Long-term Chronic Exposure Research Articles

Neonicotinoid residues in UK honey despite European Union moratorium.

Due to concerns over negative impacts on insect pollinators, the European Union has implemented a moratorium on the use of three neonicotinoid pesticide seed dressings for mass-flowering crops. We assessed the effectiveness of this policy in reducing the exposure risk to honeybees by collecting 130 samples of honey from bee keepers across the UK before (2014: N = 21) and after the moratorium was in effect (2015: N = 109). Neonicotinoids were present in about half of the honey samples taken before the moratorium, and they were present in over a fifth of honey samples following the moratorium. Clothianidin was the most frequently detected neonicotinoid. Neonicotinoid concentrations declined from May to September in the year following the ban. However, the majority of post-moratorium neonicotinoid residues were from honey harvested early in the year, coinciding with oilseed rape flowering. Neonicotinoid concentrations were correlated with the area of oilseed rape surrounding the hive location. These results suggest mass flowering crops may contain neonicotinoid residues where they have been grown on soils contaminated by previously seed treated crops. This may include winter seed treatments applied to cereals that are currently exempt from EU restrictions. Although concentrations of neonicotinoids were low (<2.0 ng g-1), and posed no risk to human health, they may represent a continued risk to honeybees through long-term chronic exposure.

Trichostatin A Shows Transient Protection from Chronic Alcohol-Induced Reactive Oxygen Species (ROS) Production in Human Monocyte-Derived Dendritic Cells.

Objective:The objective of this study was to understand whether histone deacetylase (HDACs) inhibitor Trichostatin A or TSA can block and/or reverse chronic alcohol exposure-induced ROS in human monocyte-derived dendritic cells (MDDCs). Additionally, since nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a known regulator of antioxidant responses, we studied the effects of alcohol and TSA on ROS production and modulation of Nrf2 by MDDCs.Methods:Intra-cellular, extra-cellular, and total ROS levels were measured in MDDCs treated chronically with alcohol (0.1 and 0.2 % EtOH) using 2’,7’-dichlorofluorescin diacetate (DCF-DA) followed by detection of ROS in microplate reader and imaging flow cytometer. Nrf2 expression was analyzed by qRT- PCR and western blot. In addition, NFE2L2 (Nrf2), class I HDAC genes HDAC1, HDAC2, and histone acetyltransferase genes KAT5 were analyzed in silico using the GeneMania prediction server.Results:Our results confirmed alcohol’s ability to increase intracellular ROS levels in MDDCs within minutes of treatment. Our findings have also demonstrated, for the first time, that TSA has a transient protective effect on MDDCs treated chronically with alcohol since the ability of TSA to reduce intracellular ROS levels is only detected up to 15 minutes post-chronic alcohol treatment with no significant protective effects by 10 hours. In addition, chronic alcohol treatment was able to increase the expression of the antioxidant regulator Nrf2 in a dose dependent manner, and the effect of the higher amount of alcohol (0.2%) on Nrf2 gene expression was significantly enhanced by TSA.Conclusion:This study demonstrates that TSA has a transient protective effect against ROS induced by chronic alcohol exposure of human MDDCs and chronic long-term exposure of MDDCs with alcohol and TSA induces cellular toxicity. It also highlights imaging flow cytometry as a novel tool to detect intracellular ROS levels. Overall, the effect of TSA might be mediated through Nrf2; however, further studies are needed to fully understand the molecular mechanisms.

Associations between long-term PM2.5 and ozone exposure and mortality in the Canadian Census Health and Environment Cohort (CANCHEC), by spatial synoptic classification zone

