5 is above 20 μg/m3. Methods We selected 196,167 adults in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) constructed based on the entire South Korean population. Incidence of four CVD subtypes including ischemic heart disease (IHD), myocardial infarction, heart failure, and stroke, and total CVD including all four was identified as the first diagnosis for 2007–2015. To assess individual exposures, we used annually-updated district-level residential addresses and district-specific PM concentrations predicted by a previously developed universal kriging prediction model. We computed individual-level long-term PM concentrations for four exposure windows: previous 1, 3, and 5 year(s) and 5 years before baseline. We applied time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) of incident CVDs per 10 μg/m3 increase in PM10 and PM2.5 after adjusting for individual- and area-level characteristics. Results During 1,578,846 person-year, there were 33,580 cases of total incident CVD. Average PM10 and PM2.5 concentrations for the previous 5 years were 52.3 and 28.1 μg/m3, respectively. A 10 μg/m3 increase in PM2.5 exposed for the previous 5 years was associated with 4 and 10% increases in the incidence of total CVD (95% confidence interval: 0–9%) and IHD (4–16%), respectively. HRs tended to be higher with earlier exposure for IHD and more recent exposure for stroke. The estimated shape of the concentration-response relationship showed non-linear patterns. We did not find evidence of the association for PM10. Conclusions Using a population-based nationwide cohort exposed to relatively high PM concentration, this study confirmed the association between PM2.5 and CVD incidence that was reported in previous studies mostly with low-dose environments. The magnitude and the shape of the association were generally consistent with previous findings.

Download Full-text

Long-Term Exposure to PM2.5 and Cognitive Decline: A Longitudinal Population-Based Study

Journal of Alzheimer s Disease ◽

10.3233/jad-200852 ◽

2021 ◽

pp. 1-9

Author(s):

Giulia Grande ◽

Jing Wu ◽

Petter L.S. Ljungman ◽

Massimo Stafoggia ◽

Tom Bellander ◽

...

Keyword(s):

Air Pollution ◽

Cognitive Decline ◽

Population Based ◽

Cerebrovascular Diseases ◽

Air Pollutant ◽

National Study ◽

Piecewise Regression ◽

Risk Increase ◽

Restricted Cubic Splines

Background: A growing but contrasting evidence relates air pollution to cognitive decline. The role of cerebrovascular diseases in amplifying this risk is unclear. Objectives: 1) Investigate the association between long-term exposure to air pollution and cognitive decline; 2) Test whether cerebrovascular diseases amplify this association. Methods: We examined 2,253 participants of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). One major air pollutant (particulate matter ≤2.5μm, PM2.5) was assessed yearly from 1990, using dispersion models for outdoor levels at residential addresses. The speed of cognitive decline (Mini-Mental State Examination, MMSE) was estimated as the rate of MMSE decline (linear mixed models) and further dichotomized into the upper (25%fastest cognitive decline), versus the three lower quartiles. The cognitive scores were used to calculate the odds of fast cognitive decline per levels of PM2.5 using regression models and considering linear and restricted cubic splines of 10 years exposure before the baseline. The potential modifier effect of cerebrovascular diseases was tested by adding an interaction term in the model. Results: We observed an inverted U-shape relationship between PM2.5 and cognitive decline. The multi-adjusted piecewise regression model showed an increased OR of fast cognitive decline of 81%(95%CI = 1.2–3.2) per interquartile range difference up to mean PM2.5 level (8.6μg/m3) for individuals older than 80. Above such level we observed no further risk increase (OR = 0.89;95%CI = 0.74–1.06). The presence of cerebrovascular diseases further increased such risk by 6%. Conclusion: Low to mean PM2.5 levels were associated with higher risk of accelerated cognitive decline. Cerebrovascular diseases further amplified such risk.

Download Full-text

Impact of short- and long-term exposure to air pollution on blood pressure: A two-decade population-based study in Tehran

International Journal of Hygiene and Environmental Health ◽

10.1016/j.ijheh.2021.113719 ◽

2021 ◽

Vol 234 ◽

pp. 113719

Author(s):

Alireza Khajavi ◽

Seyed Saeed Tamehri Zadeh ◽

Fereidoun Azizi ◽

Robert D. Brook ◽

Hengameh Abdi ◽

...

Keyword(s):

Blood Pressure ◽

Air Pollution ◽

Population Based ◽

Population Based Study ◽

Short And Long Term

Download Full-text

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

Psychological Medicine ◽

10.1017/s0033291700000660 ◽

1987 ◽

Vol 17 (4) ◽

pp. 869-873 ◽

Cited By ~ 37

Author(s):

C. Schmauss ◽

J.-C. Krieg

Keyword(s):

Low Dose ◽

Matched Control ◽

Control Group ◽

High Dose ◽

Withdrawal Therapy ◽

The Mean ◽

Dose Dependent ◽

Dose Dependent Effect ◽

Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Download Full-text

Quantification of mortality and morbidity in general population of heavily-industrialized city of Abadan: Effect of long-term exposure

Journal of Air Pollution and Health ◽

10.18502/japh.v5i3.5390 ◽

2021 ◽

Author(s):

Akram Ghorbanian ◽

Ahmad Jonidi Jafari ◽

Abbas Shahsavani ◽

Ali Abdolahnejad ◽

Majid Kermani ◽

...

