A STRATEGY FOR COMPARING THE CONTRIBUTIONS OF ENVIRONMENTAL CHEMICALS AND OTHER RISK FACTORS TO NEURODEVELOPMENT OF CHILDREN

ObjectiveDiabetes and cardiovascular diseases are growing burdens in rural communities worldwide. We have observed a high prevalence of diabetes among rural farming communities in India and sought to evaluate the association of non-traditional risk factors, such as metals, with diabetes and other cardiometabolic risk factors in this community.MethodsAnthropometric measurements, chemistries and carotid intima-media thickness were determined in 865 participants of the Kovai Medical Center and Hospital-Nallampatti Non-Communicable Disease Study-I (KMCH-NNCD-I, 2015), a cross-sectional study conducted in a farming village in South India. Urinary metal levels were determined by inductively couped plasma-mass spectrometry analysis and corrected to urinary creatinine level. Statistical analyses were performed to study the association between urinary metal levels and clinical parameters.Results82.5% of the study population were involved in farming and high levels of toxic metals were detected in the synthetic fertilisers used in the study village. The prevalence of pre-diabetes, diabetes and atherosclerosis was 43.4%, 16.2% and 10.3%, respectively. On logistic regression analysis, no association of traditional risk factors such as body mass index, blood pressure and total cholesterol with disease conditions was observed, but urinary levels of metals such as arsenic, chromium, aluminium and zinc showed an association with diabetes, while arsenic and zinc showed an association with pre-diabetes and atherosclerosis.ConclusionsOur data suggest a probable role of metals in the aetiology of diabetes and cardiovascular diseases in rural communities. Identifying and eliminating the causes of increased levels of these environmental chemicals could have a beneficial impact on the burden of non-communicable diseases in rural population.

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Contribution of environment and genetics to oxidative stress in pancreatic cancer (PC) patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.211 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 211-211 ◽

Cited By ~ 1

Author(s):

B. A. Hocevar ◽

E. G. Chiorean ◽

L. Kamendulis ◽

S. M. Perkins ◽

E. L. Johnston ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Dna Damage ◽

Antioxidant Capacity ◽

Oxidative Dna Damage ◽

Statistical Significance ◽

Environmental Chemicals ◽

Trolox Equivalent Antioxidant Capacity ◽

Common Denominator ◽

Stress Damage

211 Background: Several risk factors have been identified as contributors to PC development, including tobacco and alcohol use, and exposure to environmental chemicals. A common denominator of these risk factors is the ability to induce oxidative stress/damage. An individual's genetic makeup may also contribute to oxidative stress, as oxidative stress/damage genes exhibit single nucleotide polymorphisms (SNPs), which can alter protein expression or activity. The goal of this study was to (1) determine if increased oxidative stress/damage is observed in PC pts and (2) to assess the contribution of environmental and genetic factors to oxidative stress/damage parameters. Methods: An oxidative stress/damage profile was generated from blood samples of newly diagnosed PC pts (n=20), from non-cohabiting genetic relatives (n=20) and/or from non-genetic relatives living in the same household (n=20). This profile consisted of measurement of total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), direct and oxidative DNA damage (COMET), and malondialdehyde (MDA) levels. Expression of SNPs in selected oxidative stress/response genes was also evaluated. Environmental and dietary/lifestyle information was collected using a detailed questionnaire. Results: PC pts, when compared to healthy nonrelated but cohabitating relatives, displayed a significant increase in direct DNA damage (p=0.002), while oxidative DNA damage, TEAC and MDA levels were similar. When comparing PC pts to healthy genetic relatives, increased levels of TEAC, direct and oxidative DNA damage approached or were statistically significant (p = 0.061, 0.002, and 0.062 respectively). Analysis of 26 selected SNPs in oxidative stress/ damage genes in the PC pts vs healthy controls revealed that expression of CYP2A6 (L160H), rs1801272, and TNF (-308G>A), rs1800629, approached statistical significance (p=0.05 and 0.20 respectively). Conclusions: Increased oxidative DNA damage observed in PC pts vs healthy related, but non-cohabitating relatives, suggests that environmental exposures contribute to oxidative stress. In combination with a specific genetic background, environmental influences may increase the risk of PC. No significant financial relationships to disclose.