Studies suggest that long-term chronic exposure to fine particulate matter air pollution can increase lung cancer mortality. We analyzed the association between long term PM2.5 and ozone exposure and mortality due to lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease, accounting for geographic location, socioeconomic status, and residential mobility. Subjects in the 1991 Canadian Census Health and Environment Cohort (CanCHEC) were followed for 20years, and assigned to regions across Canada based on spatial synoptic classification weather types. Hazard ratios (HR) for mortality, were related to PM2.5 and ozone using Cox proportional hazards survival models, adjusting for socioeconomic characteristics and individual confounders. An increase of 10μg/m3 in long term PM2.5 exposure resulted in an HR for lung cancer mortality of 1.26 (95% CI 1.04, 1.53); the inclusion in the model of SSC zone as a stratum increased the risk estimate to HR 1.29 (95% CI 1.06, 1.57). After adjusting for ozone, HRs increased to 1.49 (95% CI 1.23, 1.88), and HR 1.54 (95% CI 1.27, 1.87), with and without zone as a model stratum. HRs for ischemic heart disease fell from 1.25 (95% CI 1.21, 1.29) for exposure to PM2.5, to 1.13 (95% CI 1.08, 1.19) when PM2.5 was adjusted for ozone. For COPD, the 95% confidence limits included 1.0 when climate zone was included in the model. HRs for all causes of death showed spatial differences when compared to zone 3, the most populated climate zone. Exposure to PM2.5 was related to an increased risk of mortality from lung cancer, and both ozone and PM2.5 exposure were related to risk of mortality from ischemic heart disease, and the risk varied spatially by climate zone.

Work-Related Noise Exposure in a Cohort of Patients with Chronic Tinnitus: Analysis of Demographic and Audiological Characteristics.

Work-related noise exposure is one of the major factors contributing to the development of adult-onset hearing loss and tinnitus. The aim of this study was to analyze, in patients with chronic tinnitus and long-term occupational noise exposure, (A) characteristics of hearing loss, tinnitus, comorbidities, demographic characteristics and a history of work-related noise exposure and (B) differences among individuals employed in occupations with high and low risk of developing work-related noise-induced hearing loss (NIHL). One hundred thirty six patients with chronic tinnitus and at least a 10 year-long working history were divided into two groups based on the risk of their profession to induce NIHL. Individuals employed in jobs at high risk for NIHL were mostly males and exhibited a poorer hearing threshold, more evident in the left ear. Tinnitus was mostly bilateral; the next largest presentation was left-sided; patients described their tinnitus as buzzing or high-pitched. Correlation between age, length of tinnitus and worse hearing was found. Patients with a higher degree of hearing impairment were mostly males and were more likely to have a family history of hearing loss and at least one cardiovascular comorbidity. Our study shows some differences in individuals with tinnitus and a history of a profession associated with increased exposure to NIHL compared to those without such a history.

Pregnancy outcomes in perinatally HIV-infected young women in Madrid, Spain: 2000-2015.

BackgroundAn increasing number of perinatally HIV-infected women (PHIV) are reaching adulthood and becoming pregnant. Most PHIV women have been exposed to a high number of antiretroviral regimens, and they may have difficulties to achieve viral suppression. Psychosocial problems are not uncommon and could be an important barrier for treatment adherence. The effects of chronic HIV infection and long-term exposure to antiretroviral treatment of PHIV women cause concerns on the developing fetus. The aims of this study were to describe the prevention of mother-to-child transmission strategies in PHIV women and the infant outcomes in the Madrid Cohort of HIV-infected mother-infant pairs.MethodsAll PHIV pregnant women registered in the Cohort that gave birth from 2000 to 2015 were included in the study.ResultsTwenty-eight pregnancies in twenty-two perinatally infected women were registered. Most women were Caucasian and heavily treatment-experienced. Nine cases (32.1%) were at high risk of HIV mother-to-child transmission. Maternal HIV-1 viral load was detectable close to delivery in four women (14.3%). The management of these cases was described, and the treatment strategies were discussed. None of the newborns acquired HIV infection. Eight infants (28.6%) were small for gestational age.ConclusionsThis study included a large series of pregnancies among PHIV women attended according to a youth-centered care model. The challenges in the management of this population by health-care providers were described. Specific strategies to minimize perinatal transmission risks should be addressed in future collaborative studies.

AHR and CYP1A expression link historical contamination events to modern day developmental effects in the American alligator

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today. Little is known regarding the effects that long-term chronic exposures to dioxin or dioxin-like compounds might have on the development and subsequent health of offspring from exposed individuals, nor is much known regarding AHR expression in reptilians. Here, we characterize AHR and CYP1A gene expression in embryonic and juvenile specimen of a long-lived, apex predator, the American alligator (Alligator mississippiensis), and investigate variation in gene expression profiles in offspring collected from sites conveying differential exposures to environmental contaminants. Both age- and tissue-dependent patterning of AHR isoform expression are detected. We characterize two downstream transcriptional targets of the AHR, CYP1A1 and CYP1A2, and describe conserved elements of their genomic architecture. When comparisons across different sites are made, hepatic expression of CYP1A2, a direct target of the AHR, appears elevated in embryos from a site associated with a dioxin point source and previously characterized PCB contamination. Elevated CYP1A2 expression is not persistent, as site-specific variation was absent in juveniles originating from field-collected eggs but reared under lab conditions. Our results illustrate the patterning of AHR gene expression in a long-lived environmental model species, and indicate a potential contemporary influence of historical contamination. This research presents a novel opportunity to link contamination events to critical genetic pathways during embryonic development, and carries significant potential to inform our understanding of potential health effects in wildlife and humans.