Keyword(s):

Air Pollution ◽

Mortality Data ◽

Air Pollution Control ◽

Medical Sciences ◽

Mortality And Morbidity ◽

Khuzestan Province ◽

Vice Chancellor ◽

One Year ◽

The One

Introduction: In the 21st century, air pollution has become a global and environmental challenge. The increase in cases of illness and mortality due to air pollution is not hidden from anyone. Therefore, in this study, we estimated the mortality rate due to cause by air pollution agents (PM2.5) in the southernmost city of Khuzestan province (Abadan city) at 2018-2019. Materials and methods: To estimate the mortality duo to air pollution, data related to PM2.5 particles daily concentrations was received from the Abadan Environmental Protection Organization. The average 24-h concentrations of PM2.5 were calculated using Excel. Then, mortality data were obtained from the Vice Chancellor for Health, Abadan University of Medical Sciences. Finally, by AirQ+ software, each of the mortality in 2018-2019 in Abadan was estimated. Results: The obtained data indicated that the concentration of PM2.5 particles within the one-year period was higher than the value set by WHO guideline and EPA standard. Which caused the citizens of Abadan to be exposed to PM2.5 more than 8.23 times than the guidelines of the WHO and 5.34 times more than the standard of the EPA. The output of the model used in this study was as follows: natural mortality (462 cases, AP: 38.25%), mortality duo to LC (6 cases, AP: 32.18%), mortality duo to COPD (8 cases, AP: 26.64%), mortality duo to Stroke (86 cases, AP: 71.26%), mortality duo to IHD (183 cases, AP: 68.34%) and mortality duo to ALRI (2 cases, AP: 32.9%). Conclusion: Planning appropriate strategies of air pollution control to reduce exposure and attributable mortalities is important and necessary.

Download Full-text

Increased mortality in patients with corticosteroid-dependent asthma: a nationwide population-based study

European Respiratory Journal ◽

10.1183/13993003.00804-2019 ◽

2019 ◽

Vol 54 (5) ◽

pp. 1900804 ◽

Cited By ~ 12

Author(s):

Hyun Lee ◽

Jiin Ryu ◽

Eunwoo Nam ◽

Sung Jun Chung ◽

Yoomi Yeo ◽

...

Keyword(s):

Baseline Period ◽

Population Based ◽

High Dose ◽

Population Based Study ◽

Risk Of Mortality ◽

Increased Risk ◽

Korean National Health Insurance ◽

Independent Cohort ◽

Long Term Mortality

IntroductionChronic systemic corticosteroid (CS) therapy is associated with an increased risk of mortality in patients with many chronic diseases. However, it has not been elucidated whether chronic systemic CS therapy is associated with increased mortality in patients with asthma. The aim of this study was to determine the effects of chronic systemic CS therapy on long-term mortality in adult patients with asthma.MethodsA population-based matched cohort study of males and females aged ≥18 years with asthma was performed using the Korean National Health Insurance Service database from 2005 to 2015. Hazard ratio (HR) with 95% confidence interval for all-cause mortality among patients in the CS-dependent cohort (CS use ≥6 months during baseline period) relative to those in the CS-independent cohort (CS use <6 months during baseline period) was evaluated.ResultsThe baseline cohort included 466 941 patients with asthma, of whom 8334 were CS-dependent and 458 607 were CS-independent. After 1:1 matching, 8334 subjects with CS-independent asthma were identified. The HR of mortality associated with CS-dependent asthma relative to CS-independent asthma was 2.17 (95% CI 2.04–2.31). In patients receiving low-dose CS, the HR was 1.84 (95% CI 1.69–2.00); in patients receiving high-dose CS, the HR was 2.56 (95% CI 2.35–2.80).ConclusionsIn this real-world, clinical practice, observational study, chronic use of systemic CS was associated with increased risk of mortality in patients with asthma, with a significant dose–response relationship between systemic CS use and long-term mortality.

Download Full-text

The Australian Child Health and Air Pollution Study (ACHAPS): A national population-based cross-sectional study of long-term exposure to outdoor air pollution, asthma, and lung function

Environment International ◽

10.1016/j.envint.2018.08.025 ◽

2018 ◽

Vol 120 ◽

pp. 394-403 ◽

Cited By ~ 29

Author(s):

Luke D. Knibbs ◽

Adriana M. Cortés de Waterman ◽

Brett G. Toelle ◽

Yuming Guo ◽

Lyn Denison ◽

...

