Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure.

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Sadrian, B; Subbanna, S; Wilson, D A; Basavarajappa, B S; Saito, M

2012-03-29

Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.

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Vikneswaran, Namasivayam; Murray, Joseph A

2016-06-08

Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH acid reflux episodes [42 vs 34 % (p acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.

Experimentally induced cerebral fat embolism with linoleic acid; MR imaging and pathologic correlation

International Nuclear Information System (INIS)

Kim, Jong Bae; Kim, Hak Jin; Kim, Yong; Lee, Suck Hong; Park, Byeong Rae

2000-01-01

To investigate the correlation between the MRI findings of cerebral fat embolism induced by injecting linoleic acid into ten cats, and pathologic diagnosis. Using a microcatheter, 30μ1 of linoleic acid was injeted into the internal carotid artery of ten cats. MR T2-weighted (T2WI), diffusion-weighted (DWI), and Gd-enhanced T1-weighted images(Gd-enhanced T1WI) were obtained after 30 minutes and after 2 hours of embolization. We pathlogically examined endothelial cell damage, cellular change, perivascular abnormality and fat vacuoles, and then determined the correlation between MRI and the pathologic findings. After 30 minutes of embolization, lesions of very high signal intensity were detected by T2WI in six cats, and of slightly high signal intensity in two:in the remaining two, signal intensity was normal. DWI showed lesions of very high intensity in nine animals and of slightly high intensity in one, while Gd-enhanced T1WI showed well-enhanced lesions in nine and a minimally enhanced lesion in one. After 2 hours of embolization, T2WI revealed lesions of very high signal intensity in nine cats, and of slightly high signal intensity in one, while DWI detected lesions of very high signal intensity in all cats. On Gd-enhanced T1WI, lesions in all cats were well enhanced. According to the findings of light microscopic examination, infarcted lesions mainly involved the gray matter, but also some white matter. In the lesions, neurophil matrix edema, neuronal degeneration, perivascular swelling, the widening of extracellular space, extravascular hemorrhage, and fat vacuoles were evident. During the initial two hours following injuction, MR imaging of cerebral fat embolism induced by linoleic acid through the internal carotid artery in cats showed high signal intensity on T2WI and DWI, and clear enhancement on Gd-enhanced T1WI. In cases involving cellular edema, cerebrovascular injury and extracellular space widening, the pathologic evidence suggested the coexistence of

Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

International Nuclear Information System (INIS)

Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2013-01-01

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

Experimental investigation of coating degradation during simultaneous acid and erosive particle exposure

DEFF Research Database (Denmark)

Møller, Victor Buhl; Dam-Johansen, Kim; Frankær, Sarah Maria

When used in industrial processes, such as stirred acid leaching in the mineral industry, thermoset coatings are exposed to a combination of aggressive chemicals and erosive particlewear. While each exposure condition has been studied separately, no research has been presented on the effects...... of a simultaneous exposure. To investigate this, a pilot-scale stirred acid leaching tank, containing erosive particles and acidic solutions, has been designed and constructed. Resin types considered are amine-cured novolac epoxy and vinyl ester. Transient coating degradation is mapped through visual inspection...

Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration

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Jesús Avila

2013-05-01

Full Text Available Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA, has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed.

Soil microbial community responses to acid exposure and neutralization treatment.

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Shin, Doyun; Lee, Yunho; Park, Jeonghyun; Moon, Hee Sun; Hyun, Sung Pil

2017-12-15

Changes in microbial community induced by acid shock were studied in the context of potential release of acids to the environment due to chemical accidents. The responses of microbial communities in three different soils to the exposure to sulfuric or hydrofluoric acid and to the subsequent neutralization treatment were investigated as functions of acid concentration and exposure time by using 16S-rRNA gene based pyrosequencing and DGGE (Denaturing Gradient Gel Electrophoresis). Measurements of soil pH and dissolved ion concentrations revealed that the added acids were neutralized to different degrees, depending on the mineral composition and soil texture. Hydrofluoric acid was more effectively neutralized by the soils, compared with sulfuric acid at the same normality. Gram-negative ß-Proteobacteria were shown to be the most acid-sensitive bacterial strains, while spore-forming Gram-positive Bacilli were the most acid-tolerant. The results of this study suggest that the Gram-positive to Gram-negative bacterial ratio may serve as an effective bio-indicator in assessing the impact of the acid shock on the microbial community. Neutralization treatments helped recover the ratio closer to their original values. The findings of this study show that microbial community changes as well as geochemical changes such as pH and dissolved ion concentrations need to be considered in estimating the impact of an acid spill, in selecting an optimal remediation strategy, and in deciding when to end remedial actions at the acid spill impacted site. Copyright © 2017 Elsevier Ltd. All rights reserved.

Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids.

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Yongyue Wei

Full Text Available Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans.To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure.The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry.Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5 exposure (p<0.05. The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [β(95% CI = -0.013(-0.022 ≈ -0.004; p = 0.005], docosapentaenoic acid n3 [β(95% CI = -0.010(-0.018 ≈ -0.002; p = 0.017], and docosapentaenoic acid n6 [β(95% CI = -0.007(-0.013 ≈ -0.001; p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009. The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders.High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.

Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia

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Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline

1989-09-01

Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.

Accelerated fatigue of dentin with exposure to lactic acid.

Science.gov (United States)

Do, D; Orrego, S; Majd, H; Ryou, H; Mutluay, M M; Xu, Hockin H K; Arola, D

2013-11-01

Composite restorations accumulate more biofilm than other dental materials. This increases the likelihood for the hard tissues supporting a restoration (i.e. dentin and enamel) to be exposed to acidic conditions beyond that resulting from dietary variations. In this investigation the fatigue strength and fatigue crack growth resistance of human coronal dentin were characterized within a lactic acid solution (with pH = 5) and compared to that of controls evaluated in neutral conditions (pH = 7). A comparison of the fatigue life distributions showed that the lactic acid exposure resulted in a significant reduction in the fatigue strength (p ≤ 0.001), and nearly 30% reduction in the apparent endurance limit (from 44 MPa to 32 MPa). The reduction in pH also caused a significant decrease (p ≤ 0.05) in the threshold stress intensity range required for the initiation of cyclic crack growth, and significant increase in the incremental rate of crack extension. Exposure of tooth structure to lactic acid may cause demineralization, but it also increases the likelihood of restored tooth failures via fatigue, and after short time periods. © 2013 Elsevier Ltd. All rights reserved.

Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

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AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis.

Science.gov (United States)

Browne, Elisse C; Parakh, Sonam; Duncan, Luke F; Langford, Steven J; Atkin, Julie D; Abbott, Belinda M

2016-04-01

Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure

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Salvatrice Calabrò

2015-08-01

Full Text Available Background/Aims: The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i, energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS from 2′,7′-dichlorodihydrofuorescein diacetate (DCFDA fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit. Results: A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml significantly increased the percentage of annexin-V-binding cells (to 9.3 ±0.9 % and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca2+]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM and SB203580 (2 µM. Conclusions: Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.

Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

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Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru

2016-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP + suggest autophagy involvement in the pathogenesis of PD, the effect of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP + exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP + toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP + exposure predominantly inhibited autophagosome degradation, whereas acute MPP + exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP + exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP + exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP + exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP + exposure and mechanistic differences between mild and acute MPP + toxicities. Mild MPP + toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP + exposure. Mechanistic differences between acute and mild MPP + toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson

Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication.

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Osanai, Makoto

2017-06-01

Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA. Consistently, stellate cells store approximately 80% of vitamin A in the body, and the state of cellular RA bioavailability regulates their function. Based on the similarities between stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate tight junction-based endothelial integrity in a paracrine manner. Since diabetic retinopathy is characterized by increased vascular permeability in its early pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes, resulting in suppression of vascular leakiness. RA also attenuated the loss of the epithelial barrier in murine experimental colitis. The concept of "cellular RA bioavailability" in various diseases will be directed at understanding various pathologies caused by RA insufficiency, implying the potential feasibility of a therapeutic strategy targeting the stellate cell system. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Chronic exposure to microcystin-LR affected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice

International Nuclear Information System (INIS)

Li, Xinxiu; Xu, Lizhi; Zhou, Wei; Zhao, Qingya; Wang, Yaping

2016-01-01

Microcystin-LR (MC-LR), an important variant of cyanotoxin family, was frequently encountered in the contaminated aquatic environment and taken as a potent hepatotoxin. However, a little was known on the association between the long-term MC-LR exposure and lung damage. In this study, we investigated the changes of the pulmonary histopathology, mitochondrial DNA (mtDNA) integrity and the expression of mtDNA encoded genes in the mice with chronic exposed to MC-LR at different concentrations (1, 5, 10, 20 and 40 μg/L) for 12 months. Our results showed that the long-term and persistent exposure to MC-LR disturbed the balance of redox system, influenced mtDNA stability, changed the expression of mitochondrial genes in the lung cells. Notably, MC-LR exposure influenced the level of inflammatory cytokines and resulted in thickening of the alveolar septa. In conclusion, chronic exposure to MC-LR affected mtDNA maintenance, and caused lung impairment in mice. - Highlights: • A simulated natural exposure to MC-LR caused the lung pathological changes. • The chronic exposure disturbed the redox system balance of lung tissue cells. • The chronic exposure impaired the mtDNA stability and mitochondria function. • The lung was one of the vulnerable organs to MC-LR exposure in mice. - Long-term exposure to MC-LR in drinking water disturbed the balance of redox system, affected mitochondrial DNA maintenance and caused lung impairment in mice.

[Nickel exposure to A549 cell damage and L-ascorbic acid interference effect].

Science.gov (United States)

Fu, Yao; Wang, Yue; Dan, Han; Zhang, Lin; Ma, Wenhan; Pan, Yulin; Wu, Yonghui

2015-05-01

Studying different concentrations of nickel smelting smoke subjects of human lung adenocarcinoma cells (A549) carcinogenic effects, discusses the influence of L-ascorbic acid protection. The A549 cells were divided into experimental and L-ascorbic acid in the intervention group. Plus exposure group concentration of nickel refining dusts were formulated 0.00, 6.25, 12.50, 25.00, 50.00, 100.00 µg/ml suspension, the intervention group on the basis of the added exposure group containing L-ascorbic acid (100 mmol/L), contact 24 h. Detection of cell viability by MTT assay. When the test substance concentration select 0.00, 25.00, 50.00, 100.00 µg/ml experiment for internal Flou-3 fluorescent probe to detect cell Ca²⁺ concentration, within DCFH-DA detect intracellular reactive oxygen (ROS) content, real-time quantitative PCR (real time, in the RT-PCR) was used to detect cell HIF-1α gene expression. With the increase of concentration, subjects increased cell growth inhibition rate, intracellular Ca²⁺ concentration increases, ROS content increased, HIF-1α gene expression increased, differences were statistically significant (P nickel exposure damage to cells. With subjects following exposure to nickel concentration increased, its effect on A549 cell damage increases, L-ascorbic acid cell damage caused by nickel has certain protective effect.

Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide

International Nuclear Information System (INIS)

Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T.

1990-01-01

Ozone (O 3 ) and nitrogen dioxide (NO 2 ) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O 3 at 0.1, 0.3, or 1 ppm; NO 2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O 3 and 3 ppm NO 2 . Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O 3 . Exposure to 10 ppm NO 2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO 2 and depressed following 3 and 10 ppm. The O 3 /NO 2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O 3 . This study has demonstrated that acute exposure to either O 3 or NO 2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

Urinary trans-trans muconic acid (exposure biomarker to benzene) and hippuric acid (exposure biomarker to toluene) concentrations in Mexican women living in high-risk scenarios of air pollution.

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Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Maldonado, Iván N

2017-11-02

This study aimed to determine t,t-muconic acid (t,t-MA; exposure biomarker for benzene) and hippuric acid (HA; exposure biomarker for toluene) concentrations in the urine of women living in Mexico. In a cross-sectional study, apparently healthy women (n = 104) were voluntarily recruited from localities with a high risk of air pollution; t,t-MA and HA in urine were quantified using a high-performance liquid chromatography (HPLC) technique. Mean urinary levels of t,t-MA ranged from 680 to 1,310 μg/g creatinine. Mean values of HA ranged from 0.38 to 0.87 g/g creatinine. In conclusion, compared to data recently reported in literature, we found high urinary levels of t,t-MA and HA in assessed women participating in this study. We therefore deem the implementation of a strategy aimed at the reduction of exposure as a necessary measure for the evaluated communities.

Behavioral, clinical, and pathological characterization of acid metalliferous water toxicity in mallards

Science.gov (United States)

Isanhart, John P.; Wu, Hongmei; Pandher, Karamjeet; MacRae, Russell K.; Cox, Stephen B.; Hooper, Michael J.

2011-01-01

From September to November 2000, United States Fish and Wildlife Service biologists investigated incidents involving 221 bird deaths at 3 mine sites located in New Mexico and Arizona. These bird deaths primarily involved passerine and waterfowl species and were assumed to be linked to consumption of acid metalliferous water (AMW). Because all of the carcasses were found in or near pregnant leach solution ponds, tailings ponds, and associated lakes or storm water retention basins, an acute-toxicity study was undertaken using a synthetic AMW (SAMW) formulation based on the contaminant profile of a representative pond believed to be responsible for avian mortalities. An acute oral-toxicity trial was performed with a mixed-sex group of mallards (Anas platyrhynchos). After a 24-h pretreatment food and water fast, gorge drinking was evident in both SAMW treatment and control groups, with water consumption rates greatest during the initial drinking periods. Seven of nine treated mallards were killed in extremis within 12 h after the initiation of dose. Total lethal doses of SAMW ranged from 69.8 to 270.1 mL/kg (mean ± SE 127.9 ± 27.1). Lethal doses of SAMW were consumed in as few as 20 to 40 min after first exposure. Clinical signs of SAMW toxicity included increased serum uric acid, aspartate aminotransferase, creatine kinase, potassium, and P levels. PCV values of SAMW-treated birds were also increased compared with control mallards. Histopathological lesions were observed in the esophagus, proventriculus, ventriculus, and duodenum of SAMW-treated mallards, with the most distinctive being erosion and ulceration of the kaolin of the ventriculus, ventricular hemorrhage and/or congestion, and duodenal hemorrhage. Clinical, pathological, and tissue-residue results from this study are consistent with literature documenting acute metal toxicosis, especially copper (Cu), in avian species and provide useful diagnostic profiles for AMW toxicity or mortality events. Blood and

Exposure assessment of food preservatives (sulphites, benzoic and sorbic acid) in Austria.

Science.gov (United States)

Mischek, Daniela; Krapfenbauer-Cermak, Christine

2012-01-01

An exposure assessment was performed to estimate the potential intake of preservatives in the Austrian population. Food consumption data of different population groups, such as preschool children aged 3-6 years, female and male adults aged 19-65 years were used for calculation. Levels of the preservatives in food were derived from analyses conducted from January 2007 to August 2010. Dietary intakes of the preservatives were estimated and compared to the respective acceptable daily intakes (ADIs). In the average-intake scenario, assuming that consumers randomly consume food products that do or do not contain food additives, estimated dietary intakes of all studied preservatives are well below the ADI for all population groups. Sulphite exposure accounted for 34%, 84% and 89% of the ADI in preschool children, females and males, respectively. The mean estimated daily intake of benzoic acid was 32% (preschool children), 31% (males) and 36% (females) of the ADI. Sorbic acid intakes correspond to 7% of the ADI in preschool children and 6% of the ADI in adults. In the high-intake scenario assuming that consumers always consume food products that contain additives and considering a kind of brand loyalty of consumers, the ADI is exceeded for sulphites among adults (119 and 124%, respectively). Major contributors to the total intake of sulphites were wine and dried fruits for adults. Mean estimated dietary intakes of benzoic acid exceeded the ADI in all population groups, 135% in preschool children, 124% in females and 118% of the ADI in males, respectively. Dietary intakes of sorbic acid are well below the ADI, accounting for a maximum of 30% of the ADI in preschool children. The highest contributors to benzoic and sorbic acid exposure were fish and fish products mainly caused by high consumption data of this large food group, including also mayonnaise-containing fish salads. Other important sources of sorbic acid were bread, buns and toast bread and fruit and vegetable

Nonredundant functions of alphabeta and gammadelta T cells in acrolein-induced pulmonary pathology.

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Borchers, Michael T; Wesselkamper, Scott C; Eppert, Bryan L; Motz, Gregory T; Sartor, Maureen A; Tomlinson, Craig R; Medvedovic, Mario; Tichelaar, Jay W

2008-09-01

Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we utilized a mouse model of pulmonary pathology induced by repeated acrolein exposures. The role of lymphocyte subsets was examined by utilizing transgenic mice genetically deficient in either alphabeta T cells or gammadelta T cells, and changes in cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 and 0.5 ppm acrolein were measured. To examine the potential functions of lymphocyte subsets, we purified these cells from the lungs of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified messenger RNA, and performed microarray analysis. Our data demonstrate that alphabeta T cells are required for macrophage accumulation, whereas gammadelta T cells are critical regulators of epithelial cell homeostasis, as identified by epithelial cell injury and apoptosis, following repeated acrolein exposure. This is supported by microarray analyses that indicated the T-cell subsets are unique in their gene expression profiles following acrolein exposures. Microarray analyses identified several genes that may contribute to phenotypes mediated by T-cell subpopulations including those involved in cytokine receptor signaling, chemotaxis, growth factor production, lymphocyte activation, and apoptosis. These data provide strong evidence that T-cell subpopulations in the lung are major determinants of pulmonary pathology and highlight the advantages of dissecting their effector functions in response to toxicant exposures.

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

Science.gov (United States)

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage

Science.gov (United States)

LaCerte, C; Peyret, T; Gosselin, NH; Marier, JF; Hofmann, AF; Shapiro, D

2016-01-01

Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment. There was good agreement between predicted and observed increases in systemic OCA exposure in subjects with mild, moderate, and severe hepatic impairment, which were 1.4‐, 8‐, and 13‐fold relative to healthy volunteers. Predicted liver exposure for subjects with mild, moderate, and severe hepatic impairment were increased only 1.1‐, 1.5‐, and 1.7‐fold. In subjects with cirrhosis, OCA exposure in the liver, the primary site of pharmacological activity along with the intestine, is increased marginally (∼2‐fold). PMID:27743502

Characteristics of gastroesophageal reflux in symptomatic patients with and without excessive esophageal acid exposure

NARCIS (Netherlands)

Bredenoord, Albert J.; Weusten, Bas L. A. M.; Timmer, Robin; Smout, Andŕe J. P. M.

2006-01-01

OBJECTIVE: In some patients with a physiological esophageal acid exposure, an association between reflux episodes and symptoms can be demonstrated. Besides acidity, other factors such as proximal extent may determine whether a reflux episode is perceived or not. We aimed to investigate the reflux

Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

Science.gov (United States)

Ajibade, Temitayo Olabisi; Omobowale, Temidayo Olutayo; Asenuga, Ebunoluwa Racheal; Afolabi, Jeremiah Moyinoluwa; Adedapo, Adeolu Alex

2016-01-01

Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (pgallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened. PMID:28652848

Can Skin Exposure to Sunlight Prevent Liver Inflammation?

Directory of Open Access Journals (Sweden)

Shelley Gorman

2015-05-01

Full Text Available Liver inflammation contributes towards the pathology of non-alcoholic fatty liver disease (NAFLD. Here we discuss how skin exposure to sunlight may suppress liver inflammation and the severity of NAFLD. Following exposure to sunlight-derived ultraviolet radiation (UVR, the skin releases anti-inflammatory mediators such as vitamin D and nitric oxide. Animal modeling studies suggest that exposure to UVR can prevent the development of NAFLD. Association studies also support a negative link between circulating 25-hydroxyvitamin D and NAFLD incidence or severity. Clinical trials are in their infancy and are yet to demonstrate a clear beneficial effect of vitamin D supplementation. There are a number of potentially interdependent mechanisms whereby vitamin D could dampen liver inflammation, by inhibiting hepatocyte apoptosis and liver fibrosis, modulating the gut microbiome and through altered production and transport of bile acids. While there has been a focus on vitamin D, other mediators induced by sun exposure, such as nitric oxide may also play important roles in curtailing liver inflammation.

Acid-base and ionic fluxes in rainbow trout (Oncorhynchus mykiss) during exposure to chloramine-T

Energy Technology Data Exchange (ETDEWEB)

Powell, M.D.; Perry, S.F. [Department of Biology, University of Ottawa, 30 Marie Curie Ottawa, Ontario, K1N 6N5 (Canada)

1998-09-01

The effects of chloramine-T and its degradation products, sodium hypochlorite (NaOCl) and para-toluenesulphonamide (pTSA), on whole body acid-base and branchial and renal ion (Na{sup +}and Cl{sup -}) fluxes were examined in rainbow trout (Oncorhynchus mykiss). Exposure to chloramine-T (3.5 h, 18 mg l{sup -1}) resulted in increases in plasma total CO{sub 2} but no coincident rise in P{sub a}CO{sub 2} or reduction in blood pH. Exposure of fish to 2, 9 or 18 mg l{sup -1} chloramine-T (3.5 h duration) resulted in a reduction in net acid uptake suggesting the development of a metabolic alkalosis. Exposure to the chloramine-T breakdown product pTSA (dissolved in DMSO) resulted in increased net acid uptake (decreased acid excretion) suggesting a metabolic acidosis. Whole body ion fluxes demonstrated increases in the losses of both Na{sup +}and Cl{sup -} with chloramine-T, NaOCl and pTSA. However, the effect of DMSO alone could not be isolated. Confirmatory studies using fish in which the urinary bladder (to allow collection of urine) and dorsal aorta (to allow injection of [{sup 14}C]polyethylene glycol 4000 ([{sup 14}C]PEG), an extracellular fluid marker) were catheterised, revealed that changes in whole body ion fluxes during chloramine-T exposure could not be explained by increased renal efflux through urine flow, glomerular filtration or renal clearance. Branchial effluxes of [{sup 14}C]PEG were not significantly affected by chloramine-T exposure suggesting that the changes in whole body ionic fluxes were caused by transcellular rather than paracellular processes. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Acid-base and ionic fluxes in rainbow trout (Oncorhynchus mykiss) during exposure to chloramine-T

International Nuclear Information System (INIS)

Powell, M.D.; Perry, S.F.

1998-01-01

The effects of chloramine-T and its degradation products, sodium hypochlorite (NaOCl) and para-toluenesulphonamide (pTSA), on whole body acid-base and branchial and renal ion (Na + and Cl - ) fluxes were examined in rainbow trout (Oncorhynchus mykiss). Exposure to chloramine-T (3.5 h, 18 mg l -1 ) resulted in increases in plasma total CO 2 but no coincident rise in P a CO 2 or reduction in blood pH. Exposure of fish to 2, 9 or 18 mg l -1 chloramine-T (3.5 h duration) resulted in a reduction in net acid uptake suggesting the development of a metabolic alkalosis. Exposure to the chloramine-T breakdown product pTSA (dissolved in DMSO) resulted in increased net acid uptake (decreased acid excretion) suggesting a metabolic acidosis. Whole body ion fluxes demonstrated increases in the losses of both Na + and Cl - with chloramine-T, NaOCl and pTSA. However, the effect of DMSO alone could not be isolated. Confirmatory studies using fish in which the urinary bladder (to allow collection of urine) and dorsal aorta (to allow injection of [ 14 C]polyethylene glycol 4000 ([ 14 C]PEG), an extracellular fluid marker) were catheterised, revealed that changes in whole body ion fluxes during chloramine-T exposure could not be explained by increased renal efflux through urine flow, glomerular filtration or renal clearance. Branchial effluxes of [ 14 C]PEG were not significantly affected by chloramine-T exposure suggesting that the changes in whole body ionic fluxes were caused by transcellular rather than paracellular processes. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Oral Pathology in Forensic Investigation.

Science.gov (United States)

Shamim, Thorakkal

2018-01-01

Forensic odontology is the subdiscipline of dentistry which analyses dental evidence in the interest of justice. Oral pathology is the subdiscipline of dentistry that deals with the pathology affecting the oral and maxillofacial regions. This subdiscipline is utilized for identification through oral and maxillofacial pathologies with associated syndromes, enamel rod patterns, sex determination using exfoliative cytology, identification from occlusal morphology of teeth, and deoxyribonucleic acid profiling from teeth. This subdiscipline is also utilized for age estimation studies which include Gustafson's method, incremental lines of Retzius, perikymata, natal line formation in teeth, neonatal line, racemization of collagen in dentin, cemental incremental lines, thickness of the cementum, and translucency of dentin. Even though the expertise of an oral pathologist is not taken in forensic investigations, this paper aims to discuss the role of oral pathology in forensic investigation.

Confidence, knowledge, and skills at the beginning of residency. A survey of pathology residents.

Science.gov (United States)

Hsieh, Cindy M; Nolan, Norris J

2015-01-01

To document the pathology learning experiences of pathology residents prior to residency and to determine how confident they were in their knowledge and technical skills. An online survey was distributed to all pathology residency program directors in the United States, who were requested to forward the survey link to their residents. Data were obtained on pathology electives, grossing experience, and frozen section experience. Likert scale questions assessed confidence level in knowledge and skills. In total, 201 pathology residents responded (8% of residents in the United States). Prior to starting residency, most respondents had exposure to anatomic pathology through elective rotations. Few respondents had work-related experience. Most did not feel confident in their pathology-related knowledge or skills, and many did not understand what pathology resident duties entail. Respondents gained exposure to pathology primarily through elective rotations, and most felt the elective experience prepared them for pathology residency. However, elective time may be enhanced by providing opportunities for students to increase hands-on experience and understanding of resident duties. Copyright© by the American Society for Clinical Pathology.

Simultaneous acid exposure and erosive particle wear of thermoset coatings

DEFF Research Database (Denmark)

Møller, Victor Buhl; Dam-Johansen, Kim; Frankær, Sarah Maria

2018-01-01

, similar to the erosion/corrosion-type phenomena found in metals. A vinyl ester-based coating was the most resistant to the simultaneous erosive/acidic exposure, with a maximum polishing rate of 3.24±0.61 μm/week, while novolac epoxy and polyurethane coatings showed high polishing rates of 11.7±1.50 and 13.4±0......Handling acidic chemicals is a challenge in the chemical industry, requiring a careful choice of contact material. Certain thermoset organic coatings are applicable in low pH environments, but when particulate erosion is also present the performance demand is increased. This is the case in, e...

Behavioural responses of Acroneuria lycoria (Ins. Plecopt. ) Larvae to acute and chronic acid exposure

Energy Technology Data Exchange (ETDEWEB)

McNichol, R.E.; Scherer, E.

1987-01-01

This study was designed to investigate the responses of a perlid stonefly, Acroneuria lycorias (Newman), to acute and chronic acid exposure. Larvae of this species are common in streams and rivers impacted by acidic precipitation. It is also a suggested standard toxicity test species, which in previous studies has proven to be very sensitive to some toxicants. The effects of acute and chronic acid exposure on the locomotor activity, microdistribution, and drift behaviour of the stonefly larvae were studied in laboratory streams. When subjected to a reduction in pH from 8.1 to 2.5 over an 8-h period, larvae showed little behavioural response down to pH 4.2. As the pH fell to 3.0, head-rubbing activity appeared and increased in frequency. At pH 3.0 and below, larvae showed increased gill-ventilatory movements and locomotor activity. Most larvae died within 14 h of exposure to pH 2.5; however, they did not abandon their preferred refuges before death. Larvae exposed to 5 pH levels between 4.5 and 8.2 for 30-50 d displayed no significant changes in locomotor activity, drift behaviour or microdistribution when compared to control animals. Results indicate that later instar larvae of this species are relatively acid tolerant. 29 refs 4 figs 1 tab

Biochemical and pathological studies in rats following dietary ...

African Journals Online (AJOL)

Biochemical and pathological studies in rats following dietary supplementation with high levels of polyunsaturated fatty acids and vitamin E. ... Furthermore, high dietary supplementation of vitamin E showed no deleterious effects on rats and no pathological changes in the liver, kidney and heart tissues were observed in the ...

The effect of theobromine 200 mg/l topical gel exposure duration against surface enamel hardness resistance from 1% citric acid

Science.gov (United States)

Herisa, H. M.; Noerdin, A.; Eriwati, Y. K.

2017-08-01

Theobromine can be used to prevent the demineralization of enamel and can stimulate the growth of new enamels. This study analyzes the effect of theobromine’s gel duration exposure on enamel hardness resistance from 1% citric acid. Twenty-eight specimens were divided into three experimental groups; were exposed to theobromine gel 200 mg/l for 16, 48, and 96 minutes; and were then immersed in 1% citric acid. The control group was only immersed in 1% citric acid. Results: A Wilcoxon test showed a significant increase and decrease in enamel microhardness after exposure to theobromine gel and citric acid (p enamel microhardness between different durations of exposure to theobromine gel and immersion in citric acid (p enamel microhardness but did not contribute to the enamel’s hardness resistance after immersion in 1% citric acid. The duration of theobromine gel application affected enamel microhardness and acid resistance.

Exposure to phthalic acid, phthalate diesters and phthalate monoesters from foodstuffs: UK total diet study results.

Science.gov (United States)

Bradley, Emma L; Burden, Richard A; Bentayeb, Karim; Driffield, Malcolm; Harmer, Nick; Mortimer, David N; Speck, Dennis R; Ticha, Jana; Castle, Laurence

2013-01-01

Phthalates are ubiquitous in the environment and thus exposure to these compounds can occur in various forms. Foods are one source of such exposure. There are only a limited number of studies that describe the levels of phthalates (diesters, monoesters and phthalic acid) in foods and assess the exposure from this source. In this study the levels of selected phthalate diesters, phthalate monoesters and phthalic acid in total diet study (TDS) samples are determined and the resulting exposure estimated. The methodology for the determination of phthalic acid and nine phthalate monoesters (mono-isopropyl phthalate, mono-n-butyl phthalate, mono-isobutyl phthalate, mono-benzyl phthalate, mono-cyclohexyl phthalate, mono-n-pentyl phthalate, mono-(2-ethylhexyl) phthalate, mono-n-octyl phthalate and mono-isononyl phthalate) in foods is described. In this method phthalate monoesters and phthalic acid are extracted from the foodstuffs with a mixture of acidified acetonitrile and dichloromethane. The method uses isotope-labelled phthalic acid and phthalate monoester internal standards and is appropriate for quantitative determination in the concentration range of 5-100 µg kg⁻¹. The method was validated in-house and its broad applicability demonstrated by the analysis of high-fat, high-carbohydrate and high-protein foodstuffs as well as combinations of all three major food constituents. The methodology used for 15 major phthalate diesters has been reported elsewhere. Phthalic acid was the most prevalent phthalate, being detected in 17 food groups. The highest concentration measured was di-(2-ethylhexyl) phthalate in fish (789 µg kg⁻¹). Low levels of mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate were detected in several of the TDS animal-based food groups and the highest concentrations measured corresponded with the most abundant diesters (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate). The UK Committee on Toxicity of Chemicals in Food, Consumer Products

Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

Directory of Open Access Journals (Sweden)

Sahbaie Peyman

2007-06-01

Full Text Available Abstract Background Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation. Methods Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment. Results The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure. Conclusion Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.

Intratumoral Vasculopathy in Leiomyoma Treated With Tranexamic Acid.

Science.gov (United States)

Kudose, Satoru; Krigman, Hannah R

2017-07-01

Although intravascular thrombi and infarct-type necrosis have been reported in leiomyomas following tranexamic acid therapy, intratumoral vasculopathy resembling acute atherosis has not been reported to date in patients without exposure to gonadotropin receptor agonist. We describe a case of intratumoral vasculopathy resembling acute atherosis in a leiomyoma in a 49-year-old woman, with hereditary hemorrhagic telangiectasia and menorrhagia, treated with tranexamic acid. The patient had no exposure to gonadotropin receptor agonists. Pathologic examination of the hysterectomy specimen showed a 5.7-cm submucosal leiomyoma containing multiple arteries with fibrinoid change accompanied with abundant subintimal foamy macrophages and occasional luminal thrombi. The vascular media showed scant lymphocytic inflammation without necrosis. The leiomyoma contained numerous mast cells and edematous areas. Vessels outside of the leiomyoma showed neither fibrinoid changes nor inflammation. The patient is alive and well with no signs of systemic vasculitis. We demonstrate that intratumoral vasculopathy resembling acute atherosis may be seen in leiomyomas from patients taking tranexamic acid and postulate that this change results in vascular thrombosis, tumoral edema, and infarct-type necrosis.

Bioinformatics Education in Pathology Training: Current Scope and Future Direction

Directory of Open Access Journals (Sweden)

Michael R Clay

2017-04-01

Full Text Available Training anatomic and clinical pathology residents in the principles of bioinformatics is a challenging endeavor. Most residents receive little to no formal exposure to bioinformatics during medical education, and most of the pathology training is spent interpreting histopathology slides using light microscopy or focused on laboratory regulation, management, and interpretation of discrete laboratory data. At a minimum, residents should be familiar with data structure, data pipelines, data manipulation, and data regulations within clinical laboratories. Fellowship-level training should incorporate advanced principles unique to each subspecialty. Barriers to bioinformatics education include the clinical apprenticeship training model, ill-defined educational milestones, inadequate faculty expertise, and limited exposure during medical training. Online educational resources, case-based learning, and incorporation into molecular genomics education could serve as effective educational strategies. Overall, pathology bioinformatics training can be incorporated into pathology resident curricula, provided there is motivation to incorporate, institutional support, educational resources, and adequate faculty expertise.

A Meta-Analysis Examining the Influence of Pro-Eating Disorder Websites on Body Image and Eating Pathology.

Science.gov (United States)

Rodgers, Rachel F; Lowy, Alice S; Halperin, Daniella M; Franko, Debra L

2016-01-01

Previous research has indicated that exposure to pro-eating disorder websites might increase eating pathology; however, the magnitude of this effect is unknown. This study aimed to conduct a systematic review and meta-analysis to examine the effect of exposure to pro-eating disorder websites on body image and eating pathology. Studies examining the relationship between exposure to pro-eating disorder websites and eating pathology-related outcomes were included. The systematic review identified nine studies. Findings revealed significant effect sizes of exposure to pro-eating disorder websites on body image dissatisfaction (five studies), d = .41, p = .003; dieting (six studies), d = .68, p eating disorder websites on body image and eating pathology, highlighting the need for enforceable regulation of these websites. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Mercapturic acids as biomarkers of exposure to electrophilic chemicals: applications to environmental and industrial chemicals.

NARCIS (Netherlands)

de Rooij, B.M.; Commandeur, J.N.M.; Vermeulen, N.P.E.

1998-01-01

The use of mercapturic acids (N-acetyl-L-cysteine S-conjugates, MAs) in the biological monitoring of human exposure to environmental and industrial chemicals is receiving more and more attention. Mercapturic acids (MAs) are formed from glutathione (GSH) S-conjugates via the MA-pathway. Although this

Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

Science.gov (United States)

Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

2015-06-01

Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

Science.gov (United States)

Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

2015-01-01

In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that

Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid

DEFF Research Database (Denmark)

Rinaldi, Tania; Silberberg, Gilad; Markram, Henry

2008-01-01

Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit...... properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties...... of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render...

Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure.

Science.gov (United States)

Bernstein, D M; Rogers, R A; Sepulveda, R; Kunzendorf, P; Bellmann, B; Ernst, H; Creutzenberg, O; Phillips, J I

2015-02-15

This study was designed to provide an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake-dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6h/day for 5 days to either brake-dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake-dust or crocidolite asbestos. The chrysotile fibers were relatively biosoluble whereas the crocidolite asbestos fibers persisted through the life-time of the animal. This was reflected in the lung and the pleura where no significant pathological response was observed at any time point in the brake dust or chrysotile/brake dust exposure groups through 365 days post exposure. In contrast, crocidolite asbestos produced a rapid inflammatory response in the lung parenchyma and the pleura, inducing a significant increase in fibrotic response in both of these compartments. Crocidolite fibers were observed embedded in the diaphragm with activated mesothelial cells immediately after cessation of exposure. While no chrysotile fibers were found in the mediastinal lymph nodes, crocidolite fibers of up to 35 μm were observed. These results provide support that brake-dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung or the pleural cavity following short term inhalation. Copyright © 2014. Published by Elsevier Inc.

Effects of chronic low-dose radiation exposure and non-radiation factors on eye pathology in the Techa River Cohort

International Nuclear Information System (INIS)

Mikryukova, L.D.; Akleyev, A.V.

2008-01-01

Full text: As a result of the Mayak PA activities, radioactive wastes were discharged into the Techa River over the period 1949-1956. Data on eye pathology among Techa riverside residents chronically exposed to radiation (external and internal) have been collected and analyzed. The cohort which includes persons of the two genders born before 1950 gives one of the rare opportunities to assess the risk of late effects on human health associated with small-dose radiation exposure. Currently, the cohort numbers 29,749 individuals. In terms of ethnicity, 80 % of the cohort members are Slavs, and 20 % are Tartars and Bashkirs. The first study and analyses of eye pathology were conducted for this cohort during the period from 2001 through 2004. It was established that the cumulative rate of eye disease incidence increased with age and exposure dose. The relative risk value for development of ophthalmopathy among members of the study group was estimated taking into account the potential effects of gender, ethnicity and attained age. The relative risk value was 2.42 per 1 Gy of absorbed dose to soft tissues (95 % CI: 1.94; 3.03). With increase in attained age by 10 years an 8 % increase in the incidence of eye pathology was registered (p<0.001). The rate of eye disease incidence estimated for women was significantly higher than that for men (p<0.05 %). No significant differences were noted in the coefficient of eye disease incidence calculated for different ethnic groups. The structure of ophthalmopathy registered in residents of the Techa riverside villages chronically exposed in the dose range from 0 to 1,180 mGy is characterized by prevalence of cataracts, retinal and chorioid disorders. The rates of eye disease incidence were found to be dependent on external exposure dose; the highest doses were observed in the dose groups with doses 25 mGy. A statistically significant increase in the incidence of retinal angiosklerosis and a manifest tendency to develop cataracts was

Assessment of occupational exposure to gaseous peracetic acid.

Science.gov (United States)

Dugheri, Stefano; Bonari, Alessandro; Pompilio, Ilenia; Colpo, Marco; Montalti, Manfredi; Mucci, Nicola; Arcangeli, Giulio

2018-02-07

In order to assess short-term exposure to peracetic acid (PAA) in disinfection processes, the Authors compared 4 industrial hygiene monitoring methods to evaluate their proficiency in measuring airborne PAA concentrations. An active sampling by basic silica gel impregnated with methyl p-tolyl sulfoxide (MTSO), a passive solid phase micro-extraction technique using methyl p-tolyl sulfide (MTS) as on-fiber derivatization reagent, an electrochemical direct-reading PAA monitor, and a novel visual test strip PAA detector doped with 2,2'-azino-bis (3-ethylbenzothiazoline)-6-sulfonate were evaluated and tested over the range of 0.06-16 mg/m3, using dynamically generated PAA air concentrations. The linear regression analysis of linearity and accuracy showed that the 4 methods were suitable for PAA monitoring. Peracetic acid monitoring in several use applications showed that the PAA concentration (1.8 mg/m3) was immediately dangerous to life or health as proposed by the National Institute of Occupational Safety and Health, and was frequently exceeded in wastewater treatment (up to 7.33 mg/m3), and sometimes during food and beverage processes and hospital high-level disinfection operations (up to 6.8 mg/m3). The methods were suitable for the quick assessment of acute exposure in PAA environmental monitoring and can assist in improving safety and air quality in the workplace where this disinfectant is used. These monitoring methods allowed the evaluation of changes to work out practices to reduce PAA vapor concentrations during the operations when workers are potentially overexposed to this strong antioxidant agent. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Effects of omeprazole or anti-reflux surgery on lower oesophageal sphincter characteristics and oesophageal acid exposure over 10 years.

Science.gov (United States)

Emken, Birgitte-Elise G; Lundell, Lars R; Wallin, Lene; Myrvold, Helge E; Engström, Cecilia; Montgomery, Madeleine; Malm, Anders R; Lind, Tore; Hatlebakk, Jan G

2017-01-01

To compare the effect of anti-reflux surgery (ARS) versus proton pump inhibitor therapy on lower oesophageal sphincter (LOS) function and oesophageal acid exposure in patients with chronic gastro-oesophageal reflux disease (GORD) over a decade of follow-up. In this randomised, prospective, multicentre study we compared LOS pressure profiles, as well as oesophageal exposure to acid, at baseline and at 1 and 10 years after randomisation to either open ARS (n = 137) or long-term treatment with omeprazole (OME) 20-60 mg daily (n = 108). Median LOS resting pressure and abdominal length increased significantly and remained elevated in patients operated on with ARS, as opposed to those on OME. The proportion of total time (%) with oesophageal pH acid exposure was normalised in both groups, with no significant differences, and bilirubin exposure was within normal limits. After 10 years, patients with or without Barrett's oesophagus did not differ in acid reflux control between the two treatment options. Open ARS and OME were both effective in normalising acid reflux into the oesophagus even when studied over a period of 10 years. Anatomically and functionally the LOS was repaired durably by surgery, with increased resting pressure and abdominal length.