High soluble endoglin levels do not induce changes in structural parameters of mouse heart.

A soluble form of endoglin (sEng) released into the circulation was suggested to be a direct inducer of endothelial dysfunction, inflammation and contributed to the development of hypertension by interfering with TGF-β signaling in cardiovascular pathologies. In the present study, we assessed the hypothesis that high sEng level-induced hypertension via a possible sEng interference with TGF-β signaling pathways may result in inflammatory, structural or fibrotic changes in hearts of Sol-Eng+ mice (mice with high levels of soluble endoglin) fed either chow or high-fat diet. Female Sol-Eng+ mice and their age matched littermates with low plasma levels of sEng were fed either chow or high-fat diet (HFD). Heart samples were subsequently analyzed by histology, qRT-PCR and Western blot analysis. In this study, no differences in myocardial morphology/hypertrophy and possible fibrotic changes between Sol-Eng+ mice and control mice were detected on both chow and HFD. The presence of sEng did not significantly affect the expression of selected members of TGF-β signaling (membrane endoglin, TGFβRII, ALK-5, ALK-1, Id-1, PAI-1 and activated Smad proteins-pSmad 1,5 and pSmad 2,3), inflammation, heart remodeling (PDGFb, Col1A1) and endothelial dysfunction (VCAM-1, ICAM-1) in the hearts of Sol-Eng+ mice compared to control mice on both chow and high-fat diet. High levels of soluble endoglin did not affect microscopic structure (profibrotic and degenerative cardiomyocyte changes), and specific parts of TGF-β signaling, endothelial function and inflammation in the heart of Sol-Eng+ mice fed both chow diet or HFD. However, we cannot rule out a possibility that a long-term chronic exposure (9months and more) to soluble endoglin alone or combined with other cardiovascular risk factors may contribute to alterations of heart function and structure in Sol-Eng+ mice, which is the topic in our lab in ongoing experiments.

Influence of long-term chronic exposure and weather conditions on Scots pine populations.

Over a period of 8years (2007-2014), we were evaluating seed quality and morphological abnormalities in Scots pine trees affected as a result of the Chernobyl accident. The calculated dose rates for the trees at the study sites varied from background values at the reference sites to 40mGy/year at the most contaminated site. We investigated whether radioactive contamination and/or weather factors could decrease the reproductive capacity or increase the frequency of morphological abnormalities of needles in pine trees. Scots pine seeds are characterized by high interannual variability of viability, which is largely determined by weather conditions. No consistent differences in reproductive capacity were detected between the impacted and reference populations. Brachyblasts with three needles were found only in the affected populations; however, their frequency was very low and only at the very border of significance at the p<0.10 level.

A Combined Spectroscopic/Molecular Dynamic Study for Investigating a Methyl-Carboxylated PEI as a Potential Uranium Decorporation Agent.