Keyword(s):

Air Pollution ◽

Lung Function ◽

Population Based ◽

Cross Sectional Study ◽

Outdoor Air ◽

Sectional Study ◽

Cross Sectional ◽

Australian Child ◽

Pollution Study

Download Full-text

Impact of Long-Term Tyrosine Kinase Inhibitor Exposure on Spermatogenesis in Juvenile Rats

Blood ◽

10.1182/blood.v128.22.1884.1884 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1884-1884 ◽

Cited By ~ 2

Author(s):

Vera Girke ◽

Josephine Tabea Tauer ◽

Ingmar Glauche ◽

Lorenz Hofbauer ◽

Meinolf Suttorp

Keyword(s):

Research Funding ◽

Wistar Rats ◽

Pediatric Patients ◽

High Dose ◽

Testis Weight ◽

Ki 67 ◽

Juvenile Rats ◽

Alpha Beta ◽

Dose Dependent

Abstract Background: Pediatric patients with chronic myeloid leukemia (CML) are exposed to off-target side effects from long-term treatment with tyrosine kinase inhibitors (TKIs) which have been observed with increasing watchfulness in the last years (Hijiya N, et al. BLOOD 127:392, 2016). TKIs inhibit c-kit and platelet-derived growth factor receptors (PDGF-R alpha/beta) which are known to regulate spermatogenesis (Zhang M, et al. SCI REP 4:5936, 2014). The influence of TKIs on spermatogenesis in pediatric patients with CML is not fully understood yet (Samis J, et al. PEDIATR BLOOD CANCER 63:1332, 2016). Therefore, we studied testicular tissue in juvenile rats following exposure to TKIs imatinib (IMA) and dasatinib (DASA) in a time and dose-dependent manner. Methods: Using an established model (Tauer JT, et al. PLOS ONE 10:e0131192, 2015) of juvenile still growing Wistar rats, animals (age: 4 weeks [w]) were exposed to IMA or DASA at different dosages for 10 w (low dose [LD], high dose [HD], intermittently high dose [ID]; total number of rats: 20 to 32 animals, 5 - 8 rats per cohort). At defined developmental stages, that is at prepubertal age (6 w), pubertal age (8 w), and postpubertal age (14 w), testis weight as well as cellularity (spermatogonia, spermatocytes, spermatids, Ki-67 positive cells) were evaluated histopathologically in seminiferous tubule microscopic cross sections after continuous IMA treatment. Expression of genes involved in spermatogenesis comprising SCF and PDGF-alpha/beta as well as their corresponding receptors c-kit and PDGFR-alpha/beta (Nurmio M, et al. REPRODUC TOXICOL 25:442, 2008) was studied after continuous DASA exposure. Results: Testis weight remained unchanged compared to non-exposed controls by exposure to any TKI. However, spermatogenic cell counts decreased significantly by 10% after IMA HD-exposure. In spermatogenesis cell cycle, the stage of the dominant cell proportion (stage VII according to Perey B, et al. AM J ANAT 108:47, 1961) was shifted to more immature stages (stage II/III) as well. LD- and ID-exposure with IMA attenuated these findings. Cell proliferation as investigated by Ki-67+ expression was significantly lowered by 10% - 20% at all applied IMA doses. Long-term DASA treatment at LD, HD and ID resulted in significantly reduced gene expression of SCF, c-kit and PDGF-R alpha/beta. Gene expression of PDGF-alpha was significantly decreased in HD and ID but not LD, whereas PDGF-beta showed no significant reduction postpubertally. Conclusion: Long-term TKI toxicity in still growing organisms can easily be modelled in juvenile rats and emulates well the so-far clinical experience with regard to osseous side effects of TKIs (Millot F, et al. EUR J CANCER, 50:3206, 2014). Assessment of gonadal toxicity by isolated determination of testis weight represents a rather unspecific approach and will neglect subtle histopathological changes. With regard to spermatogenesis long-term TKI exposure resulted in reduced progenitor cell proliferation and downregulation of involved genes in a cumulative dose-dependent fashion. Thus, at least in juvenile, still growing Wistar rats a long-lasting negative effect of long-term TKI exposure on spermatogenesis has to be taken into account. Improved preclinical testing in well-established leukemia models should help to prioritize TKI agents in the clinical studies pipeline for pediatric patients with CML. Long-term follow-up of pediatric and adolescent patients who are given new targeted agents is mandatory and will prospectively explore potential late effects, and hopefully also provide corrective or preventive measures. Disclosures Glauche: Bristol Meyer Squib: Research Funding. Suttorp:Novartis, Bristol Meyer Squib, Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Download Full-text