DDT exposure of zebrafish embryos enhances seizure susceptibility: relationship to fetal p,p'-DDE burden and domoic acid exposure of California sea lions.

Science.gov (United States)

Tiedeken, Jessica A; Ramsdell, John S

2009-01-01

California sea lions have a large body burden of organochlorine pesticides, and over the last decade they have also been subject to domoic acid poisoning. Domoic acid poisoning, previously recognized in adult animals, is now viewed as a major cause of prenatal mortality. The appearance of a chronic juvenile domoic acid disease in the sea lions, characterized by behavioral abnormalities and epilepsy, is consistent with early life poisoning and may be potentiated by organochlorine burden. We investigated the interactive effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility to domoic acid-induced seizures after completion of neurodevelopment. Embryos were exposed (6-30 hr postfertilization) to either o,p'-DDT or p,p'-DDE (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl sulfoxide solution. These larval (7 days postfertilization) fish were then exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic acid; resulting seizure behavior was monitored and analyzed for changes using cameras and behavioral tracking software. Embryonic exposure to DDTs enhanced PTZ seizures and caused distinct and increased seizure behaviors to domoic acid, most notably a type of head-shaking behavior. These studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals at completion of neurodevelopment with greater sensitivity to domoic acid-induced seizures. The body burden levels of p,p'-DDE are close to the range recently found in fetal California sea lions and suggest a potential interactive effect of p,p'-DDE embryonic poisoning and domoic acid toxicity.

Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

DEFF Research Database (Denmark)

Rasmussen, Jan; Nielsen, Olav W; Lund, Allan M

2013-01-01

Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels...

CS Riot Control Agent Exposure in US Army Mask Confidence Training: Association Between Exposure to O-Chlorobenzylidene Malononitrile (CS) and Urinary Metabolite 2-Chlorophippuric Acid

Science.gov (United States)

2016-05-20

Chromatography B 928:125-30 38. Robert H. Powers DED. 2015. Forensic Toxicology: Mechanisms and Pathology . CRC Press. 263 pp. 39. S.B. Needleman MP...with potential health effects from exposure to CS (16). Other studies were conducted to advance the forensic science and the ability to determine...analysis of CHA levels from CS. A validated urinary biomarker could assist medical, occupational health, emergency response, forensic science, and

Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

International Nuclear Information System (INIS)

Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

1983-01-01

Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

Assessment of clinical pathology and pathogen exposure in sea otters (Enhydra lutris) bordering the threatened population in Alaska

Science.gov (United States)

Goldstein, Tracey; Gill, Verena A.; Tuomi, Pamela A.; Monson, Daniel H.; Burdin, Alexander; Conrad, Patricia A.; Dunn, J. Lawrence; Field, Cara L.; Johnson, Christine K.; Jessup, David A.; Bodkin, James L.; Doroff, Angela M.

2011-01-01

Northern sea otter (Enhydra lutris kenyoni) abundance has decreased dramatically over portions of southwest Alaska, USA, since the mid-1980s, and this stock is currently listed as threatened under the Endangered Species Act. In contrast, adjacent populations in south central Alaska, USA, and Russia have been stable to increasing during the same period. Sea otters bordering the area classified in the recent decline were live-captured during 2004–2006 at Bering Island, Russia, and the Kodiak Archipelago, Alaska, USA, to evaluate differences in general health and current exposure status to marine and terrestrial pathogens. Although body condition was lower in animals captured at Bering Island, Russia, than it was at Kodiak, USA, clinical pathology values did not reveal differences in general health between the two regions. Low prevalences of antibodies (>5%) were found in Kodiak, USA, and on Bering Island, Russia, to Toxoplasma gondii, Sarcocystis neurona, and Leptospira interrogans. Exposure to phocine herpesvirus-1 was found in both Kodiak, USA (15.2%), and Bering Island, Russia (2.3%). Antibodies to Brucella spp. were found in 28% of the otters tested on Bering Island, Russia, compared with only 2.7% of the samples from Kodiak, USA. Prevalence of exposure to Phocine distemper virus (PDV) was 41% in Kodiak, USA, but 0% on Bering Island, Russia. Archived sera from southwest and south-central Alaska dating back to 1989 were negative for PDV, indicating exposure occurred in sea otters in Kodiak, USA, in recent years. Because PDV can be highly pathogenic in naïve and susceptible marine mammal populations, tissues should be examined to explore the contribution of this virus to otter deaths. Our results reveal an increase in exposure to pathogens in sea otters in Kodiak, Alaska, USA, since the 1990s.

Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

Energy Technology Data Exchange (ETDEWEB)

Monette, Michelle Y., E-mail: michelle.monette@yale.edu [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States); Yada, Takashi [Freshwater Fisheries Research Department, National Research Institute of Fisheries Science, Nikko (Japan); Matey, Victoria [Department of Biology, San Diego State University, San Diego, CA 92182 (United States); McCormick, Stephen D. [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States)

2010-08-01

We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 {mu}g l{sup -1} Al), acid and low Al (LAl: pH 5.4, 11 {mu}g l{sup -1} Al), acid and moderate Al (MAl: pH 5.3, 42 {mu}g l{sup -1} Al), and acid and high Al (HAl: pH 5.4, 56 {mu}g l{sup -1} Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na{sup +}/K{sup +}-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl{sup -} channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time

Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

International Nuclear Information System (INIS)

Monette, Michelle Y.; Yada, Takashi; Matey, Victoria; McCormick, Stephen D.

2010-01-01

We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 μg l -1 Al), acid and low Al (LAl: pH 5.4, 11 μg l -1 Al), acid and moderate Al (MAl: pH 5.3, 42 μg l -1 Al), and acid and high Al (HAl: pH 5.4, 56 μg l -1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na + /K + -ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl - channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose

Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

Science.gov (United States)

Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

2010-01-01

We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

Influence of long-term exposure to simulated acid rain on development, reproduction and acaricide susceptibility of the carmine spider mite, Tetranychus cinnabarinus

Science.gov (United States)

Wang, Jin-Jun; Zhang, Jian-Ping; He, Lin; Zhao, Zhi-Mo

2006-01-01

Development, reproduction and acaricide susceptibility of Tetranychus cinnabarinus (Boisduvals) (Acari: Tetranychidae) were investigated after long-term (about 40 generations) exposure to various levels of acid rain; pH 2.5, 3.0, 4.0, and 5.6. Deionized water (pH 6.8) served as a control. The mites were reared on eggplant leaves at 28°C, 80%RH and a photoperiod of 14:10 (L:D) in the laboratory. The results showed that the duration of the immature stage was significantly affected by acid rain exposure. The shortest duration (8.90 days) was recorded for populations exposed to pH 5.6 acid rain, while the longest duration (9.37 days) occurred after exposure to pH 2.5 acid rain. Compared with the control population, adult longevity was shortened with an increase in acidity. Similarly, the oviposition duration was also shortened by an increase in acidity. Statistically, female fecundity did not differ significantly between pH 5.6, pH 4.0 and control populations, but did differ significantly between the control population and those exposed to pH 2.5 and pH 3.0 acid rain. This suggested that the mite suffered reproductive defects after long-term exposure to acid rain with higher acidity (pH 2.5 and 3.0). The intrinsic rate of increase among different populations was not significantly affected, but the net reproductive rate of populations exposed to pH 2.5 and 3.0 acid rain was significantly less than pH4.0, 5.6, and control populations. Bioassay results showed that after long-term exposure to acid rain, susceptibility of the mites to two acaricides, dichlorvos and fenpropathrin, did not change significantly. PMID:19537978

Esophageal manometry findings and degree of acid exposure in short and long Barrett's esophagus.

Science.gov (United States)

Helman, Laura; Biccas, Beatriz Nunes; Lemme, Eponina M O; Novais, Paula; Fittipaldi, Viviane

2012-01-01

Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (3 cm - LSSBE). It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. Barrett's esophagus patients identified by upper endoscopy and confirmed by histopathology were, retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter basal pressure, prevalence of esophageal body abnormalities and acid exposure times were evaluated. Forty-six patients with SSBE (24 males - 52.2%, mean age of 55.2 years) and 28 patients with LSBE (18 males - 64.3%, mean age of 50.5 years). Mean symptom duration was 9.9 years for SSBE and 12.9 years for LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE 34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%, LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE 0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any of these values (Pmotor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.

Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet.

Science.gov (United States)

Umezawa, Masakazu; Nakamura, Masayuki; El-Ghoneimy, Ashraf A; Onoda, Atsuto; Shaheen, Hazem M; Hori, Hiroshi; Shinkai, Yusuke; El-Sayed, Yasser S; El-Far, Ali H; Takeda, Ken

2018-01-01

Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA-deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimating human exposure to perfluoroalkyl acids via solid food and drinks : Implementation and comparison of different dietary assessment methods

NARCIS (Netherlands)

Papadopoulou, Eleni; Poothong, Somrutai; Koekkoek, Jacco; Lucattini, Luisa; Padilla-Sánchez, Juan Antonio; Haugen, Margaretha; Herzke, Dorte; Valdersnes, Stig; Maage, Amund; Cousins, Ian T.; Leonards, Pim E.G.; Småstuen Haug, Line

2017-01-01

Background Diet is a major source of human exposure to hazardous environmental chemicals, including many perfluoroalkyl acids (PFAAs). Several assessment methods of dietary exposure to PFAAs have been used previously, but there is a lack of comparisons between methods. Aim To assess human exposure

Biological and Pathological Studies of Rosmarinic Acid as an Inhibitor of Hemorrhagic Trimeresurus flavoviridis (habu Venom

Directory of Open Access Journals (Sweden)

Masatake Niwa

2010-10-01

Full Text Available In our previous report, rosmarinic acid (RA was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae. The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu. This article presents mechanistic evidence of RA’s neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.

Toxicity of single walled carbon nanotubes to rainbow trout (Oncorhynchus mykiss): Respiratory toxicity, organ pathologies, and other physiological effects

Energy Technology Data Exchange (ETDEWEB)

Smith, Catherine J. [Ecotoxicology and Stress Biology Research Group, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom); Shaw, Benjamin J. [Ecotoxicology and Stress Biology Research Group, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom); Handy, Richard D. [Ecotoxicology and Stress Biology Research Group, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom)]. E-mail: rhandy@plymouth.ac.uk

2007-05-01

Mammalian studies have raised concerns about the toxicity of carbon nanotubes (CNTs), but there is very limited data on ecotoxicity to aquatic life. We describe the first detailed report on the toxicity of single walled carbon nanotubes (SWCNT) to rainbow trout, using a body systems approach. Stock solutions of dispersed SWCNT were prepared using a combination of solvent (sodium dodecyl sulphate, SDS) and sonication. A semi-static test system was used to expose rainbow trout to either a freshwater control, solvent control, 0.1, 0.25 or 0.5 mg l{sup -1} SWCNT for up to 10 days. SWCNT exposure caused a dose-dependent rise in ventilation rate, gill pathologies (oedema, altered mucocytes, hyperplasia), and mucus secretion with SWCNT precipitation on the gill mucus. No major haematological or blood disturbances were observed in terms of red and white blood cell counts, haematocrits, whole blood haemoglobin, and plasma Na{sup +} or K{sup +}. Tissue metal levels (Na{sup +}, K{sup +}, Ca{sup 2+}, Cu, Zn and Co) were generally unaffected. However some dose-dependent changes in brain and gill Zn or Cu were observed (but not tissue Ca{sup 2+}), that were also partly attributed to the solvent. SWCNT exposure caused statistically significant increases in Na{sup +}K{sup +}-ATPase activity in the gills and intestine, but not in the brain. Thiobarbituric acid reactive substances (TBARS) showed dose-dependent and statistically significant decreases especially in the gill, brain and liver during SWCNT exposure compared to controls. SWCNT exposure caused statistically significant increases in the total glutathione levels in the gills (28%) and livers (18%), compared to the solvent control. Total glutathione in the brain and intestine remained stable in all treatments. Pathologies in the brain included possible aneurisms or swellings on the ventral surface of the cerebellum. Liver cells exposed to SWCNT showed condensed nuclear bodies (apoptotic bodies) and cells in abnormal nuclear

Toxicity of single walled carbon nanotubes to rainbow trout (Oncorhynchus mykiss): Respiratory toxicity, organ pathologies, and other physiological effects

International Nuclear Information System (INIS)

Smith, Catherine J.; Shaw, Benjamin J.; Handy, Richard D.

2007-01-01

Mammalian studies have raised concerns about the toxicity of carbon nanotubes (CNTs), but there is very limited data on ecotoxicity to aquatic life. We describe the first detailed report on the toxicity of single walled carbon nanotubes (SWCNT) to rainbow trout, using a body systems approach. Stock solutions of dispersed SWCNT were prepared using a combination of solvent (sodium dodecyl sulphate, SDS) and sonication. A semi-static test system was used to expose rainbow trout to either a freshwater control, solvent control, 0.1, 0.25 or 0.5 mg l -1 SWCNT for up to 10 days. SWCNT exposure caused a dose-dependent rise in ventilation rate, gill pathologies (oedema, altered mucocytes, hyperplasia), and mucus secretion with SWCNT precipitation on the gill mucus. No major haematological or blood disturbances were observed in terms of red and white blood cell counts, haematocrits, whole blood haemoglobin, and plasma Na + or K + . Tissue metal levels (Na + , K + , Ca 2+ , Cu, Zn and Co) were generally unaffected. However some dose-dependent changes in brain and gill Zn or Cu were observed (but not tissue Ca 2+ ), that were also partly attributed to the solvent. SWCNT exposure caused statistically significant increases in Na + K + -ATPase activity in the gills and intestine, but not in the brain. Thiobarbituric acid reactive substances (TBARS) showed dose-dependent and statistically significant decreases especially in the gill, brain and liver during SWCNT exposure compared to controls. SWCNT exposure caused statistically significant increases in the total glutathione levels in the gills (28%) and livers (18%), compared to the solvent control. Total glutathione in the brain and intestine remained stable in all treatments. Pathologies in the brain included possible aneurisms or swellings on the ventral surface of the cerebellum. Liver cells exposed to SWCNT showed condensed nuclear bodies (apoptotic bodies) and cells in abnormal nuclear division. Overt fatty change or wide

Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

Science.gov (United States)

Hoenerhoff, Mark J; Hartke, James

2015-01-01

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

Science.gov (United States)

de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

2016-01-01

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity. © 2014 International Society for Diseases of the Esophagus.

Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

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Li Guan

2015-01-01

Full Text Available Carbon monoxide (CO poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct, plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA levels in red blood cells (RBCs. These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

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Muneko Nishijo

Full Text Available In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1 a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2 a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3 a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4 a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits

Color stability of CAD/CAM Zirconia ceramics following exposure to acidic and staining drinks.

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Colombo, Marco; Cavallo, Marco; Miegge, Matteo; Dagna, Alberto; Beltrami, Riccardo; Chiesa, Marco; Poggio, Claudio

2017-11-01

The aim of this in vitro study was to evaluate the color stability of CAD/CAM Zirconia ceramics following exposure to acidic drink (Coca Cola) and after exposure to staining solution (coffee). All the samples were immersed in different staining solutions over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal-Wallis ANOVA were applied to assess significant differences among restorative materials. Paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. One week immersion in acidic drink did not cause a perceivable discoloration for all restorative materials (ΔE < 3.3). Subsequent immersion in coffee affected color stability of all Zirconia samples, even if Kruskal-Wallis ANOVA found significant differences among the various restorative materials. The ∆Es of CAD/CAM Zirconia ceramics after immersion in coffee varied among the products, but color integrity is not affected by contact with acidic drinks. Key words: CAD/CAM restorative materials, CIE Lab, Zirconia ceramics.

Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

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Gamboa da Costa, Gonçalo, E-mail: goncalo.gamboa@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Jacob, Cristina C.; Von Tungeln, Linda S. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Hasbrouck, Nicholas R. [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Olson, Greg R. [Toxicologic Pathology Associates, Jefferson, AR 72079 (United States); Hattan, David G. [Center for Food Safety and Applied Nutrition, College Park, MD 20740 (United States); Reimschuessel, Renate [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Beland, Frederick A. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

2012-07-15

The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

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Gamboa da Costa, Gonçalo; Jacob, Cristina C.; Von Tungeln, Linda S.; Hasbrouck, Nicholas R.; Olson, Greg R.; Hattan, David G.; Reimschuessel, Renate; Beland, Frederick A.

2012-01-01

The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

The occurrence, exposure and risk assessment of perfluoroalkyl acids in food from mainland, China.

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Wang, Xinxuan; Zhang, Ruobing; Zhang, Hong; Wang, Yanping

2017-11-01

To study the contamination of perfluoroalkyl acids (PFAAs) in Chinese food and the risk of dietary exposure for the Chinese population, the data of 17 PFAAs covering 38 cities throughout China in 15 groups of foods were collected for meta-analysis from published and available research literature. Using food consumption and body weight parameters, estimated dietary intakes (EDIs) were calculated for evaluation using the Scenario-Based Risk Assessment (SceBRA) modelling. Among food groups, the highest ΣPFAAs concentrations and EDI contributions were both found in poultry (363 ng/g), fish and shrimp (313 ng/g), dark vegetables (309 ng/g), fruits (116 ng/g) and pork (25 ng/g). The EDI of adults in the high-exposure scenario was about twice that of the intermediate-exposure scenario, while the EDI of children was about twice that of adults' EDI in the intermediate-exposure scenario. In addition, the PFOS EDI for children under high exposure approached its tolerable daily intake (TDI). Therefore high dietary exposure to PFAAs is giving rise to an increased health risk, especially for children.

Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

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Maazouzi, Chafik [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: maazouzi@univ-metz.fr; Masson, Gerard [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: masson1@univ-metz.fr; Izquierdo, Maria Soledad [Grupo de Investigacion en Acuicultura, ULPGC and ICCM, P.O. Box 56, 35200 Telde, Las Palmas de Gran Canaria (Spain)], E-mail: mizquierdo@dbio.ulpgc.es; Pihan, Jean-Claude [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: pihan@univ-metz.fr

2008-11-15

Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 {mu}g Cu L{sup -1}). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg{sup -1} dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential {omega}3 and {omega}6 PUFA percent.

Perfluoroalkyl acids and their precursors in Swedish food: The relative importance of direct and indirect dietary exposure.

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Gebbink, Wouter A; Glynn, Anders; Darnerud, Per Ola; Berger, Urs

2015-03-01

We analyzed food market basket samples obtained in Sweden from 1999, 2005, and 2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds. Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2) were detected in the year pools with the highest ∑diPAP concentrations in 1999 and 2005. All precursors were predominantly found in meat, fish, and/or eggs based on analysis of individual food groups from 1999. Based on year pools, PFOS precursors contributed between 4 and 1% as an indirect source to total dietary PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total exposure. The lowest precursor contributions were generally seen in food samples from 2010. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Toxicologic Pathology: The Basic Building Block of Risk Assessment

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Human health risk assessment is a critical factor in many risk management decisions. Evaluation of human health risk requires research the provides information that appropriately characterizes potential hazards from exposure. Pathology endpoints are the central response around ...

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio).

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Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

2017-01-01

Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 βestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017. © 2015 Wiley Periodicals, Inc.

Cigarette smoke induced genotoxicity and respiratory tract pathology: evidence to support reduced exposure time and animal numbers in tobacco product testing.

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Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Walker, David; Camacho, Oscar M; Büttner, Ansgar; Dillon, Debbie; Meredith, Clive

2016-06-01

Many laboratories are working to develop in vitro models that will replace in vivo tests, but occasionally there remains a regulatory expectation of some in vivo testing. Historically, cigarettes have been tested in vivo for 90 days. Recently, methods to reduce and refine animal use have been explored. This study investigated the potential of reducing animal cigarette smoke (CS) exposure to 3 or 6 weeks, and the feasibility of separate lung lobes for histopathology or the Comet assay. Rats were exposed to sham air or CS (1 or 2 h) for 3 or 6 weeks. Respiratory tissues were processed for histopathological evaluation, and Alveolar type II cells (AEC II) isolated for the Comet assay. Blood was collected for Pig-a and micronucleus quantification. Histopathological analyses demonstrated exposure effects, which were generally dependent on CS dose (1 or 2 h, 5 days/week). Comet analysis identified that DNA damage increased in AEC II following 3 or 6 weeks CS exposure, and the level at 6 weeks was higher than 3 weeks. Pig-a mutation or micronucleus levels were not increased. In conclusion, this study showed that 3 weeks of CS exposure was sufficient to observe respiratory tract pathology and DNA damage in isolated AEC II. Differences between the 3 and 6 week data imply that DNA damage in the lung is cumulative. Reducing exposure time, plus analyzing separate lung lobes for DNA damage or histopathology, supports a strategy to reduce and refine animal use in tobacco product testing and is aligned to the 3Rs (replacement, reduction and refinement).

Domoic Acid Epileptic Disease

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John S. Ramsdell

2014-03-01

Full Text Available Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.

Acute exposure to acid fog. Effects on mucociliary clearance

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Laube, B.L.; Bowes, S.M. III; Links, J.M.; Thomas, K.K.; Frank, R.

1993-01-01

Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min)

Micro-CT imaging of denatured chitin by silver to explore honey bee and insect pathologies.

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Peter R Butzloff

Full Text Available BACKGROUND: Chitin and cuticle coatings are important to the environmental and immune defense of honey bees and insect pollinators. Pesticides or environmental effects may target the biochemistry of insect chitin and cuticle coating. Denaturing of chitin involves a combination of deacetylation, intercalation, oxidation, Schweiger-peeling, and the formation of amine hydrochloride salt. The term "denatured chitin" calls attention to structural and property changes to the internal membranes and external carapace of organisms so that some properties affecting biological activities are diminished. METHODOLOGY/PRINCIPAL FINDINGS: A case study was performed on honey bees using silver staining and microscopic computer-tomographic x-ray radiography (micro-CT. Silver nitrate formed counter-ion complexes with labile ammonium cations and reacted with amine hydrochloride. Silver was concentrated in the peritrophic membrane, on the abdomen, in the glossa, at intersegmental joints (tarsi, at wing attachments, and in tracheal air sacs. Imaged mono-esters and fatty acids from cuticle coating on external surfaces were apparently reduced by an alcohol pretreatment. CONCLUSIONS/SIGNIFICANCE: The technique provides 3-dimensional and sectional images of individual honey bees consistent with the chemistries of silver reaction and complex formation with denatured chitin. Environmental exposures and influences such as gaseous nitric oxide intercalant, trace oxidants such as ozone gas, oligosachharide salt conversion, exposure to acid rain, and chemical or biochemical denaturing by pesticides may be studied using this technique. Peritrophic membranes, which protect against food abrasion, microorganisms, and permit efficient digestion, were imaged. Apparent surface damage to the corneal lenses of compound eyes by dilute acid exposure consistent with chitin amine hydrochloride formation was imaged. The technique can contribute to existing insect pathology research, and may

Micro-CT Imaging of Denatured Chitin by Silver to Explore Honey Bee and Insect Pathologies

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Butzloff, Peter R.

2011-01-01

Background Chitin and cuticle coatings are important to the environmental and immune defense of honey bees and insect pollinators. Pesticides or environmental effects may target the biochemistry of insect chitin and cuticle coating. Denaturing of chitin involves a combination of deacetylation, intercalation, oxidation, Schweiger-peeling, and the formation of amine hydrochloride salt. The term “denatured chitin” calls attention to structural and property changes to the internal membranes and external carapace of organisms so that some properties affecting biological activities are diminished. Methodology/Principal Findings A case study was performed on honey bees using silver staining and microscopic computer-tomographic x-ray radiography (micro-CT). Silver nitrate formed counter-ion complexes with labile ammonium cations and reacted with amine hydrochloride. Silver was concentrated in the peritrophic membrane, on the abdomen, in the glossa, at intersegmental joints (tarsi), at wing attachments, and in tracheal air sacs. Imaged mono-esters and fatty acids from cuticle coating on external surfaces were apparently reduced by an alcohol pretreatment. Conclusions/Significance The technique provides 3-dimensional and sectional images of individual honey bees consistent with the chemistries of silver reaction and complex formation with denatured chitin. Environmental exposures and influences such as gaseous nitric oxide intercalant, trace oxidants such as ozone gas, oligosachharide salt conversion, exposure to acid rain, and chemical or biochemical denaturing by pesticides may be studied using this technique. Peritrophic membranes, which protect against food abrasion, microorganisms, and permit efficient digestion, were imaged. Apparent surface damage to the corneal lenses of compound eyes by dilute acid exposure consistent with chitin amine hydrochloride formation was imaged. The technique can contribute to existing insect pathology research, and may provide an

Color stability of CAD/CAM Zirconia ceramics following exposure to acidic and staining drinks

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Colombo, Marco; Cavallo, Marco; Miegge, Matteo; Dagna, Alberto; Beltrami, Riccardo; Chiesa, Marco

2017-01-01

Background The aim of this in vitro study was to evaluate the color stability of CAD/CAM Zirconia ceramics following exposure to acidic drink (Coca Cola) and after exposure to staining solution (coffee). Material and Methods All the samples were immersed in different staining solutions over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. Shapiro Wilk test and Kruskal-Wallis ANOVA were applied to assess significant differences among restorative materials. Paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. Results One week immersion in acidic drink did not cause a perceivable discoloration for all restorative materials (ΔE < 3.3). Subsequent immersion in coffee affected color stability of all Zirconia samples, even if Kruskal-Wallis ANOVA found significant differences among the various restorative materials. Conclusions The ∆Es of CAD/CAM Zirconia ceramics after immersion in coffee varied among the products, but color integrity is not affected by contact with acidic drinks. Key words:CAD/CAM restorative materials, CIE Lab, Zirconia ceramics. PMID:29302281

The Pathological Changes of Stomach in Experimental Rats following Single Irradiation of Supervoltage

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Choi, Myung Sun; Suh, Won Hyuck

1984-01-01

The pathological changes of stomach of the rat following 1,000 rad and 1,800 rad single exposure by Cobalt-60 has been made with 50 experimental rats. The dose of 1,000 rad and 6,000 rad in 6 weeks. Following single exposure, the groups of rat were terminated in 1, 2, 4, 8, 12 weeks intervals and the stomach were fixed to formalin solution immediately after dissection. The pathological changes were as follows: 1. Following 1,000 rad single exposure, the stomach show only mild to moderate submucosal edema in 4, 8, 12 weeks group. 1 and 2 weeks group show no changes. 2. Following 1,800 rad single exposure, 32%(8/25) of rats were dead by radiation effect and all other groups of stomach revealed variable pathological changes such as submucosal edema, squamous dysplasia, squamous papilloma as well as squamous cell carcinoma. 3. Optimal tolerance dose to the stomach was 4,500-5,000 rad when irradiation given by supervoltage. The entire stomach was included within the irradiation field, the dose to the stomach should not exceed 6,000 rad. 4. In conclusion, the radiation injury to the stomach were more direct radiation effects to the gastric mucosa rather than secondary changes of radiation injured vessels

Association of Lead Exposure, Serum Uric Acid and Parameters of Renal Function in Nigerian Lead-Exposed Workers

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DD Alasia

2010-09-01

Full Text Available Background: The presence of hyperuricemia and renal function impairment, especially in the absence of urate stone formation is strongly suggestive of lead nephropathy. The evaluation of this association is essential in areas where lead exposure is still prevalent and uncontrolled. Objective: To determine the relationship between serum uric acid and renal function indices in lead-exposed workers. Methods: A cross-sectional study of 190 adults with occupational lead exposure and 80 adults (comparison group, matched for age and sex was performed in Port Harcourt, South-south Nigeria. Blood lead was used as the biomarker of lead exposure while serum urea, serum creatinine, urine albumin (using urine albumin:creatinine ratio, estimated glomerular filtration rate (GFR and serum uric acid were the renal function indices measured. Results: Occupationally lead-exposed subjects had a significantly (p = 0.008 higher mean±SD blood lead levels (50.37±24.58 μg/dL than the comparison group (41.40±26.85. The mean±SD serum urea (8.6±2.3 mg/dL, creatinine (1.0±0.2 mg/dL and serum uric acid (4.6±1.2 mg/dL were significantly (p < 0.01 higher in the study subjects than the comparison group (7.6±2.4, 0.9±0.2, and 3.9±1.1 mg/dL, respectively. The mean±SD creatinine clearance was significantly (p = 0.002 lower in the study subjects than the comparison group (98.9±21.3 vs. 108.2±25.2 mL/min/1.72 m2. Serum uric acid level correlated positively with serum creatinine (r = 0.134 and negatively with GFR (r = ‑0.151. Conclusion: People with occupational lead exposure are at risk of developing hyperuricemia and renal impairment.

Esophageal manometry findings and degree of acid exposure in short and long Barrett's esophagus

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Laura Helman

2012-03-01

Full Text Available CONTEXT: Barrett's esophagus (BE is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (3 cm - LSSBE. It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. OBJECTIVE: To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. METHODS: Barrett's esophagus patients identified by upper endoscopy and confirmed by histopathology were, retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter basal pressure, prevalence of esophageal body abnormalities and acid exposure times were evaluated. RESULTS: Forty-six patients with SSBE (24 males - 52.2%, mean age of 55.2 years and 28 patients with LSBE (18 males - 64.3%, mean age of 50.5 years. Mean symptom duration was 9.9 years for SSBE and 12.9 years for LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE 34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%, LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE 0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any of these values (P<0.05. Average % total time pH<4 in SSBE 9.12, LSBE 17.27 (P<0.000; % time pH<4 upright in SSBE 11.91; LSBE 24.29 (P=0.003; % time pH<4 supine in SSBE 10.86, LSBE 33.26 (P = 0.000. CONCLUSION: There was no difference between the prevalence of motor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.

Pathology Competencies for Medical Education and Educational Cases

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Barbara E. C. Knollmann-Ritschel MD

2017-07-01

Full Text Available Current medical school curricula predominantly facilitate early integration of basic science principles into clinical practice to strengthen diagnostic skills and the ability to make treatment decisions. In addition, they promote life-long learning and understanding of the principles of medical practice. The Pathology Competencies for Medical Education (PCME were developed in response to a call to action by pathology course directors nationwide to teach medical students pathology principles necessary for the practice of medicine. The PCME are divided into three competencies: 1 Disease Mechanisms and Processes, 2 Organ System Pathology, and 3 Diagnostic Medicine and Therapeutic Pathology. Each of these competencies is broad and contains multiple learning goals with more specific learning objectives. The original competencies were designed to be a living document, meaning that they will be revised and updated periodically, and have undergone their first revision with this publication. The development of teaching cases, which have a classic case-based design, for the learning objectives is the next step in providing educational content that is peer-reviewed and readily accessible for pathology course directors, medical educators, and medical students. Application of the PCME and cases promotes a minimum standard of exposure of the undifferentiated medical student to pathophysiologic principles. The publication of the PCME and the educational cases will create a current educational resource and repository published through Academic Pathology .

The value of cell-free DNA for molecular pathology.

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Stewart, Caitlin M; Kothari, Prachi D; Mouliere, Florent; Mair, Richard; Somnay, Saira; Benayed, Ryma; Zehir, Ahmet; Weigelt, Britta; Dawson, Sarah-Jane; Arcila, Maria E; Berger, Michael F; Tsui, Dana Wy

2018-04-01

Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic sites, and ctDNA can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled regularly to monitor response to treatment, to define the evolution of the tumour genome, and to assess the acquisition of resistance and minimal residual disease. Recently, clinical ctDNA assays have been approved for guidance of therapy, which is an exciting first step in translating cell-free nucleic acid research tests into clinical use for oncology. In this review, we discuss the advantages of cell-free nucleic acids as analytes in different body fluids, including blood plasma, urine, and cerebrospinal fluid, and their clinical applications in solid tumours and haematological malignancies. We will also discuss practical considerations for clinical deployment, such as preanalytical factors and regulatory requirements. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Making fate and exposure models for freshwater ecotoxicity in life cycle assessment suitable for organic acids and bases.

Science.gov (United States)

van Zelm, Rosalie; Stam, Gea; Huijbregts, Mark A J; van de Meent, Dik

2013-01-01

Freshwater fate and exposure factors were determined for organic acids and bases, making use of the knowledge on electrical interaction of ionizing chemicals and their sorption to particles. The fate factor represents the residence time in the environment whereas exposure factors equal the dissolved fraction of a chemical. Multimedia fate, exposure, and effect model USES-LCA was updated to take into account the influence of ionization, based upon the acid dissociation constant (pK(a)) of a chemical, and the environmental pH. Freshwater fate (FF) and exposure (XF) factors were determined for 415 acids and 496 bases emitted to freshwater, air, and soil. The relevance of taking account of the degree of ionization of chemicals was tested by determining the ratio (R) of the new vs. fate and exposure factors determined with USES-LCA suitable for neutral chemicals only. Our results show that the majority of freshwater fate and exposure factors of chemicals that are largely ionized in the environment are larger with the ionics model compared to the factors determined with the neutrals model version. R(FF) ranged from 2.4×10(-1) to 1.6×10(1) for freshwater emissions, from 1.2×10(-2) to 2.0×10(4) for soil emissions and from 5.8×10(-2) to 6.0×10(3) for air emissions, and R(XF) from 5.3×10(-1) to 2.2×10(1). Prediction of changed solid-water partitioning, implying a change in runoff and in removal via sedimentation, and prediction of negligible air-water partition coefficient, leading to negligible volatilization were the main contributors to the changes in freshwater fate factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Arsenate exposure affects amino acids, mineral nutrient status and antioxidants in rice (Oryza sativa L.) genotypes.

Science.gov (United States)

Dwivedi, S; Tripathi, R D; Tripathi, P; Kumar, A; Dave, R; Mishra, S; Singh, R; Sharma, D; Rai, U N; Chakrabarty, D; Trivedi, P K; Adhikari, B; Bag, M K; Dhankher, O P; Tuli, R

2010-12-15

Simulated pot experiments were conducted on four rice (Oryza sativa L.) genotypes (Triguna, IR-36, PNR-519, and IET-4786) to examine the effects of As(V) on amino acids and mineral nutrient status in grain along with antioxidant response to arsenic exposure. Rice genotypes responded differentially to As(V) exposure in terms of amino acids and antioxidant profiles. Total amino acid content in grains of all rice genotypes was positively correlated with arsenic accumulation. While, most of the essential amino acids increased in all cultivars except IR-36, glutamic acid and glycine increased in IET-4786 and PNR-519. The level of nonprotein thiols (NPTs) and the activities of superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.6.4.2) and ascorbate peroxidase (APX; EC 1.11.1.11) increased in all rice cultivars except IET-4786. A significant genotypic variation was also observed in specific arsenic uptake (SAU; mg kg(-1)dw), which was in the order of Triguna (134) > IR-36 (71) > PNR-519 (53) > IET-4786 (29). Further, application of As(V) at lower doses (4 and 8 mg L(-1) As) enhanced the accumulation of selenium (Se) and other nutrients (Fe, P, Zn, and S), however, higher dose (12 mg L(-1) As) limits the nutrient uptake in rice. In conclusion, low As accumulating genotype, IET-4786, which also had significantly induced level of essential amino acids, seems suitable for cultivation in moderately As contaminated soil and would be safe for human consumption.

Pathology informatics fellowship training: Focus on molecular pathology

Directory of Open Access Journals (Sweden)

Diana Mandelker

2014-01-01

Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

Pathology informatics fellowship training: Focus on molecular pathology.

Science.gov (United States)

Mandelker, Diana; Lee, Roy E; Platt, Mia Y; Riedlinger, Gregory; Quinn, Andrew; Rao, Luigi K F; Klepeis, Veronica E; Mahowald, Michael; Lane, William J; Beckwith, Bruce A; Baron, Jason M; McClintock, David S; Kuo, Frank C; Lebo, Matthew S; Gilbertson, John R

2014-01-01

Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

Genetics and molecular pathology of Stargardt-like macular degeneration.

Science.gov (United States)

Vasireddy, Vidyullatha; Wong, Paul; Ayyagari, Radha

2010-05-01

Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third decade of life (i.e., starting in the teenage years). The clinical profile at any given age among STGD3 patients can be variable suggesting that, although STGD3 is a single gene defect, other genetic or environmental factors may play a role in moderating the final disease phenotype. Genetic studies localized the STGD3 disease locus to a small region on the short arm of human chromosome 6, and application of a positional candidate gene approach identified protein truncating mutations in the elongation of very long chain fatty acids-4 gene (ELOVL4) in patients with this disease. The ELOVL4 gene encodes a protein homologous to the ELO group of proteins that participate in fatty acid elongation in yeast. Pathogenic mutations found in the ELOVL4 gene result in altered trafficking of the protein and behave with a dominant negative effect. Mice carrying an Elovl4 mutation developed photoreceptor degeneration and depletion of very long chain fatty acids (VLCFA). ELOVL4 protein participates in the synthesis of fatty acids with chain length longer than 26 carbons. Studies on ELOVL4 indicate that VLCFA may be necessary for normal function of the retina, and the defective protein trafficking and/or altered VLCFA elongation underlies the pathology associated with STGD3. Determining the role of VLCFA in the retina and discerning the implications of abnormal trafficking of mutant ELOVL4 and depleted VLCFA content in the pathology of STGD3 will provide valuable insight in understanding the retinal structure, function, and pathology underlying STGD3

Potential citric acid exposure and toxicity to Hawaiian hoary bats (Lasiurus cinereus semotus) associated with Eleutherodactylus frog control.

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Pitt, William C; Witmer, Gary W; Jojola, Susan M; Sin, Hans

2014-04-01

We examined potential exposure of Hawaiian hoary bats (Lasiurus cinereus semotus) to citric acid, a minimum risk pesticide registered for control of invasive Eleutherodactylus frog populations. Hoary bats are nocturnal insectivores that roost solitarily in foliage, federally listed as endangered, and are endemic to Hawaii. Oral ingestion during grooming of contaminated fur appears to be the principal route by which these bats might be exposed to citric acid. We made assessments of oral toxicity, citric acid consumption, retention of material on fur, and grooming using big brown bats (Eptesicus fuscus) as a surrogate species. We evaluated both ground application and aerial application of 16 % solutions of citric acid during frog control operations. Absorbent bat effigies exposed to ground and aerial operational spray applications retained means of 1.54 and 0.02 g, respectively, of dry citric acid, although retention by the effigies was much higher than bat carcasses drenched in citric acid solutions. A high dose delivered orally (2,811 mg/kg) was toxic to the big brown bats and emesis occurred in 1 bat dosed as low as the 759 mg/kg level. No effect was observed with the lower doses examined (≤ 542 mg/kg). Bats sprayed with 5 ml of 16 % (w/w) citric acid solution showed no evidence of intoxication. In field situations, it is unlikely that bats would be sprayed directly or ingest much citric acid retained by fur. Based on our observations, we believe Hawaiian hoary bats to be at very low risk from harmful exposure to a toxic dose of citric acid during frog control operations.

Cumulative Retrospective Exposure Assessment (REA) as a predictor of amphibole asbestos lung burden: validation procedures and results for industrial hygiene and pathology estimates.

Science.gov (United States)

Rasmuson, James O; Roggli, Victor L; Boelter, Fred W; Rasmuson, Eric J; Redinger, Charles F

2014-01-01

fiber-type. Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time.

Anesthesia and Tau Pathology

Science.gov (United States)

Whittington, Robert A.; Bretteville, Alexis; Dickler, Maya F.; Planel, Emmanuel

2013-01-01

Alzheimer’s disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration. PMID:23535147

Pathology associated with inhaled plutonium in beagles

International Nuclear Information System (INIS)

Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; Stevens, D.L.