Natural uranium has a very limited radioactive dose impact, but its chemical toxicity due to chronic exposure is still a matter of debate. Once inside the human body, the soluble uranium, under its uranyl form (U(VI)), is quickly removed from the blood system, partially excreted from the body, and partially retained in targeted organs, that is, the kidneys and bone matrix essentially. It is then crucial to remove or prevent the incorporation of uranium in these organs to limit the long-term chronic exposure. A lot of small chelating agents such as aminocarboxylates, catecholamides, and hydroxypyridonates have been developed so far. However, they suffer from poor selectivity and targeting abilities. Macromolecules and polymers are known to present a passive accumulation (size related), that is, the so-called enhanced permeability and retention effect, toward the main organs, which can be used as indirect targeting. Very interestingly, the methyl carboxylated polyethylenimine (PEI-MC) derivative has been described as a potent sequestering agent for heavy metals. It would be therefore an interesting candidate to evaluate as a new class of decorporation agents with passive targeting capabilities matching uranium preferential sequestering sites. In the present work, we explored the ability of a highly functionalized (89% rate) PEI-MC to uptake U(VI) close to physiological pH using a combination of analytical and spectroscopic techniques (inductively coupled plasma optical emission spectrometry (ICP-OES); extended X-ray absorption fine structure (EXAFS); and Fourier transformed infrared (FT-IR)) together with molecular dynamics (MD) simulation. A maximum loading of 0.47 mg U(VI) per milligram of PEI-MC was determined by ICP-OES measurements. From FT-IR data, a majority of monodentate coordination of the carboxylate functions of the PEI-MC seems to occur. From EXAFS and MD, a mix of mono and bidentate coordination mode was observed. Note that agreement between the EXAFS metrical parameters and MD radial distribution functions is remarkable. To the best of our knowledge, this is the first comprehensive structural study of a macromolecular PEI-based agent considered for uranium decorporation purposes.

Do long-term noise exposure cause equilibrium problems? A cross-sectional study

Objective: The objective of the study was to assess the vestibular system among workers exposed to long-term noises.Design: This study design was a cross-sectional study. Setting: This study was conducted at Department of Otolaryngology, King Abdulaziz Special Hospital, Taif, Saudi Araia. Patients: The study involved two groups: long-term noise exposure group (N group), 126 workers, in a printing facility and a control group (Group C), 48 voluntaries, employee from a noise-free environment. Participants and Methods: Both groups had audiometrical and vestibular assessment using videonystagmograph (VNG) in a controlled environment. Results: Pure tone audiometry showed a significant reduction in N group high frequencies threshold compared with C group. Vertigo attacks were reported in 11 workers (24.4%) among the N group and VNG revealed six workers (13.3%) from N group diagnosed as peripheral insult while benign paroxysmal positional vertigo found in three workers (6.7%), while 36 workers (80%) in the same N group had normal “VNG” findings. Conclusion: Vestibular dysfunction may occur in workers with long-term chronic noise exposures.

Strategies for estimating human exposure to mycotoxins via food

In this review, five strategies to estimate mycotoxin exposure of a (sub-)population via food, including data collection, are discussed with the aim to identify the added values and limitations of each strategy for risk assessment of these chemicals. The well-established point estimate, observed individual mean, probabilistic and duplicate diet strategies are addressed, as well as the emerging human biomonitoring strategy. All five exposure assessment strategies allow the estimation of chronic (long-term) exposure to mycotoxins, and, with the exception of the observed individual mean strategy, also acute (short-term) exposure. Methods for data collection, i.e. food consumption surveys, food monitoring studies and total diet studies are discussed. In food monitoring studies, the driving force is often enforcement of legal limits, and, consequently, data are often generated with relatively high limits of quantification and targeted at products suspected to contain mycotoxin levels above these legal limits. Total diet studies provide a solid base for chronic exposure assessments since they provide mycotoxin levels in food based on well-defined samples and including the effect of food preparation. Duplicate diet studies and human biomonitoring studies reveal the actual exposure but often involve a restricted group of human volunteers and a limited time period. Human biomonitoring studies may also include exposure to mycotoxins from other sources than food, and exposure to modified mycotoxins that may not be detected with current analytical methods. Low limits of quantification are required for analytical methods applied for data collection to avoid large uncertainties in the exposure due to high numbers of left censored data, i.e. with levels below the limit of quantification.

Long-term chronic stress exposure induces PCO phenotype in rat.

Thus far the effects of chronic stress on the ovary were studied for shorter durations. However, responses of the ovary may vary with durations of exposure to stress. Hence, we investigated the responses of the ovary following exposure to different durations of chronic stress. Exposure of rats to restraint (1 h) and after a gap of 4 h to forced swimming (15 min) daily for 4 or 8 weeks resulted in significant decreases in the activities of the ovarian antioxidant enzymes, 3β-hydroxysteroid dehydrogenase and percentage of healthy granulosa cells with concomitant increases in the number of atretic follicles, the percentage of apoptotic granulosa cells and ovarian malondialdehyde concentration. However, the response of the ovary to similar stress regime for 12 weeks was paradoxical as there were increases in the activities of ovarian antioxidant enzymes and 3β-hydroxysteroid dehydrogenase, the number of healthy antral follicles, and decreases in ovarian malondialdehyde concentration and percentage of apoptotic granulosa cells. These changes were accompanied by hyperglycaemia and an increase in the serum levels of insulin, testosterone and oestradiol. In addition the cystic follicles were found in the ovaries of these rats. However, the number of oestrous cycles and active corpora lutea showed significant decrease in all the durations of stress exposure. The results demonstrate a differential response of ovary to short- and long-term exposure to chronic stress.