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Epigenetics and developmental programming of welfare and production traits in farm animals

Reproduction Fertility and Development ◽

10.1071/rd16102 ◽

2016 ◽

Vol 28 (10) ◽

pp. 1443 ◽

Cited By ~ 36

Author(s):

K. D. Sinclair ◽

K. M. D. Rutherford ◽

J. M. Wallace ◽

J. M. Brameld ◽

R. Stöger ◽

...

Keyword(s):

Risk Factors ◽

Livestock Production ◽

Carcass Composition ◽

Environmental Chemicals ◽

Farm Animals ◽

Future Research ◽

Large Animal ◽

Production Traits ◽

Experimental Conditions ◽

Commercial Importance

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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Plasma Phthalate Levels In Children With Speech Delay

10.21203/rs.3.rs-1093745/v1 ◽

2021 ◽

Author(s):

Nihal Yaman Artunç ◽

Anıl Yirun ◽

Kübra G.Özkemahlı ◽

Pınar Erkekoğlu ◽

Pınar Zengin Akkuş ◽

...

Keyword(s):

Risk Factors ◽

Linear Regression Analysis ◽

Environmental Chemicals ◽

Healthy Children ◽

Speech Delay ◽

Control Groups ◽

Developmental Problems ◽

Significant Difference ◽

And Control ◽

Ethylhexyl Phthalate

Abstract Speech delay is one of the most common developmental problems. One of the risk factors may be the exposure to environmental chemicals. There is increased environmental exposure to phthalates, an endocrine-disrupting chemical. In this study, we aimed to determine the relationship of phthalates with speech delay. We included 50 children with isolated speech delay and 40 healthy children of similar age. Children were surveyed for risk factors for speech delay and phthalate exposure. Plasma di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) levels were measured by high pressure liquid chromatography. The DEHP, MEHP and DBP levels in study and control groups were 0.377 [0.003 - 1.224] µg/ml, 0.212 [0.007 - 1.112] µg/ml (p = 0.033), 0.523 [0.031 - 2.477] µg/ml, 0.152 [0.239 - 2.129] µg/ml (p <0.001), and 0.395 [0.062 - 1.996] µg/ml, 0.270 [0.006 - 0.528] µg/ml (p = 0.004), respectively. Multiple linear regression analysis was used to adjust the association between the phthalate levels and factors differing between the two groups in terms of delayed speech risk factors. While there was no significant difference between the study and control groups in terms of DEHP level (p=0.233), the MEHP and DBP levels were found significantly higher in the study group (p<0,001). Conclusion: The statistically significant higher phthalate levels in those with speech delay indicate that these children are more exposed to phthalates and more epidemiological studies are needed to evaluate the association between phthalates and speech delay.

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Prenatal exposures to environmental chemicals and birth order as risk factors for child behavior problems

Environmental Research ◽

10.1016/j.envres.2012.02.001 ◽

2012 ◽

Vol 114 ◽

pp. 47-52 ◽

Cited By ~ 27

Author(s):

Nozomi Tatsuta ◽

Kunihiko Nakai ◽

Katsuyuki Murata ◽

Keita Suzuki ◽

Miyuki Iwai-Shimada ◽

...

Keyword(s):

Risk Factors ◽

Behavior Problems ◽

Birth Order ◽

Child Behavior ◽

Child Behavior Problems ◽

Environmental Chemicals ◽

Prenatal Exposures

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A STRATEGY FOR COMPARING THE CONTRIBUTIONS OF ENVIRONMENTAL CHEMICALS AND OTHER RISK FACTORS TO NEURODEVELOPMENT OF CHILDREN

Environmental Hazards and Neurodevelopment ◽

10.1201/b18030-4 ◽

2015 ◽

pp. 41-64

Author(s):

David Bellinger

Keyword(s):

Risk Factors ◽

Environmental Chemicals

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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