1986-01-01

The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

Science.gov (United States)

Darrow, Lyndsey A; Groth, Alyx C; Winquist, Andrea; Shin, Hyeong-Moo; Bartell, Scott M; Steenland, Kyle

2016-08-01

Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers). Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases). Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease. Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM

Immunomodulatory effects of exposure to polychlorinated biphenyls and perfluoroalkyl acids in East Greenland ringed seals (Pusa hispida)

International Nuclear Information System (INIS)

Levin, Milton; Gebhard, Erika; Jasperse, Lindsay; Desforges, Jean-Pierre; Dietz, Rune; Sonne, Christian; Eulaers, Igor; Covaci, Adrian; Bossi, Rossana; De Guise, Sylvain

2016-01-01

To better elucidate the potential immune-related health effects of exposure to environmentally persistent organic pollutants (POP), such as polychlorinated biphenyls (PCBs) and perfluoroalkyl substances (PFASs), in ringed seals (Pusa hispida), a sentinel Arctic species, we assessed 1) associations between mitogen-induced lymphocyte proliferation and in vivo tissue contaminant burdens, and 2) the concentration-response effects of in vitro exposure to PFASs and PCB congeners on mitogen-induced lymphocyte proliferation. Upon in vitro contaminant exposure, the non-coplanar PCB congeners CB 138, 153, and 180, but not the coplanar CB 169, significantly reduced lymphocyte proliferation between 10 and 20 µg g −1 ww. The respective in vitro EC 50 values for these congeners were 13.3, 20.7, 20.8, and 54.6 µg g −1 ww. No modulation of lymphocyte proliferation was observed upon in vitro exposure to two individual PFASs, perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA), at concentrations up to 1000 ng g-1. In addition, no significant correlations were found between lymphocyte proliferation and any blood or blubber contaminant measured. Taken together, these data suggest this population of ringed seals is not currently at high risk of altered lymphocyte proliferation from exposure to the POPs or PFASs in this study. - Highlights: • Assess relationships between tissue contaminants and changes in immune function. • Risk for contaminant-induced immunotoxicity in East Greenland ringed seal is low. • Weight of evidence suggest non-coplanar PCBs are immunotoxic at high concentrations.

Computational Pathology

Science.gov (United States)

Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

2016-01-01

Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

International Nuclear Information System (INIS)

Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P.

2004-01-01

The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

Pathological spirit possession as a cultural interpretation of trauma-related symptoms.

Science.gov (United States)

Hecker, Tobias; Barnewitz, Eva; Stenmark, Hakon; Iversen, Valentina

2016-07-01

Spirit possession is a phenomenon frequently occurring in war-torn countries. It has been shown to be an idiom of distress entailing dissociative symptoms. However, its association with trauma exposure and trauma-related disorders remains unclear. This study aimed to explore subjective disease models and the relationship between pathological spirit possession and trauma-related disorders in the Eastern Democratic Republic of the Congo. Seventy-three (formerly) possessed persons (74% female, mean age = 34 years), referred by traditional and spiritual healers, were interviewed about their experiences of pathological spirit possession, trauma exposure, posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, shame and guilt, psychotic symptoms, somatic complaints, and the impairment of psychosocial functioning. The most common disease model for pathological spirit possession was another person having sent the spirit, mostly a family member or a neighbor, out of jealousy or conflict over resources. Significant correlations were found between spirit possession over lifetime and PTSD symptom severity, feelings of shame and guilt, depressive symptoms, somatic complaints, and psychotic symptoms. Spirit possession during the preceding 4 weeks was associated with PTSD symptom severity, impairment of psychosocial functioning, and psychotic symptom severity. The results of this study indicate that pathological spirit possession is a broad explanatory framework for various subjectively unexplainable mental and physical health problems, including but not limited to trauma-related disorders. Understanding pathological spirit possession as a subjective disease model for various mental and physical health problems may help researchers and clinicians to develop culturally sensitive treatment approaches for affected individuals. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Original article. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

Directory of Open Access Journals (Sweden)

Ajibade Temitayo Olabisi

2016-06-01

Full Text Available Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05 reduced the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and reduced glutathione (GSH content. Malondialdehyde, hydrogen peroxide (H2O2 and nitric oxide (NO contents were also significantly (p<0.05 elevated following DZN exposure. DZN further caused a significant (p<0.05 decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05 in packed cell volume (PCV, hemoglobin concentration (Hb, red blood cell (RBC count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.

How can the postgraduate training program in pathology departments in India be improved?

Directory of Open Access Journals (Sweden)

Shivayogi R Bhusnurmath

2011-01-01

Full Text Available There exists a wide variation in the competence of the postgraduate residents trained in pathology in different institutions across India. This results in strong disparities in the clinical diagnostic skills, teaching skills, research capabilities and the managerial skills of the graduates. The end users of this training, namely the community, clinicians and health care institutions would benefit from a more uniform and better trained pathologist. The article reviews the reasons for the variation in the quality of the training programs. The main deficiencies include, lack of well-defined criteria for recruitment of residents, training facilities, faculty resources, curriculum with well-defined learning objectives and competencies, hands-on experiences in diagnostic and research activities, diagnostic specimens and medical autopsies, exposure to molecular pathology, pathology informatics, electron microscopy, research experiences, communication skills, professional behavior and bioethics, business practices in pathology and quality assurance. There is also a lack of defined career tracks in various disciplines in laboratory medicine, standard protocols for evaluation and regional and national oversight of the programs. The steps for rectification should include defining the competencies and learning objectives, development of the curriculum including teaching methods, facilities and evaluation strategies, communication skills, professional behavior skills, teaching skills, legal aspects of practicing pathology and the various career pathways to subspecialties in pathology. The training should include defined exposure to molecular pathology, electron microscopy, quality control and assurance, laboratory accreditation, business aspects of pathology practice, review of literature, evidence-based medicine, medical autopsy and medical informatics. Efforts should be made to share human and laboratory resources between regional cooperation. The

The right atrium: gateway to the heart--anatomic and pathologic imaging findings.

Science.gov (United States)

Malik, Sachin B; Kwan, Damon; Shah, Amar B; Hsu, Joe Y

2015-01-01

Knowledge of right atrial anatomic and pathologic imaging findings and associated clinical symptoms is important to avoid false-positive diagnoses and missed findings. Complete evaluation of the heart often requires a multimodality approach that includes radiography, echocardiography, computed tomography (CT), magnetic resonance (MR) imaging, and invasive angiography. In general, CT provides the highest spatial resolution of these modalities at the cost of radiation exposure to the patient. Echocardiography and MR imaging offer complementary and detailed information for functional evaluation without added radiation exposure. The advantages and disadvantages of each modality for the evaluation of right atrial anatomic structure, size, and pathologic findings are discussed. Cardiac MR imaging is the reference standard for evaluation of right atrial size and volume but often is too time consuming and resource intensive to perform in routine clinical practice. Therefore, established reference ranges for two-dimensional transthoracic echocardiography are often used. Right atrial pathologic findings can be broadly categorized into (a) congenital anomalies (cor triatriatum dexter, Ebstein anomaly, and aneurysm), (b) disorders of volume (tricuspid regurgitation, pathologic mimics such as a pseudoaneurysm, and atrial septal defect), (c) disorders of pressure (tricuspid stenosis, restrictive cardiomyopathy, and constrictive pericarditis), and (d) masses (pseudomasses, thrombus, lipomatous hypertrophy of the interatrial septum, lipoma, myxoma, sarcoma, and metastatic disease). Familiarity with each pathologic entity and its treatment options is essential to ensure that appropriate imaging modalities are selected. Online supplemental material is available for this article. RSNA, 2015

Pathological consequences of chronic low daily dose gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Seed, T.M.; Miller, A.C.; Ramakrishnan, N. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States); Fritz, T.E.

2000-07-01

The quantitative relationships between the chronic radiation exposure parameters of dose-rate and total dose in relation to associated health risks was examined in dogs. At a dose-rate of 75, 128, and 263 mGy/d the incidence of acute lymphohematopoietic suppression (aplastic anemia) and associated septic complications was 73%, 87%, and 100%, respectively, and it increased in dose-dependent manner. By contrast, at dose-rates below 75 mGy/d, late cancers contributed significantly to the death of relatively long-lived animals, whose mean survival time was 1800 days. Myeloproliferative disease (MPD), mainly myeloid leukemia, was the dominant pathology seen at the higher daily dose-rates (18.8-75 mGy/d). When daily exposure was carried out continuously, the incidence of MPD was quite high. It should be noted that the induction radiation-induced MPD in this study was highly significant, because spontaneous MPD is exceedingly rare in the dog. However, when the daily dose-rate was reduced further or exposure was discontinued, the incidence of MPD declined significantly. At these lower dose-rates, solid tumors contributed heavily to the life-shortening effects of chronic irradiation. The induction and progression of these survival-compromising, late forms of pathology appeared to be driven by the degree of hematopoietic suppression that occurred early during the exposure phase, and in turn by the capacity of hematopoietic system to repair itself, recover, and to accommodate under chronic radiation stress. (K.H.)

Does the Internet function like magazines? An exploration of image-focused media, eating pathology, and body dissatisfaction.

Science.gov (United States)

Bair, Carrie E; Kelly, Nichole R; Serdar, Kasey L; Mazzeo, Suzanne E

2012-12-01

Research has identified a relation between exposure to thin-ideal magazine and television media images and eating disorder pathology. However, few studies have examined the potential influence of Internet media on eating disorder behaviors and attitudes. This study investigated associations among image-focused media exposure, body dissatisfaction, eating pathology and thin-ideal internalization in a sample of 421 female undergraduates. Undergraduate women spent significantly more time viewing online appearance-oriented media, rather than reading image-focused magazines. Appearance-oriented Internet and television use were associated with eating pathology. Moreover, the association between image-focused Internet use and BD was mediated by thin-ideal internalization. These findings are consistent with those of previous research, and highlight the vulnerability individuals high in thin-ideal internalization might have to media exposure. They also suggest that Internet media use is an important topic to attend to in eating disorders prevention and treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

DEFF Research Database (Denmark)

Li, Ying; Han, Meihua; Liu, Tingting

2017-01-01

The aim of this study was to investigate the feasibility of using hyaluronic acid (HA), a biomucoadhesive carbohydrate polymer to prolong the pulmonary retention and reduce the systemic exposure of inhaled medicine. Salbutamol sulphate (SAS), a model bronchodilator, was co-spray dried with HA...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...

Impact of desiccation and heat exposure stress on Salmonella tolerance to acidic conditions.

Science.gov (United States)

Richardson, Kurt E; Cox, Nelson A; Cosby, Douglas E; Berrang, Mark E

2018-02-01

In a recent study, the pH of commonly used Salmonella pre-enrichment media became acidic (pH 4.0 to 5.0) when feed or feed ingredients were incubated for 24 h. Acidic conditions have been reported to injure or kill Salmonella. In this study, cultures of four known feed isolates (S. montevideo, S. senftenberg, S. tennessee, and S. schwarzengrund) and four important processing plant isolates (S. typhimurium, S. enteritidis, S. infantis, and S. heidelberg) were grown on meat and bone meal and later subjected to desiccation and heat exposure to stress the microorganism. The impact of stress on the isolates ability to survive in acidic conditions ranging from pH 4.0 to 7.0 was compared to the non-stressed isolate. Cell injury was determined on xylose lysine tergitol 4 (XLT4) and cell death determined on nutrient agar (NA). When measured by cell death in non-stressed Salmonella, S. typhimurium was the most acid tolerant and S. heidelberg was the most acid sensitive whereas in stressed Salmonella, S. senftenberg was the most acid tolerant and S. tennessee was the most acid sensitive. The pH required to cause cell injury varied among isolates. With some isolates, the pH required for 50% cell death and 50% cell injury was similar. In other isolates, cell injury occurred at a more neutral pH. These findings suggest that the pH of pre-enrichment media may influence the recovery and bias the serotype of Salmonella recovered from feed during pre-enrichment.

A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

Science.gov (United States)

Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

2016-01-01

Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

Curriculum Guidelines for Pathology and Oral Pathology.

Science.gov (United States)

Journal of Dental Education, 1985

1985-01-01

Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

Science.gov (United States)

Glasinovic, E; Wynter, E; Arguero, J; Ooi, J; Nakagawa, K; Yazaki, E; Hajek, P; Psych, C Clin; Woodland, P; Sifrim, D

2018-04-01

Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, Pacid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

Dietary exposure of Hong Kong adults to fatty acid esters of 3-monochloropropane-1,2-diol.

Science.gov (United States)

Chung, H Y; Chung, Stephen W C; Chan, B T P; Ho, Yuk Yin; Xiao, Ying

2013-01-01

A total of 290 individual food samples were collected in Hong Kong, China, for 3-monochloropropane-1,2-diol (3-MCPD) fatty acid esters analysis. Most samples were processed food and in ready-to-eat form. The results show that the levels of 3-MCPD fatty acid esters were high in biscuits, fats and oils, snacks and Chinese pastry with mean bound 3-MCPD levels of 440, 390, 270 and 270 μg kg⁻¹, respectively. The dietary exposures to bound 3-MCPD of average and high adult consumers were estimated to be 0.20 and 0.53 μg kg bw⁻¹ day⁻¹, respectively. The primary toxicological concern of 3-MCPD fatty acid esters is its potential to release 3-MCPD in vivo during digestion in the gastrointestinal tract. 3-MCPD would affect the kidney, the central nervous system and the male reproductive system of rats. Assuming that 100% of the 3-MCPD was released from 3-MCPD fatty acid esters by hydrolysis in the digestive system, the dietary exposures to 3-MCPD for average and high adult consumers were only 10% and 26% of the provisional maximum tolerable daily intake (PMTDI) of 3-MCPD established by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) (2 μg kg bw⁻¹ day⁻¹), respectively. The results suggest that both average and high adult consumers are unlikely to experience major toxicological effects of 3-MCPD.

Immunomodulatory effects of exposure to polychlorinated biphenyls and perfluoroalkyl acids in East Greenland ringed seals (Pusa hispida)

Energy Technology Data Exchange (ETDEWEB)

Levin, Milton, E-mail: Milton.levin@uconn.edu [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States); Gebhard, Erika; Jasperse, Lindsay [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States); Desforges, Jean-Pierre; Dietz, Rune; Sonne, Christian; Eulaers, Igor [Department of Bioscience, Arctic Research Centre (ARC), Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde (Denmark); Covaci, Adrian [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, BE-2610 Wilrijk (Belgium); Bossi, Rossana [Department of Environmental Science, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde (Denmark); De Guise, Sylvain [Department of Pathobiology and Veterinary Science, University of Connecticut, 61 North Eagleville Road, Storrs, CT 06269-3089 (United States)

2016-11-15

To better elucidate the potential immune-related health effects of exposure to environmentally persistent organic pollutants (POP), such as polychlorinated biphenyls (PCBs) and perfluoroalkyl substances (PFASs), in ringed seals (Pusa hispida), a sentinel Arctic species, we assessed 1) associations between mitogen-induced lymphocyte proliferation and in vivo tissue contaminant burdens, and 2) the concentration-response effects of in vitro exposure to PFASs and PCB congeners on mitogen-induced lymphocyte proliferation. Upon in vitro contaminant exposure, the non-coplanar PCB congeners CB 138, 153, and 180, but not the coplanar CB 169, significantly reduced lymphocyte proliferation between 10 and 20 µg g{sup −1} ww. The respective in vitro EC{sub 50} values for these congeners were 13.3, 20.7, 20.8, and 54.6 µg g{sup −1} ww. No modulation of lymphocyte proliferation was observed upon in vitro exposure to two individual PFASs, perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA), at concentrations up to 1000 ng g-1. In addition, no significant correlations were found between lymphocyte proliferation and any blood or blubber contaminant measured. Taken together, these data suggest this population of ringed seals is not currently at high risk of altered lymphocyte proliferation from exposure to the POPs or PFASs in this study. - Highlights: • Assess relationships between tissue contaminants and changes in immune function. • Risk for contaminant-induced immunotoxicity in East Greenland ringed seal is low. • Weight of evidence suggest non-coplanar PCBs are immunotoxic at high concentrations.

[Perception of health and safety risks among workers pathology laboratories].

Science.gov (United States)

Alvarado-Cabrero, Isabel; Valencia-Cedillo, Raquel

2015-01-01

Health care workers are experiencing increasing numbers of occupational illnesses. Safety practices in anatomical pathology laboratories (APL) are crucial to prevent unnecessary exposures to both chemical and biological agents. The main goal of this study was to determine if pathologists perceptions and actual practice mirror regulatory guidelines. Current available recommendations for APL were reviewed and used to construct an online survey distributed to pathologists. The survey was completed by 121 participants. Eighty-seven (72 %) of respondents reported receiving inadequate safety training. Most pathologists (82 %) were not well-informed about biosafety practices. Sixty-three (52 %) participants felt that the risks of chemical and infectious disease exposures in the APL were low. Most respondents reported having a needle stick or cut (71 %). Eighty-six (71 %) of participants reported musculo skeletal problems. This study indicated that there is a need for improving training in anatomical pathology safety practices in Mexican laboratories as daily practices do not reflected current guidelines.

Caffeic acid phenethyl ester as a remedial agent for reproductive functions and oxidative stress-based pathologies of gonads.

Science.gov (United States)

Akyol, Sumeyya; Akbas, Ali; Butun, Ilknur; Toktas, Muhsin; Ozyurt, Huseyin; Sahin, Semsettin; Akyol, Omer

2015-01-01

In recent years, the studies on the roles of caffeic acid phenethyl ester (CAPE) in several disease models and cell cultures are tremendously growing. It is such a great molecule that was used by ancient times to ameliorate some diseases and nowadays, it is used by modern medicine to test the effectiveness. In this mini-review article, the protection capability of CAPE, as a liposoluble antioxidant and a potent nuclear factor kappa B inhibitor, on oxidative and non-oxidative ovary, and testis damages has been summarized. In view of our laboratory findings/experience and those reported in the hitherto literature, we suggest that CAPE possesses protective effects for pathologies of the reproductive organs induced by untoward effects of harmful molecules such as free oxygen radicals, pesticides, methotrexate, and MK-801 (dizocilpine).

Pathological study of the prevalence of silicosis among coal miners in Iran: A case history

Science.gov (United States)

Zare Naghadehi, Masoud; Sereshki, Farhang; Mohammadi, F.

2014-02-01

One of the most hazardous diseases that is commonly associated with the coal mining industry is Silicosis which caused by dust inhalation. This disease occurs as a result of prolonged breathing of dust containing silica (quartz). The generation of coal mine dust during underground and surface coal mining is the most significant source of coal dust exposure. Silica dust develops scar tissue inside the lungs which reduces the lungs ability to extract oxygen from the air. All miners working in underground and surface coal mines are at risk of being exposed to mine dust containing silica. In this study, cases with pathologic diagnosis of silicosis during seven years period between 2000 and 2007 were retrieved, from the pathologic file of Department of Pathology, Massih Daneshvary Hospital in Iran. Results of this case study showed the great effects of dust exposure and inhalation from the viewpoint of symptoms especially between the miners.

Perfluoroalkyl acids and their precursors in Swedish food: The relative importance of direct and indirect dietary exposure

International Nuclear Information System (INIS)

Gebbink, Wouter A.; Glynn, Anders; Darnerud, Per Ola; Berger, Urs

2015-01-01

We analyzed food market basket samples obtained in Sweden from 1999, 2005, and 2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds. Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2) were detected in the year pools with the highest ∑diPAP concentrations in 1999 and 2005. All precursors were predominantly found in meat, fish, and/or eggs based on analysis of individual food groups from 1999. Based on year pools, PFOS precursors contributed between 4 and 1% as an indirect source to total dietary PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total exposure. The lowest precursor contributions were generally seen in food samples from 2010. - Highlights: • Three PFOS precursors and six diPAPs were detected in food pools. • Precursor concentrations were highest in 1999 and 2005 food pools, and lowest in 2010. • The relative importance of precursors to total PFOS dietary intake was <4%. • The relative importance of diPAPs as an indirect dietary source of PFCAs was chain length dependent. - The relative contribution of precursors to PFOS dietary intakes is small, whereas the contribution of diPAPs to PFCA dietary intakes varies with the PFCA chain length

Evaluation of Toluene Exposure in Workers at Industrial Area of Sidoarjo, Indonesia by Measurement of Urinary Hippuric Acid

Directory of Open Access Journals (Sweden)

Moch Sahri

2013-12-01

How to cite this article: Sahri M, Widajati N. Evaluation of Toluene Exposure in Workers at Industrial Area of Sidoarjo, Indonesia by Measurement of Urinary Hippuric Acid. Asia Pac J Med Toxicol 2013;2:145-9.

Complement-independent retinal pathology produced by intravitreal injection of neuromyelitis optica immunoglobulin G

Directory of Open Access Journals (Sweden)

Christian M. Felix

2016-10-01

Full Text Available Abstract Background Neuromyelitis optica (NMO, an autoimmune inflammatory disease of the central nervous system, is often associated with retinal abnormalities including thinning of the retinal nerve fiber layer and microcystic changes. Here, we demonstrate that passive transfer of an anti-aquaporin-4 autoantibody (AQP4-IgG produces primary retinal pathology. Methods AQP4-IgG was delivered to adult rat retinas by intravitreal injection. Rat retinas and retinal explant cultures were assessed by immunofluorescence. Results Immunofluorescence showed AQP4-IgG deposition on retinal Müller cells, with greatly reduced AQP4 expression and increased glial fibrillary acidic protein by 5 days. There was mild retinal inflammation with microglial activation but little leukocyte infiltration and loss of retinal ganglion cells by 30 days with thinning of the ganglion cell complex. Interestingly, the loss of AQP4 was complement independent as seen in cobra venom factor-treated rats and in normal rats administered a mutated AQP4-IgG lacking complement effector function. Exposure of ex vivo retinal cultures to AQP4-IgG produced a marked reduction in AQP4 expression by 24 h, which was largely prevented by inhibitors of endocytosis or lysosomal acidification. Conclusions Passive transfer of AQP4-IgG results in primary, complement-independent retinal pathology, which might contribute to retinal abnormalities seen in NMO patients.

Resistance of an enamel-bonding agent to saliva and acid exposure in vitro assessed by liquid scintillation.

Science.gov (United States)

Schmidlin, P R; Göhring, T N; Sener, B; Lutz, F

2002-06-01

To determine the leakage and resistance of a bonding agent and a light-curing fine hybrid composite when exposed to saliva or lactic acid (pH 4) in vitro. Twenty discs in each of four groups of selected irradiated bovine lower central incisors were treated with one of three sealing options: an enamel bond (Heliobond, Vivadent, Schaan, Liechenstein) in a single-step application; Heliobond in a two-step application; and Tetric Flow (Vivadent) as the negative control. One group served as the positive control and remained unsealed. Loss of apatite was determined using the radiochemical method of liquid scintillation. The Cherenkov radiation was assessed in order to evaluate the acid resistance and leakage of smooth surface enamel bonding after exposure to saliva and lactic acid. In addition, replicas were made for SEM analysis of micromorphologic surface changes. A mean loss of 416.5 g (s.d. 57.0) apatite was observed over the unsealed sites following 14 days of exposure to lactic acid. The application of Heliobond in a one- and two-step application still revealed a remarkable degree of leakage, and substance losses of 196.5 g (s.d. 38.9) and 161.8 g (s.d. 39.7), but a protective potential was evident. In saliva, untreated, as well as sealed teeth, showed a modest leakage that was less than 20 g. When Tetric Flow was used (negative control) leakage was reduced to a minimum of 2.4 g (s.d. 1.0) in saliva and 12.8 g (s.d. 19.6) in lactic acid. These results were confirmed by SEM analysis. The method of liquid scintillation was revealed to be of considerable value in evaluating leakage and acid resistance of potential smooth enamel sealing options. Sealing with an unfilled resin still demonstrated remarkable levels of acid dissolution, although a protection tendency could be observed. This leads to the conclusion that there is a need for further investigation to establish more acid-resistant enamel sealing agents.

Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.

Science.gov (United States)

Trommer, Hagen; Böttcher, Rolf; Huschka, Christoph; Wohlrab, Wolfgang; Neubert, Reinhard H H

2005-08-01

This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.

Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde

International Nuclear Information System (INIS)

Costa, Solange; Coelho, Patricia; Costa, Carla; Silva, Susana; Mayan, Olga; Silva Santos, Luis; Gaspar, Jorge; Teixeira, Joao Paulo

2008-01-01

Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04-1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < 0.05) among the exposed group (6.13 ± 0.29) compared with control group (4.49 ± 0.16). Comet assay data showed a significant increase (p < 0.05) of TL in FA-exposed workers (60.00 ± 2.31) with respect to the control group (41.85 ± 1.97). A positive correlation was

Early Effect of High Dose of Ionizing Radiation Exposure on Plasma Lipids Profile and Liver Fatty Acids Composition in Rats

International Nuclear Information System (INIS)

Noaman, E.; Mansour, S.Z.; Ibrahim, N.K.

2005-01-01

The present study was conducted to analyze the effect of acute gamma-irradiation on rats at supralethal doses of 20 Gy to determine the synthesis and amounts of free fatty acids, neutral lipids and phospholipids of plasma and liver after 24 and 48 h of gamma-irradiation. Male Wistar rats weighing 120+- 20 g were exposed to 20 Gy of gamma radiation (dose rate of 0.59 Gy/min). Exposure of rats to ionizing radiation resulted in significant alterations in the assayed parameters indicating lipid metabolism disturbance. Plasma cholesterol and phospholipid levels increased up to 71.3 and 71.5 %, respectively, after 24 h from radiation exposure and then returned to 28 and 27 % change in-compare with control values after 48 h post-irradiation. Plasma triacylglycerol concentrations increased concomitantly with irradiation, but their values are less high than cholesterol and phospholipid levels recording significant changes at 19 and 9 % comparing with control rats. Lipid peroxidation measured as MDA recorded significant elevation after 24 and 48 h post irradiation. It was shown that the synthesis of free fatty acids, cholesterol, cholesterol ethers and phospholipids was activated 48 h after irradiation at 20 Gy. The amount of free fatty acids of the rat liver decreased at 20 Gy exposures. This is assumed to be a result of the radioresistance to some degree in the system of free fatty acid synthesis of the rat to the gamma-irradiation in the lethal doses

Pathology Gross Photography: The Beginning of Digital Pathology.

Science.gov (United States)

Rampy, B Alan; Glassy, Eric F

2015-06-01

The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease

NARCIS (Netherlands)

Scheffer, R. C. H.; Wassenaar, E. B.; Herwaarden, M. A.; Holloway, R. H.; Samsom, M.; Smout, A. J. P. M.; Akkermans, L. M. A.

2005-01-01

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour

Simple intake and pharmacokinetic modeling to characterize exposure of Americans to perfluoroctanoic acid, PFOA.

Science.gov (United States)

Lorber, Matthew; Egeghy, Peter P

2011-10-01

Models for assessing intakes of perfluorooctanoic acid, PFOA, are described and applied. One model is based on exposure media concentrations and contact rates. This model is applied to general population exposures for adults and 2-year old children. The other model is a simple one-compartment, first-order pharmacokinetic (PK) model. Parameters for this model include a rate of elimination of PFOA and a blood volume of distribution. The model was applied to data from the National Health and Nutritional Examination Survey, NHANES, to backcalculate intakes. The central tendency intake estimate for adults and children based on exposure media concentrations and contact rates were 70 and 26 ng/day, respectively. The central tendency adult intake derived from NHANES data was 56 and 37 ng/day for males and females, respectively. Variability and uncertainty discussions regarding the intake modeling focus on lack of data on direct exposure to PFOA used in consumer products, precursor compounds, and food. Discussions regarding PK modeling focus on the range of blood measurements in NHANES, the appropriateness of the simple PK model, and the uncertainties associated with model parameters. Using the PK model, the 10th and 95th percentile long-term average adult intakes of PFOA are 15 and 130 ng/day.

Gene Transcription and Virulence Potential of Listeria monocytogenes Strains After Exposure to Acidic and NaCl Stress

DEFF Research Database (Denmark)

Olesen, Inger; Vogensen, Finn Kvist; Jespersen, Lene

2009-01-01

transcription were observed both after exposure to shock (six genes) and after long-term adaptation to stress (18 genes). In the shock experiments, a transient induction of clpC and clpE was seen for both strains, while transient induction of sigB, inlA, and inlB was observed for strain 4140 only; actA was only...... induced in EGD-e after NaCl shock. The longterm stress experiments were included to imitate the stress conditions encountered by L. monocytogenes when present in food products. Long-term adaptation of EGD-e to acidic stress induced transcription of iap and repressed flaA, while genes related to stress......Gene transcription and virulence potential of two strains of Listeria monocytogenes, EGD-e and 4140, were compared by quantitative real-time polymerase chain reaction and in a Caco-2 in vitro model after exposure to acidic (pH 5.5) and NaCl (4.5% w=v) stress. Strain-dependent differences in gene...

Pathology Assistant (C - Gamechanger Of Pathology Diagnostic

Directory of Open Access Journals (Sweden)

Asel Kudaybergenova

2016-06-01

When the competition ended, we received many favor- able reviews and we decided to start another project a little bit similar to the competition. Every month we show three interesting and difficult to diagnose cases provided by the leading Russian pathologists. The participants can look through the clinical data and digitized histological slides, and then discuss what they see among their professional society. There are 400  specialists  from  post  USSR countries.  Moreover, we get a few proposal of partnership to start a similar project in EU. And the last product in line is Pathology Assistant. It is a game changer. Pathology Assistant is a Digital Pathology©technology driven application for pathology diagnostics, tool to innovate pathology diagnostics in more simple, proven by analytical algo- rithm, automatically delivering anticipated support way. The service provides vast and structured database of validated cases, intuitive interface, fast and convenient system of analytical search. Pathology Assistant will streamline and simplify pathologist’s way to the right decision. Pathologists from Memorial Sloan Catering and biggest EU labs are working on preparing the con- tent for the project.  

Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis.

Science.gov (United States)

Shimazu, Rintaro; Yamamoto, Mihoko; Minesaki, Akimichi; Kuratomi, Yuichiro

2018-06-01

In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases. An experimental rat model of chronic acid reflux esophagitis was surgically created. The oral cavities were observed histologically every 2 weeks until 20 weeks after surgery. At 10 weeks after surgery, molar crown heights in GERD rats were shorter than that in control rats, and inflammatory cell infiltration by gastric acid reflux was found in the periodontal mucosa of GERD rats. Furthermore, dental erosion progressed in GERD rats at 20 weeks after surgery, and enamel erosion and dentin exposure were observed. During the same period, inflammatory cell infiltration was observed in the mucosa of the posterior part of the tongue. These findings suggest that gastric acid reflux may be one of the exacerbating factors of dental erosion, periodontitis and glossitis. We investigated oral changes in an experimental rat model of GERD and observed development of dental erosion, periodontitis and glossitis. Our findings suggested chronic gastric acid reflux may be involved in the pathogenesis of oral disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate.

Science.gov (United States)

Yan, Shengmin; Zhang, Hongxia; Wang, Jianshe; Zheng, Fei; Dai, Jiayin

2015-10-01

Perfluoroalkyl acids (PFAAs) are a group of widely used anthropogenic compounds. As one of the most dominant PFAAs, perfluorooctanoic acid (PFOA) has been suggested to induce hepatotoxicity and several other toxicological effects. However, details on the mechanisms for PFOA-induced hepatotoxicity still need to be elucidated. In this study, we observed the occurrence of endoplasmic reticulum (ER) stress in mouse livers and HepG2 cells after PFOA exposure using several familiar markers for the unfolded protein response (UPR). ER stress in HepG2 cells after PFOA exposure was not significantly influenced by autophagy inhibition or stimulation. The antioxidant defense system was significantly disturbed in mouse livers after PFOA exposure, and reactive oxygen species (ROS) were increased in cells exposed to PFOA for 24 h. However, N-acetyl-L-cysteine (NAC) pretreatment did not satisfactorily alleviate the UPR in cells exposed to PFOA even though the increase of ROS was less evident. Furthermore, exposure of HepG2 cells to PFOA in the presence of sodium 4-phenylbutyrate (4-PBA), a chemical chaperone and ER stress inhibitor, suggested that 4-PBA alleviated the UPR and autophagosome accumulation induced by PFOA in cells. In addition, several toxicological effects attributed to PFOA exposure, including cell cycle arrest, proteolytic activity impairment, and neutral lipid accumulation, were also improved by 4-PBA cotreatment in cells. In vivo study demonstrated that PFOA-induced lipid metabolism perturbation and liver injury were partially ameliorated by 4-PBA in mice after 28 days of exposure. These findings demonstrated that PFOA-induced ER stress leading to UPR might play an important role in PFOA-induced hepatotoxic effects, and chemical chaperone 4-PBA could ameliorate the effects. Copyright © 2015. Published by Elsevier Inc.

Gambling pathology is associated with dampened cortisol response among men and women.

Science.gov (United States)

Paris, J J; Franco, C; Sodano, R; Frye, C A; Wulfert, E

2010-02-09

Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect. Published by Elsevier Inc.

Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.

Science.gov (United States)

Schmidt, Rebecca J; Kogan, Vladimir; Shelton, Janie F; Delwiche, Lora; Hansen, Robin L; Ozonoff, Sally; Ma, Claudia C; McCanlies, Erin C; Bennett, Deborah H; Hertz-Picciotto, Irva; Tancredi, Daniel J; Volk, Heather E

2017-09-08

Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. In this study population, associations between pesticide exposures and ASD

Clinical and pathological analysis of IgA nephropathy with chronic renal failure.

Science.gov (United States)

Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi

2016-10-01

To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p  0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

Chronic dietary mercury exposure causes oxidative stress, brain lesions, and altered behaviour in Atlantic salmon (Salmo salar) parr

International Nuclear Information System (INIS)

Berntssen, Marc H.G.; Aatland, Aase; Handy, Richard D.

2003-01-01

Atlantic salmon (Salmo salar L.) parr were fed for 4 months on fish meal based diets supplemented with mercuric chloride (0, 10, or 100 mg Hg kg -1 DW) or methylmercury chloride (0, 5, or 10 mg Hg kg -1 DW) to assess the effects of inorganic (Hg) and organic dietary mercury on brain lipid peroxidation and neurotoxicity. Lipid peroxidative products, endogenous anti oxidant enzymes, brain histopathology, and overall behaviour were measured. Methylmercury accumulated significantly in the brain of fish fed 5 or 10 mg kg -1 by the end of the experiment, and inorganic mercury accumulated significantly in the brain only at 100 mg kg -1 exposure levels. No mortality or growth reduction was observed in any of the exposure groups. Fish fed 5 mg kg -1 methylmercury had a significant increase (2-fold) in the antioxidant enzyme super oxide dismutase (SOD) in the brain. At dietary levels of 10 mg kg -1 methylmercury, a significant increase (7-fold) was observed in lipid peroxidative products (thiobarbituric acid reactive substances, TBARS) and a subsequently decrease (1.5-fold) in anti oxidant enzyme activity (SOD and glutathione peroxidase, GSH-Px). Fish fed 10 mg kg -1 methylmercury also had pathological damage (vacoulation and necrosis), significantly reduced neural enzyme activity (5-fold reduced monoamine oxidase, MAO, activity), and reduced overall post-feeding activity behaviour. Pathological injury started in the brain stem and became more widespread in other areas of the brain at higher exposure levels. Fish fed 100 mg Hg kg -1 inorganic mercury had significant reduced neural MAO activity and pathological changes (astrocyte proliferation) in the brain, however, neural SOD and GSH-Px enzyme activity, lipid peroxidative products (TBARS), and post feeding behaviour did not differ from controls. Compared with other organs, the brain is particular susceptible for dietary methylmercury induced lipid peroxidative stress at relative low exposure concentrations. Doses of dietary

Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3.

Science.gov (United States)

Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le

2017-01-01

Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SL-NH 2 ) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH 2 to the same site. Notably, co-application of acid and SL-NH 2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.

Pathology Report for Intraperitoneal Sodium Dichromate Exposure in Rats

Science.gov (United States)

2015-08-12

injury resulting from exposure to specific metal intoxication . The investigators aim was to validate hypothesized adverse outcome pathways in rats...vessels causing them to become leaky. Injured or inflamed vessels lead to extravasated fibrinogen which rapidly clots into a cross-linked fibrin gel...Sprague-Dawley rats appear to include direct injury to the exposed, capsular surface of the liver, leading to fibrinogen leakage, fibrin formation

Growth response of Pinus ponderosa seedlings and mature tree branches to acid rain and ozone exposure

International Nuclear Information System (INIS)

Anderson, P.D.; Houpis, J.L.J.; Helms, J.A.

1994-10-01

Forests of the central and southern Sierra Nevada in California have been subjected to chronic damage by ozone and other atmospheric pollutants for the past several decades. Until recently, pollutant exposure of northern Sierra Nevada forests has been mild but increasing population and changes in land use throughout the Sacramento Valley and Sierra Nevada foothills may lead to increased pollutant damage in these forests. Although, better documented in other regions of the United States, little is known regarding the potential for acidic precipitation damage to Sierra Nevada forests. Only recently have studies directed towards understanding the potential interactive effects of ozone and acidic precipitation been undertaken. A key issue in resolving potential regional impacts of pollutants on forests is the extent to which research results can be scaled across genotypes and life-stages. Most of the pollution research to date has been performed using seedlings with varying degrees of genetic control. It is important to determine if the results obtained in such studies can be extrapolated to mature trees and to different genetic sources. In this paper, we present results from a one-year study examining the interactive effects of foliar exposure to acidic rain and ozone on the growth of ponderosa pine (Pinus ponderosa), a conifer known to be sensitive to ozone. The response to pollutants is characterized for both seedlings and mature tree branches of three genotypes grown in a common environment

The use of docosahexaenoic acid supplementation to ameliorate the hyperactivity of rat pups induced by in utero ethanol exposure

OpenAIRE

Furuya, Hiroyuki; Aikawa, Hiroyuki; Yoshida, Takahiko; Okazaki, Isao

2000-01-01

It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA...

Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

Science.gov (United States)

Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

2017-09-01

Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

Pathology in Greece.

Science.gov (United States)

Sakellariou, S; Patsouris, E

2015-11-01

Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

Dietary exposure to perfluoroalkyl acids of specific French adult sub-populations: High seafood consumers, high freshwater fish consumers and pregnant women

International Nuclear Information System (INIS)

Yamada, A.; Bemrah, N.; Veyrand, B.; Pollono, C.; Merlo, M.; Desvignes, V.; Sirot, V.

2014-01-01

Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC–MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values < LOD considered as 0), high freshwater fish consumers appear as the most exposed to PFOS (7.5 ng.kg −1 bw.d −1 ), PFUnA (1.3 ng.kg −1 bw.d −1 ), PFDA (0.4 ng.kg −1 bw.d −1 ) and PFHpS (0.03 ng.kg −1 bw.d −1 ) while high seafood consumers appear as the most exposed to PFOA (1.2 ng.kg −1 bw.d −1 ), PFNA (0.2 ng.kg −1 bw.d −1 ) and PFHxS (0.06 ng.kg −1 bw.d −1 ). For all considered populations, the major exposure contributors are fish, seafood and water under LB hypothesis, while dairy products, bread and crispbread are the main contributors under upper bound (UB) hypothesis. Besides this food exposure assessment, further studies are needed to assess the more global PFAA exposure, taking into account indoor and outdoor air, dust and cutaneous contact, which could be other important contributors for this particular class of chemicals. - Highlights: • The dietary exposure was estimated for 15 perfluoroalkyl acids. • Despite the overestimation, the FFQ remains useful to evaluate the whole diet. • The high fish consumers are the most dietary exposed population. • Fishery products are the main exposure contributors under LB hypothesis

Dietary exposure to perfluoroalkyl acids of specific French adult sub-populations: High seafood consumers, high freshwater fish consumers and pregnant women

Energy Technology Data Exchange (ETDEWEB)

Yamada, A., E-mail: ami.s.yamada@gmail.com [Risk Assessment Directorate, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 27-31 avenue du Général Leclerc, Maisons-Alfort 94701 (France); Bemrah, N., E-mail: nawel.bemrah@anses.fr [Risk Assessment Directorate, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 27-31 avenue du Général Leclerc, Maisons-Alfort 94701 (France); Veyrand, B., E-mail: bruno.veyrand@oniris-nantes.fr [LUNAM Université, Oniris, Laboratoire d' Etude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, Nantes 44307 (France); Pollono, C., E-mail: charles.pollono@oniris-nantes.fr [LUNAM Université, Oniris, Laboratoire d' Etude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, Nantes 44307 (France); Merlo, M., E-mail: mathilde.merlo@anses.fr [Risk Assessment Directorate, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 27-31 avenue du Général Leclerc, Maisons-Alfort 94701 (France); Desvignes, V., E-mail: virginie.desvignes@anses.fr [Risk Assessment Directorate, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 27-31 avenue du Général Leclerc, Maisons-Alfort 94701 (France); Sirot, V., E-mail: sirotv@gmail.com [Risk Assessment Directorate, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), 27-31 avenue du Général Leclerc, Maisons-Alfort 94701 (France); and others

2014-09-01

Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC–MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values < LOD considered as 0), high freshwater fish consumers appear as the most exposed to PFOS (7.5 ng.kg{sup −1} bw.d{sup −1}), PFUnA (1.3 ng.kg{sup −1} bw.d{sup −1}), PFDA (0.4 ng.kg{sup −1} bw.d{sup −1}) and PFHpS (0.03 ng.kg{sup −1} bw.d{sup −1}) while high seafood consumers appear as the most exposed to PFOA (1.2 ng.kg{sup −1} bw.d{sup −1}), PFNA (0.2 ng.kg{sup −1} bw.d{sup −1}) and PFHxS (0.06 ng.kg{sup −1} bw.d{sup −1}). For all considered populations, the major exposure contributors are fish, seafood and water under LB hypothesis, while dairy products, bread and crispbread are the main contributors under upper bound (UB) hypothesis. Besides this food exposure assessment, further studies are needed to assess the more global PFAA exposure, taking into account indoor and outdoor air, dust and cutaneous contact, which could be other important contributors for this particular class of chemicals. - Highlights: • The dietary exposure was estimated for 15 perfluoroalkyl acids. • Despite the overestimation, the FFQ remains useful to evaluate the whole diet. • The high fish consumers are the most dietary exposed population. • Fishery products are the main exposure contributors under LB hypothesis.

Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

Science.gov (United States)

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

2015-01-01

Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

Integration of molecular pathology, epidemiology and social science for global precision medicine.

Science.gov (United States)

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

2016-01-01

The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

Trends in Pinus ponderosa foliar pigment concentration due to chronic exposure of ozone and acid rain

International Nuclear Information System (INIS)

Neuman, L.; Houpis, J.; Anderson, P.

1991-01-01

To determine the effects of ozone and acid rain on mature Ponderosa pine trees, Lawrence Livermore National Lab. has collaborated with University of California Berkeley, University of California Davis, California State University Chico, and the US Forest Service at the latter's Chico Tree Improvement Center. Foliar tissue from mature grafted scions of Pinus ponderosa were exposed to two times ambient ozone for ten months and to acid rain (3.0 pH) weekly for 10 weeks using branch exposure chambers. Pigment extracts were analyzed spectrophotometrically for concentrations of chlorophylls a and b, and carotenoid pigments, at 662 nm, 644 nm, and 470 nm, respectively. Pigment concentrations were expressed on a surface area basis. Preliminary results revealed that chlorophyll a showed a downward trend due to the ozone treatment. Acid rain caused no effects on these three pigments, however, chlorophyll b showed an upward trend due to the interaction of ozone and acid rain. The carotenoid pigments showed no changes due to the treatments either singly, or in combination

Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort

Directory of Open Access Journals (Sweden)

Bernard Jonathan Y.

2016-01-01

Full Text Available Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA, especially long chain PUFA (LC-PUFA which are highly contained in breast milk, could explain this link, since they are needed for pre- and postnatal brain development. Our aim was to study the relationships between several measures of pre- and postnatal exposures to PUFA and child’s psychomotor development at 2 and 3 years in the EDEN cohort. We evaluated breastfeeding duration, colostrum PUFA levels and maternal dietary PUFA intake during pregnancy, that we related with three scores of psychomotor development, after taking into account potential confounders. Breastfeeding duration was positively associated with psychomotor development. No relationship was found with both pre- and postnatal exposure to LC-PUFA. However, the maternal dietary omega-6/omega-3 ratio was negatively associated with psychomotor development, mainly driven by intake in linoleic acid (LA. Among breastfed children, linoleic acid levels were negatively associated with psychomotor development. Furthermore, children exposed to the highest colostrum LA levels tended to score closer to never breastfed children than to children exposed to the lowest colostrums LA levels. Taken together, these results do not provide evidence in favour of a positive role of pre- and postnatal exposure to LC-PUFA on later psychomotor development, but highlight a potential negative role of being exposed in early life to high LA levels. From a public health perspective, this work reiterates the need to promote breastfeeding duration, and to monitor the balance of PUFA intake during pregnancy and lactation periods.

Pathology, toxicology, and latency of irritant gases known to cause bronchiolitis obliterans disease: Does diacetyl fit the pattern?

Directory of Open Access Journals (Sweden)

Brent D. Kerger

2015-01-01

Full Text Available Bronchiolitis obliterans (BO is a rare disease involving concentric bronchiolar fibrosis that develops rapidly following inhalation of certain irritant gases at sufficiently high acute doses. While there are many potential causes of bronchiolar lesions involved in a variety of chronic lung diseases, failure to clearly define the clinical features and pathological characteristics can lead to ambiguous diagnoses. Irritant gases known to cause BO follow a similar pathologic process and time course of disease onset in humans. Studies of inhaled irritant gases known to cause BO (e.g., chlorine, hydrochloric acid, ammonia, nitrogen oxides, sulfur oxides, sulfur or nitrogen mustards, and phosgene indicate that the time course between causal chemical exposures and development of clinically significant BO disease is typically limited to a few months. The mechanism of toxic action exerted by these irritant gases generally involves widespread and severe injury of the epithelial lining of the bronchioles that leads to acute respiratory symptoms which can include lung edema within days. Repeated exposures to inhaled irritant gases at concentrations insufficient to cause marked respiratory distress or edema may lead to adaptive responses that can reduce or prevent severe bronchiolar fibrotic changes. Risk of BO from irritant gases is driven substantially by toxicokinetics affecting concentrations occurring at the bronchiolar epithelium. Highly soluble irritant gases that cause BO like ammonia generally follow a threshold-dependent cytotoxic mechanism of action that at sufficiently high doses results in severe inflammation of the upper respiratory tract and the bronchiolar epithelium concurrently. This is followed by acute respiratory distress, pulmonary edema, and post inflammatory concentric fibrosis that become clinically obvious within a few months. In contrast, irritant gases with lower solubility like phosgene also follow a threshold-dependent mechanism

Lung pathology in case of acute radiation injury

International Nuclear Information System (INIS)

Vlasov, P.A.; Kvacheva, Yu.V.

1998-01-01

Results of pathomorphological studies of 27 patients exposed to total external γ- and β-radiation resulted from the Chernobyl accident and lost due to the acute radiation disease in the first weeks following radiation exposure are discussed. Dose range is 3.7-13.7 Gy. Two groups of pathological changes in lungs are revealed, those are: infection (bacterial, viral and fungous) ones caused by acute radiation disease and signs of respiratory distress-syndrome in adults [ru

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

Science.gov (United States)

Yuan, Yao Zong; Fang, Jing Yuan; Zou, Duo Wu; Levinson, Nigel; Jenner, Bartosz; Wilkinson, Joanne

2016-11-01

To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH acid reflux episodes (pH reflux time and DeMeester scores. All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

Science.gov (United States)

Zimmer, Alex M; Wood, Chris M

2014-01-01

The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species.

Prevalence of Unique Pediatric Pathologies Encountered by Paramedic Students Across Age Groups.

Science.gov (United States)

Ernest, Eric V; Brazelton, Tom B; Carhart, Elliot D; Studnek, Jonathan R; Tritt, Patricia L; Philip, Genghis A; Burnett, Aaron M

2016-08-01

Introduction Traditionally, Emergency Medical Services (EMS) educators have divided the pediatric population into age groups to assist in targeting their clinical and didactic curriculum. Currently, the accrediting body for paramedic training programs requires student exposure to pediatric patients based entirely on age without specifying exposure to specific pathologies within each age stratification. Identifying which pathologies are most common within the different pediatric age groups would allow educators to design curriculum targeting the most prevalent pathologies in each age group and incorporating the physiologic and psychological developmental milestones commonly seen at that age. Hypothesis It was hypothesized that there are unique clusterings of pathologies, represented by paramedic student primary impressions, that are found in different age groups which can be used to target provider education. This is a retrospective review of prospectively collected data documented by paramedic students in the Fisdap (Field Internship Student Data Acquisition Project; Saint Paul, Minnesota USA) database over a one-year period. For the purposes of this study, pediatric patients were defined arbitrarily as those between the ages of 0-16 years. All paramedic student primary impressions recorded in Fisdap for patients aged 0-16 years were abstracted. Primary impression by age was calculated and graphed. The frequency of primary impression was then assessed for significance of trend by age with an alpha ≤.05 considered significant. The following primary impressions showed clinically and statistically significant variability in prevalence among different pediatric age groups: respiratory distress, medical-other, abdominal pain, seizure, overdose/poisoning, behavioral, and cardiac. In patients less than 13 years old, respiratory and other-medical were the most common two primary impressions and both decreased with age. In patients 5-16 years old, the prevalence of

Environmental Exposures and Parkinson?s Disease

OpenAIRE

Nandipati, Sirisha; Litvan, Irene

2016-01-01

Parkinson’s disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industr...

Stability of fatty acids in grass and maize silages after exposure to air during the feed out period

NARCIS (Netherlands)

Khan, N.A.; Cone, J.W.; Hendriks, W.H.

2009-01-01

Lipids in forages are extensively hydrolysed in the silo with a concomitant increase in the level of free fatty acids (FFA). After opening of the silo, exposure of the FFA to air and light with, a concomitant increase in pH and microbial growth, could induce oxidization. The present study

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

Energy Technology Data Exchange (ETDEWEB)

Snyder-Talkington, Brandi N. [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Dymacek, Julian [Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506-6070 (United States); Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States); Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R. [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Pacurari, Maricica [Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States); Denvir, James [Department of Biochemistry and Microbiology, Marshall University, Huntington, WV 25755 (United States); Castranova, Vincent [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Qian, Yong, E-mail: yaq2@cdc.gov [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Guo, Nancy L., E-mail: lguo@hsc.wvu.edu [Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States)

2013-10-15

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

International Nuclear Information System (INIS)

Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2013-01-01

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung

Bisphosphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before 2005.

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Estefanía Fresco, Ruth; Ponte Fernández, Ruth; Aguirre Urizar, José Manuel

2006-11-01

Bisphosphonates are bone-turnover modulating drugs which are used in the management of a number of bone diseases ranging from osteoporosis to neoplasic pathology-associated osteolysis. In the last years a number of cases of osteonecrosis of the jaws associated with these drugs have been reported. In this review we analyze the cases published in the literature indexed from 2003 to December 2005. During this period 246 cases were reported, being more frequently associated with women in the sixth decade of life. More frequently associated bisphosphonates were the nitrogenated bisphosphonates (pamidronate, zolendronic acid) and the most common oral antecedent was a dental extraction. Nevertheless more than 25% of the cases were spontaneous. The most frequent site was the mandible and most of the cases presented clinical evidence of bone exposure and pain. Different treatments have been proposed with different antibiotic therapies with or without surgery, showing in general terms an uncertain prognosis with low healing rates.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review.

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Ajmani, Gaurav S; Suh, Helen H; Pinto, Jayant M

2016-11-01

Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution-related olfactory impacts on the general population using measured

Light exposure during storage preserving soluble sugar and l-ascorbic acid content of minimally processed romaine lettuce (Lactuca sativa L.var. longifolia).

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Zhan, Lijuan; Hu, Jinqiang; Ai, Zhilu; Pang, Lingyun; Li, Yu; Zhu, Meiyun

2013-01-01

Minimally processed romaine lettuce (MPRL) leaves were stored in light condition (2500lux) or darkness at 4°C for 7d. Light exposure significantly delayed the degradation of chlorophyll and decrease of glucose, reducing sugar, and sucrose content, and thus preserved more total soluble solid (TSS) content at the end of storage in comparison with darkness. While, it did not influenced starch content that progressively decreased over time. The l-ascorbic acid (AA) accumulated in light-stored leaves, but deteriorated in dark-stored leaves during storage. The dehydroascorbic acid (DHA) increased in all leaves stored in both light and dark condition, of which light condition resulted in less DHA than darkness. In addition, the fresh weight loss and dry matter significantly increased and these increases were accelerated by light exposure. Conclusively, light exposure in applied intensity effectively alleviated MPRL quality deterioration by delaying the decreases of pigments, soluble sugar, TSS content and accumulating AA. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of humic acids on biodegradation of polycyclic aromatic hydrocarbons depends on the exposure regime

International Nuclear Information System (INIS)

Tejeda-Agredano, Maria-Carmen; Mayer, Philipp; Ortega-Calvo, Jose-Julio

2014-01-01

Binding of polycyclic aromatic hydrocarbons (PAHs) to dissolved organic matter (DOM) can reduce the freely dissolved concentration, increase apparent solubility or enhance diffusive mass transfer. To study the effects of DOM on biodegradation, we used phenanthrene and pyrene as model PAHs, soil humic acids as model DOM and a soil Mycobacterium strain as a representative degrader organism. Humic acids enhanced the biodegradation of pyrene when present as solid crystals but not when initially dissolved or provided by partitioning from a polymer. Synchronous fluorescence spectrophotometry, scintillation counting and a microscale diffusion technique were applied in order to determine the kinetics of dissolution and diffusive mass transfer of pyrene. We suggest that humic acids can enhance or inhibit biodegradation as a result of the balance of two opposite effects, namely, solubilization of the chemicals on the one hand and inhibition of cell adhesion to the pollutant source on the other. Highlights: • Humic acids can enhance the biodegradation of PAHs. • The enhancement depends on how the bacteria are exposed to PAHs. • Humic acids stimulate if PAHs are provided by dissolution form crystals. • An inhibition occurs if PAHs are provided by partitioning from a silicone. • The balance between enhanced dissolution and decreased adhesion is the cause. -- Humic acids cause opposite effects on biodegradation of PAHs depending on the exposure regime

Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology.

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Calderón-Garcidueñas, L; Mora-Tiscareño, A; Fordham, L A; Chung, C J; García, R; Osnaya, N; Hernández, J; Acuña, H; Gambling, T M; Villarreal-Calderón, A; Carson, J; Koren, H S; Devlin, R B

2001-06-01

A complex mixture of air pollutants is present in the ambient air in urban areas. People, animals, and vegetation are chronically and sequentially exposed to outdoor pollutants. The objective of this first of 2 studies is to evaluate by light and electron microscopy the lungs of Mexico City dogs and compare the results to those of 3 less polluted cities in MEXICO: One hundred fifty-two clinically healthy stray mongrel dogs (91 males/61 females), including 43 dogs from 3 less polluted cities, and 109 from southwest and northeast metropolitian Mexico City (SWMMC, NEMMC) were studied. Lungs of dogs living in Mexico City and Cuernavaca exhibited patchy chronic mononuclear cell infiltrates along with macrophages loaded with particulate matter (PM) surrounding the bronchiolar walls and extending into adjacent vascular structures; bronchiolar epithelial and smooth muscle hyperplasia, peribronchiolar fibrosis, microthrombi, and capillary and venule polymorphonuclear leukocytes (PMN) margination. Ultrafine PM was seen in alveolar type I and II cells, endothelial cells, interstitial macrophages (Mtheta), and intravascular Mtheta-like cells. Bronchoalveolar lavage showed significant numbers of alveolar macrophages undergoing proliferation. Exposure to complex mixtures of pollutants-predominantly particulate matter and ozone-is causing lung structural changes induced by the sustained inflammatory process and resulting in airway and vascular remodeling and altered repair. Cytokines released from both, circulating inflammatory and resident lung cells in response to endothelial and epithelial injury may be playing a role in the pathology described here. Deep concern exists for the potential of an increasing rise in lung diseases in child populations exposed to Mexico City's environment.

Evaluation of illnesses associated with occupational exposure to ionizing radiation

International Nuclear Information System (INIS)

Frometa Suarez, I.

1997-01-01

A retrospective study by the Institute of Occupational Medicine is presented of all cases of pathological indications of ionizing radiation exposure during the period 1990-1995. It describes the incidence of theses diseases and their relationship with other factors. It has shown the predominance of pathologies of the haemolymphopoietic system in individuals who work in radiological diagnostics

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

International Nuclear Information System (INIS)

Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

1989-01-01

We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

Energy Technology Data Exchange (ETDEWEB)

Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

1989-04-01

We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

Pathological jealousy and pathological love: Apples to apples or apples to oranges?

Science.gov (United States)

Stravogiannis, Andrea Lorena da C; Kim, Hyoun S; Sophia, Eglacy C; Sanches, Cíntia; Zilberman, Monica L; Tavares, Hermano

2018-01-01

Pathological jealousy evokes emotions, thoughts, and behaviors that cause damage to social and interpersonal relationships. On the other hand, pathological love is the uncontrollable behavior of caring for a partner that results in neglecting the needs of the self. The aim of the present research was to assess the similarities and differences between the two psychopathologies of love. To this end, thirty-two individuals with pathological jealousy and 33 individuals with pathological love were compared on demographics, aspects of romantic relationship (jealousy, satisfaction, love style), psychiatric co-morbidities, personality and psychological characteristics (e.g., impulsivity). In a univariate analysis individuals with pathological jealousy were more likely to be in a current relationship and reported greater satisfaction. The avoidant attachment and the ludus love style were associated with pathological jealousy whereas the secure attachment and agape love style was associated with pathological love. Almost three-quarters (72.3%) of the sample met criteria for a current psychiatric disorder, however no differences emerged between the pathological jealousy and pathological love groups. In a binary logistic regression, relationship status and impairments in parenting significantly differentiated the groups. While both pathological jealousy and pathological love share similarities, they also present with unique differences, which may have important treatment implications. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic analysis revealed alterations of the Plasmodium falciparum metabolism following salicylhydroxamic acid exposure

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Torrentino-Madamet M

2011-09-01

Full Text Available Marylin Torrentino-Madamet1, Lionel Almeras2, Christelle Travaillé1, Véronique Sinou1, Matthieu Pophillat3, Maya Belghazi4, Patrick Fourquet3, Yves Jammes5, Daniel Parzy11UMR-MD3, Université de la Méditerranée, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 2Unité de Recherche en Biologie et Epidémiologie Parasitaires, Antenne IRBA de Marseille (IMTSSA, Le Pharo, 3Centre d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée, 4Centre d'Analyse Protéomique de Marseille, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, 5UMR-MD2, Physiologie et Physiopathologie en Conditions d'Oxygénations Extrêmes, Institut Fédératif de Recherche Jean Roche, Faculté de Médecine Nord, Marseille, FranceObjectives: Although human respiratory metabolism is characterized by the mitochondrial electron transport chain, some organisms present a “branched respiratory chain.” This branched pathway includes both a classical and an alternative respiratory chain. The latter involves an alternative oxidase. Though the Plasmodium falciparum alternative oxidase is not yet identified, a specific inhibitor of this enzyme, salicylhydroxamic acid (SHAM, showed a drug effect on P. falciparum respiratory function using oxygen consumption measurements. The present study aimed to highlight the metabolic pathways that are affected in P. falciparum following SHAM exposure.Design: A proteomic approach was used to analyze the P. falciparum proteome and determine the metabolic pathways altered following SHAM treatment. To evaluate the SHAM effect on parasite growth, the phenotypic alterations of P. falciparum after SHAM or/and hyperoxia exposure were observed.Results: After SHAM exposure, 26 proteins were significantly deregulated using a fluorescent two dimensional-differential gel electrophoresis. Among these deregulated proteins

Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

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Ana Laura Nicoletti Carvalho

2013-01-01

Full Text Available Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP- induced lung inflammation. BALB/c mice received an intranasal instillation of 50 μg of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 μL of cashew nut oil for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF, and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.

Cone Beam Computed Tomography Analysis of Incidental Maxillary Sinus Pathologies in North Indian Population

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Sangeeta S Malik

2017-01-01

Full Text Available Introduction: Maxillary sinus can be visualized in both two-dimensional and three-dimensional images. Computed tomography (CT is considered the gold standard method for the examination of maxillary sinus. Cone beam computed tomography (CBCT addresses the limitation of CT and provides many dental advantages. It can provide valuable knowledge about the pathology with limited exposure and low cost compared with other imaging used for diagnostic purposes. Aims and Objectives: The aim of the study is to analyze the prevalence of pathological changes in maxillary sinus of asymptomatic cases using CBCT for diagnostic purposes. Materials and Methods: This retrospective study evaluated 231 patients for incidental maxillary sinus pathologies. Pathological findings were categorized as mucosal thickening, polypoid mucosal thickening, radiopacification, and no pathological findings. Evaluation of pathological findings was done using factors of age and gender. Results: The present study showed 86 cases with maxillary sinus pathology and 145 cases with no pathological findings. Patients with maxillary sinus pathology were mostly diagnosed with mucosal thickening on both sides. In right maxillary sinus, 45 cases (52.3% showed mucosal thickening, and on the left side 36 cases (41.9% were diagnosed with mucosal thickening. Among 86 cases reported, 20 right maxillary sinus (23.3% and 25 left maxillary sinus (29.1% showed no signs of pathology. Conclusion: The incidental maxillary sinus pathologies are highly prevalent in asymptomatic patients. Therefore, oral radiologists should be aware of these incidental findings which will help in early diagnosis and treatment of disease.

Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids

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M. Grazia Cotticelli

2013-01-01

Full Text Available Friedreich ataxia is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, dysarthria, areflexia, sensory loss, skeletal deformities, and hypertrophic cardiomyopathy. Most disease alleles have a trinucleotide repeat expansion in the first intron of the FXN gene, which decreases expression of the encoded protein frataxin. Frataxin is involved in iron–sulfur-cluster (ISC assembly in the mitochondrial matrix, and decreased frataxin is associated with ISC-enzyme and mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. To assess the role of oxidative stress in lipid peroxidation in Friedreich ataxia we used the novel approach of treating Friedreich ataxia cell models with polyunsaturated fatty acids (PUFAs deuterated at bis-allylic sites. In ROS-driven oxidation of PUFAs, the rate-limiting step is hydrogen abstraction from a bis-allylic site; isotopic reinforcement (deuteration of bis-allylic sites slows down their peroxidation. We show that linoleic and α-linolenic acids deuterated at the peroxidation-prone bis-allylic positions actively rescue oxidative-stress-challenged Friedreich ataxia cells. The protective effect of the deuterated PUFAs is additive in our models with the protective effect of the CoQ10 analog idebenone, which is thought to decrease the production of free radicals. Moreover, the administration of deuterated PUFAs resulted in decreased lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY (581/591 probe. Our results are consistent with a role for lipid peroxidation in Friedreich ataxia pathology, and suggest that the novel approach of oral delivery of isotope-reinforced PUFAs may have therapeutic potential in Friedreich ataxia and other disorders involving oxidative stress and lipid peroxidation.

Correlation of two-dimensional echocardiography and pathologic findings in porcine valve dysfunction.

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Forman, M B; Phelan, B K; Robertson, R M; Virmani, R

1985-02-01

Two-dimensional echocardiographic findings in porcine valve dysfunction were compared with pathologic findings in 10 patients (12 valves). Three specific echocardiographic findings were identified in patients with regurgitant lesions: prolapse, fracture and flail leaflets. Prolapse was associated pathologically with thinning of the leaflets, longitudinal tears close to the ring margin and acid mucopolysaccharide accumulation. Valve fracture was seen with and without prolapse and was accompanied pathologically by small pinpoint perforations or tears of the leaflet. A flail leaflet was seen with a linear tear of the free margin and was associated with calcific deposits. Mild degrees of fracture seen pathologically were missed on the echocardiographic study in five patients. Thickening or calcification, when present in moderate or severe amounts, was correctly identified by echocardiography. When all abnormal features were considered collectively, two-dimensional echocardiography correctly identified at least one of them in all patients. Therefore, two-dimensional echocardiography may prove useful in assessing the source of valvular regurgitation in patients with bioprosthetic valves.

Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia

Science.gov (United States)

Planel, Emmanuel; Bretteville, Alexis; Liu, Li; Virag, Laszlo; Du, Angela L.; Yu, Wai Haung; Dickson, Dennis W.; Whittington, Robert A.; Duff, Karen E.

2009-01-01

Alzheimer’s disease and other tauopathies are characterized by the presence of intracellular neurofibrillary tangles composed of hyperphosphorylated, insoluble tau. General anesthesia has been shown to be associated with increased risk of Alzheimer’s disease, and we have previously demonstrated that anesthesia induces hypothermia, which leads to overt tau hyperphosphorylation in the brain of mice regardless of the anesthetic used. To investigate whether anesthesia enhances the long-term risk of developing pathological forms of tau, we exposed a mouse model with tauopathy to anesthesia and monitored the outcome at two time points—during anesthesia, or 1 wk after exposure. We found that exposure to isoflurane at clinically relevant doses led to increased levels of phospho-tau, increased insoluble, aggregated forms of tau, and detachment of tau from microtubules. Furthermore, levels of phospho-tau distributed in the neuropil, as well as in cell bodies increased. Interestingly, the level of insoluble tau was increased 1 wk following anesthesia, suggesting that anesthesia precipitates changes in the brain that provoke the later development of tauopathy. Overall, our results suggest that anesthesia-induced hypothermia could lead to an acceleration of tau pathology in vivo that could have significant clinical implications for patients with early stage, or overt neurofibrillary tangle pathology.—Planel, E., Bretteville, A., Liu, L., Virag, L., Du, A. L., Yu, W. Y., Dickson, D. W., Whittington, R. A., Duff, K. E. Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. PMID:19279139

New developments in digital pathology: from telepathology to virtual pathology laboratory.

Science.gov (United States)

Kayser, Klaus; Kayser, Gian; Radziszowski, Dominik; Oehmann, Alexander

2004-01-01

To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under

Health risk assessment of various metal(loid)s via multiple exposure pathways on children living near a typical lead-acid battery plant, China

International Nuclear Information System (INIS)

Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Wang, Beibei; Ma, Jin; Fan, Delong; Sun, Chengye; He, Bin; Wei, Fusheng; Jiang, Guibin

2015-01-01

Manufacture of lead-acid batteries is of widespread interest because of its emissions of heavy metals and metalloids into environment, harming environmental quality and consequently causing detrimental effects on human health. In this study, exposure pathways and health risks of children to heavy metal(loid)s (Pb, Cd, As, etc) were investigated based on field sampling and questionnaire. Pb was one of the most abundant elements in children's blood, with an elevated blood lead level of 12.45 μg dL −1 . Soil/dust and food were heavily polluted by targeted metal(loid)s. Food ingestion accounted for more than 80% of the total exposure for most metal(loid)s. The non-cancer risks to children were 3–10 times higher than the acceptable level of 1, while the cancer risks were 5–200 times higher than the maximum acceptable level of 1.0 × 10 −4 . The study emphasized the significance of effective environmental management, particularly to ensure food security near battery facilities. - Highlights: • The health risks of children living around a typical lead-acid battery was analyzed. • The exposure pathways of children to 12 heavy metal(loid)s were assessed. • Courtyard soil and indoor dust and duplicate food were contaminated by metal(loid)s. • Food ingestion was the major pathway for children's exposure to most metal(loid)s. • Higher potentially non-cancer and cancer risks happened to the local children. - The children living around a typical lead-acid battery plant suffered from serious health risks, which mainly attributed to food ingestion and air inhalation exposure

Exposure of Atlantic salmon parr (Salmo salar) to a combination of resin acids and a water soluble fraction of diesel fuel oil: A model to investigate the chemical causes of pigmented salmon syndrome

International Nuclear Information System (INIS)

Croce, B.; Scottish Environmental Protection Agency, Aberdeen; Stagg, R.M.

1997-01-01

Pigmented salmon syndrome is a pollutant-induced hemolytic anemia and hyperbilirubinemia. As part of an investigation of this condition, S2 Atlantic salmon parr (Salmo salar) were exposed to a diesel fuel oil, water soluble fraction (WSF) in combination with a mixture of three resin acids (isopimaric, dehydroabietic, and abietic acids) in a continuous-flow freshwater system. The total nominal concentrations of resin acids in the exposure tanks were 10, 50, and 100 microg/L; the diesel WSF was generated in situ and provided a mean hydrocarbon concentration of 2.0 ± 0.1 mg/L (n = 12) during the 9-d exposure period. Exposure to the diesel WSF alone depressed liver bilirubin UDP-glucuronosyl transferase (UDPGT) activity and induced phenol UDPGT activity. Exposure to the diesel WSF in the absence or presence of resin acids induced liver cytochrome P4501A and increased the concentrations in the plasma of the enzymes lactate dehydrogenase, alkaline phosphatase, and glutamic oxaloacetic transaminase. The combined exposure to diesel WSF with either 50 or 100 microg/L total resin acid caused significant elevations in the concentrations of bilirubin in the plasma and many of these fish had yellow pigmentation on the ventral surface and around the gill arches. The results demonstrate that exposure to combinations of two groups of contaminants can result in the manifestation of toxic effects not apparent from exposure to either of these chemicals in isolation

Cellular responses to tritium exposure in rainbow trout: HTO- and OBT-spiked feed exposure experiments

Energy Technology Data Exchange (ETDEWEB)

Festarini, A.; Shultz, C.; Stuart, M.; Kim, S.B., E-mail: amy.festarini@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada); Ferreri, C. [National Research Council of Italy, Dept. of Chemical Sciences and Materials Technologies, Bologna (Italy)

2016-06-15

Biological effects were evaluated in rainbow trout (Oncorhynchus mykiss) exposed to tritiated water (HTO) or food spiked with organically bound tritium (OBT). An HTO exposure study was conducted using a tritium activity concentration of 7000 Bq/L, and an OBT exposure study was conducted using a tritium activity concentration of 30 000 Bq/L. Following 140 days of in vivo HTO exposure, liver, heart, spleen, kidney, and brain cells did not show statistically significant differences in viability; kidney, liver, and spleen cells did not show significant differences in DNA double-strand break repair activity compared with control cells. Membrane fatty acid composition analysis was conducted on liver cells and no effects of HTO exposure could be detected. Following 140 days of in vivo OBT exposure, viability and DNA double-strand break repair activity were not statistically different from controls in liver, heart, spleen, kidney, and brain cells. Changes, however, were noted in the fatty acid composition of liver and muscle tissues. For both studies, all measurements were performed on each tissue and on a fraction of the same tissue that was exposed to a gamma 4 Gy dose in vitro to test for adaptive responses, and no effects were observed except for fatty acid composition. The findings demonstrated that membrane fatty acid composition is a sensitive marker and that microscopic evaluation of gamma-H2AX foci is more sensitive than the flow cytometric approach. These studies are the first to correlate uptake and depuration with biological health indicators in edible fish for tritium exposures within worldwide drinking water guidelines. (author)

Cellular responses to tritium exposure in rainbow trout: HTO- and OBT-spiked feed exposure experiments

International Nuclear Information System (INIS)

Festarini, A.; Shultz, C.; Stuart, M.; Kim, S.B.; Ferreri, C.

2016-01-01

Biological effects were evaluated in rainbow trout (Oncorhynchus mykiss) exposed to tritiated water (HTO) or food spiked with organically bound tritium (OBT). An HTO exposure study was conducted using a tritium activity concentration of 7000 Bq/L, and an OBT exposure study was conducted using a tritium activity concentration of 30 000 Bq/L. Following 140 days of in vivo HTO exposure, liver, heart, spleen, kidney, and brain cells did not show statistically significant differences in viability; kidney, liver, and spleen cells did not show significant differences in DNA double-strand break repair activity compared with control cells. Membrane fatty acid composition analysis was conducted on liver cells and no effects of HTO exposure could be detected. Following 140 days of in vivo OBT exposure, viability and DNA double-strand break repair activity were not statistically different from controls in liver, heart, spleen, kidney, and brain cells. Changes, however, were noted in the fatty acid composition of liver and muscle tissues. For both studies, all measurements were performed on each tissue and on a fraction of the same tissue that was exposed to a gamma 4 Gy dose in vitro to test for adaptive responses, and no effects were observed except for fatty acid composition. The findings demonstrated that membrane fatty acid composition is a sensitive marker and that microscopic evaluation of gamma-H2AX foci is more sensitive than the flow cytometric approach. These studies are the first to correlate uptake and depuration with biological health indicators in edible fish for tritium exposures within worldwide drinking water guidelines. (author)

Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

International Nuclear Information System (INIS)

Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

2009-01-01

Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

The Role of Brain-Reactive Autoantibodies in Brain Pathology and Cognitive Impairment

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Simone Mader

2017-09-01

Full Text Available Antibodies to different brain proteins have been recently found to be associated with an increasing number of different autoimmune diseases. They need to penetrate the blood–brain barrier (BBB in order to bind antigens within the central nervous system (CNS. They can target either neuronal or non-neuronal antigen and result in damage either by themselves or in synergy with other inflammatory mediators. Antibodies can lead to acute brain pathology, which may be reversible; alternatively, they may trigger irreversible damage that persists even though the antibodies are no longer present. In this review, we will describe two different autoimmune conditions and the role of their antibodies in causing brain pathology. In systemic lupus erythematosus (SLE, patients can have double stranded DNA antibodies that cross react with the neuronal N-methyl-d-aspartate receptor (NMDAR, which have been recently linked to neurocognitive dysfunction. In neuromyelitis optica (NMO, antibodies to astrocytic aquaporin-4 (AQP4 are diagnostic of disease. There is emerging evidence that pathogenic T cells also play an important role for the disease pathogenesis in NMO since they infiltrate in the CNS. In order to enable appropriate and less invasive treatment for antibody-mediated diseases, we need to understand the mechanisms of antibody-mediated pathology, the acute and chronic effects of antibody exposure, if the antibodies are produced intrathecally or systemically, their target antigen, and what triggers their production. Emerging data also show that in utero exposure to some brain-reactive antibodies, such as those found in SLE, can cause neurodevelopmental impairment since they can penetrate the embryonic BBB. If the antibody exposure occurs at a critical time of development, this can result in irreversible damage of the offspring that persists throughout adulthood.

Acute exposure to realistic acid fog: effects on respiratory function and airway responsiveness in asthmatics.

Science.gov (United States)

Leduc, D; Fally, S; De Vuyst, P; Wollast, R; Yernault, J C

1995-11-01

Naturally occurring fogs in industrialized cities are contaminated by acidic air pollutants. In Brussels, Belgium, the pH of polluted fogwater may be as low as 3 with osmolarity as low as 30 mOsm. In order to explore short-term respiratory effects of a realistic acid-polluted fog, we collected samples of acid fog in Brussels, Belgium, which is a densely populated and industrialized city, we defined characteristics of this fog and exposed asthmatic volunteers at rest through a face mask to fogs with physical and chemical characteristics similar to those of natural fogs assessed in this urban area. Fogwater was sampled using a screen collector where droplets are collected by inertial impaction and chemical content of fogwater was assessed by measurement of conductivity, pH, visible colorimetry, high pressure liquid chromatography, and atomic absorption spectrophotometry over a period of one year. The fogwater composition was dominated by NH4+ and SO4- ions. First we evaluated the possible effect of fog acidity alone. For this purpose 14 subjects with asthma were exposed at rest for 1 hr [mass median aerodynamic diameter to a large-particle (MMAD), 9 microns] aerosol with H2SO4 concentration of 500 micrograms/m3 (pH 2.5) and osmolarity of 300 mOsm. We did not observe significant change in pulmonary function or bronchial responsiveness to metacholine. In the second part of the work, 10 asthmatic subjects were exposed to acid fog (MMAD, 7 microns) containing sulfate and ammonium ions (major ions recovered in naturally occurring fogs) with pH 3.5 and osmolarity 30 mOsm. Again, pulmonary function and bronchial reactivity were not modified after inhalation of this fog. It was concluded that short-term exposure to acid fog reproducing acidity and hypoosmolarity of natural polluted fogs does not induce bronchoconstriction and does not change bronchial responsiveness in asthmatics.

Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists

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Evren UZUN

2018-05-01

Full Text Available Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs and cell-free circulating nucleic acids, effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: Implication to exposure pathway.

Science.gov (United States)

Tian, Zhexi; Kim, Seung-Kyu; Shoeib, Mahiba; Oh, Jeong-Eun; Park, Jong-Eun

2016-05-15

A wide range of per- and polyfluoroalkyl substances (PFASs), including fluorotelomer alcohols (FTOHs), perfluorooctane sulfonamidoethanols (FOSEs), perfluoroalkyl carboxylic acids (PFCAs), and perfluoroalkane sulfonic acids (PFSAs), were measured in fifteen house dust and two nonresidential indoor dust of Korea. Total concentrations of PFASs in house dust ranged from 29.9 to 97.6 ng g(-1), with a dominance of perfluorooctane sulfonic acid (PFOS), followed by 8:2 FTOH, N-Ethyl perfluorooctane sulfonamidoethanol (EtFOSE), perfluoroctanoic acid (PFOA). In a typical exposure scenario, the estimated daily intakes (EDIs) of total PFASs via house dust ingestion were 2.83 ng d(-1) for toddlers and 1.13 ng d(-1) for adults, which were within the range of the mean EDIs reported from several countries. For PFOA and PFOS exposure via house dust ingestion, indirect exposure (via precursors) was a minor contributor, accounting for 5% and 12%, respectively. An aggregated exposure (hereafter, overall-EDIs) of PFOA and PFOS occurring via all pathways, estimated using data compiled from the literature, were 53.6 and 14.8 ng d(-1) for toddlers, and 20.5 and 40.6 ng d(-1) for adults, respectively, in a typical scenario. These overall-EDIs corresponded to 82% (PFOA) and 92% (PFOS) of a pharmacokinetic model-based EDIs estimated from adults' serum data. Direct dietary exposure was a major contributor (>89% of overall-EDI) to PFOS in both toddlers and adults, and PFOA in toddlers. As for PFOA exposure of adults, however direct exposure via tap water drinking (37%) and indirect exposure via inhalation (22%) were as important as direct dietary exposure (41%). House dust-ingested exposure (direct+indirect) was responsible for 5% (PFOS in toddlers) and house-dust ingestion was a minor contributor in this study, but should not be ignored for toddlers' PFOS exposure due to its significance in the worst-case scenario. Copyright © 2016 Elsevier B.V. All rights reserved.

Heart and bile acids - Clinical consequences of altered bile acid metabolism.

Science.gov (United States)

Vasavan, Tharni; Ferraro, Elisa; Ibrahim, Effendi; Dixon, Peter; Gorelik, Julia; Williamson, Catherine

2018-04-01

Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids. Copyright © 2018 Elsevier B.V. All rights reserved.

Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

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Nisreen A. Rajeh

2017-02-01

Full Text Available exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA and Vitamin E (vit-Eon Acrylamide (ACR induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone. After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E

Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas

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Giada Frenzilli

2017-06-01

Full Text Available Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum of Wistar rats. Rats were exposed to loud noise (100 dBA for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH combined with increased Bax and glial fibrillary acidic protein (GFAP. Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise.

Systemic exposure to benzoic acid and hippuric acid following topical application of clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel in Japanese patients with acne vulgaris.

Science.gov (United States)

Ino, Hiroko; Takahashi, Naoki; Saenz, Alessandra Alio; Wakamatsu, Akira; Hashimoto, Hirofumi; Nakahara, Norie; Hasegawa, Setsuo

2015-01-01

Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris. © 2014, The American College of Clinical Pharmacology.

The Effects of Subacute Exposure of Peracetic Acid on Lipid Peroxidation and Hepatic Enzymes in Wistar Rats

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Abdoljalal Marjani

2010-10-01

Full Text Available Objectives: This study was undertaken to determine the effect of subacute exposure of peracetic acid on lipid peroxidation and hepatic enzymes in Wistar rats.Methods: 48 male animals in Treatment Group I, II and III received 0.2%, 2% and 20% peracetic acid daily for 2 and 4 weeks.Results: Serum malondialdehyde increased and Alanine Transaminase and Aspartate Transaminase decreased significantly in groups 2 and 3, compared to the control group. The malondialdehyde, Alanine Transaminase and Aspartate Transaminase with 0.2% and 2% doses of peracetic acid for 2 weeks do not lead to the alteration of malondialdehyde and enzyme activities.Conclusion: This study demonstrated that the enhancement of malondialdehyde could provide an oxidative damage induced by disinfectant peroxidation at 20% and 2% doses at 2 and 4 weeks. The consumption of peroxidation with 20% for 2 weeks and 2% for 4 weeks can cause the increase of malondialdehyde and the decrease of enzyme activities, respectively.

The Effects of Subacute Exposure of Peracetic Acid on Lipid Peroxidation and Hepatic Enzymes in Wistar Rats

Science.gov (United States)

Marjani, Abdoljalal; Golalipour, Mohammad J.; Gharravi, Anneh M.

2010-01-01

Objectives This study was undertaken to determine the effect of subacute exposure of peracetic acid on lipid peroxidation and hepatic enzymes in Wistar rats. Methods 48 male animals in Treatment Group I, II and III received 0.2%, 2% and 20% peracetic acid daily for 2 and 4 weeks. Results Serum malondialdehyde increased and Alanine Transaminase and Aspartate Transaminase decreased significantly in groups 2 and 3, compared to the control group. The malondialdehyde, Alanine Transaminase and Aspartate Transaminase with 0.2% and 2% doses of peracetic acid for 2 weeks do not lead to the alteration of malondialdehyde and enzyme activities. Conclusion This study demonstrated that the enhancement of malondialdehyde could provide an oxidative damage induced by disinfectant peroxidation at 20% and 2% doses at 2 and 4 weeks. The consumption of peroxidation with 20% for 2 weeks and 2% for 4 weeks can cause the increase of malondialdehyde and the decrease of enzyme activities, respectively. PMID:22043353

Metabolomic analysis of alterations in lipid oxidation, carbohydrate and amino acid metabolism in dairy goats caused by exposure to Aflotoxin B1.

Science.gov (United States)

Cheng, Jianbo; Huang, Shuai; Fan, Caiyun; Zheng, Nan; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

2017-11-01

The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, β-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.