Pesticide exposure in Sri Lanka.

Pesticides are commonly used worldwide both in agricultural and domestic settings. The benefits to society and agriculture are well documented. There are, however, dangers associated with the use of pesticides. Some pesticides, such as organophosphates (the most commonly used pesticide worldwide), kill pests through a biological pathway that may also cause harm to humans. Acute exposure to pesticides has been associated with negative health effects such as cancer, respiratory disease, Parkinson’s disease and death.1–4 People in low- and middle-income countries (LMICs), such as Sri Lanka, often experience acute exposure alongside chronic exposure due to the widespread and largely unregulated use of pesticides.5 The level of chronic pesticide exposure in LMICs is likely to be higher than in high-income countries, as a large proportion of rural families in Sri Lanka live close to agricultural fields and are not only exposed to pesticides when the fields are being sprayed (Figures 1 and ​and2)2) but also have sustained exposure through their food and drink and through air particles. In addition, villagers in rural Sri Lanka often use the irrigation canals, rivers and lakes as a free source of bathing water (Figure 3). This water source is likely to be heavily contaminated with pesticides, not only due to run-off but also as a direct consequence of the practices of pesticide sprayers (Figure 4).6 Figure 1. Pesticide spraying of banana crop using a power sprayer. No personal protection worn. Figure 2. Manual pesticide spraying of a paddy crop. No personal protection worn. Figure 3. Villagers bathing and washing clothes in the local river. Figure 4. Farmer cleaning and preparing pesticide spraying equipment using the irrigation canal. Equipment is rinsed and water taken from the canal. The success of a crop is imperative for a farmer’s livelihood in rural Sri Lanka. This need, coupled with heavy marketing of pesticides (Figure 5) has led to a nearly ubiquitous use of pesticides on crops.7 It is not clear whether this heavy use, resulting in high levels of both acute and chronic exposure, has any long-term detrimental health effects. The difficulty in assessing this arises because of challenges in the measurement of long-term pesticide exposure. Traditional biological samples, like blood and urine, are difficult to collect and only capture short-term pesticide exposure.8 Figure 5. Example of a pesticide advertisment (approximate size 1 x 2.5 m). In July 2015 a feasibility study was launched to determine whether it would be possible to measure chronic (long-term) exposure to pesticides using hair samples in rural Sri Lanka, as an alternative to blood/urine samples which are logistically difficult to manage in community settings in rural Asia. The additional benefit of hair samples is that pesticide metabolites deposit over time, and it would therefore be possible to ascertain a timeline of exposure over longer periods.9 Following a village introduction (Figure 6), fieldworkers visited households and recruited individuals to take part in the study. A hair sample (head/chest/forearm) was taken alongside self-reported information on pesticide use and exposure (Figures 7 and ​and8).8). The samples will be analysed for organophosphate metabolites using gas chromatography-mass spectrometry (Figure 9). Given that the knowledge of the long-term effects of the levels of pesticide exposure experienced in these countries is limited, there needs to be more research in this area to help inform legislation and effective community programmes for the safer use of pesticides. Figure 6. Village meeting to introduce the research project prior to home visits. Figure 7. Field staff collecting head hair sample. Figure 8. Alternative hair sample collected from men with limited or no head hair. Figure 9. An example of the analysis output (pictured on the right) from organophosphate metabolite hair analysis using a gas chromatography-mass spectrometry (pictured on the left).

Effects of long-term chronic stress on the lymphoid organs and blood leukocytes of the rat (Rattus norvegicus)

Exposure of adult female rats (Rattus norvegicus (Berkenhout,1769)) to restraint (1 h) and after a gap of 4 h to forced swimming exercise for 15 min daily for 12 weeks resulted in a significant decrease in (i) weight of the body and lymphoid organs (spleen, thymus, and axillary lymph node), (ii) counts of total leukocytes and their subpopulation (lymphocytes, neutrophils, monocytes, eosinophils, and basophils), and (iii) healthy cells of all lymphoid organs and a significant increase in the count of apoptotic cells in all the lymphoid organs. One month after cessation of exposure to stressors (recovery group), all the parameters did not significantly differ from stress-group rats. The results may indicate that either deleterious effects of long-term chronic exposure to stress are not reversible or the 4-week recovery period is not sufficient to restore normalcy.

Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature.

Background:Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings.Methods:The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed.Results:Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma.Conclusions:SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure.

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation.

Long-term radiation exposure affects human health. Ionizing radiation has long been known to raise the risk of cancer. In addition to high doses of radiation, low-dose ionizing radiation might increase the risk of cardiovascular disease, lens opacity, and some other non-cancerous diseases. Low- and high-dose exposures to ionizing radiation elicit different signaling events at the molecular level, and may involve different response mechanisms. The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated. Health workers exposed to ionizing radiation experience low-dose radiation and have an increased risk of hematological malignancies. Reproductive function is sensitive to changes in the physical environment, including ionizing radiation. However, data is scarce regarding the association between occupational radiation exposure and risk to human fertility. Sperm DNA integrity is a functional parameter of male fertility evaluation. Hence, we aimed to report sperm quality and DNA damage in men from Jilin Province, China, who were occupationally exposed to ionizing radiation. Sperm motility and normal morphology were significantly lower in the exposed compared with the non-exposed men. There was no statistically significant difference in sperm concentration between exposed and non-exposed men. The sperm DNA fragmentation index was significantly higher in the exposed than the non-exposed men. Chronic long-term exposure to low doses of ionizing radiation could affect sperm motility, normal morphology, and the sperm DNA fragmentation index in the Chinese population. Sperm quality and DNA integrity are functional parameters that could be used to evaluate occupational exposure to ionizing radiation.

Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco.

Legacy of a Chemical Factory Site: Contaminated Groundwater Impacts Stream Macroinvertebrates.

Legislative and managing entities of EU member states face a comprehensive task because the chemical and ecological impacts of contaminated sites on surface waters must be assessed. The ecological assessment is further complicated by the low availability or, in some cases, absence of ecotoxicity data for many of the compounds occurring at contaminated sites. We studied the potential impact of a contaminated site, characterised by chlorinated solvents, sulfonamides, and barbiturates, on benthic macroinvertebrates in a receiving stream. Most of these compounds are characterised by low or unknown ecotoxicity, but they are continuously discharged into the stream by way of a long-lasting source generating long-term chronic exposure of the stream biota. Our results show that taxonomical density and diversity of especially sediment dwelling taxa were reduced by >50% at the sampling sites situated in the primary inflow zone of the contaminated GW. Moreover, macroinvertebrate communities at these sampling sites could be distinguished from those at upstream control sites and sites situated along a downstream dilution gradient using multidimensional scaling. Importantly, macroinvertebrate indices currently used did not identify this impairment, thus underpinning an urgent need for developing suitable tools for the assessment of ecological effects of contaminated sites in streams.

Ambient particulate matter air pollution and cardiopulmonary diseases.

Population exposures to ambient outdoor particulate matter (PM) air pollution have been assessed to represent a major burden on global health. Ambient PM is a diverse class of air pollution, with characteristics and health implications that can vary depending on a host of factors, including a particle's original source of emission or formation. The penetration of inhaled particles into the thorax is dependent on their deposition in the upper respiratory tract during inspiration, which varies with particle size, flow rate and tidal volume, and in vivo airway dimensions. All of these factors can be quite variable from person to person, depending on age, transient illness, cigarette smoke and other short-term toxicant exposures that cause transient bronchoconstriction, and occupational history associated with loss of lung function or cumulative injury. The adverse effects of inhaled PM can result from both short-term (acute) and long-term (chronic) exposures to PM, and can range from relatively minor, such as increased symptoms, to very severe effects, including increased risk of premature mortality and decreased life expectancy from long-term exposure. Control of the most toxic PM components can therefore provide major health benefits, and can help guide the selection of the most human health optimal air quality control and climate change mitigation policy measures. As such, a continued improvement in our understanding of the nature and types of PM that are most dangerous to health, and the mechanism(s) of their respective health effects, is an important public health goal.

Adventitial alterations are the main features in pulmonary artery remodeling due to long-term chronic intermittent hypobaric hypoxia in rats.

Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.