Teaching digital pathology: The international school of digital pathology and proposed syllabus

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Vincenzo Della Mea

2017-01-01

Full Text Available Digital pathology is an interdisciplinary field where competency in pathology, laboratory techniques, informatics, computer science, information systems, engineering, and even biology converge. This implies that teaching students about digital pathology requires coverage, expertise, and hands-on experience in all these disciplines. With this in mind, a syllabus was developed for a digital pathology summer school aimed at professionals in the aforementioned fields, as well as trainees and doctoral students. The aim of this communication is to share the context, rationale, and syllabus for this school of digital pathology.

Changes in lipid content and fatty acid composition along the reproductive cycle of the freshwater mussel Dreissena polymorpha: Its modulation by clofibrate exposure

Energy Technology Data Exchange (ETDEWEB)

Lazzara, Raimondo; Fernandes, Denise, E-mail: deniseferna@gmail.com; Faria, Melissa; Lopez, Jordi F.; Tauler, Roma; Porte, Cinta, E-mail: cinta.porte@cid.csic.es

2012-08-15

Total lipids and fatty acid profiles were determined along the reproductive cycle of the zebra mussel (Dreissena polymorpha). A total of 33 fatty acids with carbon atoms from 14 to 22 were identified: palmitic acid (16:0) was the most abundant fatty acid (13-24%) followed by docosahexaenoic acid (DHA; 22:6n-3), eicosapentaenoic acid (EPA; 20:5n-3) and palmitoleic acid (16:1n-7). Some individual fatty acids (16:0, 16:2n-4, 18:1n-7, 18:2n-6, 18:3n-4, 18:4n-3, 20:4n-3, 20:5n-3) were strongly related to reproductive events, while others having structural-type functions (18:0 and 22:6n-3) were rather stable during the study period. Multivariate analysis of the whole data set using the multivariate curve resolution alternating least squares method confirmed the strong relationship of fatty acid profiles with the reproductive cycle of zebra mussel. Additionally, the effects of the pharmaceutical clofibrate on lipid composition and fatty acid profiles were assessed following 7-day exposure of zebra mussels to a wide range of concentrations (20 ng/L to 2 mg/L). A significant reduction in total triglycerides (38%-48%) together with an increase in the amount of fatty acids per gram wet weight (1.5- to 2.2-fold) was observed in the exposed mussels. This work highlights the ability of clofibrate to induce changes on the lipidome of zebra mussels at concentrations as low as 200 ng/L. -- Highlights: Black-Right-Pointing-Pointer Clofibrate exposure leads to a reduction of total triglycerides in zebra mussel. Black-Right-Pointing-Pointer The amount of fatty acids per gram wet weight increased in exposed mussels. Black-Right-Pointing-Pointer The effects were evidenced at concentrations of clofibrate as low as 200 ng/L. Black-Right-Pointing-Pointer Fatty acid profiles were closely related to reproductive events.

Changes in lipid content and fatty acid composition along the reproductive cycle of the freshwater mussel Dreissena polymorpha: Its modulation by clofibrate exposure

International Nuclear Information System (INIS)

Lazzara, Raimondo; Fernandes, Denise; Faria, Melissa; López, Jordi F.; Tauler, Romà; Porte, Cinta

2012-01-01

Total lipids and fatty acid profiles were determined along the reproductive cycle of the zebra mussel (Dreissena polymorpha). A total of 33 fatty acids with carbon atoms from 14 to 22 were identified: palmitic acid (16:0) was the most abundant fatty acid (13–24%) followed by docosahexaenoic acid (DHA; 22:6n−3), eicosapentaenoic acid (EPA; 20:5n−3) and palmitoleic acid (16:1n−7). Some individual fatty acids (16:0, 16:2n−4, 18:1n−7, 18:2n−6, 18:3n−4, 18:4n−3, 20:4n−3, 20:5n−3) were strongly related to reproductive events, while others having structural-type functions (18:0 and 22:6n−3) were rather stable during the study period. Multivariate analysis of the whole data set using the multivariate curve resolution alternating least squares method confirmed the strong relationship of fatty acid profiles with the reproductive cycle of zebra mussel. Additionally, the effects of the pharmaceutical clofibrate on lipid composition and fatty acid profiles were assessed following 7-day exposure of zebra mussels to a wide range of concentrations (20 ng/L to 2 mg/L). A significant reduction in total triglycerides (38%–48%) together with an increase in the amount of fatty acids per gram wet weight (1.5- to 2.2-fold) was observed in the exposed mussels. This work highlights the ability of clofibrate to induce changes on the lipidome of zebra mussels at concentrations as low as 200 ng/L. -- Highlights: ► Clofibrate exposure leads to a reduction of total triglycerides in zebra mussel. ► The amount of fatty acids per gram wet weight increased in exposed mussels. ► The effects were evidenced at concentrations of clofibrate as low as 200 ng/L. ► Fatty acid profiles were closely related to reproductive events.

Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

Science.gov (United States)

Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J

2009-02-01

Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

Executive functions in mono- and bilingual children with language impairment - issues for speech-language pathology.

Science.gov (United States)

Sandgren, Olof; Holmström, Ketty

2015-01-01

The clinical assessment of language impairment (LI) in bilingual children imposes challenges for speech-language pathology services. Assessment tools standardized for monolingual populations increase the risk of misinterpreting bilingualism as LI. This Perspective article summarizes recent studies on the assessment of bilingual LI and presents new results on including non-linguistic measures of executive functions in the diagnostic assessment. Executive functions shows clinical utility as less subjected to language use and exposure than linguistic measures. A possible bilingual advantage, and consequences for speech-language pathology practices and future research are discussed.

Study of inhaled radio-active pollutants: 1. Current data; II. Pathology; III. Validity of animal model. Dose-effect relations

International Nuclear Information System (INIS)

Lafuma, J.; Masse, R.; Metivier, H.; Nolibe, D.; Fritsch, P.; Nenot, J.C.; Morin, M.

1974-01-01

An attempt has been made to develop an animal for human industrial exposure to airradiation. That will give results applicable to man both qualitatively and quantitavely. Using over 2000 animals. The following studies were made. Radon, rat and occupationally exposed man; 239 plutonium oxide, rat and monkey; 12 different α and emitters, rat with different exposure media (aerosols particles) and exposure shcedules (acute chronic). Scrupulous pathological, microscopic, autoradiographic and ultrastructural analysis of animals followed their deaths. Acute changes are characterized by alveolaroedema, capillary and arteriolar thrombisus, and desquamation of type 1 pneumatocytes. There is interstitial pneumonia, hyaline membrane formation, and extensive bronchiolar and alveolar metaplasia. In a study of long-term effects a wide variety of both benign and malignant tumours was discovered. There are variations in species lateney and radiation sensitivity. The pathological changes, found in these studies are qualitatively very similar to changes found in man [fr

The Danish Pathology Register

DEFF Research Database (Denmark)

Bjerregaard, Beth; Larsen, Ole B

2011-01-01

The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

Pathological gambling and criminality.

Science.gov (United States)

Folino, Jorge Oscar; Abait, Patricia Estela

2009-09-01

To review research results on the relationship between pathological gambling and criminality, published in 2007 and 2008, in English and in Spanish. An important association between pathological gambling and criminality was confirmed in populations of anonymous gamblers, helpline callers and substance abusers. Helplines provide a timely service to gamblers who have not reached the maximum stages in the development of a pathological gambling pattern. Pathological gambling is associated with violence in couples and dysfunctional families. Inversely, violence is also an antecedent promoting vulnerability toward pathological gambling. Impulsiveness shows diverse relationships with pathological gambling and violence as well. A pathological gambler's involvement in crime is exceptionally considered without responsibility by justice, but it may be an indicator of the disorder severity and the need for special therapeutic tactics. While reviewing the present study, research work was published that contributed to a better understanding of the association between pathological gambling and criminality and went further into their complex relationship and the formulation of explanatory models related to impulsiveness.

Effects of sublethal exposure to boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta.

Science.gov (United States)

Ali, Arshad; Xue, Rui-De; Barnard, Donald R

2006-09-01

Effects of sublethal exposure to 0.1% boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta were studied in the laboratory. Survival of males as well as females was significantly reduced when exposed to the bait, compared to control adults. The host-seeking and bloodfeeding activities in the baited females decreased, but the mean duration of blood engorgement (probing to voluntary withdrawal of proboscis) was not significantly different between the baited and control females. The landing and biting rates (human forearm) were significantly reduced in the baited females compared to nonbaited controls. Fecundity and fertility (based on number of laid eggs per female and percentage egg hatch, respectively) in the baited females were significantly reduced, and ovarian development was retarded. Sublethal exposure to sugar-based boric acid bait has the potential to reduce adult populations of St. albopicta.

Effects of chronic fly ash exposure on golden hamsters: changes in lung phospholipids and their fatty acid composition as a result of inhalation

Energy Technology Data Exchange (ETDEWEB)

Nishimura, I; Negishi, T; Kamihira, M

1986-01-01

Changes in lung phospholipids of golden hamsters exposed to 2 mg/mT coal fly ash for 180 days, 7 days/week, 20 hours/day were examined. In the exposed group the amount of phospholipids in lavaged lung organ increased significantly compared with the control group, but in pulmonary surfactant did not. As regards lipid composition of phospholipids in lavaged lung organ, phosphatidylcholine was slightly increased but sphingomyelin was decreased by exposure. Some significant changes in fatty acid composition of phospholipids were observed between exposed and control group. In pulmonary surfactant, palmitic acid showed no change but myristic acid and oleic acid decreased. On the other hand, in lavaged lung organ, palmitic acid increased but stearic acid and decosatetraenoic acid decreased. Arachidonic acid composition increased in both parts of lung. An increase in the proportion of polyunsaturated fatty acid in whole fatty acid of phospholipids was found in pulmonary surfactant of exposed hamsters. 24 refs., 2 figs., 3 tabs.

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

International Nuclear Information System (INIS)

Woźny, Maciej; Lewczuk, Bogdan; Ziółkowska, Natalia; Gomułka, Piotr; Dobosz, Stefan; Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł

2016-01-01

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg −1 ) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg −1 ) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Wang, Qiao; Cheng, Jun [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhang, Jingshun; Xu, Jiaojiao [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China)

2015-09-24

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

International Nuclear Information System (INIS)

Zhang, Yu; Wang, Qiao; Cheng, Jun; Zhang, Jingshun; Xu, Jiaojiao; Ren, Yiping

2015-01-01

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Long-chain perfluoroalkyl carboxylic acids in Pacific cods from coastal areas in northern Japan: A major source of human dietary exposure

International Nuclear Information System (INIS)

Fujii, Yukiko; Sakurada, Tsukasa; Harada, Kouji H.; Koizumi, Akio; Kimura, Osamu; Endo, Tetsuya; Haraguchi, Koichi

2015-01-01

This study investigates perfluoroalkyl carboxylic acids (PFCAs) contamination of edible fish muscle from Japanese coastal waters. The concentrations of PFCAs with 8–14 carbon atoms (C8–C14) in Pacific cods in Hokkaido, Japan were 51 (median: pg/g-wet weight) for C8, 93 for C9, 99 for C10, 746 for C11, 416 for C12, 404 for C13, and 93 for C14. The levels of C9–C14 PFCAs in fish were strongly correlated to each other, but not to C8 and the other chlorinated persistent organic pollutants, indicating that C9–C14 PFCAs have a different emission source and/or bioaccumulation mechanism. The relative ratios between estimated PFCAs intake through fish consumption and the reported total dietary exposure of PFCAs were less than 1 for C8 to C9, but were more than 1 for C10 to C14. This result strongly suggests that fish consumption is a significant source of human dietary exposure to C10–C14 PFCAs. - Highlights: • Perfluoroalkyl carboxylic acids were detected in edible cod fish from Japanese coastal waters. • The levels of long-chain PFCAs in fish were independent from those of C8 and other POPs. • Long chain PFCAs intake through fish and the reported total dietary exposure were comparable. • Sea fish such as Pacific cod may be a significant human dietary source of long-chain PFCAs. - Sea fish are a significant source of long-chain perfluoroalkyl carboxylic acids for the Japanese population

The Australian Work Exposures Study: Prevalence of Occupational Exposure to Formaldehyde.

Science.gov (United States)

Driscoll, Timothy R; Carey, Renee N; Peters, Susan; Glass, Deborah C; Benke, Geza; Reid, Alison; Fritschi, Lin

2016-01-01

The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to formaldehyde, to identify the main circumstances of exposure and to describe the use of workplace control measures designed to decrease those exposures. The analysis used data from the Australian Workplace Exposures Study, a nationwide telephone survey, which investigated the current prevalence and exposure circumstances of work-related exposure to 38 known or suspected carcinogens, including formaldehyde, among Australian workers aged 18-65 years. Using the web-based tool OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. Of the 4993 included respondents, 124 (2.5%) were identified as probably being exposed to formaldehyde in the course of their work [extrapolated to 2.6% of the Australian working population-265 000 (95% confidence interval 221 000-316 000) workers]. Most (87.1%) were male. About half worked in technical and trades occupations. In terms of industry, about half worked in the construction industry. The main circumstances of exposure were working with particle board or plywood typically through carpentry work, building maintenance, or sanding prior to painting; with the more common of other exposures circumstances being firefighters involved in fighting fires, fire overhaul, and clean-up or back-burning; and health workers using formaldehyde when sterilizing equipment or in a pathology laboratory setting. The use of control measures was inconsistent. Workers are exposed to formaldehyde in many different occupational circumstances. Information on the exposure circumstances can be used to support decisions on appropriate priorities for intervention and control of occupational exposure to formaldehyde, and estimates of burden of cancer arising from occupational exposure to formaldehyde

Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.

Science.gov (United States)

Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N; Schantz, Susan L

2016-02-01

Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics

Directory of Open Access Journals (Sweden)

Franka Klatte-Schulz

2018-01-01

Full Text Available Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7, chronic ruptures (n = 6, acute ruptures (n = 13, and intact tendons (n = 4 were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation (interleukin (IL 1β, tumor necrosis factor α, IL6, IL10, IL33, soluble ST2, transforming growth factor β1, cyclooxygenase 2, inflammatory cells (cluster of differentaition (CD 3, CD68, CD80, CD206, fat metabolism (fatty acid binding protein 4, peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, adiponectin, and innervation (protein gene product 9.5, growth associated protein 43, macrophage migration inhibitory factor were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies.

Links between casino proximity and gambling participation, expenditure, and pathology.

Science.gov (United States)

Sévigny, Serge; Ladouceur, Robert; Jacques, Christian; Cantinotti, Michael

2008-06-01

Two studies investigated the relationship between casino proximity and gambling participation, expenditure, and pathology. In Study 1, 8,842 participants were categorized into 1 of 4 driving distances from their home to the nearest casino in the province of Quebec: 0-100 km, 100.01-200 km, 200.01-300 km, or 300.01-981 km. In Study 2, 5,158 participants, who lived within a 100-km driving distance from the Montreal casino, were classified into 1 of 5 equidistant, 20-km driving distances. A survey company interviewed participants regarding their gambling habits. Results indicated a positive link between casino proximity and gambling participation (at the provincial and Montreal levels) and expenditure (at the provincial level only) but no link with the current prevalence rate of probable pathological gambling or of problem gambling. In a setting in which many types of gambling activities are available, casino proximity in itself does not appear to explain the rate of gambling-related problems. It is necessary to continue prospective research on exposure and adaptation theories as potential explanations for the development of pathological gambling. 2008 APA

Medical laboratory technician professional pathologies: a 2006-2016 literature review.

Science.gov (United States)

Pougnet, Richard; Loddé, Brice; Uguen, Marie; Sawicki, Bénédicte; Pougnet, Laurence

2017-12-01

The trade of laboratory technician (TL) exposes to many risks to health, because of biological or chemical or physical exposures. But the TL occupation is constantly evolving, the techniques are constantly changing. The purpose of this article is to take stock of the occupational TL pathologies which were recently described in the literature. This is a literature review, based on Medline® and Scopus® medical databases, on publications between 01/01/2006 and 31/12/2016. The research was conducted in French and English. Only articles about TL in Hospital or Teaching Hospital were selected. Twenty-eight articles were studied. The main infectious pathology described was brucellosis and a case of meningitis was studied. The cutaneous allergies reported concerned sensitization to certain solvents. There was no allergy to latex. Musculoskeletal disorders (MSD) were studied in 4 articles. The main MSDs were low back pain and neck pain. Several articles have alerted on the occurrence of burnout syndrome (BO). However, no prevalence studies were conducted over the period studied. In conclusion, TL can present many occupational pathologies. Few articles studied the prevalence of MSD and BO.

Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

International Nuclear Information System (INIS)

Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

2009-01-01

Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks α7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-β-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 μg/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

Contribution of job-exposure matrices for exposure assessment in occupational safety and health monitoring systems: application from the French national occupational disease surveillance and prevention network.

Science.gov (United States)

Florentin, Arnaud; Zmirou-Navier, Denis; Paris, Christophe

2017-08-01

To detect new hazards ("signals"), occupational health monitoring systems mostly rest on the description of exposures in the jobs held and on reports by medical doctors; these are subject to declarative bias. Our study aims to assess whether job-exposure matrices (JEMs) could be useful tools for signal detection by improving exposure reporting. Using the French national occupational disease surveillance and prevention network (RNV3P) data from 2001 to 2011, we explored the associations between disease and exposure prevalence for 3 well-known pathology/exposure couples and for one debatable couple. We compared the associations measured when using physicians' reports or applying the JEMs, respectively, for these selected diseases and across non-selected RNV3P population or for cases with musculoskeletal disorders, used as two reference groups; the ratio of exposure prevalences according to the two sources of information were computed for each disease category. Our population contained 58,188 subjects referred with pathologies related to work. Mean age at diagnosis was 45.8 years (95% CI 45.7; 45.9), and 57.2% were men. For experts, exposure ratios increase with knowledge on exposure causality. As expected, JEMs retrieved more exposed cases than experts (exposure ratios between 12 and 194), except for the couple silica/silicosis, but not for the MSD control group (ratio between 0.2 and 0.8). JEMs enhanced the number of exposures possibly linked with some conditions, compared to experts' assessment, relative to the whole database or to a reference group; they are less likely to suffer from declarative bias than reports by occupational health professionals.

Clinical pathology and assessment of pathogen exposure in southern and Alaskan sea otters

Science.gov (United States)

Hanni, K.D.; Mazet, J.A.K.; Gulland, F.M.D.; Estes, James A.; Staedler, M.; Murray, M.J.; Miller, M.; Jessup, David A.

2003-01-01

The southern sea otter (Enhydra lutris nereis) population in California (USA) and the Alaskan sea otter (E. lutris kenyoni) population in the Aleutian Islands (USA) chain have recently declined. In order to evaluate disease as a contributing factor to the declines, health assessments of these two sea otter populations were conducted by evaluating hematologic and/or serum biochemical values and exposure to six marine and terrestrial pathogens using blood collected during ongoing studies from 1995 through 2000. Samples from 72 free-ranging Alaskan, 78 free-ranging southern, and (for pathogen exposure only) 41 debilitated southern sea otters in rehabilitation facilities were evaluated and compared to investigate regional differences. Serum chemistry and hematology values did not indicate a specific disease process as a cause for the declines. Statistically significant differences were found between free-ranging adult southern and Alaskan population mean serum levels of creatinine kinase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatinine, glucose, phosphorous, total bilirubin, blood urea nitrogen, and sodium. These were likely due to varying parasite loads, contaminant exposures, and physiologic or nutrition statuses. No free-ranging sea otters had signs of disease at capture, and prevalences of exposure to calicivirus, Brucella spp., and Leptospira spp. were low. The high prevalence (35%) of antibodies to Toxoplasma gondii in free-ranging southern sea otters, lack of antibodies to this parasite in Alaskan sea otters, and the pathogen's propensity to cause mortality in southern sea otters suggests that this parasite may be important to sea otter population dynamics in California but not in Alaska. The evidence for exposure to pathogens of public health importance (e.g., Leptospira spp., T. gondii) in the southern sea otter population, and the naïveté of both populations to other pathogens (e.g., morbillivirus

Clinical pathology and assessment of pathogen exposure in southern and Alaskan sea otters.

Science.gov (United States)

Hanni, Krista D; Mazet, Jonna A K; Gulland, Frances M D; Estes, James; Staedler, Michelle; Murray, Michael J; Miller, Melissa; Jessup, David A

2003-10-01

The southern sea otter (Enhydra lutris nereis) population in California (USA) and the Alaskan sea otter (E. lutris kenyoni) population in the Aleutian Islands (USA) chain have recently declined. In order to evaluate disease as a contributing factor to the declines, health assessments of these two sea otter populations were conducted by evaluating hematologic and/or serum biochemical values and exposure to six marine and terrestrial pathogens using blood collected during ongoing studies from 1995 through 2000. Samples from 72 free-ranging Alaskan, 78 free-ranging southern, and (for pathogen exposure only) 41 debilitated southern sea otters in rehabilitation facilities were evaluated and compared to investigate regional differences. Serum chemistry and hematology values did not indicate a specific disease process as a cause for the declines. Statistically significant differences were found between free-ranging adult southern and Alaskan population mean serum levels of creatinine kinase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatinine, glucose, phosphorous, total bilirubin, blood urea nitrogen, and sodium. These were likely due to varying parasite loads, contaminant exposures, and physiologic or nutrition statuses. No free-ranging sea otters had signs of disease at capture, and prevalences of exposure to calicivirus, Brucella spp., and Leptospira spp. were low. The high prevalence (35%) of antibodies to Toxoplasma gondii in free-ranging southern sea otters, lack of antibodies to this parasite in Alaskan sea otters, and the pathogen's propensity to cause mortality in southern sea otters suggests that this parasite may be important to sea otter population dynamics in California but not in Alaska. The evidence for exposure to pathogens of public health importance (e.g., Leptospira spp., T. gondii) in the southern sea otter population, and the naïveté of both populations to other pathogens (e.g., morbillivirus

An anatomo-pathological study of injury development in the pig following acute local irradiation

International Nuclear Information System (INIS)

Lefaix, J.L.; Daburon, F.; Tricaud, Y.; Haag, J.; Verola, O.; Brocheriou, C.

1984-01-01

The clinical and anatomo-pathological evolution of the injuries due to acute collimated exposure ( 192 Ir) of pigs' thigh has been studied. After a first stage of superficial injuries -coagulation and ischemic necrosis- spreading on during the first three weeks, there followed a stage of fast extension of deep injuries, especially at the beginning of the third month following exposure. Together with the destructive injuries, a very large mutilating sclerosis developed from the fourth week; its particular characteristics -pseudosarcomatous aspect and anarchistic vascularization- did not allow to stop the evolution of tissular impairment [fr

Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

Energy Technology Data Exchange (ETDEWEB)

Strecker, Ruben, E-mail: Ruben.Strecker@cos.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Weigt, Stefan, E-mail: stefan.weigt@merckgroup.com [Institute of Toxicology, Merck KGaA, 64293 Darmstadt (Germany); Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)

2013-04-15

In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head.

Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

International Nuclear Information System (INIS)

Strecker, Ruben; Weigt, Stefan; Braunbeck, Thomas

2013-01-01

In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head

Occupational exposure to HDI: progress and challenges in biomarker analysis.

Science.gov (United States)

Flack, Sheila L; Ball, Louise M; Nylander-French, Leena A

2010-10-01

1,6-Hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenges in HDI biomarker analysis including the quantification of N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N'-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA) in urine samples based on previously established methods for HDA analysis. In addition, we describe the optimization of reaction conditions for the synthesis of monoacetyl-HDA and diacetyl-HDA, and utilize these standards for the quantification of these metabolites in the urine of three occupationally exposed workers. Diacetyl-HDA was present in untreated urine at 0.015-0.060 μg/l. Using base hydrolysis, the concentration range of monoacetyl-HDA in urine was 0.19-2.2 μg/l, 60-fold higher than in the untreated samples on average. HDA was detected only in one sample after base hydrolysis (0.026 μg/l). In contrast, acid hydrolysis yielded HDA concentrations ranging from 0.36 to 10.1 μg/l in these three samples. These findings demonstrate HDI metabolism via N-acetylation metabolic pathway and protein adduct formation resulting from occupational exposure to HDI. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: Interim results

International Nuclear Information System (INIS)

Bernstein, David M.; Rogers, Rick; Sepulveda, Rosalina; Kunzendorf, Peter; Bellmann, Bernd; Ernst, Heinrich; Phillips, James I.

2014-01-01

Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (> 20 μm) cleared quickly with T 1/2 estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T 1/2 > 1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation. - Highlights: • We evaluated brake dust w/wo added chrysotile in comparison to crocidolite asbestos. • Persistence, translocation, pathological response in the lung and pleural cavity. • Chrysotile cleared rapidly from the lung while the crocidolite asbestos persisted. • No significant pathology observed at any time point in the brake-dust groups. • Crocidolite produced pathological response - Wagner 4 interstitial fibrosis by 32d

Pathology in Undergraduate Training Program

Directory of Open Access Journals (Sweden)

Shiva Raj K.C.

2018-04-01

Full Text Available Pathology is a study of disease which deals with etiology, pathogenesis and morphological features and the associated clinical features. Pathology acts as a bridge that fills the gap between basic sciences and clinical medicine. With proper understanding of pathological processes, one can understand the disease process. In Nepal, since the beginning of medical school teaching, Pathology as a basic science discipline and is a component of the preclinical medical school curriculum.Pathology teaching in 19th century was vague, disorganized and very little, though precious. The lectures used to be conducted by surgeons. At Barts, surgeon Sir James Paget had taught surgical pathology. The real revolution in pathology teaching began in the early 1900s when, spurred on by increasing understanding of disease mechanisms, pathology began to be accepted as a specialty in its own right.During the early and mid of 20th century, pathology teaching was a part of clinical teaching with daily, autopsy demonstration. By the late 1980s, significant change had taken place. In many medical schools, debate started regarding relevance of vigorous preclinical teaching. Then system-based approach was incorporated and traditional preclinical course had been abandoned. With this pathology teaching also began to change with pathologists being involved in teaching histology, often alongside pathology to highlight its clinical relevance. In medical schools the pathology teaching time was cut. Autopsy demonstrations, which had been so popular with generations of medical students, were becoming irregular and less well attended.Though teaching of pathology in blocks to ‘avoid fragmentation’ has disappeared in western countries; it is still practice in Nepal. In western countries there was traditional practice of teaching general pathology in the first two years and systemic pathology in the clinical years. Now pathology teaching is integrated throughout the course. A

ENDOCRINE-METABOLIC PATHOLOGY IN CHILDREN OF FEMALE WORKERS ON NUCLEAR INDUSTRY ENTERPRISE

Directory of Open Access Journals (Sweden)

S. F. Sosnina

2017-01-01

Full Text Available The study of deviations in health status of children whose parents were exposed to radiation on production enterprise is important for radiation safety of people of reproductive age and their subsequent generations.The purpose of the study: the analysis of endocrine-metabolic pathology in the offspring of female workers of nuclear production, which had accumulated preconceptual doses of external gamma-irradiation.Material and methods: Retrospective data analysis of medical records of 650 children under 15 years old was carried out, 130 of whom were the offspring of mothers exposed to radiation in the workplace. Methods of nonparametric statistics were applied. To identify latent factors, factor analysis by the main component method was used.Results: The range of preconceptive doses of external gamma irradiation to mothers’ gonads was 0.09–3523.7 mGy, the average absorbed dose for gonads was 423.2±52.2 mGy. The structure of the class «Endocrine, nutritional and metabolic diseases» among the descendants of irradiated and intact mothers did not significantly differ. There was predominance of rickets, malnutrition among infants in both groups. Iodine-deficiency-related thyroid disorders were most frequently recorded in the structure of thyroid gland diseases without statistically significant differences in the groups. The gender dependence was noted: endocrine-metabolic pathology occurred in girls by 1.8 times more often than among boys. Frequent occurrence of polypathies and secondary endocrine pathology were indicated in the group of children of irradiated mothers. Factor analysis in study group identified four factors characterizing the antenatal period in children (19.4% of the variance, obstetric-gynecologic anamnesis (14.1% of the variance, mothers’ bad health habits (10.6% of the variance and preconceptional external gamma-radiation exposure of female workers (9.6% of the variance.Conclusion: The features identified in the analysis

Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59.

Science.gov (United States)

Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

2017-09-01

To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an

Peculiarities of psychological status of liquidators of Chernobyl accident after-effects having psychosomatic pathology

International Nuclear Information System (INIS)

Vishnevskaya, V.P.

2006-01-01

Eight hundred and ninety two men aged 25-55 yrs including five hundred and eighty three persons taking part in the Chernobyl accident after-effects liquidation and three hundred and nine persons having similar psychosomatic pathologies but lacking radiation 'anamnesis'. The radiation risk understanding was shown to effect negatively on the disease run and the remission period duration. The psychic process after the radiation exposure was determined to be caused by a radiation effect on the central nervous system as well. The outcomes of the clinical and psychological study evidenced that the psychosomatic pathology including the discirculating encephalopathy developed in the persons exposed to irradiation in the early age. (authors)

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

Science.gov (United States)

Nanayakkara, Shanika; Komiya, Toshiyuki; Ratnatunga, Neelakanthi; Senevirathna, S T M L D; Harada, Kouji H; Hitomi, Toshiaki; Gobe, Glenda; Muso, Eri; Abeysekera, Tilak; Koizumi, Akio

2012-05-01

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata.

Science.gov (United States)

Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel

2015-03-01

The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (γ-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative.

Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

DEFF Research Database (Denmark)

Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

2007-01-01

as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients.

Science.gov (United States)

Emerenziani, S; Ribolsi, M; Guarino, M P L; Balestrieri, P; Altomare, A; Rescio, M P; Cicala, M

2014-01-01

Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure. © 2013 John Wiley & Sons Ltd.

Element uptake and physiological responses of Lactuca sativa upon co-exposures to tourmaline and dissolved humic acids.

Science.gov (United States)

Jia, Weili; Wang, Cuiping; Ma, Chuanxin; Wang, Jicheng; Sun, Hongwen

2018-03-27

Element migration and physiological response in Lactuca sativa upon co-exposure to tourmaline (T) and dissolved humic acids (DHAs) were investigated. Different fractions of DHA 1 and DHA 4 and three different doses of T were introduced into Hoagland's solution. The results indicated that T enhanced the contents of elements such as N and C, Si and Al in the roots and shoots. The correlation between TF values of Si and Al (R 2  = 0.7387) was higher than that of Si and Mn (R 2  = 0.4961) without the presence of DHAs. However, both DHA 1 and DHA 4 increased the correlation between Si and Mn, but decreased the one between Si and Al. CAT activities in T treatments were positively correlated to the contents of N and Al in the shoots, whose R 2 was 0.9994 and 0.9897, respectively. In the co-exposure of DHAs and tourmaline, DHA 4 exhibited more impacts on element uptake, CAT activities, as well as ABA contents in comparison with the presence of DHA 1 , regardless of the T exposure doses. These results suggested that DHAs have effects on mineral element behaviors and physiological response in Lactuca sativa upon exposure to tourmaline for the first time, which had great use in guiding soil remediation.

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

Science.gov (United States)

2017-11-01

Iraqi war veteran with posttraumatic stress disorder who committed suicide . Neurosurgical focus 2011;31:E3. 14. Perl D. Plenary Lecture: Chronic...Washington DC, 2011. 31. Montenigro PH, Alosco ML, Martin BM, et al. Cumulative Head Impact Exposure Predicts Later-Life Depression , Apathy, Executive...anxiety, spatial learning and memory, and depressive behavior. Animals were also assessed for chronic tau pathology, astrogliosis, and white

Occupational Exposure to HDI: Progress and Challenges in Biomarker Analysis

OpenAIRE

Flack, Sheila L.; Ball, Louise M.; Nylander-French, Leena A.

2010-01-01

1,6-hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenge...

Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort

OpenAIRE

Bernard Jonathan Y.; Armand Martine; Forhan Anne; De Agostini Maria; Charles Marie-Aline; Heude Barbara

2016-01-01

Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA), especially long chain PUFA (LC-PUFA) which are highly contained in breast milk, could explain this link, since they are needed for pre- and postnatal brain development. Our aim was to study the relationships between several measures of pre- and postnatal exposures to PUFA and child’s psychomotor...

Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

Science.gov (United States)

Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

2010-10-01

Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

Science.gov (United States)

Rajeh, Nisreen A.; Al-Dhaheri, Najlaa M.

2017-01-01

Objectives: To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E PMID:28133684

Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis.

Science.gov (United States)

Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Leite, Carlos Eduardo; De Paula Cognato, Giana; Bonan, Carla Denise

2015-01-01

Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48μM) exposure during the first 48hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24hpf, 48hpf, and 72hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70dpf and 120dpf. VPA exposure did not affect aggression in the adult stage at 70dpf and 120dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue.

Science.gov (United States)

Gapeyev, Andrew B; Kulagina, Tatiana P; Aripovsky, Alexander V

2013-08-01

To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles.

Science.gov (United States)

Stokes-Riner, Abbie; Thurston, Sally W; Myers, Gary J; Duffy, Emeir M; Wallace, Julie; Bonham, Maxine; Robson, Paula; Shamlaye, Conrad F; Strain, J J; Watson, Gene; Davidson, Philip W

2011-01-01

Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure. Copyright © 2010 Elsevier B.V. All rights reserved.

Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

Science.gov (United States)

Maniaci, G; Goudriaan, A E; Cannizzaro, C; van Holst, R J

2018-03-01

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

Influence of long-term exposure to simulated acid rain on development, reproduction and acaricide susceptibility of the carmine spider mite, Tetranychus cinnabarinus

OpenAIRE

Wang, Jin-Jun; Zhang, Jian-Ping; He, Lin; Zhao, Zhi-Mo

2006-01-01

Development, reproduction and acaricide susceptibility of Tetranychus cinnabarinus (Boisduvals) (Acari: Tetranychidae) were investigated after long-term (about 40 generations) exposure to various levels of acid rain; pH 2.5, 3.0, 4.0, and 5.6. Deionized water (pH 6.8) served as a control. The mites were reared on eggplant leaves at 28?C, 80%RH and a photoperiod of 14:10 (L:D) in the laboratory. The results showed that the duration of the immature stage was significantly affected by acid rain ...

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

Energy Technology Data Exchange (ETDEWEB)

Woźny, Maciej, E-mail: maciej.wozny@uwm.edu.pl [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland); Lewczuk, Bogdan; Ziółkowska, Natalia [Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn (Poland); Gomułka, Piotr [Department of Ichthyology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn (Poland); Dobosz, Stefan [Department of the Salmonid Research in Rutki, Inland Fisheries Institute in Olsztyn, Rutki, 83-330 Żukowo (Poland); Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland)

2016-12-15

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg{sup −1}) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg{sup −1}) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE

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EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE. D.K. Tarka1,2 , G.R. Klinefelter2, J.C. Rockett2, J.D. Suarez2, N.L. Roberts2 and J.M. Rogers1,2. 1 University of North Carol...

The impact of long term exposure to phthalic acid esters on reproduction in Chinese rare minnow (Gobiocypris rarus)

International Nuclear Information System (INIS)

Guo, Yongyong; Yang, Yuanjin; Gao, Yong; Wang, Xianfeng; Zhou, Bingsheng

2015-01-01

The environmental risk of phthalic acid esters (PAEs) is of great concern. We investigated the reproductive impairment of di-(2-ethylhexyl)-phthalate (DEHP) on Chinese rare minnow, an endemic fish inhabiting the upper streams of the Yangtze River. Chinese rare minnow larvae were exposed to environmentally relevant concentrations of DEHP (0, 4.2, 13.3, and 40.8 μg/L) for 6 months. Plasma testosterone and 17β-estradiol levels decreased in females, accompanied by downregulation of cyp19a and cyp17 gene transcription in ovary. Increases in plasma testosterone concentration were observed in males, accompanied by downregulation of cyp19a gene transcription in testes. Hepatic VTG gene transcription was upregulated in males and females. Exposure to DEHP reduced egg production and inhibited oocyte maturation in females and retarded spermiation in males. Decreased egg protein content was measured in F1 embryos. These results indicate that long-term exposure to low concentrations of DEHP (13.3 μg/L) causes endocrine disruption and impairs fish reproduction. - Highlights: • PAEs in the aquatic environment may pose risk to endemic fish species. • Long-term exposure to DEHP affected sex hormone levels in rare minnow. • DEHP affected gonad development. • Long-term exposure caused reduction of fecundity, but not sex ratio. • Environmentally relevant concentrations of DEHP impair fish reproduction. - Long-term exposure to low concentrations of DEHP adversely impact Chinese rare minnow reproduction

Effects of Tributyltin Chloride on Cybrids with or without an ATP Synthase Pathologic Mutation.

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López-Gallardo, Ester; Llobet, Laura; Emperador, Sonia; Montoya, Julio; Ruiz-Pesini, Eduardo

2016-09-01

The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)- and mitochondrial DNA (mtDNA)-encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. López-Gallardo E, Llobet L, Emperador S, Montoya J, Ruiz-Pesini E. 2016. Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation. Environ Health Perspect 124:1399-1405; http://dx.doi.org/10.1289/EHP182.

Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

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Milton Levin

2008-12-01

Full Text Available The immunotoxic potential of domoic acid (DA, a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 µg/g b.w. and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 µM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr, a significant decrease in neutrophil phagocytosis (24-hr, a significant decrease in monocyte phagocytosis (48-hr, and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr. In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 µM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 µM, and significantly decreased at 100 µM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species.

Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians.

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Tøttenborg, Sandra Søgaard; Choi, Anna L; Bjerve, Kristian S; Weihe, Pal; Grandjean, Philippe

2015-07-01

Polychlorinated biphenyl (PCB) exposure may affect serum concentrations of polyunsaturated fatty acids (PUFAs) by inhibiting desaturases ∆5 and ∆6 that drive their synthesis from precursor fatty acids. Such changes in the composition of fatty acids may affect cardiovascular disease risk, which is thought to increase at elevated PCB exposures. This population-based cross-sectional study examined 712 Faroese men and women aged 70-74 years. The serum phospholipid fraction of fasting blood samples was used to determine the PUFA profile, including linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosatrienoic acid, and other relevant fatty acids. Ratios between precursor and metabolite fatty acids were used as proxies for ∆5 and ∆6 desaturase activity. Tertiles of serum-PCB concentrations were used in multiple regression analyses to determine the association between the exposure and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure to PCBs. Although the desaturase estimates were likely influenced by dietary intakes of product PUFAs, the association between PCB exposure and ∆6 desaturase activity is plausible and may affect cardiovascular disease risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Stem Cell Pathology.

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Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

2018-01-24

Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

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Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

2016-09-01

The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity

Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

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Ruenz, Meike; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

2016-04-01

The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) μg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 μg AA/kg bw/d.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015.

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Shamim, Thorakkal

2016-01-01

There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal.

Color Stability of Enamel following Different Acid Etching and Color Exposure Times

Directory of Open Access Journals (Sweden)

Arezoo Jahanbin

2014-06-01

Full Text Available Background and aims. The aim of this study was to evaluate the effect of different etching times on enamel color stability after immediate versus delayed exposure to colored artificial saliva (CAS. Materials and methods. Human first premolars were divided into five groups of twenty. A colorimeter was used according to the CIE system on the mid-buccal and mid-lingual surfaces to evaluate initial tooth color. Samples in group A remained unetched. In groups B to E, buccal and lingual surfaces were initially etched with phosphoric acid for 15 and 60 seconds, respectively. Then, the samples in groups A and C were immersed in colored artificial saliva (cola+saliva. In group B, the teeth were immersed in simple artificial saliva (AS. Samples in groups D and E were immersed in AS for 24 and 72 hours, respectively before being immersed in colored AS. The teeth were immersed for one month in each solution before color measurement. During the test period, the teeth were retrieved from the staining solution and stored in AS for five minutes. This was repeated 60 times. Color changes of buccal and lingual surfaces were calculated. Kruskal-Wallis and Wilcoxon tests were used for statistical analysis (α ≤ 0.05. Results. There were no significant differences between the groups in term of ΔE of buccal (P = 0.148 and lingual surfaces (P = 0.73. Conclusion. Extended time of etching did not result in significant enamel color change. Immediate and delayed exposure of etched enamel to staining solutions did not result in clinically detectable tooth color changes.

High-resolution metabolomics of occupational exposure to trichloroethylene.

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Walker, Douglas I; Uppal, Karan; Zhang, Luoping; Vermeulen, Roel; Smith, Martyn; Hu, Wei; Purdue, Mark P; Tang, Xiaojiang; Reiss, Boris; Kim, Sungkyoon; Li, Laiyu; Huang, Hanlin; Pennell, Kurt D; Jones, Dean P; Rothman, Nathaniel; Lan, Qing

2016-10-01

Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver cancer; however, TCE's mode of action for development of these diseases in humans is not well understood. Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppm a )] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population. Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10 -5 ), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = -1.6, P-value = 0.0043), taurine (β = -2.4, P-value = 0.0011) and chenodeoxycholic acid (β = -1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations. High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology. © The Author 2016; all rights

Pathogen exposure and blood chemistry in the Washington population of northern sea otters (Enhydra lutris kenyoni)

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White, C. LeAnn; Schuler, Krysten L.; Thomas, Nancy J.; Webb, Julie L.; Saliki, Jeremiah T.; Ip, Hon S.; Dubey, J.P.; Frame, Elizabeth R.

2013-01-01

Northern sea otters (Enhydra lutris kenyoni) from Washington State, United States were evaluated in 2011 to determine health status and pathogen exposure. Antibodies to Brucella spp. (10%) and influenza A virus (23%) were detected for the first time in this population in 2011. Changes in clinical pathology values (serum chemistries), exposure to pathogens, and overall health of the population over the last decade were assessed by comparing 2011 data to the data collected on this population in 2001–2002. Several serum chemistry parameters were different between study years and sexes but were not clinically significant. The odds of canine distemper virus exposure were higher for otters sampled in 2001–2002 (80%) compared to 2011 (10%); likelihood of exposure significantly increased with age. Prevalence of exposure to Sarcocystis neurona was also higher in 2001–2002 (29%) than in 2011 (0%), but because testing methods varied between study years the results were not directly comparable. Exposure to Leptospira spp. was only observed in 2001–2002. Odds of Toxoplasma gondii exposure were higher for otters sampled in 2011 (97%) than otters in 2001–2002 (58%). Substantial levels of domoic acid (n = 2) and saxitoxin (n = 2) were found in urine or fecal samples from animals sampled in 2011. No evidence of calicivirus or Coxiella burnetii exposure in the Washington population of northern sea otters was found in either 2001–2002 or 2011. Changes in exposure status from 2001–2002 to 2011 suggest that the Washington sea otter population may be dealing with new disease threats (e.g., influenza) while also increasing their susceptibility to diseases that may be highly pathogenic in naïve individuals (e.g., canine distemper).

Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

DEFF Research Database (Denmark)

Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

2015-01-01

, whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing......Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential...... consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0...

Delineating pathological pathways in a chemically induced mouse model of Gaucher disease.

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Vardi, Ayelet; Zigdon, Hila; Meshcheriakova, Anna; Klein, Andrés D; Yaacobi, Chen; Eilam, Raya; Kenwood, Brandon M; Rahim, Ahad A; Massaro, Giulia; Merrill, Alfred H; Vitner, Einat B; Futerman, Anthony H

2016-08-01

Great interest has been shown in understanding the pathology of Gaucher disease (GD) due to the recently discovered genetic relationship with Parkinson's disease. For such studies, suitable animal models of GD are required. Chemical induction of GD by inhibition of acid β-glucosidase (GCase) using the irreversible inhibitor conduritol B-epoxide (CBE) is particularly attractive, although few systematic studies examining the effect of CBE on the development of symptoms associated with neurological forms of GD have been performed. We now demonstrate a correlation between the amount of CBE injected into mice and levels of accumulation of the GD substrates, glucosylceramide and glucosylsphingosine, and show that disease pathology, indicated by altered levels of pathological markers, depends on both the levels of accumulated lipids and the time at which their accumulation begins. Gene array analysis shows a remarkable similarity in the gene expression profiles of CBE-treated mice and a genetic GD mouse model, the Gba(flox/flox) ;nestin-Cre mouse, with 120 of the 144 genes up-regulated in CBE-treated mice also up-regulated in Gba(flox/flox) ;nestin-Cre mice. We also demonstrate that various aspects of neuropathology and some behavioural abnormalities can be arrested upon cessation of CBE treatment during a specific time window. Together, our data demonstrate that injection of mice with CBE provides a rapid and relatively easy way to induce symptoms typical of neuronal forms of GD. This is particularly useful when examining the role of specific biochemical pathways in GD pathology, since CBE can be injected into mice defective in components of putative pathological pathways, alleviating the need for time-consuming crossing of mice. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats.

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Dwivedi, Nidhi; Flora, Govinder; Kushwaha, Pramod; Flora, Swaran J S

2014-01-01

We investigated protective efficacy of α-lipoic acid (LA), an antioxidant against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of oxidative stress, neurological dysfunction, and tissue histopathological alterations were determined. Male rats were exposed either to 50 ppm sodium arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously) for 10 weeks. α-Lipoic acid (50mg/kg, pos) was also co-administered in above groups. Arsenic exposure led to significant oxidative stress along, hepatotoxicity, hematotoxicity and altered brain biogenic amines levels accompanied by increased arsenic accumulation in blood and tissues. These altered biochemical variables were supported by histopathological examinations leading to oxidative stress and cell death. These biochemical alterations were significantly restored by co-administration of α-lipoic acid with arsenic and DDVP alone and concomitantly. The results indicate that arsenic and DDVP induced oxidative stress and cholinergic dysfunction can be significantly protected by the supplementation of α-lipoic acid. Copyright © 2013 Elsevier B.V. All rights reserved.

Plasma Ascorbic Acid and Non-Enzymatic Antioxidants Level in ...

African Journals Online (AJOL)

Free radicals have been implicated in the pathology of several diseases including cataract. Ascorbic acid functions as the major chain breaking antioxidant vitamin in the aqueous phase. Bilirubin, albumin and uric acid are regarded as natural antioxidants. There are conflicting reports on plasma concentrations of these ...

Risk assessment of plant food supplements and other herbal products containing aristolochic acids using the margin of exposure (MOE) approach.

Science.gov (United States)

Abdullah, Rozaini; Diaz, Leolean Nyle; Wesseling, Sebastiaan; Rietjens, Ivonne M C M

2017-02-01

After the incidences of induction of aristolochic acid nephropathy after consumption of herbal weight loss preparations that accidentally contained aristolochic acids (AAs), several countries defined national restrictions on the presence of AAs in food, including plant food supplements (PFS) and herbal products. This study investigates whether the risks associated with exposure to AAs via PFS and herbal products are at present indeed negligible. Data reported in literature on AA levels in PFS and other herbal products and also obtained from a new series of PFS in the present study were used to calculate the estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs). Available literature data revealed that 206 out of 573 samples were found to contain aristolochic acid I (AAI) and/or aristolochic acid II (AAII). The results obtained from recently collected PFS revealed that both AAI and AAII were detected in three out of 18 analysed PFS at levels up to 594.8 and 235.3 µg g -1 , respectively, being in line with the levels reported in literature. The EDIs resulting from intake of these PFS resulted in MOEs that were generally below 10,000, corroborating the priority for risk management. Although these results refer to PFS collected by targeted sampling strategies, the data reveal that AA-containing PFS are still freely available. When considering that the use of these samples may be limited to shorter periods of time, the EDIs might be lower, but MOE values would still be lower than 10,000 for more than 50% of the AA-containing PFS and herbal products. In conclusion, the presence of AAs in PFS and herbal products even several years after instalment of the legal restrictions still raises concern, especially for people who frequently use the respective PFS and herbal products.

Pathology of the vestibulocochlear nerve

Energy Technology Data Exchange (ETDEWEB)

De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

2010-05-15

There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

Pathology of the vestibulocochlear nerve

International Nuclear Information System (INIS)

De Foer, Bert; Kenis, Christoph; Van Melkebeke, Deborah; Vercruysse, Jean-Philippe; Somers, Thomas; Pouillon, Marc; Offeciers, Erwin; Casselman, Jan W.

2010-01-01

There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

Digital pathology in nephrology clinical trials, research, and pathology practice.

Science.gov (United States)

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Exposure to perfluorooctane sulfonic acid (PFOS) adversely affects the life-cycle of the damselfly Enallagma cyathigerum

International Nuclear Information System (INIS)

Bots, Jessica; De Bruyn, Luc; Snijkers, Tom; Van den Branden, Bert; Van Gossum, Hans

2010-01-01

We evaluated whether life-time exposure to PFOS affects egg development, hatching, larval development, survival, metamorphosis and body mass of Enallagma cyathigerum (Insecta: Odonata). Eggs and larvae were exposed to five concentrations ranging from 0 to 10 000 μg/L. Our results show reduced egg hatching success, slower larval development, greater larval mortality, and decreased metamorphosis success with increasing PFOS concentration. PFOS had no effect on egg developmental time and hatching or on mass of adults. Eggs were the least sensitive stage (NOEC = 10 000 μg/L). Larval NOEC values were 1000 times smaller (10 μg/L). Successful metamorphosis was the most sensitive response trait studied (NOEC < 10 μg/L). The NOEC value suggests that E. cyathigerum is amongst the most sensitive freshwater organisms tested. NOEC for metamorphosis is less than 10-times greater than the ordinary reported environmental concentrations in freshwater, but is more than 200-times smaller than the greatest concentrations measured after accidental releases. - Long-term laboratory exposure to perfluorooctane sulfonic acid reduces survival and interferes with metamorphosis of Enallagma cyathigerum (Insecta: Odonata).

Exposure to perfluorooctane sulfonic acid (PFOS) adversely affects the life-cycle of the damselfly Enallagma cyathigerum

Energy Technology Data Exchange (ETDEWEB)

Bots, Jessica, E-mail: Jessica.bots@ua.ac.b [Evolutionary Ecology Group, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium); De Bruyn, Luc, E-mail: luc.debruyn@ua.ac.b [Evolutionary Ecology Group, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium); Research Institute for Nature and Forest (INBO), Kliniekstraat 25, 1070 Brussels (Belgium); Snijkers, Tom, E-mail: tomsnijkers@gmail.co [Evolutionary Ecology Group, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium); Van den Branden, Bert, E-mail: bvandenbranden@gmail.co [Department PIH Environment, University College West Flanders (HOWEST), Graaf K. 11 de Goedelaan 5, B-8500 Kortrijk (Belgium); Van Gossum, Hans, E-mail: hans.vangossum@ua.ac.b [Evolutionary Ecology Group, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium)

2010-03-15

We evaluated whether life-time exposure to PFOS affects egg development, hatching, larval development, survival, metamorphosis and body mass of Enallagma cyathigerum (Insecta: Odonata). Eggs and larvae were exposed to five concentrations ranging from 0 to 10 000 mug/L. Our results show reduced egg hatching success, slower larval development, greater larval mortality, and decreased metamorphosis success with increasing PFOS concentration. PFOS had no effect on egg developmental time and hatching or on mass of adults. Eggs were the least sensitive stage (NOEC = 10 000 mug/L). Larval NOEC values were 1000 times smaller (10 mug/L). Successful metamorphosis was the most sensitive response trait studied (NOEC < 10 mug/L). The NOEC value suggests that E. cyathigerum is amongst the most sensitive freshwater organisms tested. NOEC for metamorphosis is less than 10-times greater than the ordinary reported environmental concentrations in freshwater, but is more than 200-times smaller than the greatest concentrations measured after accidental releases. - Long-term laboratory exposure to perfluorooctane sulfonic acid reduces survival and interferes with metamorphosis of Enallagma cyathigerum (Insecta: Odonata).

[Adolescent pathological gambling].

Science.gov (United States)

Petit, A; Karila, L; Lejoyeux, M

2015-05-01

Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Molecular pathology of prostate cancer.

Science.gov (United States)

Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

2010-01-01

This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

Measuring water ingestion from spray exposures.

Science.gov (United States)

Sinclair, Martha; Roddick, Felicity; Nguyen, Thang; O'Toole, Joanne; Leder, Karin

2016-08-01

Characterisation of exposure levels is an essential requirement of health risk assessment; however for water exposures other than drinking, few quantitative exposure data exist. Thus, regulatory agencies must use estimates to formulate policy on treatment requirements for non-potable recycled water. We adapted the use of the swimming pool chemical cyanuric acid as a tracer of recreational water ingestion to permit detection of small water volumes inadvertently ingested from spray exposures. By using solutions of 700-1000 mg/L cyanuric acid in an experimental spray exposure scenario, we were able to quantify inadvertent water ingestion in almost 70% of participants undertaking a 10 min car wash activity using a high pressure spray device. Skin absorption was demonstrated to be negligible under the experimental conditions, and the measured ingestion volumes ranged from 0.06 to 3.79 mL. This method could be applied to a range of non-potable water use activities to generate exposure data for risk assessment processes. The availability of such empirical measurements will provide greater assurance to regulatory agencies and industry that potential health risks from exposure to non-potable water supplies are well understood and adequately managed to protect public health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Future-proofing pathology: the case for clinical adoption of digital pathology.

Science.gov (United States)

Williams, Bethany Jill; Bottoms, David; Treanor, Darren

2017-12-01

This document clarifies the strategic context of digital pathology adoption, defines the different use cases a healthcare provider may wish to consider as part of a digital adoption and summarises existing reasons for digital adoption and its potential benefits. The reader is provided with references to the relevant literature, and illustrative case studies. The authors hope this report will be of interest to healthcare providers, pathology managers, departmental heads, pathologists and biomedical scientists that are considering digital pathology, deployments or preparing business cases for digital pathology adoption in clinical settings. The information contained in this document can be shared and used in any documentation the reader wishes to present for their own institutional case for adoption report or business case. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessment of gill pathological responses in the tropical fish yellowfin seabream of Persian Gulf under mercury exposure

Directory of Open Access Journals (Sweden)

Leila Hassaninezhad

2014-01-01

Full Text Available Gill histomorphological alterations were used to assess the effects of chronic exposure to HgCl2 on the yellowfin seabream, Acanthopagrus latus. In this regard, 90 A. latus were exposed to sublethal concentrations of HgCl2 (10, 20, 35 and 50 μg/L for 3 weeks. Treated fish were erratic and showed respiratory distress. The most common morphological abnormalities included: filaments disorganization, increase of mucus secretion, debris and blood plaques on the filaments, losing or shortening of some filaments. The most frequent histopathological changes detected in the gills included extensive lifting of the lamellar epithelium and edema of lamellae with enlarged sub-epithelial spaces, exfoliated epithelium of lamellae, telangiectasia, hypertrophy and hyperplasia of the epithelial cell resulted in partial fusion of the secondary lamellae and a reduction of the water space, club shaping of gill lamellae, blood congestion. Some more severe alternations found in the gill of fish exposed to higher levels of HgCl2 (35 and 50 μg/L included lamellar aneurysm and hemorrhages with rupture of the lamellar epithelium. According to the results of the present study, mercuric chloride could cause major histomorphological changes in the gill of A. latus, decreasing its gas exchange capability. Two mercury concentrations (10 and 20 μg/L used in the present study were in agreement with the concentration of mercury in the water of different parts of Mahshahr creeks (the north of Persian Gulf (3.66 to 15 μg/L. Therefore, based on the results the presence of pathological alteration in A. latus inhibited in the natural environment (Mahshahr creeks seems to be logical.

Human exposure assessment of silver and copper migrating from an antimicrobial nanocoated packaging material into an acidic food simulant.

Science.gov (United States)

Hannon, Joseph Christopher; Kerry, Joseph P; Cruz-Romero, Malco; Azlin-Hasim, Shafrina; Morris, Michael; Cummins, Enda

2016-09-01

To examine the human exposure to a novel silver and copper nanoparticle (AgNP and CuNP)/polystyrene-polyethylene oxide block copolymer (PS-b-PEO) food packaging coating, the migration of Ag and Cu into 3% acetic acid (3% HAc) food simulant was assessed at 60 °C for 10 days. Significantly lower migration was observed for Ag (0.46 mg/kg food) compared to Cu (0.82 mg/kg food) measured by inductively coupled plasma - atomic emission spectrometry (ICP-AES). In addition, no distinct population of AgNPs or CuNPs were observed in 3% HAc by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The predicted human exposure to Ag and Cu was used to calculate a margin of exposure (MOE) for ionic species of Ag and Cu, which indicated the safe use of the food packaging in a hypothetical scenario (e.g. as fruit juice packaging). While migration exceeded regulatory limits, the calculated MOE suggests current migration limits may be conservative for specific nano-packaging applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Next-Generation Pathology.

Science.gov (United States)

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

The Kidney in Aging: Physiological Changes and Pathological Implications.

Science.gov (United States)

Sobamowo, H; Prabhakar, S S

2017-01-01

Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

Bile acids in regulation of intestinal physiology.

LENUS (Irish Health Repository)

Keating, Niamh

2009-10-01

In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

Biological functions of iduronic acid in chondroitin/dermatan sulfate

OpenAIRE

Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, ?ke; Maccarana, Marco; Malmstrom, Anders

2013-01-01

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse...

Bile acids: regulation of apoptosis by ursodeoxycholic acid.

Science.gov (United States)

Amaral, Joana D; Viana, Ricardo J S; Ramalho, Rita M; Steer, Clifford J; Rodrigues, Cecília M P

2009-09-01

Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.

Use of VAP3D software in the construction of pathological anthropomorphic phantoms for dosimetric evaluations

International Nuclear Information System (INIS)

Lima, Lindeval Fernandes de; Lima, Fernando R.A.

2011-01-01

This paper performs a new type of dosimetric evaluation, where it was used a phantom of pathological voxels (representative phantom of sick person). The software VAP3D (Visualization and Analysis of Phantoms 3D) were used for, from a healthy phantom (phantom representative of healthy person), to introduce three dimensional regions to simulate tumors. It was used the Monte Carlo ESGnrc code to simulate the X ray photon transport, his interaction with matter and evaluation of absorbed dose in organs and tissues from thorax region of the healthy phantom and his pathological version. This is a computer model of typical exposure for programming the treatments in radiodiagnostic

Use orotic acid in the treatment of pathological conditions associated with hyperuricemia

Directory of Open Access Journals (Sweden)

D.D. Ivanov

2014-10-01

Full Text Available Hyperuricemia - a condition characterized by elevated relative to normal ranges, levels of uric acid in the blood. Among the diseases caused by hyperuricemia, most noteworthy are gout, urate nephropathy, and urolithiasis. The topic of this article is devoted to the comparative characteristics of drugs used to correct hyperuricemia. The main part of the article is an analysis of pharmacodynamics, efficacy, safety and expediency of using orotic acid agents.

Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

Science.gov (United States)

Ly, Lundi; Chan, Donovan; Aarabi, Mahmoud; Landry, Mylène; Behan, Nathalie A; MacFarlane, Amanda J; Trasler, Jacquetta

2017-07-01

Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA

Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

Directory of Open Access Journals (Sweden)

Chidiebere Uchendu

2014-01-01

Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

[Responsible gambling: is it an alternative for prevention and treatment of pathological gambling?].

Science.gov (United States)

Echeburua, Enrique; de Corral, Paz

2008-01-01

This paper deals with the new development of controlled gambling embedded in a harm-reduction context as a viable solution both for primary prevention at school and for treatment of some kinds of problematic gamblers. Pathological gambling significantly improves with psychological therapies, such as stimulus control and in vivo exposure with response prevention or cognitive interventions. In some cases psychopharmacological therapy may complement the benefits of treatment for pathological gambling when patients have comorbid depression or high impulsivity. However, in this mental disorder the goal of treatment (total abstinence or controlled gambling) is currently a controversial issue. Controlled gambling may be a therapeutic option for young gamblers or patients without severe dependence. Furthermore, controlled gambling may be a relevant issue for health education in schools, with a view to teaching teenagers how to cope with actual and virtual exposure to gambling. Likewise, the gambling industry and governments are involved in harm minimization initiatives. Thus, it is necessary to coordinate a program of research that includes the industry, science, and public representatives, based on cooperative research that will permit the introduction of controlled gambling within a global strategic framework. We discuss the relevance of this review for clinical practice and for future research, as well as the unsolved problems in this field.

Managing ecosystems without prior knowledge: pathological outcomes of lake liming

Directory of Open Access Journals (Sweden)

David G. Angeler

2017-12-01

Full Text Available Management actions often need to be taken in the absence of ecological information to mitigate the impact of pressing environmental problems. Managers counteracted the detrimental effects of cultural acidification on aquatic ecosystems during the industrial era using liming to salvage biodiversity and ecosystem services. However, historical contingencies, i.e., whether lakes were naturally acidic or degraded because of acidification, were largely unknown and therefore not accounted for in management. It is uncertain whether liming outcomes had a potentially detrimental effect on naturally acidic lakes. Evidence from paleolimnological reconstructions allowed us to analyze community structure in limed acidified and naturally acidic lakes, and acidified and circumneutral references. We analyzed community structure of phytoplankton, zooplankton, macroinvertebrates (littoral, sublittoral, profundal, and fish between 2000 and 2004. Naturally acidic limed lakes formed communities that were not representative of the other lake types. The occurrence of fish species relevant for ecosystem service provisioning (fisheries potential in naturally acidic limed lakes were confounded by biogeographical factors. In addition, sustained changes in water quality were conducive to harmful algal blooms. This highlights a pathological outcome of liming lakes when their naturally acidic conditions are not accounted for. Because liming is an important social-ecological system, sustained ecological change of lakes might incur undesired costs for societies in the long term.

Comparison of personal air benzene and urine t,t-muconic acid as a benzene exposure surrogate during turnaround maintenance in petrochemical plants.

Science.gov (United States)

Koh, Dong-Hee; Lee, Mi-Young; Chung, Eun-Kyo; Jang, Jae-Kil; Park, Dong-Uk

2018-04-12

Previous studies have shown that biomarkers of chemicals with long half-lives may be better surrogates of exposure for epidemiological analyses, leading to less attenuation of the exposure-disease association, than personal air samples. However, chemicals with short half-lives have shown inconsistent results. In the present study, we compared pairs of personal air benzene and its short-half-life urinary metabolite trans,trans-muconic acid (t,t-MA), and predicted attenuation bias of theoretical exposure-disease association. Total 669 pairs of personal air benzene and urine t,t-MA samples were taken from 474 male workers during turnaround maintenance operations held in seven petrochemical plants. Maintenance jobs were classified into 13 groups. Variance components were calculated for personal air benzene and urine t, t-MA separately to estimate the attenuation of the theoretical exposure-disease association. Personal air benzene and urine t, t-MA showed similar attenuation of the theoretical exposure-disease association. Analyses for repeated measurements showed similar results, while in analyses for values above the limits of detection (LODs), urine t, t-MA showed less attenuation of the theoretical exposure-disease association than personal air benzene. Our findings suggest that there may be no significant difference in attenuation bias when personal air benzene or urine t,t-MA is used as a surrogate for benzene exposure.

An investigation using atomic force microscopy nanoindentation of dental enamel demineralization as a function of undissociated acid concentration and differential buffer capacity

International Nuclear Information System (INIS)

Barbour, Michele E; Shellis, R Peter

2007-01-01

Acidic drinks and foodstuffs can demineralize dental hard tissues, leading to a pathological condition known as dental erosion, which is of increasing clinical concern. The first step in enamel dissolution is a demineralization of the outer few micrometres of tissue, which results in a softening of the structure. The primary determinant of dissolution rate is pH, but the concentration of undissociated acid, which is related to buffer capacity, also appears to be important. In this study, atomic force microscopy nanoindentation was used to measure the first initial demineralization (softening) induced within 1 min by exposure to solutions with a range of undissociated acid concentration and natural pH of 3.3 or with an undissociated acid concentration of 10 mmol l -1 and pH adjusted to 3.3. The results indicate that differential buffering capacity is a better determinant of softening than undissociated acid concentration. Under the conditions of these experiments, a buffer capacity of >3 mmol l -1 pH -1 does not have any further effect on dissolution rate. These results imply that differential buffering capacity should be used for preference over undissociated acid concentration or titratable acidity, which are more commonly employed in the literature

An investigation using atomic force microscopy nanoindentation of dental enamel demineralization as a function of undissociated acid concentration and differential buffer capacity

Science.gov (United States)

Barbour, Michele E.; Shellis, R. Peter

2007-02-01

Acidic drinks and foodstuffs can demineralize dental hard tissues, leading to a pathological condition known as dental erosion, which is of increasing clinical concern. The first step in enamel dissolution is a demineralization of the outer few micrometres of tissue, which results in a softening of the structure. The primary determinant of dissolution rate is pH, but the concentration of undissociated acid, which is related to buffer capacity, also appears to be important. In this study, atomic force microscopy nanoindentation was used to measure the first initial demineralization (softening) induced within 1 min by exposure to solutions with a range of undissociated acid concentration and natural pH of 3.3 or with an undissociated acid concentration of 10 mmol l-1 and pH adjusted to 3.3. The results indicate that differential buffering capacity is a better determinant of softening than undissociated acid concentration. Under the conditions of these experiments, a buffer capacity of >3 mmol l-1 pH-1 does not have any further effect on dissolution rate. These results imply that differential buffering capacity should be used for preference over undissociated acid concentration or titratable acidity, which are more commonly employed in the literature.

Olfactory dysfunction, olfactory bulb pathology and urban air pollution

Science.gov (United States)

Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

2010-01-01

Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

Combined effects of dietary polyunsaturated fatty acids and parasite exposure on eicosanoid-related gene expression in an invertebrate model.

Science.gov (United States)

Schlotz, Nina; Roulin, Anne; Ebert, Dieter; Martin-Creuzburg, Dominik

2016-11-01

Eicosanoids derive from essential polyunsaturated fatty acids (PUFA) and play crucial roles in immunity, development, and reproduction. However, potential links between dietary PUFA supply and eicosanoid biosynthesis are poorly understood, especially in invertebrates. Using Daphnia magna and its bacterial parasite Pasteuria ramosa as model system, we studied the expression of genes coding for key enzymes in eicosanoid biosynthesis and of genes related to oogenesis in response to dietary arachidonic acid and eicosapentaenoic acid in parasite-exposed and non-exposed animals. Gene expression related to cyclooxygenase activity was especially responsive to the dietary PUFA supply and parasite challenge, indicating a role for prostanoid eicosanoids in immunity and reproduction. Vitellogenin gene expression was induced upon parasite exposure in all food treatments, suggesting infection-related interference with the host's reproductive system. Our findings highlight the potential of dietary PUFA to modulate the expression of key enzymes involved in eicosanoid biosynthesis and reproduction and thus underpin the idea that the dietary PUFA supply can influence invertebrate immune functions and host-parasite interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption

DEFF Research Database (Denmark)

Mahaffey, K. R.; Sunderland, E. M.; Chan, H. M.

2011-01-01

Fish and shellfish are widely available foods that provide important nutrients, particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations globally. These nutrients, especially docosahexaenoic acid, confer benefits to brain and visual system development in infants and reduce...... risks of certain forms of heart disease in adults. However, fish and shellfish can also be a major source of methylmercury (MeHg), a known neurotoxicant that is particularly harmful to fetal brain development. This review documents the latest knowledge on the risks and benefits of seafood consumption...... for perinatal development of infants. It is possible to choose fish species that are both high in n-3 PUFAs and low in MeHg. A framework for providing dietary advice for women of childbearing age on how to maximize the dietary intake of n-3 PUFAs while minimizing MeHg exposures is suggested. (C) 2011...

Arsanilic acid blindness in pigs

Energy Technology Data Exchange (ETDEWEB)

Menges, R.W.; Kintner, L.D.; Selby, L.A.; Stewart, R.W.; Marlenfeld, C.J.

1970-06-01

Blindness in pigs that were given an overdosage of arsanilic acid is reported. A 0.0375% level of arsanilic acid was fed to 640 pigs for 90 days beginning when the animals were 3 months old. Approximately one month after the start of feeding, partial or complete blindness was observed in 50 of the pigs. Clinical signs, pathologic findings and the chemical analysis of hair are discussed. The level of arsanilic acid used was that recommended for the control of swine dysentery, to be fed for only five or six days. The overdosage resulted from a misunderstanding between the farmer and the feed mill.

Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency.

Science.gov (United States)

Wezynfeld, Nina Ewa; Bonna, Arkadiusz; Bal, Wojciech; Frączyk, Tomasz

2015-04-01

Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.

Perceptions of pathology informatics by non-informaticist pathologists and trainees

Directory of Open Access Journals (Sweden)

Addie Walker

2016-01-01

Full Text Available Background: Although pathology informatics (PI is essential to modern pathology practice, the field is often poorly understood. Pathologists who have received little to no exposure to informatics, either in training or in practice, may not recognize the roles that informatics serves in pathology. The purpose of this study was to characterize perceptions of PI by noninformatics-oriented pathologists and to do so at two large centers with differing informatics environments. Methods: Pathology trainees and staff at Cleveland Clinic (CC and Massachusetts General Hospital (MGH were surveyed. At MGH, pathology department leadership has promoted a pervasive informatics presence through practice, training, and research. At CC, PI efforts focus on production systems that serve a multi-site integrated health system and a reference laboratory, and on the development of applications oriented to department operations. The survey assessed perceived definition of PI, interest in PI, and perceived utility of PI. Results: The survey was completed by 107 noninformatics-oriented pathologists and trainees. A majority viewed informatics positively. Except among MGH trainees, confusion of PI with information technology (IT and help desk services was prominent, even in those who indicated they understood informatics. Attendings and trainees indicated desire to learn more about PI. While most acknowledged that having some level of PI knowledge would be professionally useful and advantageous, only a minority plan to utilize it. Conclusions: Informatics is viewed positively by the majority of noninformatics pathologists at two large centers with differing informatics orientations. Differences in departmental informatics culture can be attributed to the varying perceptions of PI by different individuals. Incorrect perceptions exist, such as conflating PI with IT and help desk services, even among those who claim to understand PI. Further efforts by the PI community could

Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism

DEFF Research Database (Denmark)

Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

2014-01-01

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20mg/kg or 100mg/kg) continuously during the last 9-12 day...

Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli

Science.gov (United States)

Bhat, Supriya V.; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E. S.

2018-01-01

Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro, and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force – laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage. PMID:29472899

In ovo exposure to omega-3 fatty acids does not enhance omega-3 long-chain polyunsaturated fatty acid metabolism in broiler chickens.

Science.gov (United States)

Kanakri, K; Carragher, J; Muhlhausler, B; Hughes, R; Gibson, R

2017-10-01

The content of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n-3 LCPUFA. However, most of the accumulated n-3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n-3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n-3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n-3 LCPUFA) or tallow- (low n-3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days' post-hatch. The n-3 PUFA content of egg yolk and day-old chick meat closely matched the n-3 PUFA composition of the maternal diet. In contrast, the n-3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n-3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.

The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology.

Science.gov (United States)

Pollanen, M S

2016-09-01

The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions. © The Author(s) 2016.

Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period.

Science.gov (United States)

Rohof, W O; Bennink, R J; de Ruigh, A A; Hirsch, D P; Zwinderman, A H; Boeckxstaens, G E

2012-12-01

The risk for acidic reflux is mainly determined by the position of the gastric acid pocket. It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position. To study the effect of azithromycin (Azi) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease (GORD). Nineteen patients with GORD were included, of whom seven had a large hiatal hernia (≥3 cm) (L-HH) and 12 had a small or no hiatal hernia (S-HH). Patients were randomised to Azi 250 mg/day or placebo during 3 days in a crossover manner. On each study day, reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a standardised meal. The acid pocket was visualised using scintigraphy, and its position was determined relative to the diaphragm. Azi reduced the number of acid reflux events (placebo 8.0±2.2 vs Azi 5.6±1.8, pacid exposure (placebo 10.5±3.8% vs Azi 5.9±2.5%, preflux episodes. Acid reflux occurred mainly when the acid pocket was located above, or at the level of, the diaphragm, rather than below the diaphragm. Treatment with Azi reduced hiatal hernia size and resulted in a more distal position of the acid pocket compared with placebo (below the diaphragm 39% vs 29%, p=0.03). Azi reduced the rate of acid reflux episodes in patients with S-HH (38% to 17%) to a greater extent than in patients with L-HH (69% to 62%, p=0.04). Azi reduces acid reflux episodes and oesophageal acid exposure. This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket, further indicating the importance of the acid pocket in the pathogenesis of GORD. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1970 NTR1970.

New Radiofrequency Exposure System with Real Telecommunication Signals

Directory of Open Access Journals (Sweden)

Jakub Misek

2018-01-01

Full Text Available In recent years, there has been an increase in the number of studies on biological effects of Electromagnetic (EM fields emitted from Base Transceiver Stations (BTSs. The biological effects of generated and real telecommunication signals produced by different types of exposure systems are discussed. However, the proper exposure methods for such experiments are very limited. We successfully developed a simple and cost-effective exposure unit with real GSM/DCS/UMTS signal from BTS containing proper modulations or intermittence (continuous, interrupted. Signal processing and conditioning unit is based on a Radiofrequency (RF repeater. The downlink signal is filtered by integrated high selectivity passband filters and amplified to a required level. The main part of exposure unit is a Faraday cage with the specimen (exposure area measuring 150 x 250 mm with E-field percent deviation less than 18%. This exposure system can be helpful in experiments with living organisms in in vivo studies and in vitro studies with normal or pathological cells and other micro scale structures being exposed to RF EM fields from BTS.

Evaluation of the toxicity data for peracetic acid in deriving occupational exposure limits: a minireview.

Science.gov (United States)

Pechacek, Nathan; Osorio, Magdalena; Caudill, Jeff; Peterson, Bridget

2015-02-17

Peracetic acid (PAA) is a peroxide-based chemistry that is highly reactive and can produce strong local effects upon direct contact with the eyes, skin and respiratory tract. Given its increasing prominence in industry, attention has focused on health hazards and associated risks for PAA in the workplace. Occupational exposure limits (OEL) are one means to mitigate risks associated with chemical hazards in the workplace. A mini-review of the toxicity data for PAA was conducted in order to determine if the data were sufficient to derive health-based OELs. The available data for PAA frequently come from unpublished studies that lack sufficient study details, suffer from gaps in available information and often follow unconventional testing methodology. Despite these limitations, animal and human data suggest sensory irritation as the most sensitive endpoint associated with inhalation of PAA. Rodent RD50 data (the concentration estimated to cause a 50% depression in respiratory rate) were selected as the critical studies in deriving OELs. Based on these data, a range of 0.36-0.51mg/m(3) (0.1-0.2ppm) was calculated for a time-weighted average (TWA), and 1.2-1.7mg/m(3) (0.4-0.5ppm) as a range for a short-term exposure limit (STEL). These ranges compare favorably to other published OELs for PAA. Considering the applicable health hazards for this chemistry, a joint TWA/STEL OEL approach for PAA is deemed the most appropriate in assessing workplace exposures to PAA, and the selection of specific values within these proposed ranges represents a risk management decision. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nitric Acid Poisoning: Case Report

International Nuclear Information System (INIS)

Quintero Giraldo, Maria Paulina; Quiceno Calderon, William de Jesus; Melo Arango Catalina

2011-01-01

Nitric acid (HNO 3 ) is a corrosive fluid that, when in contact with reducing agents, generates nitrogen oxides that are responsible for inhalation poisoning. We present two cases of poisoning from nitric acid gas inhalation resulting from occupational exposure. Imaging findings were similar in both cases, consistent with adult respiratory distress syndrome (ARDS): bilaterally diffuse alveolar opacities on the chest X-ray and a cobblestone pattern on computed tomography (CT).one of the patients died while the other evolved satisfactorily after treatment with n-acetyl cysteine and mechanical ventilation. The diagnosis of nitric acid poisoning was made on the basis of the history of exposure and the way in which the radiological findings evolved.

Pathological video-gaming among Singaporean youth.

Science.gov (United States)

Choo, Hyekyung; Gentile, Douglas A; Sim, Timothy; Li, Dongdong; Khoo, Angeline; Liau, Albert K

2010-11-01

Increase in internet use and video-gaming contributes to public concern on pathological or obsessive play of video games among children and adolescents worldwide. Nevertheless, little is known about the prevalence of pathological symptoms in video-gaming among Singaporean youth and the psychometric properties of instruments measuring pathological symptoms in video-gaming. A total of 2998 children and adolescents from 6 primary and 6 secondary schools in Singapore responded to a comprehensive survey questionnaire on sociodemographic characteristics, video-gaming habits, school performance, somatic symptoms, various psychological traits, social functioning and pathological symptoms of video-gaming. After weighting, the survey data were analysed to determine the prevalence of pathological video-gaming among Singaporean youth and gender differences in the prevalence. The construct validity of instrument used to measure pathological symptoms of video-gaming was tested. Of all the study participants, 8.7% were classified as pathological players with more boys reporting more pathological symptoms than girls. All variables, including impulse control problem, social competence, hostility, academic performance, and damages to social functioning, tested for construct validity, were significantly associated with pathological status, providing good evidence for the construct validity of the instrument used. The prevalence rate of pathological video-gaming among Singaporean youth is comparable with that from other countries studied thus far, and gender differences are also consistent with the findings of prior research. The positive evidence of construct validity supports the potential use of the instrument for future research and clinical screening on Singapore children and adolescents' pathological video-gaming.

Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results.

Science.gov (United States)

Bernstein, David M; Rogers, Rick; Sepulveda, Rosalina; Kunzendorf, Peter; Bellmann, Bernd; Ernst, Heinrich; Phillips, James I

2014-04-01

Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (>20 μm) cleared quickly with T(½) estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T(½)>1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Lipid peroxidation and ascorbic acid levels in Nigeria children with ...

African Journals Online (AJOL)

This study was undertaken to establish data on the roles of lipid peroxidation and ascorbic acid in the pathology of malaria in Nigeria children. We measured the levels of malondialdehyde (MDA), a marker of lipid peroxidation and ascorbic acid in the plasma of 406 parasitaemic and 212 non-parasitaemic Nigerian children.

Interactive effects of ambient acidity and salinity on thyroid function during acidic and post-acidic acclimation of air-breathing fish (Anabas testudineus Bloch).

Science.gov (United States)

Peter, M C Subhash; Rejitha, V

2011-11-01

The interactive effects of ambient acidity and salinity on thyroid function are less understood in fish particularly in air-breathing fish. We, therefore, examined the thyroid function particularly the osmotic and metabolic competences of freshwater (FW) and salinity-adapted (SA; 20 ppt) air-breathing fish (Anabas testudineus) during acidic and post-acidic acclimation, i.e., during the exposure of fish to either acidified water (pH 4.2 and 5.2) for 48 h or clean water for 96 h after pre-exposure. A substantial rise in plasma T(4) occurred after acidic exposure of both FW and SA fish. Similarly, increased plasma T(3) and T(4) were found in FW fish kept for post-acidic acclimation and these suggest an involvement of THs in short-term acidic and post-acidic acclimation. Water acidification produced significant hyperglycaemia and hyperuremia in FW fish but not in SA fish. The SA fish when kept for post-acclimation, however, produced a significant hypouremia. In both FW and SA fish, gill Na(+), K(+)-ATPase activity decreased but kidney Na(+), K(+)-ATPase activity increased upon acidic acclimation. During post-acidic acclimation, gill Na(+), K(+)-ATPase activity of the FW fish showed a rise while decreasing its activity in the SA fish. Similarly, post-acidic acclimation reduced the Na(+), K(+)-ATPase activity of intestine but elevated its activity in the liver of SA fish. A higher tolerance of the SA fish to water acidification was evident in these fish as they showed tight plasma and tissue mineral status due to the ability of this fish to counteract the ion loss. In contrast, FW fish showed more sensitivity to water acidification as they loose more ions in that medium. The positive correlations of plasma THs with many tested metabolic and hydromineral indices of both FW and SA fish and also with water pH further confirm the involvement of THs in acidic and post-acidic acclimation in these fish. We conclude that thyroid function of this fish is more sensitive to

[Intra-articular injections of hyaluronic acid for anterior disc displacement of temporomandibular joint].

Science.gov (United States)

Long, X

2017-03-09

Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is regarded as one of the major findings in temporomandibular disorders (TMD). It is related to joint noise, pain, mandibular dysfunction, degenerative change and osteoarthritis. In the mean time, the pathological changes were found in synovial membrane and synovial fluid. Hyaluronic acid is a principal component of the synovial fluid which plays an important role in nutrition, lubrication, anti-inflammation and cartilage repair. The synthesis, molecule weight, and concentration of hyaluronic acid are decreased during TMD and cause TMJ degenerative changes. The clinical conditions, pathological changes, the mechanism of action for hyaluronic acid and the treatment of anterior disc displacement of TMJ are discussed in this article.

An efficient analytical method for determination of S-phenylmercapturic acid in urine by HPLC fluorimetric detector to assessing benzene exposure.

Science.gov (United States)

Mendes, Michele P Rocha; Silveira, Josianne Nicácio; Andre, Leiliane Coelho

2017-09-15

Benzene is an important occupational and environmental contaminant, naturally present in petroleum and as by-product in the steel industry. Toxicological studies showed pronounced myelotoxic action, causing leukemic and others blood cells disorders. Assessing of benzene exposure is performed by biomarkers as trans, trans-muconic acid (AttM) and S-phenylmercapturic acid (S-PMA) in urine. Due to specificity of S-PMA, this biomarker has been proposed to asses lower levels of benzene in air. The aim of this study was to validate an analytical method for the quantification of S-PMA by High-Performance Liquid Chromatography with fluorometric detector. The development of an analytical method of S-PMA in urine was carried out by solid phase extraction (SPE) using C-18 phase. The eluated were submitted to water bath at 75°C and nitrogen to analyte concentration, followed by alkaline hydrolysis and derivatization with monobromobimane. The chromatography conditions were reverse phase C-18 column (240mm, 4mm and 5μm) at 35°C; acetonitrile and 0.5% acetic acid (50:50) as mobile phase with a flow of 0.8mL/min. The limits of detection and quantification were 0.22μg/L and 0.68μg/L, respectively. The linearity was verified by simple linear regression, and the method exhibited good linearity in the range of 10-100μg/L. There was no matrix effect for S-PMA using concentrations of 40, 60, 80 and 100μg/L. The intra- and interassay precision showed coefficient of variation of less than 10% and the recovery ranged from 83.4 to 102.8% with an average of 94.4%. The stability of S-PMA in urine stored at -20°C was of seven weeks. The conclusion is that this method presents satisfactory results per their figures of merit. This proposed method for determining urinary S-PMA showed adequate sensitivity for assessment of occupational and environmental exposure to benzene using S-PMA as biomarker of exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Lead and eagles: demographic and pathological characteristics of poisoning, and exposure levels associated with other causes of mortality

Science.gov (United States)

Franson, J. Christian; Russell, Robin E.

2014-01-01

We conducted a retrospective analysis to evaluate demographic and pathologic characteristics in 484 bald eagles (Haliaeetus leucocephalus) and 68 golden eagles (Aquila chrysaetos) diagnosed with lead poisoning at the U.S. Geological Survey National Wildlife Health Center. As part of our analysis, we compared characteristics of lead poisoned eagles with those that died of other causes. Odds of lead poisoning were greater for bald eagles versus golden eagles, females versus males, adults versus juveniles, and eagles from the Mississippi and Central flyways versus the Atlantic and Pacific flyways. In addition to spatial, species, and demographic associations, we detected a distinct temporal trend in the collection date of lead poisoned bald eagle carcasses. These carcasses were found at greater frequency in late autumn and winter than spring and summer. Lesions in lead poisoned birds included emaciation, evidence of bile stasis, myocardial degeneration and necrosis, and renal tubular nephrosis and necrosis. Ingested lead ammunition or fragments were found in 14.2 % of bald eagles and 11.8 % of golden eagles. The overall mean liver lead concentration (wet weight basis) for eagles diagnosed with lead poisoning was 28.9 ± 0.69 SE mg/kg in bald eagles and 19.4 ± 1.84 SE mg/kg in golden eagles. In eagles diagnosed with collision trauma, electrocution, poisoning (other than lead), emaciation, infectious disease, trapping death, other, and undetermined causes, average liver lead concentrations were low (<1 mg/kg) and did not differ among causes of mortality. Thus, based on our data, we found no evidence that lead exposure of eagles predisposed them to other causes of mortality.

Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

Science.gov (United States)

Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

2015-03-01

Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

Directory of Open Access Journals (Sweden)

Susanna L Lundström

Full Text Available Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.Sixty-four oxylipins representing the cyclooxygenase (COX, lipoxygenase (LOX and cytochrome P450 (CYP metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS of bronchoalveolar lavage (BAL-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ. Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2 (PGE(2. Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

Science.gov (United States)

Lundström, Susanna L; Levänen, Bettina; Nording, Malin; Klepczynska-Nyström, Anna; Sköld, Magnus; Haeggström, Jesper Z; Grunewald, Johan; Svartengren, Magnus; Hammock, Bruce D; Larsson, Britt-Marie; Eklund, Anders; Wheelock, Åsa M; Wheelock, Craig E

2011-01-01

Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

Stroop performance in pathological gamblers.

Science.gov (United States)

Kertzman, Semion; Lowengrub, Katherine; Aizer, Anat; Nahum, Zeev Ben; Kotler, Moshe; Dannon, Pinhas N

2006-05-30

Pathological gambling is a relatively prevalent psychiatric disorder that typically leads to severe family, social, legal, and occupational problems and is associated with a high rate of suicide attempts. Understanding the neurobiological basis of pathological gambling is a current focus of research, and emerging data have demonstrated that pathological gamblers may have impaired decision-making because of an inability to inhibit irrelevant information. In this study, we examined pathological gamblers by using the Stroop Color-Word Test, a neurocognitive task used to assess interference control. The "reverse" variant of the Stroop Color-Word Test was administered to a cohort of medication-free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In the reverse variant of the Stroop task, subjects are asked to read the meaning of the word rather than name the ink color. The reverse Stroop task was chosen because it highly discriminates ability to inhibit interference in a population of psychiatric patients. In our study, performance on the reverse Stroop task in the pathological gamblers was significantly slower and less accurate than in the healthy subjects. A new finding in our study was that for pathological gamblers, the average reaction time in the neutral condition (where the color names are displayed in black letters) was slower than the average reaction time in the incongruent condition (where the meaning of the color name and the color of the printed letters are different). This controlled study extends previous findings by showing that performance on the Stroop task is impaired in a sample of medication-free pathological gamblers.

Synthesis of labelled compound of ferulic acid and caffeic acid with tritium

International Nuclear Information System (INIS)

Yi Mingguang; Wang Caiyun

1986-01-01

Effective components of Chinese traditional herbs consist of many compounds, but some of the compounds usually contain unsaturated carbon-carbon double bonds. The unsaturated organic compounds 3 H-Ferulic acid and 3 H-Caffeic acid are prepared with their tritiated intermediates made by electric-dischange exposure method, which ensures the compounds contaning double bonds not hydrogenated. The 3 H-Ferulic acid is composed of 3 H-vanillin and Malonic acid. The 3 H-Caffeic acid is composed of 3 H-protocatechuyl aldehyde and Malonic acid and the specific activity of the products is 0.2 mCi/mg. The radiochemicaly purity is greater than 90%

Intraocular osseous metaplasia. A clinico-pathological study.

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Vemuganti, Geeta K; Honavar, Santosh G; Jalali, Subhadra

2002-09-01

To evaluate the clinico-pathologic features of intraocular osseous metaplasia. Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membrane, fibrovascular proliferation and inflammation. Immunohistochemistry using monoclonal antibody against glial fibrillary acidic protein was performed to assess the glial component within the membranes and the proliferative vitreoretinal mass. Clinical records were reviewed and correlated with histopathologic findings. Osseous metaplasiaS was noted in 8 of 151 (5.2%) eyes examined. Clinical diagnosis in these was phthisis bulbi, staphyloma, absolute glaucoma and microphthalmos. Enucleation was performed for relief of symptoms (in painful blind eyes) or for cosmesis, and in an eye inciting sympathetic ophthalmia. Retinal detachment, gliosis and retinal pigment epithelial hyperplasia were noted in all the cases. Drusen with calcification or ossification (5 of 8), fibrovascular proliferation in the vitreous (5 of 8) and active inflammation (4 of 8) were the other associated histologic features. Location of ossification was subretinal in 3 cases, preretinal (ora serrata) in 1 case and in both locations in 4 cases. The eyes with subretinal osseous metaplasia had associated calcified drusen, while preretinal ossification was seen within the fibrovascular membranes. Chronic retinal detachment, hyperplasia and transdifferentiation of retinal pigment epithelium appear to be a few of the prerequisites for intraocular osseous metaplasia. Ossification can occur at isolated subretinal and preretinal locations or can involve both. Though a larger study is required to postulate the chronology of events, in

Intraocular osseous metaplasia. A clinico-pathological study

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Vemuganti Geeta

2002-01-01

Full Text Available Purpose: To evaluate the clinico-pathologic features of intraocular osseous metaplasia. Methods: Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membrane, fibrovascular proliferation and inflammation. Immunohistochemistry using monoclonal antibody against glial fibrillary acidic protein was performed to assess the glial component within the membranes and the proliferative vitreoretinal mass. Clinical records were reviewed and correlated with histopathologic findings. Results: Osseous metaplasiaS was noted in 8 of 151 (5.2% eyes examined. Clinical diagnosis in these was phthisis bulbi, staphyloma, absolute glaucoma and microphthalmos. Enucleation was performed for relief of symptoms (in painful blind eyes or for cosmesis, and in an eye inciting sympathetic ophthalmia. Retinal detachment, gliosis and retinal pigment epithelial hyperplasia were noted in all the cases. Drusen with calcification or ossification (5 of 8, fibrovascular proliferation in the vitreous (5 of 8 and active inflammation (4 of 8 were the other associated histologic features. Location of ossification was subretinal in 3 cases, preretinal (ora serrata in 1 case and in both locations in 4 cases. The eyes with subretinal osseous metaplasia had associated calcified drusen, while preretinal ossification was seen within the fibrovascular membranes. Conclusion: Chronic retinal detachment, hyperplasia and transdifferentiation of retinal pigment epithelium appear to be a few of the prerequisites for intraocular osseous metaplasia. Ossification can occur at isolated subretinal and preretinal locations or can involve both. Though a larger study is

Experimental pulmonary fibrosis in rats with chronic gastric acid reflux esophagitis.

Science.gov (United States)

Shimazu, Rintaro; Aoki, Shigehisa; Kuratomi, Yuichiro

2015-10-01

To elucidate the association between gastric acid reflux and respiratory diseases by studying the histological changes of the lower airway in rats with chronic acid reflux esophagitis. An experimental rat model of chronic acid reflux esophagitis was surgically created. The lower airways of these rats were histologically observed for more than 50 weeks. Although there were no histological changes which induced gastric acid reflux at 10 weeks after surgery, thickening of the basal laminae and the proliferation of the collagenous fibers were observed in the alveolar epithelium at 20 weeks after surgery. At 50 weeks after surgery, the collagenous fibers obliterated the pulmonary alveoli and bronchial lumen. These findings observed in the GERD rats are similar to the pathological findings of human pulmonary fibrosis. In this study, we reported pathological changes in the lower airways of GERD rat models observed for more than 50 weeks. These results suggest that gastric acid reflux may be one of the pathogenic or exacerbating factors of pulmonary fibrosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cerebellar atrophy related to chronic exposure to toluene: case report

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Benito Pereira Damasceno

1994-03-01

Full Text Available A 31-year-old woman presented slowly progressing ataxia and neurasthenic symptoms after 14-year occupational exposure to low concentration toluene vapour. Examination disclosed only cerebellar signs. Cognitive functions were normal except moderate visuo-spatial and constructive deficit CT imaging showed severe pancerebellar atrophy without pathological signs in other brain structures. Two years after she was removed from workplace, CT imaging and ataxia showed no worsening, while visuo-constructive function improved. The authors warn against possible neurotoxic risk associated with this kind of exposure.

Amino acids as dietary excitotoxins: a contribution to understanding neurodegenerative disorders.

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Meldrum, B

1993-01-01

The possibility that some acidic amino acids occurring naturally or as additives in the diet can act as excitotoxins producing central nervous system pathology has been the subject of extensive debate in the last 20 years and is here reviewed. High doses of glutamate, aspartate or related excitatory amino acids given in isolation to neonatal rodents produce acute degeneration organs. Neuropathology resulting from consumption of glutamate or aspartate has not been described in man. Various unusual amino acids of plant origin can produce acute excitotoxic syndromes. In man domoate (consumed in mussels that have fed on (Nitschia pungens) can produce an acute syndrome associated with limbic system lesions and anterograde amnesia. Kainate and domoate produce similar syndromes in rodents; acromelate produces spinal pathology. The mechanisms and manifestations of chronic excitotoxicity are less clearly established. A combination of impaired energy metabolism or impaired buffering of calcium and free radicals and endogenous or exogenous excitotoxins may contribute to neuronal loss in human neurodegenerative disorders.

Elimination of mouse tumor cells from neonate spermatogonial cells utilizing cisplatin-entrapped folic acid-conjugated poly(lactic-co-glycolic acid) nanoparticles in vitro.

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Shabani, Ronak; Ashjari, Mohsen; Ashtari, Khadijeh; Izadyar, Fariborz; Behnam, Babak; Khoei, Samideh; Asghari-Jafarabadi, Mohamad; Koruji, Morteza

2018-01-01

Some male survivors of childhood cancer are suffering from azoospermia. In addition, spermatogonial stem cells (SSCs) are necessary for the improvement of spermatogenesis subsequent to exposure to cytotoxic agents such as cisplatin. The aim of this study was to evaluate the anticancer activity of cisplatin-loaded folic acid-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on mouse malignant cell line (EL4) and SSCs in vitro. SSCs were co-cultured with mouse malignant cell line (EL4) cells and divided into four culture groups: 1) control (cells were co-cultured in the culture medium), 2) co-cultured cells were treated with cisplatin (10 μg/mL), 3) co-cultured cells were treated with cisplatin-loaded folic acid-conjugated PLGA NPs, and 4) co-cultures were treated with folic acid-conjugated PLGA for 48 hours. The NPs were prepared, characterized, and targeted with folate. In vitro release characteristics, loading efficiency, and scanning electron microscopy and transmission electron microscopy images were studied. Cancer cells were assayed after treatment using flow cytometry and TUNEL assay. The co-cultures of SSCs and EL4 cells were injected into seminiferous tubules of the testes after treating with cis-diaminedichloroplatinum/PLGA NPs. The mean diameter of PLGA NPs ranged between 150 and 250 nm. The number of TUNEL-positive cells increased, and the expression of Bax and caspase-3 were upregulated in EL4 cells in Group 4 compared with Group 2. There was no pathological tumor in testes after transplantation with treated co-cultured cells. The PLGA NPs appeared to act as a promising carrier for cisplatin administration, which was consistent with a higher activation of apoptosis than free drug.

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

Energy Technology Data Exchange (ETDEWEB)

Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

2006-03-01

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

Integrated Pathology Informatics Enables High-Quality Personalized and Precision Medicine: Digital Pathology and Beyond.

Science.gov (United States)

Volynskaya, Zoya; Chow, Hung; Evans, Andrew; Wolff, Alan; Lagmay-Traya, Cecilia; Asa, Sylvia L

2018-03-01

- The critical role of pathology in diagnosis, prognosis, and prediction demands high-quality subspecialty diagnostics that integrates information from multiple laboratories. - To identify key requirements and to establish a systematic approach to providing high-quality pathology in a health care system that is responsible for services across a large geographic area. - This report focuses on the development of a multisite pathology informatics platform to support high-quality surgical pathology and hematopathology using a sophisticated laboratory information system and whole slide imaging for histology and immunohistochemistry, integrated with ancillary tools, including electron microscopy, flow cytometry, cytogenetics, and molecular diagnostics. - These tools enable patients in numerous geographic locations access to a model of subspecialty pathology that allows reporting of every specimen by the right pathologist at the right time. The use of whole slide imaging for multidisciplinary case conferences enables better communication among members of patient care teams. The system encourages data collection using a discrete data synoptic reporting module, has implemented documentation of quality assurance activities, and allows workload measurement, providing examples of additional benefits that can be gained by this electronic approach to pathology. - This approach builds the foundation for accurate big data collection and high-quality personalized and precision medicine.

Sleep disorders and the prevalence of asymptomatic nocturnal acid and non-acid reflux.

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Herdman, Christine; Marzio, Dina Halegoua-De; Shah, Paurush; Denuna-Rivera, Susie; Doghramji, Karl; Cohen, Sidney; Dimarino, Anthony J

2013-01-01

Nocturnal acid reflux is associated with symptomatic and asymptomatic sleep arousals, leading to fragmented sleep. The frequency and influence of acid reflux in patients with various forms of insomnia has not been reported. The aim of this study was to quantify nocturnal acid and nonacid reflux in patients with primary sleep disorders as previously diagnosed by polysomnography. THIRTY ONE SUBJECTS WERE STUDIED: (A) 9 subjects with a polysomnographically diagnosed sleep disorder (1 with restless legs syndrome, 4 with narcolepsy, 4 with periodic limb movement disorder); (B) 12 subjects with primary insomnia (PI) and unrevealing polysomnography; and (C) 10 controls without disturbed sleep. All subjects underwent a physical examination and 24 h transnasal pH and impedance monitoring to detect acid and non-acid reflux. The 21 subjects with fragmented sleep due to a primary sleep disorder had significantly more recumbent acid exposure (>1.2% of time) as compared with control subjects (33% versus 0%). When fragmented sleep subjects were divided into two groups, 17% of PI subjects and 55% of subjects with a diagnosed sleep disorder had significant recumbent acid exposure (P=0.009). Likewise, the median recumbent nonacid events were increased in the sleep disordered group (P=0.011). This study indicates that patients with primary sleep disorders have prominent nocturnal acid reflux without symptoms of daytime acid reflux. Acid reflux is most prominent in patients with polysomnographic findings of disturbed sleep as compared to patients with PI; while non acid reflux is increased minimally in these patients.

Maternal dietary n-6 polyunsaturated fatty acid deprivation does not exacerbate post-weaning reductions in arachidonic acid and its mediators in the mouse hippocampus.

Science.gov (United States)

Alashmali, Shoug M; Kitson, Alex P; Lin, Lin; Lacombe, R J Scott; Bazinet, Richard P

2017-09-13

The present study examines how lowering maternal dietary n-6 polyunsaturated fatty acids (PUFA) (starting from pregnancy) compared to offspring (starting from post-weaning) affect the levels of n-6 and n-3 fatty acids in phospholipids (PL) and lipid mediators in the hippocampus of mice. Pregnant mice were randomly assigned to consume either a deprived or an adequate n-6 PUFA diet during pregnancy and lactation (maternal exposure). On postnatal day (PND) 21, half of the male pups were weaned onto the same diet as their dams, and the other half were switched to the other diet for 9 weeks (offspring exposure). At PND 84, upon head-focused high-energy microwave irradiation, hippocampi were collected for PL fatty acid and lipid mediator analyses. Arachidonic acid (ARA) concentrations were significantly decreased in both total PL and PL fractions, while eicosapentaenoic acid (EPA) concentrations were increased only in PL fractions upon n-6 PUFA deprivation of offspring, regardless of maternal exposure. Several ARA-derived eicosanoids were reduced, while some of the EPA-derived eicosanoids were elevated by n-6 PUFA deprivation in offspring. There was no effect of diet on docosahexaenoic acid (DHA) or DHA-derived docosanoids concentrations under either maternal or offspring exposure. These results indicate that the maternal exposure to dietary n-6 PUFA may not be as important as the offspring exposure in regulating hippocampal ARA and some lipid mediators. Results from this study will be helpful in the design of experiments aimed at testing the significance of altering brain ARA levels over different stages of life.

Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student.

Science.gov (United States)

Magid, Margret S; Shah, Darshana T; Cambor, Carolyn L; Conran, Richard M; Lin, Amy Y; Peerschke, Ellinor I B; Pessin, Melissa S; Harris, Ilene B

2015-01-01

The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula.

Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

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Cecilia Berg

Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

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Calderón-Garcidueñas, Lilian; Reed, William; Maronpot, Robert R; Henríquez-Roldán, Carlos; Delgado-Chavez, Ricardo; Calderón-Garcidueñas, Ana; Dragustinovis, Irma; Franco-Lira, Maricela; Aragón-Flores, Mariana; Solt, Anna C; Altenburg, Michael; Torres-Jardón, Ricardo; Swenberg, James A

2004-01-01

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

Occupational exposures at a polyvinyl chloride production facility are associated with significant changes to the plasma metabolome

International Nuclear Information System (INIS)

Guardiola, John J.; Beier, Juliane I.; Falkner, K. Cameron; Wheeler, Benjamin; McClain, Craig James; Cave, Matt

2016-01-01

Background: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. Methods: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS 2 analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed. Results: 613 unique named metabolites were identified. Of these, 189 metabolites were increased in the VC exposure group while 94 metabolites were decreased. Random Forest analysis indicated that the metabolite signature could separate the groups with 94% accuracy. VC exposures were associated with increased long chain (including arachidonic acid) and essential (including linoleic acid) fatty acids. Occupational exposure increased lipid peroxidation products including monohydroxy fatty acids (including 13-HODE); fatty acid dicarboxylates; and oxidized arachidonic acid products (including 5,9, and 15-HETE). Carnitine and carnitine esters were decreased, suggesting peroxisomal/mitochondrial dysfunction and alternate modes of lipid oxidation. Differentially regulated metabolites were shown to interact with extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, AMP-activated protein kinase (AMPK), and the N-Methyl-D-aspartate (NMDA) receptor. The top canonical pathways affected by occupational exposure included tRNA charging, nucleotide degradation, amino acid synthesis/degradation and urea cycle. Methionine and homocysteine was increased with decreased cysteine, suggesting altered 1-carbon metabolism. Conclusions: Occupational exposure generated a distinct plasma metabolome with markedly altered lipid and amino acid metabolites. ERK1/2, Akt, AMPK, and NMDA were identified as protein targets for vinyl chloride toxicity. - Highlights: �

Occupational exposures at a polyvinyl chloride production facility are associated with significant changes to the plasma metabolome

Energy Technology Data Exchange (ETDEWEB)

Guardiola, John J. [University of Louisville Department of Medicine, Louisville, KY 40206 (United States); Beier, Juliane I. [Department of Pharmacology and Toxicology, Louisville, KY 40206 (United States); Falkner, K. Cameron; Wheeler, Benjamin [Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Louisville, KY 40206 (United States); McClain, Craig James [Department of Pharmacology and Toxicology, Louisville, KY 40206 (United States); Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Louisville, KY 40206 (United States); The Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206 (United States); The Kentucky One Health Jewish Hospital Liver Transplant Program, Louisville, KY 40202 (United States); Cave, Matt, E-mail: matt.cave@louisville.edu [Department of Pharmacology and Toxicology, Louisville, KY 40206 (United States); Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Louisville, KY 40206 (United States); The Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206 (United States); The Kentucky One Health Jewish Hospital Liver Transplant Program, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, Louisville, KY, 40202 (United States)

2016-12-15

Background: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. Methods: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS{sup 2} analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed. Results: 613 unique named metabolites were identified. Of these, 189 metabolites were increased in the VC exposure group while 94 metabolites were decreased. Random Forest analysis indicated that the metabolite signature could separate the groups with 94% accuracy. VC exposures were associated with increased long chain (including arachidonic acid) and essential (including linoleic acid) fatty acids. Occupational exposure increased lipid peroxidation products including monohydroxy fatty acids (including 13-HODE); fatty acid dicarboxylates; and oxidized arachidonic acid products (including 5,9, and 15-HETE). Carnitine and carnitine esters were decreased, suggesting peroxisomal/mitochondrial dysfunction and alternate modes of lipid oxidation. Differentially regulated metabolites were shown to interact with extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, AMP-activated protein kinase (AMPK), and the N-Methyl-D-aspartate (NMDA) receptor. The top canonical pathways affected by occupational exposure included tRNA charging, nucleotide degradation, amino acid synthesis/degradation and urea cycle. Methionine and homocysteine was increased with decreased cysteine, suggesting altered 1-carbon metabolism. Conclusions: Occupational exposure generated a distinct plasma metabolome with markedly altered lipid and amino acid metabolites. ERK1/2, Akt, AMPK, and NMDA were identified as protein targets for vinyl chloride toxicity

Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

OpenAIRE

Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

2010-01-01

Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

Science.gov (United States)

Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

2007-09-01

Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

Who Seeks Treatment When Medicine Opens the Door to Pathological Gambling Patients-Psychiatric Comorbidity and Heavy Predominance of Online Gambling.

Science.gov (United States)

Håkansson, Anders; Mårdhed, Emma; Zaar, Mats

2017-01-01

Few studies have assessed treatment-seeking behavior and patient characteristics in pathological gambling focusing on psychiatric comorbidity, particularly in a setting of heavy exposure to online gambling. This study aimed to address patient characteristics in a novel health care-based treatment modality for pathological gambling, including potential associations between gambling types, psychiatric comorbidity, and gender. All patients undergoing structured assessment between January 2016 and April 2017 were included ( N  = 106), and patient records were reviewed for cooccurring psychiatric disorders and types of problem games. Eighty percent were men, and 58% received a psychiatric disorder apart from pathological gambling. Problematic gambling on online casino and online sports betting represented 84% of patients. Non-substance-related psychiatric comorbidity was significantly associated with female gender. Online gambling is more clearly predominating in this setting than in studies from other countries. High rates of comorbidity call for structured psychiatric assessment in problem gambling, with a particular focus on female patients with pathological gambling.

Who Seeks Treatment When Medicine Opens the Door to Pathological Gambling Patients—Psychiatric Comorbidity and Heavy Predominance of Online Gambling

Directory of Open Access Journals (Sweden)

Anders Håkansson

2017-11-01

Full Text Available BackgroundFew studies have assessed treatment-seeking behavior and patient characteristics in pathological gambling focusing on psychiatric comorbidity, particularly in a setting of heavy exposure to online gambling. This study aimed to address patient characteristics in a novel health care-based treatment modality for pathological gambling, including potential associations between gambling types, psychiatric comorbidity, and gender.MethodsAll patients undergoing structured assessment between January 2016 and April 2017 were included (N = 106, and patient records were reviewed for cooccurring psychiatric disorders and types of problem games.ResultsEighty percent were men, and 58% received a psychiatric disorder apart from pathological gambling. Problematic gambling on online casino and online sports betting represented 84% of patients. Non-substance-related psychiatric comorbidity was significantly associated with female gender.ConclusionOnline gambling is more clearly predominating in this setting than in studies from other countries. High rates of comorbidity call for structured psychiatric assessment in problem gambling, with a particular focus on female patients with pathological gambling.

Effects of a cold environment and of ammonia on the toxicity of sulfuric acid mist to guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Pattle, R E; Burgess, F; Cullumbine, H

1956-01-01

Exposure of guinea pigs for 8 hr to H/sub 2/SO/sub 4/ mist (2.7 ..mu..m MMD) yielded an LC/sub 50/ of 6.8 ppM. Animals either became dyspneic within 3 hr and died within 8 hr or suffered little effect during exposure. Some animals were particularly resistant. LC/sub 50/ for mist of 0.8 ..mu..m MMD was 14.9 ppM at room temperature (20/sup 0/C) and 11.7 ppM at 0/sup 0/C. Decrease was significant at 2% level. That cold especially affects more resistant animals is suggested. No evidence for tolerance was observed. Ammonium carbonate (NH/sub 3/ to neutralize mist) negated mortal effect of mist sufficient to produce > 50% mortality. Fatal effect was laryngeal spasm and bronchoconstriction. Pathology included emphysematous lungs. No pathological findings were observed in animals surviving short LC/sub 50/, but prolonged exposure produced slowly-repairable pathological lesions including capillary engorgement (perhaps sequel to bronchospasm).

Social cost of pathological gambling.

Science.gov (United States)

Ladouceur, R; Boisvert, J M; Pépin, M; Loranger, M; Sylvain, C

1994-12-01

Pathological gambling creates enormous problems for the afflicted individuals, their families, employers, and society, and has numerous disastrous financial consequences. The present study evaluates the financial burdens of pathological gambling by questioning pathological gamblers in treatment in Gamblers Anonymous (n=60; 56 males, 4 females; mean age = 40 years old) about personal debts, loss of productivity at work, illegal activities, medical costs and the presence of other dependencies. Results show that important debts, loss of productivity at work and legal problems are associated with pathological gambling. Discussion is formulated in terms of the social cost of adopting a liberal attitude toward the legalization of various gambling activities.

Systems pathology: a critical review.

Science.gov (United States)

Costa, Jose

2012-02-01

The technological advances of the last twenty years together with the dramatic increase in computational power have injected new life into systems-level thinking in Medicine. This review emphasizes the close relationship of Systems Pathology to Systems Biology and delineates the differences between Systems Pathology and Clinical Systems Pathology. It also suggests an algorithm to support the application of systems-level thinking to clinical research, proposes applying systems-level thinking to the health care systems and forecasts an acceleration of preventive medicine as a result of the coupling of personal genomics with systems pathology. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).

Science.gov (United States)

Russell, Mark H; Waterland, Robert L; Wong, Fiona

2015-06-01

Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

Science.gov (United States)

Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

Science.gov (United States)

Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

PathBot: A Radiology-Pathology Correlation Dashboard.

Science.gov (United States)

Kelahan, Linda C; Kalaria, Amit D; Filice, Ross W

2017-12-01

Pathology is considered the "gold standard" of diagnostic medicine. The importance of radiology-pathology correlation is seen in interdepartmental patient conferences such as "tumor boards" and by the tradition of radiology resident immersion in a radiologic-pathology course at the American Institute of Radiologic Pathology. In practice, consistent pathology follow-up can be difficult due to time constraints and cumbersome electronic medical records. We present a radiology-pathology correlation dashboard that presents radiologists with pathology reports matched to their dictations, for both diagnostic imaging and image-guided procedures. In creating our dashboard, we utilized the RadLex ontology and National Center for Biomedical Ontology (NCBO) Annotator to identify anatomic concepts in pathology reports that could subsequently be mapped to relevant radiology reports, providing an automated method to match related radiology and pathology reports. Radiology-pathology matches are presented to the radiologist on a web-based dashboard. We found that our algorithm was highly specific in detecting matches. Our sensitivity was slightly lower than expected and could be attributed to missing anatomy concepts in the RadLex ontology, as well as limitations in our parent term hierarchical mapping and synonym recognition algorithms. By automating radiology-pathology correlation and presenting matches in a user-friendly dashboard format, we hope to encourage pathology follow-up in clinical radiology practice for purposes of self-education and to augment peer review. We also hope to provide a tool to facilitate the production of quality teaching files, lectures, and publications. Diagnostic images have a richer educational value when they are backed up by the gold standard of pathology.

Gene expression profiling in mouse lung following polymeric hexamethylene diisocyanate exposure

International Nuclear Information System (INIS)

Lee, C.-T.; Ylostalo, Joni; Friedman, Mitchell; Hoyle, Gary W.

2005-01-01

Isocyanates are a common cause of occupational lung disease. Hexamethylene diisocyanate (HDI), a component of polyurethane spray paints, can induce respiratory symptoms, inflammation, lung function impairment, and isocyanate asthma. The predominant form of HDI in polyurethane paints is a nonvolatile polyisocyanate known as HDI biuret trimer (HDI-BT). Exposure of mice to aerosolized HDI-BT results in pathological effects, including pulmonary edema, lung inflammation, cellular proliferation, and fibrotic lesions, which occur with distinct time courses following exposure. To identify genes that mediate lung pathology in the distinct temporal phases after exposure, gene expression profiles in HDI-BT-exposed C57BL/6J mouse lungs were analyzed. RNase protection assay (RPA) of genes involved in apoptosis, cell survival, and inflammation revealed increased expression of IκBα, Fas, Bcl-X L , TNFα, KC, MIP-2, IL-6, and GM-CSF following HDI-BT exposure. Microarray analysis of approximately 10 000 genes was performed on lung RNA collected from mice 6, 18, and 90 h after HDI-BT exposure and from unexposed mice. Classes of genes whose expression was increased 6 h after exposure included those involved in stress responses (particularly oxidative stress and thiol redox balance), growth arrest, apoptosis, signal transduction, and inflammation. Types of genes whose expression was increased at 18 h included proteinases, anti-proteinases, cytoskeletal molecules, and inflammatory mediators. Transcripts increased at 90 h included extracellular matrix components, transcription factors, inflammatory mediators, and cell cycle regulators. This characterization of the gene expression profile in lungs exposed to HDI-BT will provide a basis for investigating injury and repair pathways that are operative during isocyanate-induced lung disease

A method for normalizing pathology images to improve feature extraction for quantitative pathology

International Nuclear Information System (INIS)

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline

A method for normalizing pathology images to improve feature extraction for quantitative pathology

Energy Technology Data Exchange (ETDEWEB)

Tam, Allison [Stanford Institutes of Medical Research Program, Stanford University School of Medicine, Stanford, California 94305 (United States); Barker, Jocelyn [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States); Rubin, Daniel [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California 94305 (United States)

2016-01-15

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Electrophysiological and pathological study of focal cortical dysplasia

International Nuclear Information System (INIS)

Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

2008-01-01

Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

Slot Machine Response Frequency Predicts Pathological Gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

2013-01-01

. This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...... in individuals with exacerbated pathological gambling symptoms. These findings may have important implications for detecting behaviors underlying pathological gambling....

Assessing the survival of MRC5 and a549 cell lines upon exposure to pyruvic Acid, sodium citrate and sodium bicarbonate - biomed 2013.

Science.gov (United States)

Farah, Ibrahim O; Lewis, Veshell L; Ayensu, Wellington K; Cameron, Joseph A

2013-01-01

Lung cancer is among the most prevalent and deadly cancers in United States. In general, cancer cells are known to exhibit higher rates of glycolysis in comparison to normal cells. In attempting to exploit this unique cancer-dependent ATP generation phenomenon, it was our hypothesis that upon exposure to organic inhibitors of glycolysis, cancer cells would not survive normally and that their growth and viability would be vastly decreased; essential glycolytic ATP production will be exhausted to the point of collapsing energy utilization. Furthermore, we hypothesize that no negative effect would be seen with exposures to organic inhibitors for normal lung cells. The human lung fibroblast MRC-5 and the human A549 alveolar epithelial cell lines were used as in vitro models of normal lung and lung cancers respectively. Using standard methods, both cell lines were maintained and exposed to pyruvic acid, sodium citrate and sodium bicarbonate reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging for parallel morphological displays of any changes in the course of their vitality and metabolic activities. Our results indicate that exposure of both cell lines to these organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Pyruvic acid, sodium citrate and sodium bicarbonate showed statistically significant (pcancer biotherapeutics.

Exposure to perfluoroundecanoic acid (PFUnDA accelerates insulitis development in a mouse model of type 1 diabetes

Directory of Open Access Journals (Sweden)

Johanna Bodin

Full Text Available Perfluoralkylated substances (PFAS are classified as persistent, bioaccumulative and toxic substances and are widespread environmental contaminants. Humans are exposed through food, drinking water and air. We have previously reported that bisphenol A accelerates spontaneous diabetes development in non-obese diabetic (NOD mice and observed in the present study that perfluoroundecanoic acid, PFUnDA, increased insulitis development, a prerequisite for diabetes development in NOD mice. We exposed NOD mice to PFUnDA in drinking water (3, 30 and 300 μg/l at mating, during gestation and lactation and until 30 weeks of age. After 300 μg/l PFUnDA exposure, we report (i increased pancreatic insulitis, (ii increased number of apoptotic cells in pancreatic islets prior to insulitis and (iii decreased phagocytosis in peritoneal macrophages. There was also a trend of decreased number of tissue resident macrophages in pancreatic islets prior to insulitis after exposure to 300 μg/l, and altered cytokine secretion in activated splenocytes after exposure to 3 μg/l PFUnDA. Although insulitis is a prerequisite for autoimmune diabetes, the accelerated insulitis was not associated with accelerated diabetes development. Instead, the incidence of diabetes tended to be reduced in the animals exposed to 3 and 30 μg/l PFUnDA, suggesting a non-monotonic dose response. The effects of PFUnDA exposure on increased apoptosis in pancreas and reduced macrophage function as well as accelerated insulitis development in NOD mice, may also be relevant for human insulitis. Further observational autoimmune diabetes clinical cohort studies and animal experiments for PFUnDA as well as other PFASs are therefore encouraged. Keywords: Perfluoralkylated substances, PFUnDA, T1DM, Diabetes, NOD mice, Insulitis

Minimal health impacts but detectable tissue residues after exposure of northern leopard frogs (Lithobates pipiens) to commercial naphthenic acids

International Nuclear Information System (INIS)

Hersikorn, B.; Young, R.; Fedorak, P.; Smits, J.

2010-01-01

This presentation reported on a study that examined whether naphthenic acids (NAs) are a toxic component in oil sands process-affected materials (OSPM). The study investigated the toxicity of commercial (Refined Merichem) NAs to native amphibians (northern leopard frogs) exposed to saline conditions comparable to those of reclaimed wetlands on oil sand leases. Gas chromatography-mass spectroscopy analysis showed that the exposure of frogs to NAs solutions for 28 days resulted in proportional NA concentrations in extracts of frog muscle tissue. Biological assays were performed to determine if the increasing exposure to NAs caused a proportional compromise in the health of test animals. The innate immune function, thyroid hormones, and hepatic detoxification enzyme induction did not differ in response to increased tissue concentrations of NAs. The commercial NAs were absorbed and deposited in muscle tissue. It was concluded that NAs play only a small, if any, role in the toxicity of OSPM to frogs.

Pathology annual. Part 2

International Nuclear Information System (INIS)

Rosen, P.P.

1987-01-01

This book contains 11 selections. Some of the titles are: Applications of in situ DNA hybridization technology to diagnostic surgical pathology; Neoplasms associated with immune deficiencies; Chronic gastritis: The pathologists's role; Necrosis in lymph nodes; Pathologic changes of osteochondrodysplasia in infancy: A review; and Immunoglobulin light chain nephropathies

Effects of ammonia exposure on carcass traits and fatty acid composition of broiler meat

Directory of Open Access Journals (Sweden)

Huan Xing

2016-12-01

Full Text Available We aimed to study the effects of ammonia on carcass traits, organ indices and fatty acid composition of broilers. Four hundred 21-d-old male Arbor Acres broilers with initial weight 563.52 ± 2.82 g were randomly allotted to 1 of 4 groups treated with ammonia at <3 mg/kg (control, 25 ± 3, 50 ± 3, and 75 ± 3 mg/kg concentrations. Each group consisted of 4 replicates of 25 birds. Broilers from 21 to 42 d were reared on the net floor in the respiration-metabolism chambers where similar environmental conditions were maintained. At 32 and 42 d of age, carcass traits and organ indices were determined for 4 birds per pen. At 42 d of age, fatty acid composition in the breast and thigh muscle of broilers was measured. Results showed as follows: 1 At 32 d, the dressing percentage of broilers exposed to 25 and 75 mg/kg ammonia were lower than those in the control group (P < 0.05; eviscerated yield percentage of broilers in the 25 mg/kg ammonia group was also lower (P < 0.05. At 42 d, the dressing percentage of broilers in the ammonia treatments and the thigh muscle percentage of broilers in the 50 and 75 mg/kg ammonia groups were lower (P < 0.05 than those in the control. Breast muscle percentage of broilers exposed to 25 and 50 mg/kg ammonia and eviscerated yield percentage exposed to 50 mg/kg ammonia were lower than those in the control (P < 0.05. 2 The kidney index of broilers (d 32 exposed to ammonia was greater (P < 0.05 than that of the control. At 42 d, hepatic index of broilers exposed to ammonia was increased (P < 0.05, and spleen index was decreased (P < 0.05. 3 At 42 d, stearic (C18:0 and saturated fatty acids (SFA in the thigh muscle of broilers were higher, while the unsaturated fatty acid:saturated fatty acid (U:F ratio and unsaturated fatty acid (UFA were lower in the 50 mg/kg ammonia treatment than in the control group (P < 0.05. In conclusion, ammonia over 25 mg/kg could decline carcass traits

A comprehensive study on energy absorption and exposure buildup factors for some essential amino acids, fatty acids and carbohydrates in the energy range 0.015-15 MeV up to 40 mean free path

International Nuclear Information System (INIS)

Kurudirek, Murat; Ozdemir, Yueksel

2011-01-01

The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) have been calculated for some essential amino acids, fatty acids and carbohydrates in the energy region 0.015-15 MeV up to a penetration depth of 40 mfp (mean free path). The five parameter geometric progression (G-P) fitting approximation has been used to calculate both EABF and EBF. Variations of EABF and EBF with incident photon energy, penetration depth and weight fraction of elements have been studied. While the significant variations in EABF and EBF for amino acids and fatty acids have been observed at the intermediate energy region where Compton scattering is the main photon interaction process, the values of EABF and EBF appear to be almost the same for all carbohydrates in the continuous energy region. It has been observed that the fatty acids have the largest EABF and EBF at 0.08 and 0.1 MeV, respectively, whereas the maximum values of EABF and EBF have been observed for aminoacids and carbohydrates at 0.1 MeV. At the fixed energy of 1.5 MeV, the variation of EABF with penetration depth appears to be independent of the variations in chemical composition of the amino acids, fatty acids and carbohydrates. Significant variations were also observed between EABF and EBF which may be due to the variations in chemical composition of the given materials.

Hyperammonemia Associated with Valproic Acid Concentrations

Directory of Open Access Journals (Sweden)

Marta Vázquez

2014-01-01

Full Text Available Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%. Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.

[Acid-base imbalance in acute obstructive uropathies].

Science.gov (United States)

Belyĭ, L E

2007-01-01

The aim of this study was to evaluate impairment of acid-base balance (ABB) in acute obstructive uropathies. Evaluation of acid-base balance was performed by pH, partial carbon dioxide pressure, plasma bicarbonate concentration, buffer bases, basis excess, hydrogen ion concentration. An automatic gas analyzer was used, plasma anion gap was calculated. Characteristic ABB alterations in different acute obstructive uropathies were detected. Acidotic shifts in acute obstruction of the upper urinary tracts and its inflammatory complications were assessed pathophysiologically. A comparative study of pathological acid-base disorders in acute supra- and infravesical obstructive uropathies was performed.

Protective effect of 4-coumaric acid from UVB ray damage in the rabbit eye.

Science.gov (United States)

Lodovici, Maura; Caldini, Silvia; Morbidelli, Lucia; Akpan, Victor; Ziche, Marina; Dolara, Piero

2009-01-08

UV-induced oxidation damage seems to play a major role in a number of specific pathological conditions of intraocular tissues, such as cataract formation and retinal degeneration. Therefore, antioxidant and/or scavenger compounds might protect the eyes from UV-induced cellular damage. We previously reported that 4-coumaric acid (4-CA) is able to protect rabbit corneal-derived cells (SIRC) from UVB-induced oxidation damage. In this study we evaluated the protective effect of 4-CA against UVB-induced cell damage in rabbit cornea in vivo. Twelve male New Zealand albino rabbits were used; four rabbits were used as a control and received vehicle in one eye and 4-CA acid in the contralateral eye; eight rabbits were exposed to UVB rays (79.2mJ/cm(2)) and three days before to UV exposure each animal received 1 drop/day of vehicle in one eye and 1 drop/day of vehicle containing 4-CA (164ng) in the contralateral eye. Corneal and sclera tissues were removed and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels were measured. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities were determined in aqueous humour. UVB-induced vessel hyper-reactivity was strongly reduced at 4 and 24h after UVB exposure after local treatment with 4-CA, 8-oxodGuo levels, a marker of oxidative DNA damage, were significantly increased (Peyes. Our results indicate that the administration of 4-CA protects eye tissues, thus reducing the harmful effect of UVB radiation at low concentration, probably through its free radical scavenging and antioxidant properties. Therefore, 4-CA may be useful in protecting the eye from free radical damage following UVB exposure from sunlight, UV lamps and welding torches.

Occupational Exposure of Petroleum Depot Workers to BTEX Compounds

Directory of Open Access Journals (Sweden)

M Rezazadeh Azari

2011-12-01

Full Text Available Background: Benzene, toluene, ethylbenzene and xylene (BTEX are the most important toxic volatile compounds in the air and could be easily absorbed through the respiratory tract. In recent years, the risk of exposure to BTEX compounds, especially benzene as a carcinogen, has been considered in petroleum depot stations. Objective: To assess the occupational exposure of petroleum depot workers in Iran to BTEX compounds. Methods: After completing a questionnaire and assessing occupational exposure to BTEX compounds, 78 (46 exposed and 32 non-exposed depot workers were randomly selected to participate in this study. Air sampling and analysis of BTEX was conducted according to the NIOSH method No. 1501. Analysis of urinary hippuric acid, as an indicator of toluene exposure, was carried out according to NIOSH method No. 8300. Personal monitoring of the high exposure group to BTEX compounds was repeated to verify the results obtained in the first phase of the monitoring. Results: Among the 9 operating groups studied, occupational exposure to benzene and toluene was higher in quality control and gasoline loading operators—the median exposure ranged from 0.16 to 1.63 ppm for benzene and 0.2 to 2.72 ppm for toluene. Median exposure of other group members to BTEX compounds was below the detection limit of analytical method (0.07, 0.06, 0.05, and 0.05 ppm, respectively. The level of toluene exposure measured showed correlation with neither post-shift urinary hippuric acid (Spearman's rho=0.128, p=0.982 nor with the difference between post- and pre-shift urinary hippuric acid (Spearman's rho=0.089, p=0.847 in depot operational workers. Conclusion: Gasoline loading operators are exposed to a relatively high level of benzene.

Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes

International Nuclear Information System (INIS)

Aspenstroem-Fagerlund, Bitte; Ring, Linda; Aspenstroem, Pontus; Tallkvist, Jonas; Ilbaeck, Nils-Gunnar; Glynn, Anders W.

2007-01-01

Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90 min to mannitol in emulsions of oleic acid (5, 15 or 30 mM) or DHA (5, 15 or 30 mM) in an experimental medium with or without Ca 2+ and Mg 2+ . Absorption of 14 C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30 mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5 mM DHA for 90 min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for β-catenin. Oleic acid (30 mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180 min to 250 nM cadmium (Cd) in emulsions of oleic acid (5 or 30 mM) or DHA (1 or 5 mM), in an experimental medium with Ca 2+ and Mg 2+ . Retention of Cd in Caco-2 cells was higher after exposure to 5 mM oleic acid but lower after exposure to 30 mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly

DNA fragmentation dynamics allows the assessment of cryptic sperm damage in human: Evaluation of exposure to ionizing radiation, hyperthermia, acidic pH and nitric oxide

Energy Technology Data Exchange (ETDEWEB)

Santiso, Rebeca; Tamayo, Maria [Laboratorio de Genetica Molecular y Radiobiologia, Centro Oncologico de Galicia, Doctor Camilo Veiras 1, 15009-A Coruna (Spain); Genetics Unit, INIBIC-Complejo Hospitalario Universitario A Coruna (CHUAC), As Xubias, 84, 15006-A Coruna (Spain); Gosalvez, Jaime [Genetics Unit, Facultad de Biologia, Universidad Autonoma de Madrid, Ciudad Universitaria de Cantoblanco, 28049 Madrid (Spain); Johnston, Steve [School of Agriculture and Food Science, University of Queensland, Gatton 4343 (Australia); Marino, Alfonso [Servicio de Oncologia Radioterapica, Centro Oncologico de Galicia, Doctor Camilo Veiras 1, 15009-A Coruna (Spain); Fernandez, Carlos; Losada, Carlos [Servicio de Radiofisica, Centro Oncologico de Galicia, Doctor Camilo Veiras 1, 15009-A Coruna (Spain); Fernandez, Jose Luis, E-mail: Jose.Luis.Fernandez.Garcia@sergas.es [Laboratorio de Genetica Molecular y Radiobiologia, Centro Oncologico de Galicia, Doctor Camilo Veiras 1, 15009-A Coruna (Spain); Genetics Unit, INIBIC-Complejo Hospitalario Universitario A Coruna (CHUAC), As Xubias, 84, 15006-A Coruna (Spain)

2012-06-01

Sperm DNA fragmentation (SDF) is not a static seminal parameter, since the longevity of sperm DNA decreases progressively with time following ejaculation or thawing. While the dynamics of SDF is a species-specific characteristic, in the case of humans, there is still significant variation within patients. To evaluate the suitability of the dynamic SDF assay to assess the adverse effects of agents that cause genetic damage, fresh semen samples from different donors were exposed in vitro to (1) increasing acute doses of ionizing radiation, (2) elevated temperature (41 Degree-Sign C and 45 Degree-Sign C), (3) acidic pH (pH 4) and (4) the nitric oxide (NO) donor sodium nitroprusside (SNP). Sperm DNA fragmentation was analyzed after an incubation period of chronic (24 h), or acute (1 h) exposure to each treatment followed by incubation at 37 Degree-Sign C over a period of 24 h. SDF was assessed using the sperm chromatin dispersion (SCD) test. Dynamic SDF for each treatment was analyzed using Kaplan-Meier survival curves. All agents, except for ionizing radiation, accelerated SDF kinetics following chronic exposure over a 24 h period. Transient exposure to NO and heat but not acidic pH increased the basal (T0) level of SDF. Despite the removal of the three toxicants, the remaining sperm following acute exposure showed a decrease in their expected DNA longevity. It is concluded that the assessment of sperm DNA fragmentation dynamics is an effective methodological approach for revealing latent damage associated with toxicants that is not initially expressed following a single initial observation of SDF.

Slot Machine Response Frequency Predicts Pathological Gambling

DEFF Research Database (Denmark)

Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

2013-01-01

Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

Science.gov (United States)

Centuori, Sara M; Martinez, Jesse D

2014-10-01

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

AMINO ACIDS APPLICATION TO CREATE OF NANOSTRUCTURES

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I. S. Chekman

2014-12-01

Full Text Available Review is devoted to the amino acids that could be used for nanostructures creation. The investigation of corresponding properties of amino acids is essential for their role definition in creation of nanomedicines. However, amino acid studying as components of nanostructures is insufficient. Study of nanoparticles for medicines creation was initiated by the development of nanotechnology. Amino acids in complexes with the nanoparticles of organic and inorganic nature play an important role for medicines targeting in pathological process. They could reduce toxicity of the nanomaterials used in nanomedicine and are used for creation of biosensors, lab-on-chip and therefore they are a promising material for synthesis of new nanodrugs and diagnostic tools.

The association between phthalate exposure and asthma

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Ming-Ju Tsai

2012-07-01

Full Text Available Asthma is a chronic inflammatory disorder of the airway, characterized by airway hyperresponsiveness. It is a disabling disease with an increasing prevalence, resulting in heavy social and economic burdens worldwide. Humans are extensively exposed to phthalates, and many epidemiological studies have shown a relationship between phthalate exposure and asthma in recent decades. Earlier experimental studies focused on inflammatory cells, demonstrating the adjuvant effects, immunomodulatory effects, or immunosuppressive effects related to phthalate exposure. Recent studies have shown that phthalates may have a direct effect on airway epithelial cells and contribute to airway remodeling, which is the cardinal pathologic characteristic of chronic asthma, with a high correlation with disease severity. Through these efforts, phthalates have been recognized as important environmental factors in the pathogenesis of asthma, but further studies are still required to elucidate the detailed mechanism. This review discusses the current status of human exposure to phthalates in Taiwan and summarizes the epidemiological and experimental evidence related to the roles of phthalate exposure in the development of asthma and associated diseases.

Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

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Carla Ferreri

2016-12-01

Full Text Available Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress—with an excess of radical and oxidative processes—cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1; and (ii the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.

Podocyte Pathology and Nephropathy

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Sandra eMerscher

2014-07-01

Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

42 CFR 493.853 - Condition: Pathology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes of...

Development and use of a genitourinary pathology digital teaching set for trainee education

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Li Li

2010-01-01

Full Text Available Background : Automated, high-speed, high-resolution whole slide imaging (WSI robots are becoming increasingly robust and capable. This technology has started to have a significant impact on pathology practice in various aspects including resident education. To be sufficient and adequate, training in pathology requires gaining broad exposure to various diagnostic patterns through teaching sets, which are traditionally composed of glass slides. Methods: A teaching set of over 295 glass slides has been used for resident training at the Division of Genitourinary Pathology, Department of Pathology, University of Pittsburgh Medical Center. Whole slide images were prepared from these slides using an Aperio ScanScope CS scanner. These images and case-related information were uploaded on a web-based digital teaching model. Results: The web site is available at: https://www.secure.opi.upmc.edu/genitourinary/index.cfm. Once logged in, users can view the list of cases, or search cases with or without diagnoses shown. Each case can be accessed through an option button, where the clinical history, gross findings are initially shown. Whole slide images can be accessed through the links on the page, which allows users to make diagnoses on their own. More information including final diagnosis will display when the diagnosis-button is clicked. Conclusion: The web-based digital study set provides additional educational benefits to using glass slides. Residents or other users can remotely access whole slide images and related information at their convenience. Searching and sorting functions and self-testing mode allow a more targeted study. It would also prepare residents with competence to work with whole slide images. Further, the model can be expanded to include pre-rotation and post-rotation exams, and/or a virtual rotation system, which may potentially make standardization of pathology resident training possible in the future.

Pathological fractures in children

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De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

2012-01-01

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

Science.gov (United States)

Mortimer, James A

2012-07-01

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.

Science.gov (United States)

Meyer, Stephanie K; Probert, Philip M E; Lakey, Anne F; Axon, Andrew R; Leitch, Alistair C; Williams, Faith M; Jowsey, Paul A; Blain, Peter G; Kass, George E N; Wright, Matthew C

2017-05-05

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Culturally diverse attitudes and beliefs of students majoring in speech-language pathology.

Science.gov (United States)

Franca, Maria Claudia; Smith, Linda McCabe; Nichols, Jane Luanne; Balan, Dianna Santos

Academic education in speech-language pathology should prepare students to provide professional services that mirror current knowledge, skills, and scope of practice in a pluralistic society. This study seeks to examine the impact of speech-language pathology (SLP) students prior multicultural experiences and previous formal education on attitudes and beliefs toward language diversity. A survey to investigate SLP students attitudes toward language diversity was applied. After the research study and instructions to complete the consent form questionnaire was presented by a research assistant, an announcement was given by a graduate student who speaks English as a second language with an accent. The participants then completed a questionnaire containing questions related to attitudes about the presentation of the announcement in particular and toward language diversity in general. Responses suggested a relationship between self-reported cultural bias and ability to concentrate on speech with an accent, and the extent of interaction with individuals from a cultural and linguistic diverse (CLD) background. Additional outcomes revealed that cultural bias may be predicted by factors related to amount of CLD exposure. Results of this study indicated critical areas that need to be considered when developing curricula in speech-language pathology programs. The results will be useful in determining procedures applicable in larger investigations, and encourage future research on attitudes and beliefs toward aspects of cultural diversity.

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

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Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

2013-11-01

Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

Communication skills in diagnostic pathology.

Science.gov (United States)

Lehr, Hans-Anton; Bosman, Fred T

2016-01-01

Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

Clinical and pathological features of dense deposit disease in Chinese patients.

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Wang, Jinquan; Tang, Zheng; Luo, Chunlei; Hu, Yanglin; Zeng, Caihong; Chen, Huiping; Liu, Zhihong

2012-09-01

Dense deposit disease (DDD) is a rare disease that has no universally effective treatment. Herein we explore the clinical and pathological features of DDD in Chinese patients and the therapeutic effect of Tripterygium wilfordii (TW). Clinical and pathological data of 10 Chinese patients with biopsy-proved DDD were collected and analyzed retrospectively. The patients consisted of 6 males and 4 females. All of them had heavy proteinuria and microscopic hematuria. Gross hematuria, renal insufficiency, anemia, hypertension and low serum complement 3 (C3) occurred in 3, 3, 5, 6 and 8 cases, respectively. Under light microscopy (LM), 8 cases exhibited membranoproliferative glomerulonephritis (MPGN). Periodic acid-Schiff (PAS) stain disclosed intense PAS-positive bright ribbon-like thickening of glomerular basement membranes (GBM). Immunofluorescence mainly showed diffuse fine granular and short linear deposition of C3 along the glomerular capillary wall. Under electron microscopy, ribbon-like electrondense intramembranous deposits were identified in the lamina densa of the GBM, along the tubule basement membranes (TBM) and wall of Bowman's capsule. Before admission, 6 cases were treated with prednisone, cyclophosphamide and/or cyclosporin A with no response. Proteinuria in 8 cases who received TW during the course decreased at different degrees. The clinical and pathological features in DDD patients were various. The effect of TW in patients with DDD merits further investigation.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

Science.gov (United States)

Roman, S; Gyawali, C P; Savarino, E; Yadlapati, R; Zerbib, F; Wu, J; Vela, M; Tutuian, R; Tatum, R; Sifrim, D; Keller, J; Fox, M; Pandolfino, J E; Bredenoord, A J

2017-10-01

An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled. © 2017 John Wiley & Sons Ltd.

Evolution of the Pathology Residency Curriculum

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Wesley Y. Naritoku MD, PhD

2016-10-01

Full Text Available The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s. To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1 reflect upon what are the critical need subjects, (2 identify areas that have become of lesser importance, and then (3 prioritize training accordingly.

Evolution of the Pathology Residency Curriculum

Science.gov (United States)

Powell, Suzanne Z.; Black-Schaffer, W. Stephen

2016-01-01

The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s). To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1) reflect upon what are the critical need subjects, (2) identify areas that have become of lesser importance, and then (3) prioritize training accordingly. PMID:28725779

Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study.

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Stuart G Snowden

2017-03-01

Full Text Available The metabolic basis of Alzheimer disease (AD pathology and expression of AD symptoms is poorly understood. Omega-3 and -6 fatty acids have previously been linked to both protective and pathogenic effects in AD. However, to date little is known about how the abundance of these species is affected by differing levels of disease pathology in the brain.We performed metabolic profiling on brain tissue samples from 43 individuals ranging in age from 57 to 95 y old who were stratified into three groups: AD (N = 14, controls (N = 14 and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD neuropathology at death but without evidence for cognitive impairment during life (N = 15 from the autopsy sample of the Baltimore Longitudinal Study of Aging (BLSA. We measured 4,897 metabolite features in regions both vulnerable in the middle frontal and inferior temporal gyri (MFG and ITG and resistant (cerebellum to classical AD pathology. The levels of six unsaturated fatty acids (UFAs in whole brain were compared in controls versus AD, and the differences were as follows: linoleic acid (p = 8.8 x 10-8, FC = 0.52, q = 1.03 x 10-6, linolenic acid (p = 2.5 x 10-4, FC = 0.84, q = 4.03 x 10-4, docosahexaenoic acid (p = 1.7 x 10-7, FC = 1.45, q = 1.24 x 10-6, eicosapentaenoic acid (p = 4.4 x 10-4, FC = 0.16, q = 6.48 x 10-4, oleic acid (p = 3.3 x 10-7, FC = 0.34, q = 1.46 x 10-6, and arachidonic acid (p = 2.98 x 10-5, FC = 0.75, q = 7.95 x 10-5. These fatty acids were strongly associated with AD when comparing the groups in the MFG and ITG, respectively: linoleic acid (p ASYMAD>AD and increases in docosahexanoic acid (AD>ASYMAD>control may represent regionally specific threshold levels of these metabolites beyond which the accumulation of AD pathology triggers the expression of clinical symptoms. The main limitation of this study is the relatively small sample size. There are few cohorts with extensive longitudinal cognitive assessments

Chronic ethanol exposure induces SK-N-SH cell apoptosis by increasing N-methyl-D-aspartic acid receptor expression and intracellular calcium.

Science.gov (United States)

Wang, Hongbo; Wang, Xiaolong; Li, Yan; Yu, Hao; Wang, Changliang; Feng, Chunmei; Xu, Guohui; Chen, Jiajun; You, Jiabin; Wang, Pengfei; Wu, Xu; Zhao, Rui; Zhang, Guohua

2018-04-01

It has been identified that chronic ethanol exposure damages the nervous system, particularly neurons. There is scientific evidence suggesting that neuronal loss caused by chronic ethanol exposure has an association with neuron apoptosis and intracellular calcium oscillation is one of the primary inducers of apoptosis. Therefore, the present study aimed to investigate the inductive effects of intracellular calcium oscillation on apoptosis in SK-N-SH human neuroblastoma cells and the protective effects of the N-methyl-D-aspartic acid receptor (NMDAR) antagonist, memantine, on SK-N-SH cell apoptosis caused by chronic ethanol exposure. SK-N-SH cells were treated with 100 mM ethanol and memantine (4 µM) for 2 days. Protein expression of NR1 was downregulated by RNA interference (RNAi). Apoptosis was detected by Annexin V/propidium iodide (PI) double-staining and flow cytometry and cell viability was detected using an MTS kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration and the levels of NR1 and caspase-3 were detected using western blotting. NR1 mRNA levels were also detected using qPCR. It was found that chronic ethanol exposure reduced neuronal cell viability and caused apoptosis of SK-N-SH cells, and the extent of damage in SK-N-SH cells was associated with ethanol exposure concentration and time. In addition, chronic ethanol exposure increased the concentration of intracellular calcium in SK-N-SH cells by inducing the expression of NMDAR, resulting in apoptosis, and memantine treatment reduced ethanol-induced cell apoptosis. The results of the present study indicate that the application of memantine may provide a novel strategy for the treatment of alcoholic dementia.

Radiographic pathology for technologists

International Nuclear Information System (INIS)

Mace, J.D.; Kowalczyk, N.

1988-01-01

This book explains the fundamentals of disease mechanisms and relates this to the practice of radiologic science. Each chapter begins with a discussion of normal anatomy and physiology, then covers pathology and demonstrates how the pathology appears on film. Imaging modalities such as computed tomography, MRI, and ultrasound are also discussed. Clinical case studies are included

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

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Maryam Goudarzi

2016-05-01

Full Text Available With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR of 3.0 mGy/min and a high dose rate (HDR of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs and Strontium-90 (90Sr. The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation.

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation.

Science.gov (United States)

Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J; Weber, Waylon M; Brenner, David J; Fornace, Albert J

2016-05-20

With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; external γ irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 ((137)Cs) and Strontium-90 ((90)Sr). The multiple reaction monitoring analysis showed that, while exposure to (137)Cs and (90)Sr induced a statistically significant and persistent decrease, similar doses of external γ beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to (90)Sr and (137)Cs and to external γ beam radiation.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

Science.gov (United States)

Tucker, Deirdre K; Macon, Madisa B; Strynar, Mark J; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E

2015-07-01

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. Published by Elsevier Inc.

The effect of time in the exposure of theobromine gel to enamel and surface hardness after demineralization with 1% citric acid

Science.gov (United States)

Irawan, M. I. P.; Noerdin, A.; Eriwati, Y. K.

2017-08-01

Theobromine is one of the alkaloid compounds that can be found in cacao (Theobroma cacao). It is said that theobromine can prevent enamel demineralization. The aim of this research was to evaluate the effect of different exposure times to 200 mg/L theobromine gel on enamel microhardness after demineralization in 1% citric acid. Twenty-eight specimens of human premolar teeth were divided into four groups and were immersed in 1% citric acid (pH 4) for 2.5 minutes. Then 200 mg/L theobromine gel was exposed to the specimens for 16 minutes (n = 7), 48 minutes (n = 7), and 96 minutes (n = 7). Enamel microhardness (KHN) values were tested using the Knoop Microhardness Tester (Shimadzu, Japan) using a 50-gram load for 5 seconds. A statistical test was performed using the Friedman test, Wilcoxon test, Kruskal-Wallis test, and Mann-Whitney test. The results showed a significant decrease, of microhardness values after demineralization with 1% citric acid. There was also a significant increase in hardness (penamel microhardness.

Endocrine pathology: past, present and future.

Science.gov (United States)

Asa, Sylvia L; Mete, Ozgur

2018-01-01

Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system. This relatively young subspecialty was initially focused mainly on thyroid and parathyroid pathology, with some participants also involved in studies of the pituitary, the endocrine pancreas, and the adrenal glands. However, the endocrine system involves much more than these traditional endocrine organs and the discipline has grown to encompass lesions of the dispersed neuroendocrine cells, including neuroendocrine tumours (NETs) of the lungs, gastrointestinal tract, thymus, breast and prostate, as well as paraganglia throughout the body, not just in the adrenals. Indeed, the production of hormones is the hallmark of the endocrine system, and some aspects of gynecological/testicular, bone and liver pathology also fall into the realm of this specialty. Many of the lesions that are the focus of this discipline are increasing in incidence and their pathology is becoming more complex with increased understanding of molecular pathology and a high incidence of familial disease. The future of endocrine pathology will demand a depth of understanding of structure, function, prognosis and prediction as pathologists play a key role in the multidisciplinary care team of patients with endocrine diseases. It is anticipated that new technologies will allow increased subspecialisation in pathology and growth of this important area of expertise. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

[Dual pathology].

Science.gov (United States)

Rougier, A

2008-05-01

Dual pathology is defined as the association of two potentially epileptogenic lesions, hippocampal (sclerosis, neuronal loss) and extrahippocampal (temporal or extratemporal). Epileptic activity may be generated by either lesion and the relative importance of every lesion's epileptogenicity conditions the surgical strategy adopted. Most frequently associated with hippocampal sclerosis are cortical dysplasias. The common physiopathology of the two lesions is not clearly established. Extrahippocampal lesions may be undetectable on MRI (microdysgenesis, for example) and ictal discharge patterns may vary among dual pathology patients. The surgical strategy depends on the location of the extrahippocampal lesion and its relative role in seizure generation; however, reported surgical results suggest that simultaneous resection of mesial temporal structures along with the extrahippocampal lesion should be performed.

Uric Acid, Hyperuricemia and Vascular Diseases

Science.gov (United States)

Jin, Ming; Yang, Fan; Yang, Irene; Yin, Ying; Luo, Jin Jun; Wang, Hong; Yang, Xiao-Feng

2011-01-01

Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation. PMID:22201767

Hip joint pathology

DEFF Research Database (Denmark)

Tijssen, M; van Cingel, R E H; de Visser, E

2017-01-01

The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18......-65 years) were included if they were referred to a physical therapist to gather pre-operative data and were then diagnosed during arthroscopy. Results of pre-operative patient history and physical tests were collected and compared to arthroscopy. Data of 77 active patients (mean age: 37 years) were...

Levels of Cs-137 and pathological shifts in the organs and tissues of dead humans

International Nuclear Information System (INIS)

Lushnikov, E.F.; Koleganov, Yu.F.; Lantsov, S.I.; Mozhaev, V.K.; Solov'eva, L.P.; Fomin, S.D.

1996-01-01

Measurements of the levels of Cs-137, alpha- and beta-radionuclides in the organs and tissues of 30 subjects dead 6 years after the accident, assessment of the pathological shifts and relationships between these shifts and exposure was carried out at territories contaminated with radionuclides in the Bryansk and Kaluga districts, in the town of Obninsk, and in region of Russia free of radionuclides. Study of radioautographs did not show alpha- or beta-radionuclides in any of the dead subjects. Cs-137 was detected in small quantities in the organs of all cadavers (3 to 424 Bq/kg) irrespective of their residence. The extent of radioactivity varied for different organs and was unrelated to organ pathology. Moreover, Cs-137 was detected in the organs of dead newborns and two-month-old infants, whose patients lived at territories contaminated with radionuclides [ru

Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum

NARCIS (Netherlands)

de Vries, D. R.; van Herwaarden, M. A.; Smout, A. J. P. M.; Samsom, M.

2009-01-01

Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring

The role of organic acids exuded from roots in phosphorus nutrition and aluminium tolerance in acidic soils

Energy Technology Data Exchange (ETDEWEB)

Hocking, P J; Randall, P J; Delhaize, E [CSIRO Plant Industry, Canberra (Australia); Keerthisinghe, G [International Atomic Energy Agency, Vienna (Austria)

2000-06-01

Soil acidity is a major problem of large areas of arable land on a global scale. Many acid soils are low in plant-available phosphorus (P) or are highly P-fixing, resulting in poor plant growth. In addition, aluminium (Al) is soluble in acid soils in the toxic Al{sup 3+} form, which also reduces plant growth. There is considerable evidence that both P deficiency and exposure to Al{sup 3+} stimulate the efflux of organic acids from roots of a range of species. Organic acids such as citrate, malate and oxalate are able to desorb or solubilise fixed soil P, making it available for plant uptake. Organic acids also chelate Al{sup 3+} to render it non-toxic, and are, therefore, involved in Al tolerance mechanisms. In this review, we discuss the literature on the role of organic acids exuded from roots in improving plant P uptake and Al-tolerance in acid soils. Research is now attempting to understand how P deficiency or exposure to Al{sup 3+} activates or induces organic acid efflux at the molecular level, with the aim of improving P acquisition and Al tolerance by conventional plant breeding and by genetic engineering. At the agronomic level, it is desirable that existing crop and pasture plants with enhanced soil-P uptake and tolerance to Al due to organic acid exudation are integrated into farming systems. (author)

The role of organic acids exuded from roots in phosphorus nutrition and aluminium tolerance in acidic soils

International Nuclear Information System (INIS)

Hocking, P.J.; Randall, P.J.; Delhaize, E.; Keerthisinghe, G.

2000-01-01

Soil acidity is a major problem of large areas of arable land on a global scale. Many acid soils are low in plant-available phosphorus (P) or are highly P-fixing, resulting in poor plant growth. In addition, aluminium (Al) is soluble in acid soils in the toxic Al 3+ form, which also reduces plant growth. There is considerable evidence that both P deficiency and exposure to Al 3+ stimulate the efflux of organic acids from roots of a range of species. Organic acids such as citrate, malate and oxalate are able to desorb or solubilise fixed soil P, making it available for plant uptake. Organic acids also chelate Al 3+ to render it non-toxic, and are, therefore, involved in Al tolerance mechanisms. In this review, we discuss the literature on the role of organic acids exuded from roots in improving plant P uptake and Al-tolerance in acid soils. Research is now attempting to understand how P deficiency or exposure to Al 3+ activates or induces organic acid efflux at the molecular level, with the aim of improving P acquisition and Al tolerance by conventional plant breeding and by genetic engineering. At the agronomic level, it is desirable that existing crop and pasture plants with enhanced soil-P uptake and tolerance to Al due to organic acid exudation are integrated into farming systems. (author)

Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1970-1992: The JANUS Program Survival and Pathology Data

International Nuclear Information System (INIS)

Grahn, D.; Wright, B.J.; Carnes, B.A.; Williamson, F.S.; Fox, C.

1995-02-01

A research reactor for exclusive use in experimental radiobiology was designed and built at Argonne National Laboratory in the 1960's. It was located in a special addition to Building 202, which housed the Division of Biological and Medical Research. Its location assured easy access for all users to the animal facilities, and it was also near the existing gamma-irradiation facilities. The water-cooled, heterogeneous 200-kW(th) reactor, named JANUS, became the focal point for a range of radiobiological studies gathered under the rubic of open-quotes the JANUS programclose quotes. The program ran from about 1969 to 1992 and included research at all levels of biological organization, from subcellular to organism. More than a dozen moderate- to large-scale studies with the B6CF 1 mouse were carried out; these focused on the late effects of whole-body exposure to gamma rays or fission neutrons, in matching exposure regimes. In broad terms, these studies collected data on survival and on the pathology observed at death. A deliberate effort was made to establish the cause of death. This archieve describes these late-effects studies and their general findings. The database includes exposure parameters, time of death, and the gross pathology and histopathology in codified form. A series of appendices describes all pathology procedures and codes, treatment or irradiation codes, and the manner in which the data can be accessed in the ORACLE database management system. A series of tables also presents summaries of the individual experiments in terms of radiation quality, sample sizes at entry, mean survival times by sex, and number of gross pathology and histopathology records

Studies of acute and chronic radiation injury at the Biological and Medical Research Division, Argonne National Laboratory, 1970-1992: The JANUS Program Survival and Pathology Data

Energy Technology Data Exchange (ETDEWEB)

Grahn, D.; Wright, B.J.; Carnes, B.A.; Williamson, F.S.; Fox, C.

1995-02-01

A research reactor for exclusive use in experimental radiobiology was designed and built at Argonne National Laboratory in the 1960`s. It was located in a special addition to Building 202, which housed the Division of Biological and Medical Research. Its location assured easy access for all users to the animal facilities, and it was also near the existing gamma-irradiation facilities. The water-cooled, heterogeneous 200-kW(th) reactor, named JANUS, became the focal point for a range of radiobiological studies gathered under the rubic of {open_quotes}the JANUS program{close_quotes}. The program ran from about 1969 to 1992 and included research at all levels of biological organization, from subcellular to organism. More than a dozen moderate- to large-scale studies with the B6CF{sub 1} mouse were carried out; these focused on the late effects of whole-body exposure to gamma rays or fission neutrons, in matching exposure regimes. In broad terms, these studies collected data on survival and on the pathology observed at death. A deliberate effort was made to establish the cause of death. This archieve describes these late-effects studies and their general findings. The database includes exposure parameters, time of death, and the gross pathology and histopathology in codified form. A series of appendices describes all pathology procedures and codes, treatment or irradiation codes, and the manner in which the data can be accessed in the ORACLE database management system. A series of tables also presents summaries of the individual experiments in terms of radiation quality, sample sizes at entry, mean survival times by sex, and number of gross pathology and histopathology records.

Pre-exposure Schedule Effects on Generalization of Taste Aversion and Palatability for Thirsty and Not Thirsty Rats

Directory of Open Access Journals (Sweden)

Rocío Angulo

2018-06-01

Full Text Available The study reported four experiments aiming to test the effects of the pre-exposure schedule and water deprivation on the generalization of a conditioned taste aversion in rats, with a particular focus on testing whether or not the concurrent schedule might enhance generalization. In two experiments, non-water-deprived rats received concurrent, intermixed, or blocked exposure to a sweet-acid solution and a salty-acid solution before conditioning of one of these compounds and testing of both flavors. During pre-exposure, the rats consumed a greater amount of the sweet-acid solution than the salty-acid solution (Experiments 1 and 2, consumption of the former increasing during pre-exposure while consumption of the latter decreased (Experiment 1. Furthermore, consumption of the salty-acid solution was lower during concurrent than intermixed or blocked pre-exposure (Experiment 1 and 2 while consumption of the sweet-acid solution was greater during intermixed than concurrent or blocked pre-exposure (Experiment 1. It is discussed whether the pre-exposure schedule might modify stimulus perception beyond the mere enhancement of stimulus differentiation, by, for instance, affecting the palatability of gustatory stimuli. Evidence for enhanced generalization after concurrent pre-exposure was not found for either deprived (Experiments 1, 2, and 3 or non-deprived rats (Experiments 3 and 4, with deprivation leading to a general increase in consumption of both the conditioned and test flavors. This then raised the question of whether or not concurrent pre-exposure to flavors always increases generalization between them. The present study highlights the importance of this issue for various accounts of perceptual learning.

PHYSIOLOGY OF ACID BASE BALANCE

Directory of Open Access Journals (Sweden)

Awati

2014-12-01

Full Text Available Acid-base, electrolyte, and metabolic disturbances are common in the intensive care unit. Almost all critically ill patients often suffer from compound acid-base and electrolyte disorders. Successful evaluation and management of such patients requires recognition of common patterns (e.g., metabolic acidosis and the ability to dissect one disorder from another. The intensivists needs to identify and correct these condition with the easiest available tools as they are the associated with multiorgan failure. Understanding the elements of normal physiology in these areas is very important so as to diagnose the pathological condition and take adequate measures as early as possible. Arterial blood gas analysis is one such tool for early detection of acid base disorder. Physiology of acid base is complex and here is the attempt to simplify it in our day to day application for the benefit of critically ill patients.

Pathological Gambling: Neuropsychopharmacology and Treatment.

Science.gov (United States)

Bullock, Scott A; Potenza, Marc N

2012-02-01

Pathological gambling (PG) affects about 0.2-2% of adults and the impact extends to family members, employers and society as a whole. Recent research has identified similarities in the pathophysiologies of PG and substance use disorders (SUDs). As such, findings regarding SUDs provide a framework for investigating PG. The aims of the manuscript are two-fold. First, we will briefly revivew neural systems implicated in PG. Cortico-limbic circuitry involving the ventral striatum, ventromedial prefrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex are discussed as are the neurotransmitters norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma-aminobutyric acid (GABA). This background will provide a framework for reviewing the psychopharmacological treatments that have been tested for efficacy and safety in treating PG. Of medications, the strongest data suggest the efficacy and tolerability of opioid antagonists in the treatment of PG, and other agents have varying degree of empirical support. As behavioral therapies have also shown efficacy, they will be briefly considered as well. Future research is needed to understand how treatments work in PG and for whom specific treatments might work best.

Does folic acid use decrease the risk for spina bifida after in utero exposure to valproic acid?

NARCIS (Netherlands)

Jentink, J.; Bakker, M.K.; Nijenhuis, C.M.; Wilffert, B.; de Jong-van den Berg, L.T.W.

Purpose Women with child wish are advised to take folic acid supplements to reduce the risk for spina bifida. However, there is less evidence for this protective effect in women using valproic acid (VPA). We investigated the effect of folic acid in women exposed to VPA in the first trimester of

Pathological gambling: a general overview.

Science.gov (United States)

Ashley, Larry L; Boehlke, Karmen K

2012-01-01

Throughout the course of history, gambling has been a popular activity across most cultures. In the United States, gambling has transitioned from early acceptance to prohibition to widespread proliferation. For most, gambling is a relaxing and recreational activity; however, for some individuals gambling becomes more than harmless fun. The most severe form of gambling, pathological gambling, is recognized as a mental health disorder. Pathological gambling is currently classified as an impulse control disorder in the DSM-IV-TR, but it shares many important features with substance use disorders, especially in terms of diagnostic criteria, clinical course, and treatment. Consequently, the DSM-V Task Force has suggested that pathological gambling be reclassified and included in a new category entitled "Addiction and Related Disorders." The category would include both substance-related and non-substance/behavioral addictions. This article provides a general overview of some of the available literature regarding pathological gambling and includes the presentation of a number of relevant topics including etiology, risk factors, comorbidity, prevention, and treatment. However, as with most complex, multifaceted, and multidimensional phenomena, more research is needed in order to improve both prevention and treatment efforts for pathological gambling.

Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

Science.gov (United States)

Janero, D R; Burghardt, C; Feldman, D

1988-10-01

Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

Optimization of SPE for Analysis of Mandelic Acid as a Biomarker of Exposure to Ethyl Benzene

Directory of Open Access Journals (Sweden)

SJ Shahtaheri, M Abdollahi, F Golbabaei, A Rahimi-Froushani, F Ghamari

2004-10-01

Full Text Available Ethyl benzene is an important constituent of widely used solvents in industries and laboratories, causing widespread environmental and industrial pollutions. For evaluation of occupational exposure to such pollutants, biological monitoring is an essential process, in which, preparation of environmental and biological samples is one of the most time-consuming and error-prone aspects prior to chromatographic techniques. The use of solid-phase extraction (SPE has been grown and is a fertile technique of sample preparation as it provides better results than those of liquid-liquid extraction (LLE. In this study, SPE using bonded silica has been optimized with regard to sample pH, sample concentration, elution solvent, elution volume, sorbent type, and sorbent mass. Through experimental evaluation, a strong anion exchange silica cartridge (SAX has been found successful in simplifying sample preparation. The present approach proved that, mandelic acid could be retained on SAX sorbent based on specific interaction. Further study was employed using 10% acetic acid to extract the analyte from spiked urine and gave a clean sample for HPLC-UV system. In this study, a high performance liquid chromatography, using reverse-phase column was used. The isocratic run was done at a constant flow rate of 0.85 ml/min, the mobile phase was water/methanol/acetic acid and a UV detector was used, setting at 225 nm. At the developed conditions the extraction recovery was exceeded 98%. The factors were evaluated statically and also validated with three different pools of spiked urine samples and showed a good reproducibility over six consecutive days as well as six within-day experiments.

Utilization management in anatomic pathology.

Science.gov (United States)

Lewandrowski, Kent; Black-Schaffer, Steven

2014-01-01

There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management. © 2013.

Cortical myoclonus and cerebellar pathology

NARCIS (Netherlands)

Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P

2000-01-01

Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

Cortical myoclonus and cerebellar pathology

NARCIS (Netherlands)

Tijssen, M. A.; Thom, M.; Ellison, D. W.; Wilkins, P.; Barnes, D.; Thompson, P. D.; Brown, P.

2000-01-01

OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve

Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood.

Science.gov (United States)

DeAngeli, Nicole E; Todd, Travis P; Chang, Stephen E; Yeh, Hermes H; Yeh, Pamela W; Bucci, David J

2014-01-01

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence.

Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

Science.gov (United States)

DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

2015-01-01

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

Exposure to Kynurenic Acid during Adolescence Increases Sign-tracking and Impairs Long-term Potentiation in Adulthood

Directory of Open Access Journals (Sweden)

Nicole eDeAngeli

2015-01-01

Full Text Available Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently there are few treatments for persons with a dual-diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA, a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with l-kynurenine (L-KYN, the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP. Rats treated with L-KYN exhibited no LTP after a burst of high frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during

Pathologic conditions in pregnancy

International Nuclear Information System (INIS)

Beomonte Zobel, B.; Tella, S.; Innacoli, M.; D'Archivio, C.; Cardone, G.; Masciocchi, C.; Gallucci, M.; Passariello, R.; Cappa, F.

1991-01-01

Soma authors suggested that MR imaging could rapresent an effective diagnostic alternative in the study of pathologic conditions of mother and fetus during pregnancy. To verify the actual role of MR imaging, we examined 20 patients in the 2nd and 3rd trimester of gestation, after a preliminary US examination. Fifteen patients presented fetal or placental pathologies; in 4 patients the onset of the pathologic condition occurred during pregnancy; in 1 case of US diagnosis of fetal ascites, MR findings were nornal and the newborn was healty. As for placental pathologies, our series included a case of placental cyst, two hematomas between placenta and uterine wall, and two cases of partial placenta previa. As for fetal malformation, we evaluated a case of omphalocele, one of Prune-Belly syndrome, a case of femoral asimmetry, one of thanatophoric dwarfism, a case of thoracopagus twins with cardiovascular abnormalities, two fetal hydrocephali, and three cases of pyelo-ureteral stenosis. As for maternal pathologies during pregnancy, we observed a case of subserous uterine fibromyoma, one of of right hydronephrosis, one of protrusion of lumbar invertebral disk, and a large ovarian cyst. In our experience, MR imaging exhibited high sensitivity and a large field of view, which were both useful in the investigation of the different conditions occurring during pregnancy. In the evaluation of fetal and placental abnormalities, especially during the 3rd trimester, the diagnostic yieldof MR imaging suggested it as a complementary technique to US for the evaluation of fetal malformation and of intrauterine growth retardation

Impaired decisional impulsivity in pathological videogamers.

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